ORCID Profile
0000-0002-4177-9503
Current Organisations
Epsom College
,
Calvary Mater Newcastle
,
University College London Medical School
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Biomedical and clinical sciences | Oncology and carcinogenesis | Clinical sciences | Biological sciences | Psychology | Genetics | Pharmacology and pharmaceutical sciences | Clinical and health psychology | Information and computing sciences | Software engineering | Applied and developmental psychology | Midwifery | Dentistry | Analytical chemistry | Engineering | Health sciences | Human society | Commerce, management, tourism and services | Chemical sciences | Gender studies | Medical biotechnology | Electronics, sensors and digital hardware | Reproductive medicine | Tourism
There are no SEO codes available for JAMES DENHAM
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1080/1042819021000015970
Abstract: Telomere length can be used to predict the replicative capacity of haematological progenitor cells and may be an important prognostic factor for the onset of cellular immune dysfunction. However, such measurements require invasive bone marrow (BM) biopsies and laborious stem cell isolations that are impractical in a clinical setting. Previous studies have used peripheral blood (PB) cells as an indicator of stem cell telomere length without demonstrating a correlation. In this study, we examined the telomere length in PB, isolated mononuclear cells (MNC) and BM aspirates from each of 19 patients ranging in age from 45 to 81 years. Correlation analysis confirmed that mean telomere length of BM aspirates was equivalent to that of PB (r = 0.85, P < 0.001), or MNC (r = 0.94, P < 0.001). Since BM is a heterogeneous population of cells, we have also shown in 13 separate patients that the mean telomere length in isolated peripheral blood stem cell (PBSC) harvests was equivalent to that of isolated CD34+ stem cells (r = 0.83, P < 0.001). Thus, telomere length in haemopoietic stem cells can be determined from that of whole or fractionated PB in future studies of haematological disorders.
Publisher: Wiley
Date: 09-02-2017
Abstract: To investigate the accuracy of deriving dose-volume histogram (DVH) parameters from deformably registered data by comparing values with the simple addition of DVHs from each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate (HDR-BT) brachytherapy prostate treatment. Eighty-two patients received EBRT in 23 fractions of 2 Gy and HDR-BT TG43 in three fractions of 6.5 Gy. The HDR-BT CT was deformably registered to the EBRT CT. The rectum D The D Distribution-adding was confounded by unsystematic inter/intra-observer rectum-contouring errors and registration accuracy near the anterior rectal wall. Consequently, clinical use of distribution-adding to assess rectal doses requires careful contour and registration evaluation.
Publisher: Elsevier BV
Date: 1998
DOI: 10.1016/S0167-8140(97)00115-1
Abstract: Two prospective trials were designed to determine whether there may be a role for inflammatory mediators in human skin erythema at both high and low doses per fraction and for 'out of field' effects. Trial 1. Effects of topical indomethacin (1%) and hydrocortisone (1%) applied before and during radiotherapy were compared for erythema induced by 20 Gy in four fractions (n = 26, 6 MV). Trial 2. Effects of topical hydrocortisone (1 %) applied before and during radiotherapy and no medication were compared for erythema induced by 1, 3, 5 and 7 Gy in five fractions (n = 21, 120 kV). Erythema was measured using reflectance spectrophotometry (RFS) and laser Doppler (LD) on a weekly basis. Trial 1. A bi-phasic reaction time course was suggested in two-thirds of the cases. The first phase did not appear to be influenced by hydrocortisone cream but the second was significantly attenuated. Indomethacin had no effect on either reaction phase. Erythema measured several centimetres outside of the field was reduced by hydrocortisone but not by indomethacin. Trial 2. Trial 2 confirmed the presence of measurable erythema, invisible to the eye, that coincided in its time course to the first phase of erythema noted in trial 1. This reaction was more intense than predicted by the LQ formula and was non-significantly attenuated by topical hydrocortisone. RFS readings proved to be less subject to inter- and intra-patient variations than the LD unit used. Inflammatory responses may play a role in the mediation of the erythematous response to radiation in human skin. Further studies are warranted.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.RADONC.2015.10.003
Abstract: This study aimed to compare urinary dose-symptom correlates after external beam radiotherapy of the prostate using commonly utilised peak-symptom models to multiple-event and event-count models which account for repeated events. Urinary symptoms (dysuria, haematuria, incontinence and frequency) from 754 participants from TROG 03.04-RADAR trial were analysed. Relative (R1-R75 Gy) and absolute (A60-A75Gy) bladder dose-surface area receiving more than a threshold dose and equivalent uniform dose using exponent a (range: a ∈[1 … 100]) were derived. The dose-symptom correlates were analysed using peak-symptom (logistic), multiple-event (generalised estimating equation) and event-count (negative binomial regression) models. Stronger dose-symptom correlates were found for incontinence and frequency using multiple-event and/or event-count models. For dysuria and haematuria, similar or better relationships were found using peak-symptom models. Dysuria, haematuria and high grade (⩾ 2) incontinence were associated to high dose (R61-R71 Gy). Frequency and low grade (⩾ 1) incontinence were associated to low and intermediate dose-surface parameters (R13-R41Gy). Frequency showed a parallel behaviour (a=1) while dysuria, haematuria and incontinence showed a more serial behaviour (a=4 to a ⩾ 100). Relative dose-surface showed stronger dose-symptom associations. For certain endpoints, the multiple-event and event-count models provide stronger correlates over peak-symptom models. Accounting for multiple events may be advantageous for a more complete understanding of urinary dose-symptom relationships.
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1016/S0167-8140(03)00193-2
Abstract: To determine the acceptability of short term neo-adjuvant maximal androgen deprivation (MAD) to patients treated with external beam radiation for locally advanced prostate cancer. Between 1996 and 2000, 818 patients with locally advanced, but non-metastatic, prostate cancer were entered into a randomised clinical trial (TROG 96.01), which compared radiation treatment alone with the same radiation treatment and 3 or 6 months neo-adjuvant MAD with goserelin and flutamide. Relevant symptoms, and how troublesome they were to the patient, were scored using a self-assessment questionnaire. This was completed by the patient at registration, and at specified times during and after treatment. Patients taking flutamide had liver function tests checked at regular intervals. All patients have completed at least 12 months follow-up after treatment. Nearly all patients completed planned treatment with goserelin, but 27% of patients in the 6-month MAD treatment arm, and 20% in the 3-month arm, had to stop flutamide early. This was mainly due to altered liver function (up to 17% patients) and bowel side effects (up to 8% patients). However, although flutamide resulted in more bowel symptoms for patients on MAD, there was significant reduction in some urinary symptoms on this treatment. Acute bowel and urinary side effects at the end of radiation treatment were similar in all treatment arms. Side effect severity was unrelated to radiation target volume size, which was reduced by MAD, but symptomatology prior to any treatment was a powerful predictor. Of the 36% of patients who were sexually active before any treatment, the majority became inactive whilst on MAD. However, sexual activity at 12 months after radiation treatment was similar in all treatment arms, indicating that the effects of short term MAD on sexual function are reversible. Despite temporary effects on sexual activity, and compliance difficulties with flutamide, short-term neo-adjuvant MAD was not perceived by patients to be a major inconvenience. If neo-adjuvant MAD in the way tested can be demonstrated to lead to improved biochemical control and/or survival, then patients would view these therapeutic gains as worthwhile. Compliance with short-term goserelin was excellent, confirming that LH-RH analogues have a potential role in more long-term adjuvant treatment. However, for more protracted androgen deprivation, survival advantages and deleterious effects need to be assessed in parallel, in order to determine the optimal duration of treatment.
Publisher: Wiley
Date: 05-1993
DOI: 10.1111/J.1440-1673.1993.TB00053.X
Abstract: Tumour responses in 25 patients with locally advanced head and neck cancer, treated on an experimental fractionated low dose rate (FLDR) teletherapy program are reported. Treatment was given at dose rates ranging from 1.8 to 3 Gy/h to a range of total doses from 32-38 Gy, with palliative intent. The total doses delivered have been predicted by the linear quadratic formula to be equivalent to 33-41 Gy using conventionally fractionated high dose rate treatment, in terms of acute normal tissue effects. A complete response rate (no visible or palpable disease 2 months after treatment) was observed in 28% of cases. Analysis of these response rates suggests that the linear quadratic formula may underestimate the anti-tumour effect of FLDR teletherapy at the various dose rates and total dose permutations in this study.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Elsevier BV
Date: 11-2001
DOI: 10.1016/S0360-3016(01)01689-3
Abstract: To examine whether changes in the effective doubling time of tumor cells during irradiation of head-and-neck cancer are linked to accumulating dose. Optimal fitting of the results of four apparently iso-effective regimens in three recently reported randomized controlled trials (continuous hyperfractionated accelerated radiation therapy [CHART], Radiation Therapy Oncology Group [RTOG] 90-03, and Trans-Tasman Radiation Oncology Group [TROG] 91.01) was attempted using two different types of model of the change in effective doubling time that may occur during treatment. The first involved the traditional approach where doubling time changes at specific times after the start of treatment regardless of fractionation used (''fixed response time'' models). The second is where changes in doubling time are linked to accumulating biologic dose (''cellular depletion'' models). Changes in effective doubling time occur during radiotherapy for head-and-neck cancer. Data from the three trials can be fitted successfully by functions that imply a continuous reduction in effective doubling time. Models linking the reductions in effective doubling time to the cellular depletion that occurs in the tumor during radiotherapy fit the data satisfactorily. Effective doubling time ultimately reduces to 2 days, or slightly less, during high-dose radiotherapy regimens designed to cure squamous head-and-neck cancer. If the assumption of iso-effectivity is justified then this study indicates that the ''repopulation phenomenon'' may be best described by a function that depicts a reduction in effective tumor cell doubling time that decreases continuously during treatment down to a certain minimum value. Furthermore, this reduction may be linked to cellular depletion.
Publisher: Springer Science and Business Media LLC
Date: 14-11-2016
DOI: 10.1007/S13246-016-0496-0
Abstract: Perirectal space segmentation in computed tomography images aids in quantifying radiation dose received by healthy tissues and toxicity during the course of radiation therapy treatment of the prostate. Radiation dose normalised by tissue volume facilitates predicting outcomes or possible harmful side effects of radiation therapy treatment. Manual segmentation of the perirectal space is time consuming and challenging in the presence of inter-patient anatomical variability and may suffer from inter- and intra-observer variabilities. However automatic or semi-automatic segmentation of the perirectal space in CT images is a challenging task due to inter patient anatomical variability, contrast variability and imaging artifacts. In the model presented here, a volume of interest is obtained in a multi-atlas based segmentation approach. Un-supervised learning in the volume of interest with a Gaussian-mixture-modeling based clustering approach is adopted to achieve a soft segmentation of the perirectal space. Probabilities from soft clustering are further refined by rigid registration of the multi-atlas mask in a probabilistic domain. A maximum a posteriori approach is adopted to achieve a binary segmentation from the refined probabilities. A mean volume similarity value of 97% and a mean surface difference of 3.06 ± 0.51 mm is achieved in a leave-one-patient-out validation framework with a subset of a clinical trial dataset. Qualitative results show a good approximation of the perirectal space volume compared to the ground truth.
Publisher: Wiley
Date: 05-1992
DOI: 10.1111/J.1440-1673.1992.TB03101.X
Abstract: A questionnaire has been completed by 16 practising Radiation Oncologists from 10 centres in Australia and New Zealand which confirms that considerable variation in dose normalisation and specification practices exists between Australasian centres. The establishment of a working party to determine whether a uniform code of practice (such as ICRU 29 or a modification thereof) is desirable, and can be adopted in Australasia, is recommended.
Publisher: Wiley
Date: 10-2008
DOI: 10.1111/J.1440-1673.2008.02006.X
Abstract: The aims of this study were to investigate whether intrafraction prostate motion can affect the accuracy of online prostate positioning using implanted fiducial markers and to determine the effect of prostate rotations on the accuracy of the software-predicted set-up correction shifts. Eleven patients were treated with implanted prostate fiducial markers and online set-up corrections. Orthogonal electronic portal images were acquired to determine couch shifts before treatment. Verification images were also acquired during treatment to assess whether intrafraction motion had occurred. A limitation of the online image registration software is that it does not allow for in-plane prostate rotations (evident on lateral portal images) when aligning marker positions. The accuracy of couch shifts was assessed by repeating the registration measurements with separate software that incorporates full in-plane prostate rotations. Additional treatment time required for online positioning was also measured. For the patient group, the overall postalignment systematic prostate errors were less than 1.5 mm (1 standard deviation) in all directions (range 0.2-3.9 mm). The random prostate errors ranged from 0.8 to 3.3 mm (1 standard deviation). One patient exhibited intrafraction prostate motion, resulting in a postalignment prostate set-up error of more than 10 mm for one fraction. In 14 of 35 fractions, the postalignment prostate set-up error was greater than 5 mm in the anterior-posterior direction for this patient. Maximum prostate rotations measured from the lateral images varied from 2 degrees to 20 degrees for the patients. The differences between set-up shifts determined by the online software without in-plane rotations to align markers, and with rotations applied, was less than 1 mm (root mean square), with a maximum difference of 4.1 mm. Intrafraction prostate motion was found to reduce the effectiveness of the online set-up for one of the patients. A larger study is required to determine the magnitude of this problem for the patient population. The inability in the current software to incorporate in-plane prostate rotations is a limitation that should not introduce large errors, provided that the treatment isocentre is positioned near the centre of the prostate.
Publisher: Wiley
Date: 27-10-2011
DOI: 10.1118/1.3656946
Publisher: Wiley
Date: 19-06-2015
DOI: 10.1002/CNCR.29457
Publisher: Elsevier BV
Date: 06-1997
DOI: 10.1016/S0167-8140(97)00059-5
Abstract: Hair cortical cell counting (HCCC) represents a non-invasive, in-vivo measure of cell kill in the human integument. Sixty-six patients undergoing conventionally fractionated, external beam radiotherapy for early stage carcinoma of the prostate had groin hair s les counted. This technique is a sensitive and reproducible measure of radiation effect and may have applicability as an in-vivo prediction tool or in the field of biological dosimetry. A repopulative follicular response occurring at 3-4 weeks may explain flattening of the dose response curve.
Publisher: Springer Science and Business Media LLC
Date: 12-2011
Publisher: Elsevier BV
Date: 12-2011
Publisher: Wiley
Date: 05-1999
DOI: 10.1046/J.1440-1673.1999.00638.X
Abstract: The purpose of the present paper was to evaluate treatment outcome after conservative breast surgery or mastectomy followed by simultaneous adjuvant radiotherapy and cyclophosphamide, methotrexate and fluorouracil (CMF) therapy. Two hundred and sixty eight (268) patients were treated at two Australian and two New Zealand centres between 1981 and July 1995. One hundred and sixty-nine patients underwent conservation surgery and 99 had mastectomies. Median follow-up was 53 months. Conventionally fractionated radiation was delivered simultaneously during the first two cycles of CMF, avoiding radiation on the Fridays that the intravenous components of CMF were delivered. In conservatively treated patients, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 34.5 +/- 5.2%, 25.4 +/- 4.5% and 75.5 +/- 4.8%, respectively. Crude incidence of local relapse at 4 years was 6.3% and at regional/distant sites was 26.3%. Highest grades of granulocyte toxicity (< 0.5 x 10(9)/L), moist desquamation, radiation pneumonitis and persistent breast oedema were recorded in 10.7, 8.5, 8.9 and 17.2%, respectively. In patients treated by mastectomy, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 59.7 +/- 7.3%, 56.7 +/- 7.4% and 50.1 +/- 7%. The crude incidence of local relapse at 4 years was 5.6% and at regional/distant sites it was 45.7%. The issue of appropriate timing of adjuvant therapies has become particularly important with the increasing acknowledgement of the value of anthracycline-based regimens. For women in lower risk categories (e.g. 1-3 nodes positive or node negative), CMF may offer a potentially better therapy, particularly where breast-conserving surgical techniques have been used. In such cases CMF allows the simultaneous delivery of radiotherapy with the result of optimum local control, without compromise or regional or systemic relapse rates. Further randomized trials that directly address the optimal integration of the two modalities, such as the one carried out in Boston, are clearly necessary.
Publisher: Elsevier BV
Date: 06-1999
DOI: 10.1016/S0959-8049(99)00065-9
Abstract: The aim of this study was to identify why increasing myelosuppression accompanies increasing age in patients treated for oesophageal cancer by chemoradiation. Weekly neutrophil and platelet counts were obtained throughout treatment in 86 patients undergoing chemoradiation without surgery for oesophageal cancer. One or two cycles of cisplatin 80 mg/m2/day followed by 5-fluorouracil 800 mg/m2/day for 4-5 days were administered during the first and fourth or fifth week of radiotherapy using 2 Gy daily fractions. 44 of the patients underwent 5-fluorouracil pharmacokinetic studies. Multiple regression procedures were used to determine the strength of factors that contribute to initial and nadir neutrophil and platelet counts. The kinetics of myeloid response were evaluated from the rates of disappearance and re-appearance of neutrophils and platelets during treatment. Age, fluorouracil dose (or AUC), baseline body weight and neutrophil (or platelet) count were found to be powerfully and independently predictive of both first neutrophil and platelet nadir count. Baseline neutrophil and platelet counts were also found to correlate negatively with advancing age independently of other factors. The rate of descent of both indices, however, was independent of age, baseline count and fluorouracil dose suggesting that variations in the size of the myeloproliferative compartment prior to treatment were responsible for interpatient variations. In addition, the rate of recovery of both indices was not influenced by age amongst patients in whom data was assessable suggesting that proliferation of surviving marrow elements is not compromised by age. These data are compatible with the hypothesis that a progressive depletion of the myeloid stem cell compartment accompanies advancing age, and that this is responsible for increasing myelotoxicity.
Publisher: IOP Publishing
Date: 08-1997
DOI: 10.1088/0967-3334/18/3/001
Abstract: This study was designed to determine normal variations in cutaneous blood content, red blood cell content and skin thickness in healthy human volunteers. The blood content (BC) of human skin and the velocity of red blood cells (RBV) has been comprehensively mapped over 30 anatomical sites in 28 volunteers between the age of 7 and 77 years using reflectance spectrophotometry (RFS) and laser Doppler (LD) techniques respectively. Total skin thickness, which may have a relationship with blood content, has been mapped at the same anatomical sites in six of the volunteers using two-dimensional array, 12 MHz ultrasound equipment. The major determinant of BC and RBV was found to be anatomical site. Regardless of age, gender or prior sun exposure, anatomical sites above the waist produced higher readings than below. BC and RBV were found to be dependent on age and gender at most sites with higher readings being observed in males and younger volunteers. The largest difference was seen in males under 55 years whose RFS readings above the waist were significantly higher than in older males or females of any age. Heavy prior sun exposure and skin thickness could not be demonstrated to impact on either RFS or LD readings independently of the effects of anatomical site, gender or age. In general, RFS and LD readings paralleled one another and correlated linearly at most anatomical sites. While RFS readings tended to decrease in the cranio-caudal direction, LD readings were relatively uniform across the body except for the head and groin where they were higher, and the abdomen where they were lower. The site-to-site variations in RFS readings observed in this study correspond well to capillary density variations noted in previous studies.
Publisher: Elsevier BV
Date: 03-2002
DOI: 10.1016/S0360-3016(01)02721-3
Abstract: To quantify the oral mucosal cell density and proliferation rate during conventional radiotherapy of head-and-neck tumors and to compare these parameters with clinical scoring of oral mucositis. Between 1996 and 1999, 22 patients were included in this study. Mucosal biopsies were taken before or during the radiotherapy course (5 x 2 Gy/wk). Biopsies were incubated in vitro with tritiated thymidine immediately after excision to label DNA-synthesizing cells. Epithelial cell density followed a biphasic radiation response. A steep decrease to about 50% of the preirradiation value (1000 cells/mm epithelium) during Week 1 was followed by a more gradual loss to about 400 cells at the end of treatment. The initial phase was based on the depression of proliferation, with 5-10 labeled cells/mm at the end of Week 1 vs. 60 labeled cells/mm in controls. Subsequently, proliferation was partially restituted at 20 labeled cells/mm. A significant difference in cell numbers was seen between Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Grade 0 (approximately 850 cell/mm) and Grade 2 (325/mm) or Grade 3 (370/mm). No significant differences were observed between reaction grades 1, 2, and 3. Conventionally fractionated radiotherapy induces a rapid suppression in cell production in Week 1, which results in a prompt reduction in cell numbers. Subsequently, a partial restoration of proliferation significantly reduces the rate of cell loss. These processes clearly precede the clinical response. Regeneration, defined as restoration of cellularity, is already under way when the maximal clinical response is observed. Clinical reaction grading corresponds poorly to cellular density measures during conventional fractionation.
Publisher: Elsevier BV
Date: 10-2002
DOI: 10.1016/S0360-3016(02)02931-0
Abstract: To assess the potential for sucralfate administered rectally to reduce the risk of late rectal morbidity in patients undergoing nonconformal radiotherapy (RT) for carcinoma of the prostate and to study the variables potentially contributing to late rectal morbidity and particularly to explore the relationship between acute and late toxicity. Eighty-six patients with localized prostate carcinoma were randomized in a double-blind, placebo-controlled study to a daily enema of 3 g of sucralfate in a 15-mL suspension or the same suspension without sucralfate. The enema began the first day of RT and was continued for 2 weeks after treatment completion. The primary end point of the study was acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) toxicity however, the patients were followed for an additional 5 years on a 6-month basis. The evaluation included late RTOG/EORTC toxicity and a patient self-assessment questionnaire. With a median follow-up of 5 years, the Kaplan-Meier probability of late Grade 2 RTOG/EORTC toxicity was 12% (95% confidence interval [CI] 2-22%) for placebo and 5% (95% CI 0-12%) for sucralfate (p = 0.26). The probability of late rectal bleeding was 59% (95% CI 45-73%) for placebo and 54% (95% CI 40-68%) for sucralfate. No statistically significant difference was found between the treatment arms for the peak incidence of any of the other patient self-assessment variables. Cox proportional hazards modeling indicated acute RTOG/EORTC toxicity of Grade 2 or greater was associated with a hazard ratio of 2.74 (95% CI 1.31-5.73) for the development of late toxicity of Grade 1 or greater. Substituting the patient self-assessment variables for acute RTOG/EORTC toxicity revealed that rectal pain of a moderate or severe grade during RT was the best predictor of the subsequent development of late toxicity, with a hazard ratio of 3.44 (95% CI 1.68-7). The results of this study do not support the use of sucralfate administered rectally as a method for reducing the late toxicity of nonconformal RT for prostate cancer. There appears to be an association between the development of acute and subsequent late toxicity, although the nature of this association remains to be determined.
Publisher: Springer Berlin Heidelberg
Date: 2011
Publisher: Wiley
Date: 1986
Publisher: Elsevier BV
Date: 10-1996
Publisher: Informa UK Limited
Date: 1982
DOI: 10.3109/02841868209134317
Abstract: Retrospective analysis of 56 cases of carcinoma on the lateral border of the anterior two thirds of the tongue treated at Mount Vernon Hospital using radium needle implant alone yielded 5-year actuarial survivals of 75.3 per cent in 25 T1N0 cases and 81.8 per cent in 25 T2N0 cases. Five-year actuarial local recurrence of 17.5 per cent was recorded in the T1 group and 35 per cent in the T2 group. Local recurrences were attributed to failure of the implant to encompass extensions of the tumour along the lateral border or into the musculature of the tongue. Five-year actuarial local recurrence of 66.2 per cent was recorded in 18 patients with carcinoma of the breast treated by radium needle implant alone 4 of these 9 local recurrences occurred at some distance from the treated area and could not be classed as marginal recurrences. A preliminary investigation carried out in 1981 indicated that significant improvements in source distribution, particularly at poorly accessible sites, could be achieved using afterloading techniques. In addition the use of 192Ir as a source could result in improvements in staff protection.
Publisher: Springer Science and Business Media LLC
Date: 04-2014
Publisher: Elsevier BV
Date: 11-2008
Publisher: Elsevier BV
Date: 1995
Publisher: Elsevier BV
Date: 10-2000
DOI: 10.1016/S0360-3016(00)00708-2
Abstract: The present study modeled data from a large series of experiments originally designed to investigate the influence of time, dose, and fractionation on early and late pathologic endpoints in rat small intestine after localized irradiation. The objective was to obtain satisfactory descriptions of the regenerative response to injury together with the possible relationships between early and late endpoints. Two- and 26-week pathologic radiation injury data in groups of Sprague-Dawley rats irradiated with 27 different fractionation schedules were modeled using the incomplete repair (IR) version of the linear-quadratic model with or without various time correction models. The following time correction models were tested: (1) No time correction (2) A simple exponential (SE) regenerative response beginning at an arbitrary time after starting treatment and (3) A bi-exponential response with its commencement linked to accumulated cellular depletion and fraction size (the 'intelligent response model' [INTR]). Goodness of fit of the various models was assessed by correlating the predicted biological effective dose for each dose group with the observed radiation injury score. (1) The incomplete repair model without time correction did not provide a satisfactory description of either the 2- or 26-week data. (2) The models using SE time correction performed better, providing modest descriptions of the data. (3) The INTR model provided reasonable descriptions of both the 2- and 26-week data, confirming a treatment time dependence of both early and late pathological endpoints. (4) The most satisfactory descriptions of the data by the INTR model were obtained when the regenerative response was assumed to cease 2 weeks after irradiation rather than at the end of irradiation. A fraction-size-dependent delay of the regenerative response was also suggested in the best fitting models. (5) Late endpoints were associated with low-fractionation sensitivity and treatment-time dependence even in animal groups that exhibited minimal early mucosal reactions. Radiation injury scores in this rat small intestinal experimental model cannot be adequately described without time correction. 'Consequential' mechanisms contribute to the development of late effects, even in animals that do not develop severe early mucosal injuries. The initiation of the regenerative response is subject to a fraction-size-dependent mitotic delay and is linked to the level of accumulated cellular depletion. The response does not cease at the end of therapy but probably continues until maximal healing has taken place.
Publisher: Wiley
Date: 26-05-2005
DOI: 10.1118/1.1997919
Publisher: Wiley
Date: 02-2009
DOI: 10.1111/J.1754-9485.2009.02047.X
Abstract: The present paper describes the logistics of the 2004-2008 Australasian Level III Dosimetry Intercomparison. Dosimetric intercomparisons (or 'audits') can be used in radiotherapy to evaluate the accuracy and quality of radiation delivery. An intercomparison was undertaken in New Zealand and Australia to evaluate the feasibility and logistics of ongoing dosimetric intercomparisons that evaluate all steps in the radiotherapy treatment process, known as a 'Level III' intercomparison. The study commenced in 2002 with the establishment of a study team, definition of the study protocol, acquisition of appropriate equipment and recruitment of participating radiotherapy centres. Measurements were undertaken between October 2004 and March 2008, and included collation of data on time, costs and logistics of the study. Forty independent Australian and New Zealand radiotherapy centres agreed to participate. Measurement visits were made to 37 of these centres. Data is presented on the costs of the study and the level of support required. The study involved the participation of 16 staff at the study centre who invested over 4000 hours in the study, and of over 200 professionals at participating centres. Recommendations are provided for future phantom-based intercomparisons. It is hoped that the present paper will be of benefit to any centres or groups contemplating similar activities by identifying the processes involved in establishing the study, the potential hazards and pitfalls, and expected resource requirements.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.EJRAD.2018.11.026
Abstract: This study is aimed at evaluating the potential role of quantitative magnetic resonance diffusion tensor imaging (DTI) and tractography parameters in the detection and characterization of peripheral zone prostate cancer with a particular attention for fiber tract density. DTI was acquired from eleven high risk, transrectal ultrasound (TRUS)-guided biopsy proven prostate cancers with perineural invasion (histological Gleason score ≥ 7) on a 3 T magnet. Twenty parameters derived from DTI were quantified in cancer and healthy regions of the prostate. In addition, fiber tract density in normal versus cancer tissues was also calculated using DTI tractography. Support vector machine with a radial basis function kernel and area under receiver operator characteristic (ROC) were used to describe and compare the diagnostic performance of combined fractional anisotropy (FA) and mean diffusivity (MD) and other statistically significant DTI parameters. Spearman correlation analysis between DTI parameters and Gleason scores was conducted. Eighteen DTI parameters yielded statistically significant differences between cancer and healthy regions (p-value < 0.05). The ROC curve of all statistically significant DTI parameters between cancer and healthy regions was higher than the area under ROC curve using FA + MD alone (95% confidence interval = 0.988, range = 0.975-1.00) vs (95% confidence interval = 0.935, range = 0.898-0.999), respectively (p-value < 0.05). Fiber tract density was also found to be higher in cancer than in healthy tissues (+38.22%, p-value = 0.010) and may be related to the increase in nerve and vascular density reported in prostate cancer. The linear and relative anisotropy were highly correlated with Gleason score (Spearman correlation factor r = 0.655, p-value = 0.001 and r = 0.667, p-value < 0.001, respectively). DTI has the potential to provide imaging biomarkers in the detection and characterization of prostate cancer. Novel quantitative parameters derived from DTI and DTI tractography, including fiber tract density, support the use of DTI in the assessment of high grade prostate cancer.
Publisher: Springer Berlin Heidelberg
Date: 2013
Publisher: Wiley
Date: 09-2004
Publisher: S. Karger AG
Date: 2012
DOI: 10.1159/000334999
Abstract: i Objective: /i To determine if 6 months of neo-adjuvant androgen deprivation is associated with the long-term risk of cardiac mortality. i Methods: /i In the TROG 96.01 trial, 802 men with locally advanced prostate cancer were randomized to radiotherapy either alone or with 3 or 6 months of neo-adjuvant androgen deprivation therapy (NADT). Competing risk methodology was used to derive the cumulative incidence of fatal cardiac events. i Results: /i At 10 years, the cumulative incidence of fatal cardiac events for the radiation therapy alone arm was 7.54% compared to a nonstatistically significant decreased incidence of 6.44% in the 6-month NADT arm (p = 0.65). Men aged over 65 years were not at an increased risk. Additional androgen deprivation therapy given as secondary treatment at tumor progression did not confer an increased risk. i Conclusion: /i These data suggest that fatal cardiac events are not more common in men receiving up to 6 months of NADT.
Publisher: Wiley
Date: 22-09-2018
DOI: 10.1111/BJU.14008
Abstract: To explore if duration of previous exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a year-long exercise programme moderates the exercise response with regard to body composition and muscle performance, and also to explore the moderator effects of baseline testosterone, time since ADT, and baseline value of the outcome. In a multicentre randomized controlled trial, 100 men who had previously undergone either 6 months (short-term) or 18 months (long-term) of ADT in combination with radiotherapy, as part of the TROG 03.04 RADAR trial, were randomized to 6 months supervised exercise, followed by a 6-month home-based maintenance programme, or to printed physical activity educational material for 12 months across 13 university-affiliated exercise clinics in Australia and New Zealand. The participants were long-term survivors of PCa with a mean age of 71.7 ± 6.4 years, and were assessed for lower extremity performance (repeated chair rise), with a subset of men (n = 57) undergoing additional measures for upper and lower body muscle strength and body composition (lean mass, fat mass, appendicular skeletal muscle [ASM]) by dual X-ray absorptiometry. Data were analysed using generalized estimating equations. Time on ADT significantly moderated the exercise effects on chair rise (β Men with PCa previously treated long-term with ADT respond more favourably to exercise in terms of lower body muscle performance and body composition (lean and fat mass, and ASM) than those with short-term ADT exposure. As a result, men who were formerly on long-term androgen suppression regimens should be especially prescribed exercise medicine interventions to alleviate residual treatment-related adverse effects.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-12-2011
Abstract: We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer–specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories. Between February 2, 1996, and December 27, 2001, 761 men with unfavorable-risk PC were treated in Australia, New Zealand, Ireland, or the United States in a randomized trial with radiotherapy and 3, 4, or 6 months of AST (the study cohort). Competing risks regression was used to evaluate whether the duration of AST interacted with GS and was significantly associated with the risk of PCSM, adjusting for age, trial site, and PC prognostic factors. After a median follow-up of 10.9 years, 263 men died, 111 (42%) from PC. For all men, 6 versus 3 or 4 months of AST was associated with a reduced risk of PCSM (adjusted hazard ratio [AHR], 0.55 95% CI, 0.36 to 0.82 P = .004). AHRs evaluating the impact of the duration of AST on the risk of PCSM were 0.67 (95% CI, 0.29 to 1.56 P = .35), 0.47 (95% CI, 0.25 to 0.85 P = .01), and 0.59 (95% CI, 0.30 to 1.19 P = .14) for men with GS ≤ 6, 7, and 8 to 10 PC, respectively. Therefore, the strongest evidence for this benefit was in men with GS 7 PC. AST durations of no less than 6 months should be considered when treating GS 7 PC with conventional dose RT.
Publisher: Elsevier BV
Date: 08-2003
DOI: 10.1016/S0167-8140(03)00198-1
Abstract: The aims of this analysis were to determine the effect of anaemia on loco-regional control, relapse-free survival, cause-specific survival, overall survival, and acute and late radiation therapy toxicity in patients with Stage III and IV squamous cell carcinoma of the head and neck treated with radiotherapy. Between 1991 and 1998, 350 patients were randomly assigned to either conventional radiotherapy, (70 Gy in 35 fractions in 49 days) or to accelerated radiotherapy (59.4 Gy in 33 fractions in 24 days). Patients were ided into two groups according to their haemoglobin level: a normal haemoglobin group (>/=13 g/dl in males, >/=12 g/dl in females) and a low haemoglobin group (<13 g/dl in males, <12 g/dl in females). The influence of anaemia on cause-specific survival and the development of confluent mucositis independent of other variables was tested using Cox proportional hazards model. Of 350 patients recruited to the trial, 238 had haemoglobin measurements and were eligible for inclusion in this secondary analysis. One hundred and ninety-three were considered to have normal haemoglobin, and 45 patients were considered to be anaemic. There were significant differences between the groups in loco-regional control, relapse-free survival, cause-specific survival and overall survival, with hazards ratios of 0.56 (95% confidence interval (CI) 0.34-0.94), 0.57 (95% CI 0.35-0.92), 0.49 (95% CI 0.29-0.85) and 0.43 (95% CI 0.26-0.70) in favour of the normal haemoglobin group. Using Cox proportional hazards modelling, haemoglobin level was a significant predictor of cause-specific survival in addition to disease site, stage, and Eastern Cooperative Oncology Group status. There were no statistically significant differences between the groups in the development of acute or late reactions. Significant reductions in loco-regional control, disease-free survival, cause-specific survival and overall survival occur in the presence of anaemia. No significant differences in normal tissue toxicity have been identified in this analysis.
Publisher: Wiley
Date: 08-12-2017
Abstract: Quality assurance methods are incorporated into multicentre radiotherapy clinical trials for ensuring consistent application of trial protocol and quantifying treatment uncertainties. The study's purpose was to determine whether post-treatment disease progression is associated with measures of the quality of radiotherapy treatment. The TROG 03.04 RADAR trial tested the impact of androgen deprivation on prostate cancer patients receiving dose-escalated external beam radiation therapy. The trial incorporated a plan-review process and Level III dosimetric intercomparison at each centre, from which variables suggestive of treatment quality were collected. Kaplan-Meier statistics and Fine and Gray competing risk modelling were employed to test for associations between quality-related variables and the participant outcome local composite progression. Increased 'dose-difference' at the prostatic apex and at the anterior rectal wall, between planned and measured dose, was associated with reduced progression. Participants whose treatment plans included clinical target volume (CTV) to planning target volume (PTV) margins exceeding protocol requirements also experienced reduced progression. Other quality-related variables, including total accrual from participating centres, measures of target coverage and other variations from protocol, were not significantly associated with progression. This analysis has revealed the association of several treatment quality factors with disease progression. Increased dose and dose margin coverage in the prostate region can reduce disease progression. Extensive and rigorous monitoring has helped to maximise treatment quality, reducing the incidence of quality-indicator outliers, and thus reduce the chance of observing significant associations with progression rates.
Publisher: Elsevier BV
Date: 10-1998
DOI: 10.1016/S0167-8140(98)00078-4
Abstract: This report presents long-term follow-up data from a prospective but unrandomized trial of a continuous 3.5-week course of accelerated radiation treatment (ART) used as primary treatment for patients with loco-regionally advanced head and neck cancer. Ninety-three patients in three centres in New Zealand and Australia were treated with ART (59.40 Gy in 33 fractions over 24-25 days). Their disease originated from three anatomical regions (oral cavity, 35 patients pharynx, 31 patients larynx, 27 patients). Seventy-nine of these patients had stage III or IV cancers. Follow-up ranged from 68 to 203 months (median 139 months). Loco-regional (LR) failure occurred in 52 patients leading to a 10-year actuarial expectation of LR control of 38%. The actuarial expectation of LR control at 10 years was highly dependent on stage and for stage III, IVA and IVB patients it was 57+/-8.1%, 32+/-1.7% and 7+/-0.5%, respectively. Multivariate analysis could not confirm an independent impact of primary site or histological differentiation on LR failure. Two patients died of acute toxicity of treatment and six patients developed grade 3/4 late complications affecting soft tissues only, yielding an actuarial expectation of complications of this severity at 5 years of 9%. No cases of osteoradionecrosis or myelitis were observed. This ART, which has proved easy to use at a number of large and small centres, has produced encouraging long-term LR control at a cost of limited soft tissue morbidity.
Publisher: Wiley
Date: 08-2014
Abstract: Multicentre radiotherapy clinical trials can incorporate quality assurance (QA) procedures for ensuring consistent application of the trial protocol in the planning, delivery and reporting of participant treatments. Subsequently detected variations from trial protocol have previously been shown to reduce treatment efficacy, although little has been shown for toxicity rates. The purpose of this study was to investigate the association of QA measures and protocol variations on toxicity incidence in the context of a prostate radiotherapy trial. Using QA records from the TROG 03.04 RADAR trial, the impact of variations on gastrointestinal (GI) and genito-urinary (GU) toxicities was investigated. Protocol variation rates were lower than reported in previous studies, and showed little correlation with GI toxicity outcomes. Variations classified as 'major' showed a non-significant trend for increased toxicity relative to those classified as 'minor'. Results from a Level III phantom-based dosimetry study showed some correlation with GI toxicity, whereas ranking on a set-up accuracy study did not impact on toxicity. Toxicity in general increased with the number of participants accrued per centre, at odds with previous reports relating to disease progression, with a potential link to increases in low-mid-range rectal doses in the cohort from higher-accruing centres. No QA-related variables correlated with GU toxicities. Besides non-significant trends, minimal association was observed between QA variables and toxicity rates for the RADAR trial. The intention of the trial's QA programme was to reduce treatment variations and minimise toxicity in the context of a relevantly advanced treatment approach.
Publisher: Informa UK Limited
Date: 1990
DOI: 10.1080/09553009014552471
Abstract: We applied the cytokinesis-block micronucleus assay to measure chromosome damage in lymphocytes of 11 cancer patients undergoing fractionated partial-body irradiation. Measurements performed before, during and after cessation of radiotherapy showed a dose-related increase in micronucleus frequency in each of the patients studied. When the results for micronucleus frequency (Y) were plotted against the estimated equivalent whole-body dose (X) the dose-response relationship obtained was Y = 75.8X + 49.5 (r = 0.783, P less than 0.0001). A general decline in MN frequency was observed during the post-treatment period down to 57 per cent (+/- 10) after 12 months but there was considerable variation between in iduals. The advantages and disadvantages of the application of the cytokinesis-block micronucleus assay as a biological dosimeter for lymphocytes irradiated in vivo are discussed.
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.IJROBP.2008.12.085
Abstract: We sought to determine whether short-term neoadjuvant androgen deprivation (STAD) duration influences the optimal time point from which Phoenix fail (time to biochemical failure TTBF) should be measured. In the Trans-Tasman Radiation Oncology Group 96.01 trial, men with locally advanced prostate cancer were randomized to 3 or 6 months STAD before and during prostatic irradiation (XRT) or to XRT alone. The prognostic value of TTBF measured from the end of radiation (ERT) and randomization were compared using Cox models. Between 1996 and 2000, 802 eligible patients were randomized. In 436 men with Phoenix failure, TTBF measured from randomization was a powerful predictor of prostate cancer-specific survival and marginally more accurate than TTBF measured from ERT in Cox models. Insufficient data were available to confirm that TTBF measured from testosterone recovery may also be a suitable option. TTBF measured from randomization (commencement of therapy) performed well in this trial dataset and will be a convenient option if this finding holds in other datasets that include long-term androgen deprivation data.
Publisher: Wiley
Date: 12-2008
Publisher: Wiley
Date: 06-2011
DOI: 10.1118/1.3611541
Publisher: Elsevier BV
Date: 05-2011
Publisher: IOP Publishing
Date: 24-03-2015
DOI: 10.1088/0031-9155/60/8/3097
Abstract: To clinically implement MRI simulation or MRI-alone treatment planning requires comprehensive end-to-end testing to ensure an accurate process. The purpose of this study was to design and build a geometric phantom simulating a human male pelvis that is suitable for both CT and MRI scanning and use it to test geometric and dosimetric aspects of MRI simulation including treatment planning and digitally reconstructed radiograph (DRR) generation.A liquid filled pelvic shaped phantom with simulated pelvic organs was scanned in a 3T MRI simulator with dedicated radiotherapy couch-top, laser bridge and pelvic coil mounts. A second phantom with the same external shape but with an internal distortion grid was used to quantify the distortion of the MR image. Both phantoms were also CT scanned as the gold-standard for both geometry and dosimetry. Deformable image registration was used to quantify the MR distortion. Dose comparison was made using a seven-field IMRT plan developed on the CT scan with the fluences copied to the MR image and recalculated using bulk electron densities. Without correction the maximum distortion of the MR compared with the CT scan was 7.5 mm across the pelvis, while this was reduced to 2.6 and 1.7 mm by the vendor's 2D and 3D correction algorithms, respectively. Within the locations of the internal organs of interest, the distortion was <1.5 and <1 mm with 2D and 3D correction algorithms, respectively. The dose at the prostate isocentre calculated on CT and MRI images differed by 0.01% (1.1 cGy). Positioning shifts were within 1 mm when setup was performed using MRI generated DRRs compared to setup using CT DRRs.The MRI pelvic phantom allows end-to-end testing of the MRI simulation workflow with comparison to the gold-standard CT based process. MRI simulation was found to be geometrically accurate with organ dimensions, dose distributions and DRR based setup within acceptable limits compared to CT.
Publisher: Elsevier BV
Date: 02-2012
Publisher: Wiley
Date: 02-1999
Publisher: American Society of Clinical Oncology (ASCO)
Date: 09-2010
Publisher: Elsevier BV
Date: 12-2012
Publisher: Wiley
Date: 11-1987
DOI: 10.1111/J.1445-2197.1987.TB01278.X
Abstract: Eleven patients with Merkel cell carcinoma of the skin were reviewed retrospectively. The aggressive nature of this tumour is reflected by the incidence of local recurrence, regional nodal metastases and systemic dissemination, which is 36%, 55%, and 18% respectively. This high frequency of local recurrence and metastases is confirmed in the literature. Management strategies should be planned accordingly, following accurate assessment of the extent of disease. Wide excision, with or without nodal dissection, together with adjuvant wide field irradiation is necessary for loco-regional control of this radiosensitive tumour. Radiotherapy alone may be appropriate treatment for extensive loco-regional tumours or in those that have already metastasized. Although the role of chemotherapy is unclear, there are an increasing number of reports of chemosensitivity and further investigation in this area is required.
Publisher: Springer Science and Business Media LLC
Date: 12-2009
Publisher: Elsevier BV
Date: 02-1993
Publisher: Wiley
Date: 06-2013
DOI: 10.1118/1.4815455
Publisher: Wiley
Date: 05-1999
DOI: 10.1046/J.1440-1673.1999.00639.X
Abstract: The Trans-Tasman Radiation Oncology Group (TROG) initiated a randomized trial, testing accelerated (twice daily) radiotherapy against conventional radiotherapy for stage III and stage IV squamous cell carcinoma of the head and neck in 1991. In 1996, the Trial Management Committee arranged for a technical audit of 76 cases from 11 institutions, conducted by investigators from interstate institutions. A 10% unacceptable protocol violation rate was detected, which compares favourably with initial Radiation Therapy Oncology Group (RTOG) experience in the late 1970s. Infrastructural deficits with poor quality of documentation, incomplete retrieval of films and document return have been demonstrated in some cases. The Trans-Tasman Radiation Oncology Group is actively pursuing procedural and resourcing issues in order to redress this and is actively expanding its Quality Assurance (QA) Programme with an intercentre dosimetry study. Ultimately, comprehensive clinical and technical QA site visits are planned.
Publisher: Elsevier BV
Date: 12-2013
Publisher: IOP Publishing
Date: 26-04-2017
Abstract: This study investigates the associations between spatial distribution of dose to the rectal surface and observed gastrointestinal toxicities after deformably registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate brachytherapy (HDRBT) prostate cancer treatment. The study contains data for 118 patients where the HDRBT CT was deformably-registered to the EBRT CT. The EBRT and registered HDRBT TG43 dose distributions in a reference 2 Gy/fraction were 3D-summed. Rectum dose-surface maps (DSMs) were obtained by virtually unfolding the rectum surface slice-by-slice. Associations with late peak gastrointestinal toxicities were investigated using voxel-wise DSM analysis as well as parameterised spatial patterns. The latter were obtained by thresholding DSMs from 1-80 Gy (increment = 1) and extracting inferior-superior extent, left-right extent, area, perimeter, compactness, circularity and ellipse fit parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate features with toxicities. Rectal bleeding, stool frequency, diarrhoea and urgency/tenesmus were associated with greater lateral and/or longitudinal spread of the high doses near the anterior rectal surface. Rectal bleeding and stool frequency were also influenced by greater low-intermediate doses to the most inferior 20% of the rectum and greater low-intermediate-high doses to 40-80% of the rectum length respectively. Greater low-intermediate doses to the superior 20% and inferior 20% of the rectum length were associated with anorectal pain and urgency/tenesmus respectively. Diarrhoea, completeness of evacuation and proctitis were also related to greater low doses to the posterior side of the rectum. Spatial features for the intermediate-high dose regions such as area, perimeter, compactness, circularity, ellipse eccentricity and confinement to ellipse fits were strongly associated with toxicities other than anorectal pain. Consequently, toxicity is related to the shape of isodoses as well as dose coverage. The findings indicate spatial constraints on doses to certain sections of the rectum may be important for reducing toxicities and optimising dose.
Publisher: Wiley
Date: 28-11-2014
DOI: 10.1002/PON.3448
Abstract: To identify the factors underlying prostate cancer (PCa) patients' depression-anxiety, sexual problems, urinary dysfunction and androgen deprivation therapy (ADT)-linked breast changes and hot flushes, and test these as predictors of loss of masculinity (LoM) over 36 months following diagnosis. One thousand seventy patients from the TROG 03.04 (RADAR) trial the EORTC QLQ C-30 and PR 25 questionnaires, and the International Prostate Cancer Symptom Score of the American Urological Association at baseline, 3, 7, 12, 18, 24 and 36 months. Selected items from these scales were factor-analysed to identify a four-component solution for responses at 18 and 36 months, and these components were regressed against a single-item measuring LoM. Depression-anxiety factor was the most powerful predictor of LoM at both time points, followed by sexual problems of ADT side effects (breast changes and hot flushes). Urinary dysfunction was not a consistent predictor of LoM. Depression-anxiety was also the most significant factor distinguishing between those men who reported LoM and those who did not. Although LoM is often reported as arising from ADT, the relative power of depression-anxiety in predicting LoM, both at the selected time points and using a time-lagged analysis, plus the finding that depression-anxiety was the most consistent difference between men who reported LoM and those who did not, argues for the presence of adverse mood states as being the key ingredient in deciding if PCa patients experience loss of their feelings of masculinity.
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1016/J.RADONC.2005.10.005
Abstract: To identify contributing factors to delayed rectal and urinary symptoms in a randomised trial comparing different durations of maximal androgen deprivation (MAD), given prior to radiotherapy, for locally advanced prostate cancer. Between 1996 and 2000, 818 patients with stages T2b,c, 3 and 4 prostate cancer were entered into a trial comparing 0, 3 and 6 months of MAD prior to and during radiotherapy. Their delayed normal tissue effects were recorded by their treating doctors using standardised scales and by the patients using a self-assessment questionnaire regularly. Time to occurrence and prevalence data were analysed. Rectal and urinary symptom levels were observed to vary markedly over time in at least 80% of patients, with some indicating lasting resolution of symptoms. Prevalence rates were found to be substantially lower than actuarial probability rates. Baseline symptom levels and greatest acute symptom levels were both very powerful predictors. Obstructive lower urinary tract symptoms were noted to improve during the first 4 years after radiotherapy in approximately 60% of cases in each treatment arm. However, the treatment arm itself was not shown to influence these improvements in other univariate or multivariate analyses. MAD was shown to reduce both time to occurrence and prevalence of delayed proctopathic symptoms, but this effect was confirmed statistically in the 3 month treatment arm only. Multivariate models indicated that higher levels of haemoglobin prior to any treatment may in some way protect against delayed proctopathic symptoms. Prevalence data provide more clinically meaningful estimates of risk of delayed effects in normal tissues where assessment relies substantially on reported symptom levels. In these tissues consideration of the impact of baseline symptom levels and pathologies, and greatest acute symptom levels in analyses of delayed effects appears mandatory. Obstructive lower urinary symptoms improve over several years in the majority of patients treated for locally advanced prostate cancer by radiotherapy. Future research could address whether rectal toxicity is affected by initial haemoglobin levels and declines in it due to MAD.
Publisher: Informa UK Limited
Date: 1986
DOI: 10.3109/02841868609136386
Abstract: The complications following surgery and postoperative radiation therapy in the management of the axilla in 187 patients with primary breast cancer treated between 1978 and 1982 have been studied. Although no difference in complication rate could be detected between the three different postoperative radiation schedules utilised there was a strong and positive correlation between complication rate and increasing extent of surgical intervention. When the groups were sub- ided according to the extent of surgery performed, no differences in regional recurrence rates were observed but complication rates (defined as significant lymphoedema of the arm and/or restriction of shoulder movements) were significantly different (p less than 0.001) at 30 months between those who had no surgical intervention (25%), those who had had 's ling' performed (50%) and those who had had formal dissection performed (84%).
Publisher: Elsevier BV
Date: 05-2012
Publisher: Elsevier BV
Date: 03-2013
Publisher: Wiley
Date: 11-1990
DOI: 10.1111/J.1440-1673.1990.TB02658.X
Abstract: Interactive computerised tomographic (CT) planning techniques offer the prospect of better anatomical localisation, more consistent tumour coverage, and limiting normal tissue dose. However, its value in the management of prostate cancer remains undefined. The present study addresses the impact of planning CT on the designated target volumes for localised carcinoma of the prostate at a multi-institution national level. Nine radiation oncologists from different centres in Australia and New Zealand were asked to designate a target volume on five s le patients with different disease stages (A2-C2) using both conventional cystogram films and planning CT scans. Target volumes estimated by CT means in this study differed by more than 10% from those estimated by conventional means in 75.6% of instances, being smaller in 55.6%. Volumes varied widely between in idual radiation oncologists, both using conventional planning and CT information. These variations were found to exceed any differences in the volume caused by the planning technique itself. Results from this survey suggest that volumes appear to change more according to the in idual radiation oncologist rather than to any other factor. In most or all of the s le cases six of nine radiation oncologists defined the borders of their CT volumes to be either consistently smaller (5 out of 9) or greater (1 out of 9) than their conventionally defined borders. The results of this survey are potentially important and warrant repetition with larger s le numbers in other countries where interactive CT planning facilities exist, both with and without diagnostic radiological input, to exclude similar variation and to define causes for any variations that do become apparent.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.RADONC.2017.10.021
Abstract: To evaluate the impact of treatment planning and delivery factors on treatment outcome as measured by post-treatment disease progression. Accruing 813 external beam radiotherapy participants during 2003-2007, the RADAR trial collected a comprehensive range of clinical treatment factor data for each participant. Both the Fine and Gray competing risks modelling and the Kaplan-Meier (KM) analysis were undertaken to determine the impact of these factors on local-composite progression (LCP), with 709 participants available for analysis. Participants with treatments involving 7 or more beams experienced significantly higher incidence of LCP, with a sub-hazard ratio (relative to 3-beam participants) of 3.056 (CI: 1.446-6.458, p < 0.0034). Participants treated with a more rigorous dose calculation algorithm also displayed significantly higher incidence of LCP, with a sub-hazard ratio of 1.686 (CI: 1.334-2.132, p < 0.0001). The KM analysis resulted in the same groups showing a higher incidence of LCP, with log-rank test results of p = 0.0005 and p = 0.0008 respectively. The RADAR dataset has enabled a successful secondary analysis in which the impact of technical modifications has been assessed, challenging several established hypotheses. Increasingly precise treatments should be complemented with increasing accuracy to avoid potential geometric miss.
Publisher: Wiley
Date: 26-06-2018
DOI: 10.1111/BJU.14384
Abstract: To investigate the association between lean mass (LM) and fat mass (FM) with fatigue and vitality before and after exercise in patients with prostate cancer already undergoing androgen-deprivation therapy (ADT). Cross-sectional associations between LM and FM with fatigue and/or vitality measures were examined in 229 patients (aged 43-90 years). Prospective analysis was undertaken in 129 patients who underwent a supervised 3-6 months exercise programme (predominantly resistance + aerobic). Whole body and appendicular LM, and total and trunk FM were assessed by dual X-ray absorptiometry. Fatigue was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-30) and vitality using the Short Form-36. Based on the EORTC QLQ-30, 19% of patients had clinically relevant fatigue. There was no association between LM and fatigue however, total (P = 0.013), trunk (P = 0.015) and percentage (P = 0.008) FM were higher in fatigued than not fatigued patients, with total and trunk FM 5.0 and 2.6 kg higher, respectively. For quartiles of vitality, a similar pattern emerged for FM with those in the lowest quartile of vitality having the highest FM values (P = 0.014-0.034). In contrast, following supervised exercise, change in fatigue and vitality were associated with change in total LM (r = -0.182, P = 0.042 and r = 0.309, P = 0.001, respectively) but not FM. Patients fatigued at baseline but not fatigued following the exercise programme gained a median (interquartile range) of 2.1 (0.7-3.2) kg LM. In patients with prostate cancer treated with ADT, body composition is associated with fatigue, with higher total and trunk FM in those with clinically relevant fatigue. However, following exercise those no longer fatigued had an accompanying substantial increase in LM. Modifying body composition, both LM and FM, in patients with prostate cancer may favourably alter cancer-related fatigue levels and should be a target of exercise medicine in this population.
Publisher: IOP Publishing
Date: 12-06-2014
Publisher: Wiley
Date: 11-1999
DOI: 10.1046/J.1440-1673.1999.00718.X
Abstract: The primary purpose of the present analysis was to assess the feasibility and acute toxicity of a pure accelerated fractionation regimen in a cooperative group setting. This analysis included the first 320 patients entered on to the Trans-Tasman Radiation Oncology Group (TROG) randomized controlled trial which compared accelerated radiotherapy (ART) with conventional radiotherapy (CRT) in stage III and IV squamous cell carcinoma (SCC) of the head and neck. Patients were randomized to either 59.4 Gy in 33 fractions over 24 days (ART) or to 70 Gy 35 fractions over 49 days (CRT) after being stratified for site and stage. Accrual began in 1991 and the trial was closed on 3 April 1998 with the targeted 350 patients. The 3-year survival for the whole group was 54%, and the 3-year disease-free survival was 41%. Toxicity data were available on 303 patients (148 ART 155 CRT). Mucosal toxicity was worse in the accelerated arm, and it peaked approximately 3 weeks earlier than the conventional arm. Skin toxicity was equivalent but occurred approximately 7 days earlier in the accelerated arm. Acute effects in both arms healed completely. Hospitalization was more common in the ART arm (71 vs 52 patients P = 0.01) but the total bed days in hospital was not greatly different (1707 bed days for ART and 1607 bed days for CRT). Patients were more likely to require nasogastric (NG) feeding in the ART arm (49 vs 33 patients P = 0.02). There were 1157 NG feeding days for ART and 1154 NG feeding days for CRT. The average cost of radiation treatment per patient including hospitalization, NG feeding and accommodation was $11,750 in the ART arm and $11,587 in the CRT arm. The accelerated arm has been shown to be a tolerable, practical and cost-equivalent regimen. The assessment of the therapeutic ratio of this accelerated protocol (ART) will be determined when the analysis of late effects and loco-regional control is made when the data are more mature.
Publisher: Informa UK Limited
Date: 20-03-2017
DOI: 10.1080/07347332.2017.1306733
Abstract: Repeated surveys of prostate cancer (PCa) patients indicate that their prevalence of depression is well above that for their non-PCa peers. Although standard first-line treatments for depression are only about 35% effective, some recent comments have suggested that a focus upon the possible correlates (factors that aggravate or mediate depression) might help improve treatment efficacy. To investigate this issue, 144 10 year PCa survivors were asked about the frequency of urinary incontinence, a common side effect of some PCa treatments. The 53 patients who suffered urinary incontinence had significantly higher depression scores on the Zung Self-rating Depression Scale than those patients who did not report urinary incontinence. Using mediation analysis, patients' psychological resilience (PR) significantly mediated the depressive effects of urinary incontinence, but those effects were confined to just one of the five components of PR-a sense of control over the things that happen to oneself. Implications for treatment models of psychosocial oncology support for PCa survivors are discussed.
Publisher: Elsevier BV
Date: 08-2001
DOI: 10.1016/S0167-8140(01)00347-4
Abstract: The aims of this randomized controlled trial were to determine whether there were differences in the disease-free survival (DFS) and toxicity between conventional radiotherapy (CRT) and a continuous 3 week accelerated radiotherapy regimen (ART) in stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx. Patients from 14 centres throughout Australia and New Zealand were randomly assigned to either CRT, using a single 2 Gy/day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. The accrual began in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. The median potential follow-up time was 53 months (range, 14-101). The DFS at 5 years was 41% (95% CI, 33-50%) for ART and 35% (95% CI, 27-43%) for CRT (P=0.323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66-1.15). The 5-year disease-specific survival rates were 40% for CRT and 46% for ART (P=0.398) and the loco-regional control was 47% for CRT vs. 52% for ART (P=0.300). The respective hazard ratios were 0.88 (95% CI, 0.65-1.2) and 0.85 (0.62-1.16), favouring the accelerated arm. In the ART arm, confluent mucositis was more severe (94 vs. 71% P<0.001) and peaked about 3 weeks earlier than in the CRT arm, but healing appeared complete in all cases. There were statistically significant reductions in the probability of grade 2 or greater late soft tissue effects over time in the ART arm (P<0.05), except for the mucous membrane where late effects were similar in both arms. Differences in DFS, disease-specific survival and loco-regional control have not been demonstrated. ART resulted in more acute mucosal toxicity, but this did not result in greater prolongation of the treatment time compared with the CRT arm. There were less late effects in the ART arm, with the exception of late mucosal effects. This trial has confirmed that tumour cell repopulation occurs during conventionally fractionated radiotherapy for head and neck cancer. However, it has also provided additional evidence that overall improvements in the therapeutic ratio using accelerated fractionation strategies are seriously constrained by the need to limit total doses to levels that do not exceed acute mucosal tolerance. The accelerated schedule tested has been shown in this trial to be an acceptable alternative to conventionally fractionated irradiation to 70 Gy.
Publisher: IOP Publishing
Date: 24-03-2014
Publisher: Wiley
Date: 04-01-2019
Abstract: This study quantified inter-observer contouring variations for multiple male pelvic structures, many of which are of emerging relevance for prostate cancer radiotherapy progression and toxicity response studies. Five prostate cancer patient datasets (CT and T2-weighted MR) were distributed to 13 observers for contouring. CT structures contoured included the clinical target volume (CTV), seminal vesicles, rectum, colon, bowel bag, bladder and peri-rectal space (PRS). MR contours included CTV, trigone, membranous urethra, penile bulb, neurovascular bundle and multiple pelvic floor muscles. Contouring variations were assessed using the intraclass correlation coefficient (ICC), Dice similarity coefficient (DSC), and multiple additional metrics. Clinical target volume (CT and MR), bladder, rectum and PRS contours showed excellent inter-observer agreement (median ICC = 0.97 0.99 1.00 0.95 0.90, DSC = 0.83 ± 0.05 0.88 ± 0.05 0.93 ± 0.03 0.81 ± 0.07 0.80 ± 0.06, respectively). Seminal vesicle contours were more variable (ICC = 0.75, DSC = 0.73 ± 0.14), while colon and bowel bag contoured volumes were consistent (ICC = 0.97 0.97), but displayed poor overlap (DSC = 0.58 ± 0.22 0.67 ± 0.21). Smaller MR structures showed significant inter-observer variations, with poor overlap for trigone, membranous urethra, penile bulb, and left and right neurovascular bundles (DSC = 0.44 ± 0.22 0.41 ± 0.21 0.66 ± 0.21 0.16 ± 0.17 0.15 ± 0.15). Pelvic floor muscles recorded moderate to strong inter-observer agreement (ICC = 0.50-0.97), although large outlier variations were observed. Inter-observer contouring variation was significant for multiple pelvic structures contoured on MR.
Publisher: Wiley
Date: 30-03-2007
DOI: 10.1002/CNCR.22628
Abstract: The study evaluated whether the use of 3 years as compared with 6 months of androgen suppression therapy (AST) combined with external beam radiation therapy (RT) in the treatment of high-risk prostate cancer was associated with prolonged survival in advanced age men. A pooled analysis of 311 men enrolled in 3 prospective randomized trials between 1987 and 2000 who received 6 months or 3 years of AST and RT for locally advanced or high-grade localized adenocarcinoma of the prostate comprised the study cohort. Cox regression multivariable analysis was performed adjusting for known prognostic factors to determine whether the treatment received was associated with time to death after randomization. The median age and follow-up was 70 and 5.9 years, respectively, during which 82 (26%) deaths occurred. Treatment received was not significantly associated with survival time after randomization (adjusted hazard ratio [AHR]: 1.1 95% confidence interval [CI]: 0.7, 1.8 P = .70), whereas age at randomization (AHR: 1.05 95% CI: 1.01, 1.09 P = .02) was. The presence of Gleason score 8 to 10 cancers approached significance (AHR: 1.6 95% CI: 0.9, 2.6 P = .09). After adjusting for known prognostic factors, the treatment of node-negative, high-risk prostate cancer using 3 years as compared with 6 months of AST with RT was not associated with prolonged survival in men of advanced age. The European Organization for Research and Treatment of Cancer randomized trial will help answer whether unknown confounding factors affected the results of the study.
Publisher: Springer Science and Business Media LLC
Date: 16-08-2011
Publisher: Elsevier BV
Date: 11-1996
DOI: 10.1016/S0167-8140(96)01795-1
Abstract: Prediction of skin reactions requires knowledge of the dose at various depths in the human skin. Using thermoluminescence dosimeters of three different thicknesses, the dose can be extrapolated to the surface and interpolated between the different depths. A TLD holder was designed for these TLD extrapolation measurements on patients during treatment which allowed measurements of entrance and exit skin dose with a day to day variability of +/-7% (S.D. of mean reading). In a pilot study on 18 patients undergoing breast irradiation, it was found that the angle of incidence of the radiation beam is the most significant factor influencing skin entrance dose. In most of these measurements the beam exit dose contributed 50% more to the surface dose than the entrance dose.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.RADONC.2016.07.021
Abstract: It remains unclear whether eradication of oligometastases by stereotactic body radiation therapy or other means will result in cure or prolongation of survival in some cases, or merely provide palliation. We address this issue with prospectively collected progression and treatment data from the TROG 03.04 RADAR randomised controlled trial for men with locally advanced prostate cancer (PC). Three Fine and Gray competing risk survival models with time-dependent covariates were used to determine whether metastatic progression status at first diagnosis of bony metastases, i.e. number of bony sites involved and presence of prior or simultaneous other sites of progression, impacts on prostate cancer-specific mortality (PCSM) when adjusted for baseline prognostic factors and allocated primary treatment. Between 2003 and 2014, 176 of the 1071 subjects developed bone metastases, 152 developed other sites of progression and 91 died of PC. All subjects received secondary treatment using androgen suppression but none received extirpative treatments. The three models found evidence: 1 - of a clear prognostic gradient according to number of bony metastatic sites 2 - that other sites of progression contributed to PCSM to a lesser extent than bone progression and 3 - that further bony metastatic progression in men with up to 3 bony metastases had a major impact on PCSM. Randomised trials are essential to determine the value of extirpative treatment for oligometastatic bony metastases due to PC.
Publisher: Wiley
Date: 12-09-2011
DOI: 10.1118/1.3626573
Abstract: An anthropomorphic pelvic phantom was designed and constructed to meet specific criteria for multicenter radiotherapy dosimetric intercomparison. Three dimensional external and organ outlines were generated from a computed tomography image set of a male pelvis, forming the basis of design for an anatomically realistic phantom. Clinically relevant points of interest were selected throughout the dataset where point-dose values could be measured with thermoluminescence dosimeters and a small-volume ionization chamber. Following testing, three materials were selected and the phantom was manufactured using modern prototyping techniques into five separate coronal slices. Time lines and resource requirements for the phantom design and manufacture were recorded. The ability of the phantom to mimic the entire treatment chain was tested. The phantom CT images indicated that organ densities and geometries were comparable to those of the original patient. The phantom proved simple to load for dosimetry and rapid to assemble. Due to heat release during manufacture, small air gaps and density heterogeneities were present throughout the phantom. The overall cost for production of the prototype phantom was comparable to other commercial anthropomorphic phantoms. The phantom was shown to be suitable for use as a "patient" to mimic the entire treatment chain for typical external beam radiotherapy for prostate and rectal cancer. The phantom constructed for the present study incorporates all characteristics necessary for accurate Level III intercomparison studies. Following use in an extensive Level III dosimetric comparison over a large time scale and geographic area, the phantom retained mechanical stability and did not show signs of radiation-induced degradation.
Publisher: Elsevier BV
Date: 03-1996
DOI: 10.1016/0959-8049(95)00607-9
Abstract: The follicular lymphomas pursue an indolent course in many patients. Long-term follow-up in large series is therefore necessary to establish whether cure is taking place, and if so, at what stage in the dissemination of the disease process it becomes unlikely. The time to, and site of relapse, together with its impact on survival has been studied in 398 patients entered into the British National Lymphoma Investigation limited and disseminated disease trials between 1974 and 1980. Relapse data were compared with various models to obtain maximum likelihood estimates of the proportions permanently remaining relapse-free following treatment. Long-term relapse-free survival was observed in 54.8 +/- 14.9% (95% CI) of patients at 15 years with Ann Arbor stage I disease, 29.2 +/- 13.6% in patients with stage II disease, 18.1 +/- 6.6% with stage III and 13.0 +/- 5.9% with IV disease. Relapse time-course data for all trial arms conform closely to lognormal distributions allowing maximum likelihood estimates of proportions remaining permanently relapse-free to be derived. Using this methodology, over a quarter of patients treated with involved radiotherapy alone or radiotherapy plus 6 months of chlorambucil in the limited disease (Ann Arbor stage I and II) trial are unlikely to relapse at any time in the future. Over 10% of patients treated in the disseminated disease trials with disease classified as Ann Arbor stage III are also statistically unlikely to relapse. The finding that a proportion of patients is statistically unlikely to experience a clinically obvious relapse is consistent with clinical cure. It is especially interesting that a small proportion of patients with disseminated disease and treated by chemotherapy have fallen into this category, but additional data are required to know at what point statistical cure becomes unlikely. Whether "clinical cure" is the same as "pathological cure" in this disease remains uncertain.
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.RADONC.2012.09.018
Abstract: The RADAR trial determines whether adjuvant androgen suppression, bisphosphonates and radiation dose escalation for localised prostate cancer (PC) may improve oncologic outcomes. This study examines whether these measures increase rectal and urinary dysfunction and are secondary trial endpoints. Using a 2×2 factorial trial design men with locally advanced PC were randomly allocated 6 months i.m. leuprorelin prior to radiotherapy either alone or followed by 12 months i.m. leuprorelin. These two groups received 18 months i.v. zoledronic acid (Z) commencing at randomisation or no further treatment. Radiotherapy dose was escalated in a regulated way using external beam techniques (EBRT) or by a high dose rate brachytherapy (HDRB) boost. Prevalence rates of rectal and urinary dysfunctional symptoms were compared at baseline, the end of RT, 18 and 36 months according to treatment arm, dose and technique using multiple regression models. Between 2003 and 2007, 1071 men were randomly allocated and eligible for inclusion in this study. No persistent differences in rectal or urinary dysfunction were attributable to treatment arm or to increasing EBRT dose. However following HDRB statistical increases (p<0.001) in urinary dysfunction were measured using the EORTC PR25 instrument at 18 and 36 months. Adjuvant androgen suppression, bisphosphonates and increasing EBRT dose did not increase rectal or urinary dysfunction in this trial. However dose escalation using HDRB increased urinary dysfunction.
Publisher: IMR Press
Date: 12-2014
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.RADONC.2015.05.016
Abstract: The relative effects of radiation dose escalation (RDE) and androgen suppression (AS) duration on local prostatic progression (LP) remain unclear. We addressed this in the TROG 03.04 RADAR trial by incorporating a RDE programme by stratification at randomisation. Men were allocated 6 or 18 months AS±18 months zoledronate (Z). The main endpoint was a composite of clinically diagnosed LP or PSA progression with a PSA doubling time ⩾6 months. Fine and Gray competing risk modelling with adjustment for site clustering produced cumulative incidence estimates at 6.5 years for each RDE group. Composite LP declined coherently in the 66, 70 and 74 Gy external beam dosing groups and was lowest in the high dose rate brachytherapy boost (HDRB) group. At 6.5 years, adjusted cumulative incidences were 22%, 15%, 13% and 7% respectively. Compared to 6 months AS, 18 months AS also significantly reduced LP (p<0.001). Post-radiation urethral strictures were documented in 45 subjects and increased incrementally in the dosing groups. Crude incidences were 0.8%, 0.9%, 3.8% and 12.7% respectively. RDE and increasing AS independently reduce LP and increase urethral strictures. The risks and benefits to the in idual must be balanced when selecting radiation dose and AS duration.
Publisher: Wiley
Date: 07-2010
DOI: 10.1118/1.3476205
Publisher: Elsevier BV
Date: 07-1996
DOI: 10.1016/0167-8140(96)01764-1
Abstract: The erythematous response of human skin to radiotherapy has proven useful for testing the predictions of the linear quadratic (LQ) model in terms of fractionation sensitivity and repair half time. No formal investigation of the response of human skin to doses less than 2 Gy per fraction has occurred. This study aims to test the validity of the LQ model for human skin at doses ranging from 0.4 to 5.2 Gy per fraction. Complete erythema reaction profiles were obtained using reflectance spectrophotometry in two patient populations: 65 patients treated palliatively with 5, 10, 12 and 20 daily treatment fractions (varying thicknesses of bolus, various body sites) and 52 patients undergoing prostatic irradiation for localised carcinoma of the prostate (no bolus, 30-32 fractions). Gender, age, site and prior sun exposure influence pre- and post-treatment erythema values independently of dose administered. Out-of-field effects were also noted. The linear quadratic model significantly underpredicted peak erythema values at doses less than 1.5 Gy per fraction. This suggests that either the conventional linear quadratic model does not apply for low doses per fraction in human skin or that erythema is not exclusively initiated by radiation damage to the basal layer. The data are potentially explained by an induced repair model.
Publisher: Wiley
Date: 09-02-2000
DOI: 10.1046/J.1440-1673.2000.00775.X
Abstract: Portal films continue to play an important role in the verification of radiotherapy treatment. There is still some discussion, however, as to what action should be taken after a port film has shown a radiation field deviation from the prescribed volume. It was the aim of the present pilot study to investigate the performance of three decision-making models ('Amsterdam', 'Quebec' and 'Newcastle') and an expert panel basing their decision on intuition rather than formal rules after portal film acquisition in a clinical setting. Portal films were acquired on every day during the first week of treatment for five head and neck and five prostate cancer patients (diagnostic phase). If required, the field position was modified according to our normal practice following the recommendation of the expert panel. In order to analyse the results of the models, however, additional port films were taken in the following 3 treatment weeks with the patient moved as required by the different models (intervention phase). The portal films were taken over 4 consecutive days, positioning the patient according to each of the different models on one day each. None of the models diagnosed a field misplacement in the head and neck patients, while the 'Amsterdam' and 'Quebec' models predicted a move in one prostate patient. The 'Newcastle' model, which is based on Hotelling's T2 statistic, proved to be more sensitive and diagnosed a systematic displacement for three prostate patients. The intervention phase confirmed the diagnosis of the model, even if the three portal films taken with the patient position adjusted as required by the model proved to be insufficient to demonstrate an improvement. The 'Newcastle' model does not rely on assumptions about the random movement of patients and requires five portal films before a decision can be reached. This approach lends itself well to incorporation into electronic portal imaging 'packages', where repeated image acquisitions present no logistical difficulty.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.IJROBP.2017.06.2448
Abstract: To explore the prostate-specific membrane antigen (PSMA)-avid distribution of prostate cancer (PC) on positron emission tomography (PET), both at the time of initial diagnosis and at the time of relapse after definitive local treatment. A total of 179 PSMA PET scans in patients with nil or ≤3 lesions on conventional imaging were retrospectively categorized into 3 subgroups: group A, high-risk PC with no prior definitive therapy (n=34) group B, prior prostatectomy (n=75) and group C, prior radiation therapy (n=70). The numbers and locations of the PSMA-avid lesions were mapped. The PSMA-positive lesions were identified subjectively by a nuclear medicine physician on the basis of clinical experience and taking into account the recent literature and artefacts. A total of 893 PSMA-avid lesions were identified at least 1 lesion was detected in 80% of all scans. A high detection rate was present even at very low serum PSA levels (eg, at PSA ≤0.20 ng/mL in group B, the detection rate was 46%). Thirty-eight percent of studies revealed extrapelvic disease (41%, 31%, and 46% in groups A, B, and C, respectively). Almost one-third of all studies showed only oligometastases (24%, 36%, and 31% in groups A, B, and C, respectively). A large proportion of these (40%) were a solitary lesion. Prostate-specific membrane antigen PET demonstrated a large number of otherwise unknown metastatic lesions. Therefore we recommend PSMA PET for more accurate assessment of disease burden in initial staging of high-risk PC, as well as for restaging in patients with prostate-specific antigen relapse after primary therapies. Furthermore, a high proportion of oligometastases on PSMA PET provides a prime opportunity to investigate the role of targeted local therapies for oligometastatic PCs.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.TRECAN.2017.10.001
Abstract: Nerves are emerging as drivers of tumorigenesis, as demonstrated in the mouse where denervation suppresses prostate cancer however, clinical evidence is needed. Patients with spinal cord injuries (SCIs) resulting in functional denervation of the prostate have a lower incidence of prostate cancer. This may constitute a clinical evidence for nerve dependence in human prostate tumorigenesis.
Publisher: Informa UK Limited
Date: 29-12-2010
DOI: 10.3109/00365521.2010.545832
Abstract: Cancer therapies increasingly achieve cure, but result in chronic moderate or severe gastrointestinal side effects in millions of patients worldwide. Paradoxically, modern therapies threaten to increase the burden of chronic gastrointestinal toxicity, not reduce it. To define pelvic radiation disease. A reinterpretation of published data. The lack of interest in patients with pelvic radiation disease is startling. Symptoms after radiotherapy are only a manifestation of new onset gastrointestinal physiological deficits induced by the radiotherapy. With proper diagnosis and treatment of these deficit(s), the symptoms are curable. Science suggests that much radiotherapy-induced gastrointestinal morbidity is preventable. Once the true nature of radiation injury is understood, straightforward solutions emerge and inaccurate dogmas can be discarded. Imprecise language is a fundamental barrier to progress in complex disorders. Radiation-induced gastrointestinal toxicity is bedeviled by inappropriate terminology, causing confusion, and myth which legitimizes inappropriate clinical behavior. We must address honestly the uncomfortable reality that doctors, sometimes do harm. Not to do so in an era where survivorship is a reality, will deny millions often with severe symptoms from "pelvic radiation disease", the care which will help them.
Publisher: Wiley
Date: 07-2010
DOI: 10.1118/1.3476220
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.RADONC.2008.09.019
Abstract: We sought to categorize longitudinal radiation-induced rectal toxicity data obtained from men participating in a randomised controlled trial for locally advanced prostate cancer. Data from self-assessed questionnaires of rectal symptoms and clinician recorded remedial interventions were collected during the TROG 96.01 trial. In this trial, volunteers were randomised to radiation with or without neoadjuvant androgen deprivation. Characterization of longitudinal variations in symptom intensity was achieved using prevalence data. An integrated visualization and clustering approach based on memetic algorithms was used to define the compositions of symptom clusters occurring before, during and after radiation. The utility of the CTC grading system as a means of identifying specific injury profiles was evaluated using concordance analyses. Seven well-defined clusters of rectal symptoms were present prior to treatment, 25 were seen immediately following radiation and 7 at years 1, 2 and 3 following radiation. CTC grading did not concord with the degree of rectal 'distress' and 'problems' at all time points. Concordance was not improved by adding urgency to the CTC scale. The CTC scale has serious shortcomings. A powerful new technique for non-hierarchical clustering may contribute to the categorization of rectal toxicity data for genomic profiling studies and detailed patho-physiological studies.
Publisher: Elsevier BV
Date: 07-2003
Publisher: Elsevier BV
Date: 05-2004
Publisher: Springer Science and Business Media LLC
Date: 31-10-2016
Publisher: Wiley
Date: 09-1986
DOI: 10.1111/J.1445-2197.1986.TB02373.X
Abstract: The notion of subject in human language has a privileged status relative to other arguments. This special status is manifested in the behavior of subjects at the morphological, syntactic, semantic and discourse levels. Here we bring evidence that subjects have privileged status at the lexical level as well, by analyzing lexicalization patterns of verbs in three different sign languages. Our analysis shows that the sublexical structure of iconic signs denoting state of affairs in these languages manifests an inherent pattern of form-meaning correspondence: the signer's body consistently represents one argument of the verb, the subject. The hands, moving in relation to the body, represent all other components of the event - including all other arguments. This analysis shows that sign languages provide novel evidence in support of the centrality of the notion of subject in human language. It also solves a typological puzzle about the apparent primacy of object in sign language verb agreement, a primacy not usually found in spoken languages, in which subject agreement ranks higher. Our analysis suggests that the subject argument is represented by the body and is part of the lexical structure of the verb. Because it is always inherently represented in the structure of the sign, the subject is more basic than the object, and tolerates the omission of agreement morphology.
Publisher: Wiley
Date: 18-08-2009
DOI: 10.1002/CNCR.24484
Abstract: The value of pretreatment (initial) prostate-specific antigen (iPSA) and biochemical recurrence (BR) as prognostic factors for survival remains unclear. The authors sought to determine why using randomized trial data with 7-year minimum follow-up. In the Trans-Tasman Radiation Oncology Group 96.01 trial, 802 men with T2b, T2c, T3, or T4 N0 prostate cancer (PC) were randomized to radiotherapy alone or with 3 or 6 months neoadjuvant androgen deprivation between 1996 and 2000. Cox modeling was used to identify outcome predictors at follow-up landmark points. Higher iPSA was found to be a potent predictor of BR-free survival (P /=4 years however, it dropped to 44% +/- 6% for men with TTBR <1 year. After BR, rapid PSA doubling time (DT), low iPSA, and short TTBR were identified as the most important predictors of inferior PCSS. When BR occurs, prognostic factors for survival change. Low iPSA, short TTBR, and rapid PSA DT take over at this point, providing reasons why iPSA and occurrence of BR alone predict PCSS unsatisfactorily.
Publisher: Elsevier BV
Date: 09-2014
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.IJROBP.2008.08.047
Abstract: We studied prostate-specific antigen (PSA) changes after radiation with or without neoadjuvant androgen deprivation to determine posttreatment PSA scenarios in which false-positive biochemical failures (FPBF) are most likely to occur. In the Trans-Tasman Radiation Oncology 96.01 Group trial, patients with T2b, 2c, 3, 4 N0 prostate cancer were randomized to 3 or 6 months goserelin and flutamide (STAD) before and during 66 Gy to the prostate and seminal vesicles (XRT) or to XRT alone. Piecewise longitudinal changes in PSA before relapse were characterized and quantified to determine which might cause FPBF calls. Between 1996 and 2000, 802 eligible patients were randomized. Of these, 492 met the criteria for American Society for Therapeutic Radiology and Oncology (ASTRO) failure and 467 for Phoenix failure. Seventy-seven ASTRO fails and 39 Phoenix fails were deemed false positives (FPs). The majority of FPBFs were associated with the "plateauing" in PSA values that follow posttreatment nadir. FPBFs were particularly common in men treated with STAD, in whom small, consecutive PSA rises before or during this phenomenon triggered 56 FP ASTRO fail calls. In these men, the Phoenix fail criteria triggered only 15 FPBF calls. However, the Phoenix criteria were more vulnerable than ASTRO to short-term isolated PSA rises during plateau, which resulted in 15 Phoenix fail calls but only 3 FP ASTRO fails. The Phoenix definition avoided 50% of FPBF calls that occurred with the ASTRO definition. Failures should be confirmed by further PSA rises before investigation and treatment is considered.
Publisher: Wiley
Date: 08-1986
DOI: 10.1111/J.1440-1673.1986.TB01751.X
Abstract: Respiratory depression is a therapy-limiting side effect of opioid analgesics, yet our understanding of the brain circuits mediating this potentially lethal outcome remains incomplete. Here we studied the contribution of the rostral ventromedial medulla (RVM), a region long implicated in pain modulation and homeostatic regulation, to opioid-induced respiratory depression. Microinjection of the μ-opioid agonist DAMGO in the RVM of lightly anesthetized rats produced both analgesia and respiratory depression, showing that neurons in this region can modulate breathing. Blocking opioid action in the RVM by microinjecting the opioid antagonist naltrexone reversed the analgesic and respiratory effects of systemically administered morphine, showing that this region plays a role in both the analgesic and respiratory-depressant properties of systemically administered morphine. The distribution of neurons directly inhibited by RVM opioid microinjection was determined with a fluorescent opioid peptide, dermorphin-Alexa 594, and found to be concentrated in and around the RVM. The non-opioid analgesic improgan, like DAMGO, produced antinociception but, unlike DAMGO, stimulated breathing when microinjected into the RVM. Concurrent recording of RVM neurons during improgan microinjection showed that this agent activated RVM ON-cells, OFF-cells, and NEUTRAL-cells. Since opioids are known to activate OFF-cells but suppress ON-cell firing, the differential respiratory response to these two analgesic drugs is best explained by their opposing effects on the activity of RVM ON-cells. These findings show that pain relief can be separated pharmacologically from respiratory depression and identify RVM OFF-cells as important central targets for continued development of potent analgesics with fewer side effects.
Publisher: Elsevier BV
Date: 07-1995
DOI: 10.1016/0360-3016(94)00449-U
Abstract: This report updates local control and survival experience and focuses on treatment toxicity in 294 patients with esophageal cancer who have been treated at six Australasian centers using three prospective unrandomized protocols that used concurrent radiation, cisplatin, and modest dose infusional fluorouracil. Protocol 1--"definitive" chemoradiation. One hundred and thirty-seven patients have been treated with "definitive" radiation to 60 Gy in 6 weeks plus two courses of cisplatin (80 mg/m2) and infusional fluorouracil (800 mg/m2/day over 4 days) during the first and fourth weeks of radiation. Protocol 2--"preoperative" chemoradiation and surgery. Seventy-eight patients received chemoradiation using the same chemotherapy, but 30-35 Gy in 3-4 weeks prior to surgery. Protocol 3--"palliative" chemoradiation. Seventy-nine patients deemed incurable were treated "palliatively" with the same chemoradiation protocol without surgery. Follow-up ranges from 6 months to 7 years (mean 22 months) in live patients. Durable palliation of dysphagia in all three treatment groups has been reflected by encouraging 3-year survival expectations of 43.2 +/- 5% in definitively treated patients, 40.3 +/- 7.65% in surgically treated patients, and 8.5% +/- 3.9% in the palliatively treated patients. There are early indications that female patients have fared better than males. Toxicity levels were modest in all three groups. Following definitive treatment, severe myelotoxicity (World Health Organization grades 3 and 4) occurred in 19%, severe esophagitis (World Health Organization grade 3) in 11%, and moderate or severe benign stricture in 17%, depending upon age and sex of the patient (being worse in female patients). These studies demonstrate that the concurrent addition of modest dose cisplatin and infusional dose fluorouracil to radiation in the definitive, preoperative, and palliative settings contribute to high rates of durable dysphagia-free survival, with overall survival comparable to (and possibly better than) the chemoradiation arm of the recently reported Intergroup Study, but at the cost of less morbidity.
Publisher: Elsevier BV
Date: 05-2002
DOI: 10.1016/S0167-8140(02)00060-9
Abstract: Radiotherapeutic normal tissue injury can be viewed as two simultaneously ongoing and interacting processes. The first has many features in common with the healing of traumatic wounds. The second is a set of transient or permanent alterations of cellular and extracellular components within the irradiated volume. In contrast to physical trauma, fractionated radiation therapy produces a series of repeated insults to tissues that undergo significant changes during the course of radiotherapy. Normal tissue responses are also influenced by rate of dose accumulation and other factors that relate to the radiation therapy schedule. This article reviews the principles of organised normal tissue responses during and after radiation therapy, the effect of radiation therapy on these responses, as well as some of the mechanisms underlying the development of recognisable injury. Important clinical implications relevant to these processes are also discussed.
Publisher: Springer Berlin Heidelberg
Date: 2010
Publisher: Elsevier BV
Date: 1998
DOI: 10.1016/S0936-6555(98)80064-2
Abstract: Dermofilm (Innovatec, Australia Pty Ltd) is a topical preparation containing hydrophilic and lipophilic agents that enhance the barrier functions of damaged skin. It has been assessed in a pilot study of 50 patients with desquamative skin reactions to establish whether it is a suitable candidate to test against an existing, widely used alternative in a randomized controlled trial. Symptomatic improvement, compliance and healing time were the study endpoints. Symptomatic improvement occurred in 49 patients and compliance with the prescribing instructions was uniform. The range of healing times observed at all sites was large but a relationship with the size of the initial desquamated area was noted. It is concluded that a randomized trial comparing Dermofilm with a widely used and cheaper alternative would require a multicentre effort involving approximately 400 patients (200 per arm). Other trial design considerations are discussed.
Publisher: Wiley
Date: 11-02-2014
DOI: 10.1111/BJU.12497
Abstract: To study the influence of adjuvant androgen suppression and bisphosphonates on incident vertebral and non-spinal fracture rates and bone mineral density (BMD) in men with locally advanced prostate cancer. Between 2003 and 2007, 1071 men with locally advanced prostate cancer were randomly allocated, using a 2 × 2 trial design, to 6 months i.m. leuprorelin (androgen suppression [AS]) before radiotherapy alone ± 12 months additional leuprorelin ± 18 months zoledronic acid (ZdA), commencing at randomization. The main endpoint was incident thoraco-lumbar vertebral fractures, which were assessed radiographically at randomization and at 3 years, then reassessed by centralized review. Subsidiary endpoints included incident non-spinal fractures, which were documented throughout follow-up, and BMD, which was measured in 222 subjects at baseline, 2 years and 4 years. Incident vertebral fractures at 3 years were observed in 132 subjects. Their occurrence was not increased by 18 months' AS, nor reduced by ZdA. Incident non-spinal fractures occurred in 72 subjects and were significantly related to AS duration but not to ZdA. Osteopenia and osteoporosis prevalence rates at baseline were 23.4 and 1.4%, respectively, at the hip. Treatment for 6 and 18 months with AS caused significant reductions in hip BMD at 2 and 4 years (P < 0.01) and ZdA prevented these losses at both time points. In an AS-naïve population, 18 months of ZdA treatment prevented the sustained BMD losses caused by 18 months of AS treatment however, the study power was insufficient to show that AS duration or ZdA influenced vertebral fracture rates.
Publisher: Wiley
Date: 06-2004
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.RADONC.2011.01.006
Abstract: To assess the accuracy of the initial CT plan dose-volume histograms (DVH's) for prostate, rectum and bladder by comparison to delivered doses determined from cone beam CT (CBCT) scans acquired during image-guided treatment. Twelve prostate patients were treated using daily implanted fiducial guidance and following local protocol for bladder and rectal preparation. CBCT scans were acquired twice weekly and contoured for prostate, rectum and bladder. The planned beams were applied to all CBCT scans to determine the delivered doses. Prostate dose coverage was assessed by the proportion of the CTV fully encompassed by the 95% and 98% isodose lines. Rectal and bladder volumes receiving 40 Gy, 60 Gy and 70 Gy at treatment were compared to the initial plan, with significance determined using the one-s le t-test. Four patients showed marginally compromised CTV coverage by the 95% isodose at all CBCT plans. For nine patients the initial plan rectal DVH was significantly outside the range of the treatment DVH's. Dose coverage of the prostate was not achieved for all patients. Observed rectal and bladder doses were higher than predicted. The initial treatment plan cannot be assumed to represent accurate normal tissue doses.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 2005
Abstract: To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial. One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m 2 ) plus tirapazamine (290 mg/m 2 /d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m 2 /d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m 2 ) on day 1 and infusional fluorouracil (360 mg/m 2 /d) on days 1 through 5 of weeks 6 and 7 (chemoboost). Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60% log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79% P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms. Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.
Publisher: Wiley
Date: 02-1990
DOI: 10.1111/J.1440-1673.1990.TB02799.X
Abstract: We report here that cells present in embryonic chick retinal monolayer cultures express differentiated properties characteristic of chick cones developing in vivo. Cell suspensions from 8-d chick embryo retina (a stage when photoreceptor differentiation has not yet started) were cultured for up to 7 d in low density, glial-free monolayers. Under these conditions, monopolar cells represent approximately 40% of the total number of process-bearing neurons. After 6 d in vitro, most of these monopolar cells showed morphological features reminiscent of developing chick cones. These features could be detected with phase-contrast microscopy, lectin cytochemistry, and transmission and scanning electron microscopy. Characteristic cone traits expressed by cultured monopolar cells included the following: (a) a highly polarized organization (b) a single, short, usually unbranched neurite (c) the polarized position of the nucleus close to the origin of the neurite (d) characteristic cone inner segment features such as abundant free ribosomes, a polarized Golgi apparatus, a cluster of mitochondria distal to the nucleus, a big, membrane-bound, pigment-containing vacuole reminiscent of the "lipid droplet" characteristic of chick cones, and at least in some cases, a well-developed paraboloid (e) the presence of a complex of apical differentiations including abundant microvilli and in some cases also a cilium-like process and (f) the staining of the apical region of the cell with peanut lectin, which has been shown to be selective for chick embryo cones (Blanks, J.C., and L.V. Johnson, 1983, J. Comp. Neurol., 221:31-41 and Blanks, J.C., and L.V. Johnson, 1984, Invest. Ophthalmol. Visual Sci., 25:546-557). This pattern of differentiation achieved by 8-d chick retina cells after 6 d in vitro is similar to that shown by 14-d-old chick embryo cones in vivo. Outer segments are not present at this stage of development either in vivo or in vitro. This experimental system is now being used to search for cellular and molecular signals controlling survival and differentiation of cone cells.
Publisher: Elsevier BV
Date: 06-2005
Publisher: Elsevier BV
Date: 06-2007
Publisher: Wiley
Date: 07-01-2013
Abstract: The Trans-Tasman Radiation Oncology Group 03.04 'Randomised Androgen Deprivation and Radiotherapy' multicentre prostate cancer trial examined the optimal duration of androgen deprivation in combination with dose-escalated radiotherapy. Rigorous quality assurance (QA) processes were undertaken to ensure the validity and reliability of the radiation therapy treatment plan data. QA processes included a planning benchmarking exercise and a periodic audit of target and normal tissue delineation. Centralised electronic review of digital plan data for external-beam radiotherapy was undertaken to detect protocol variations. The impact of clinical factors and feedback to submitting centres during the trial on variation rates was investigated. Twenty-three centres across Australia and New Zealand recruited 1071 participants to the trial. Treatment plans for 754 participants receiving external-beam treatment alone were reviewed. From these, 1185 minor and 86 major variations were identified, leading to feedback to treating centres to reduce variations for subsequent patients' treatment and plans, suggesting improvement in treatment quality through these QA programs. Participant anatomical factors (delineated clinical target volume and rectal volume) and treatment planning factors (beam energy, beam definition and patient position orientation) were found to significantly impact variation rates. The dummy run demonstrated disagreement in identification of the base of the prostate and the superior extent of the rectum. Feedback from the periodic audit led to a change of practice at five contributing centres. The application of a suite of complementary QA activities allows the quality of trial data to be optimised and quantified, and can provide a catalyst for reforming treatment practices.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.IJROBP.2016.10.024
Abstract: We assessed the association of the spatial distribution of dose to the bladder surface, described using dose-surface maps, with the risk of urinary dysfunction. The bladder dose-surface maps of 754 participants from the TROG 03.04-RADAR trial were generated from the volumetric data by virtually cutting the bladder at the sagittal slice, intersecting the bladder center-of-mass through to the bladder posterior and projecting the dose information on a 2-dimensional plane. Pixelwise dose comparisons were performed between patients with and without symptoms (dysuria, hematuria, incontinence, and an International Prostate Symptom Score increase of ≥10 [ΔIPSS10]). The results with and without permutation-based multiple-comparison adjustments are reported. The pixelwise multivariate analysis findings (peak-event model for dysuria, hematuria, and ΔIPSS10 event-count model for incontinence), with adjustments for clinical factors, are also reported. The associations of the spatially specific dose measures to urinary dysfunction were dependent on the presence of specific symptoms. The doses received by the anteroinferior and, to lesser extent, posterosuperior surface of the bladder had the strongest relationship with the incidence of dysuria, hematuria, and ΔIPSS10, both with and without adjustment for clinical factors. For the doses to the posteroinferior region corresponding to the area of the trigone, the only symptom with significance was incontinence. A spatially variable response of the bladder surface to the dose was found for symptoms of urinary dysfunction. Limiting the dose extending anteriorly might help reduce the risk of urinary dysfunction.
Publisher: Elsevier BV
Date: 08-1999
DOI: 10.1016/S0167-8140(99)00107-3
Abstract: The relationship between acute and late mucosal reactions remains ill defined but is of considerable relevance to efforts to produce therapeutic gains through the use of altered fractionation schemes and concurrent chemotherapy. We therefore investigated whether acute mucosal reactions in patients treated with an accelerated and a conventionally fractionated radiotherapy regime predicted the severity of late mucosal reactions. The study population consisted of 191 patients randomised on a prospective trial comparing conventional fractionation at 2 Gy/fraction per day, 70 Gy over 47 days with an accelerated regimen of 59.4 Gy, 1.8 Gy b.i.d over 24 days for Stage III-IV carcinoma of the head and neck. Acute and late mucosal reactions were scored according to RTOG/EORTC criteria and analyzed using multiple regression techniques. The duration of time spent by patients at the acute confluent mucositis grade 3 level was inversely related to the time to onset of the reaction for both fractionation schedules. Time to onset was more rapid for patients treated on the accelerated schedule but time spent at the reaction grade did not differ significantly between the schedules. After correction for treatment and patient related factors, anatomical site (oral cavity/oropharynx versus hypopharynx/larynx) and increasing duration of confluent mucositis emerged as independent predictors of the hazard of late mucosal reactions with the latter effect being more pronounced in the accelerated treatment arm. The expected reduction in late mucosal effects in the accelerated fractionation arm, predicted by the LQ model for late effects was identified only in patients whose acute confluent mucosal reactions lasted less than 20 days. The presence of in idual patient susceptibility factors that determine the severity of acute mucosal reactions is suggested. A link between severe and prolonged acute reactions and the risk of developing late mucosal reactions that is independent of biological dose, has also been found. Purpose designed prospective studies of these issues are necessary.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.RADONC.2010.11.013
Abstract: Temporal distributions in PSA levels following therapeutic intervention for prostate cancer are known to contain characteristics prognostic of disease progression. An algorithm was developed for extracting such characteristics, specifically in the context of previous observations following radiotherapy. Segmented regression methods were investigated for characterising the 'signatures' in log(PSA) descent patterns between intervention and nadir. The segmented regression method can automatically identify and parameterise features in a PSA distribution including failure points and doubling time patterns following nadir. The method has previously been applied to the analysis of descent patterns on a large clinical data series (Radiother Oncol 2009 :382-8). Batch-processing of data using the method for all patients in a clinical trial would establish population parameter values and ranges. Subsequent application to an in idual patient's PSA data would determine which resulting prognostic group they fall into. As more complete and higher-resolution PSA progression datasets become available, techniques such as presented here will allow flexible definition of the characteristics being examined and rapid extraction of parameters for correlation with clinical progression data.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2018
Publisher: Elsevier BV
Date: 05-2003
Abstract: The detailed review of patterns of failure in this report was undertaken to identify the continuing obstacles to the successful management of oesophageal cancer, and to establish whether there is a case to compare definitive chemo-radiation (Def-CR) and surgery for patients with squamous cancer in a randomized controlled trial. First and subsequent sites of failure were reviewed in 274 patients treated with Def-CR using two cycles of cisplatin, infusional fluorouracil and 60 Gy and 92 patients with limited chemo-radiation (CR), using one cycle and 35 Gy, followed by surgery (CR-Surg). All were treated on prospective non-randomized trials run by the Trans-Tasman Radiation Oncology Group between 1985 and 1999. Failure patterns were analysed using competing risks methodology, and pre-treatment variables predicting survival were identified by proportional hazards modelling. Site, stage, performance status and gender were independently predictive of survival following Def-CR. Local failure was evident in 42.3% of patients, but distant failure in isolation occurred in an additional 18.1%. Lowest rates of local and distant failure at 5 years (29.9% and 26%) occurred in patients with squamous cancer (SCC) located in the upper-third, whose 5-year survival was also the most favourable (49.2%). Survival was least favourable in patients with adenocarcinoma (AC) in the lower two-thirds (18.1%) due to higher rates of local (51.5%) and distant (36.1%) failure. Local failure occurred in 31.5% of patients undergoing CR-Surg but distant failure in isolation was observed in a further 34.7%. Outcomes were least favourable in patients with AC of the lower-third in whom 57.7% failed distantly and 5-year survival was 3.8%. Response to pre-operative chemo-radiation was also strongly predictive of outcome. Patients with no residual cancer in the resection specimen had the lowest rates of local (0%) and distant (16.7%) failure and the best survival (64.9%). Survival in patients with residual cancer in nodes, however, was extremely poor (3.5%) with distant failure occurring in 66.7%. The concurrent administration of chemotherapy with radiotherapy seems to have improved loco-regional control and has exposed distant failure as an obstacle to further improvements in outcome. Site, histological subtype, gender and response to chemo-radiation may predict biological differences in oesophageal cancer (OC) that influence outcome. A good case for a randomized comparison between Def-CR and CR-Surg in patients with SCC in the lower two-thirds exists.
Publisher: SAGE Publications
Date: 04-2007
Abstract: There is currently very little research on how physicians respond to patients with cancer who decide to forgo or stop medically recommended “curative” therapy. The purpose of this article is to report on a qualitative study with 12 oncology specialists in Israel and Australia that addresses this question. The findings indicate that physicians tend to construct patients and their decisions in terms of mutually exclusive categories that focus on curability of the disease, rationality of the patient's decision, and patients' personal attributes. Physicians' constructions of their experience focus on uncertainty and concern. Although contextual factors play a role in how physicians act in this situation, Israeli and Australian oncologists are remarkably similar in how they describe their own and their patients' experiences.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.RADONC.2011.01.012
Abstract: Dose planning requires a CT scan which provides the electron density distribution for dose calculation. MR provides superior soft tissue contrast compared to CT and the use of MR-alone for prostate planning would provide further benefits such as lower cost to the patient. This study compares the accuracy of MR-alone based dose calculations with bulk electron density assignment to CT-based dose calculations for prostate radiotherapy. CT and whole pelvis MR images were contoured for 39 prostate patients. Plans with uniform density and plans with bulk density values assigned to bone and tissue were compared to the patient's gold standard full density CT plan. The optimal bulk density for bone was calculated using effective depth measurements. The plans were evaluated using ICRU point doses, dose volume histograms, and Chi comparisons. Differences in spatial uniformity were investigated for the CT and MR scans. The calculated dose for CT bulk bone and tissue density plans was 0.1±0.6% (mean±1 SD) higher than the corresponding full density CT plan. MR bulk bone and tissue density plans were 1.3±0.8% lower than the full density CT plan. CT uniform density plans and MR uniform density plans were 1.4±0.9% and 2.6±0.9% lower, respectively. Paired t-tests performed on specific points on the DVH graphs showed that points on DVHs for all bulk electron density plans were equivalent with two exceptions. There was no significant difference between doses calculated on Pinnacle and Eclipse. The dose distributions of six patients produced Chi values outside the acceptable range of values when MR-based plans were compared to the full density plan. MR-alone bulk density planning is feasible provided bone is assigned a density, however, manual segmentation of bone on MR images will have to be replaced with automatic methods. The major dose differences for MR bulk density plans are due to differences in patient external contours introduced by the MR couch-top and pelvic coil.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-06-2007
Abstract: We evaluated whether the timing of fatal myocardial infarction (MI) was influenced by the administration of androgen suppression therapy (AST). The study cohort comprised 1,372 men who were enrolled onto three randomized trials between February 1995 and June 2001. In the three trials, the men were randomly assigned to receive radiation therapy with 0 versus 3 versus 6, 3 versus 8, or 0 versus 6 months of AST. Fine and Gray's regression was used to determine the clinical factors associated with the time to fatal MI, and estimates of time to fatal MI were calculated using a cumulative incidence method. When comparing the cumulative incidence estimates using Gray's k-s le P values, increased weight was ascribed to the earlier data because recovery of testosterone is expected for most men within 2 years after short-course AST. Men age 65 years or older who received 6 months of AST experienced shorter times to fatal MIs compared with men in this age group who did not receive AST (P = .017) and men younger than 65 years (P = .016). No significant difference (P = .97) was observed in the time to fatal MIs in men age 65 years or older who received 6 to 8 months of AST compared with 3 months of AST. The use of AST is associated with earlier onset of fatal MIs in men age 65 years or older who are treated for 6 months compared with men who are not treated with AST.
Publisher: SPIE
Date: 26-02-2009
DOI: 10.1117/12.812460
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.RADONC.2016.05.010
Abstract: Most predictive models are not sufficiently validated for prospective use. We performed independent external validation of published predictive models for urinary dysfunctions following radiotherapy of the prostate. Multivariable models developed to predict atomised and generalised urinary symptoms, both acute and late, were considered for validation using a dataset representing 754 participants from the TROG 03.04-RADAR trial. Endpoints and features were harmonised to match the predictive models. The overall performance, calibration and discrimination were assessed. 14 models from four publications were validated. The discrimination of the predictive models in an independent external validation cohort, measured using the area under the receiver operating characteristic (ROC) curve, ranged from 0.473 to 0.695, generally lower than in internal validation. 4 models had ROC >0.6. Shrinkage was required for all predictive models' coefficients ranging from -0.309 (prediction probability was inverse to observed proportion) to 0.823. Predictive models which include baseline symptoms as a feature produced the highest discrimination. Two models produced a predicted probability of 0 and 1 for all patients. Predictive models vary in performance and transferability illustrating the need for improvements in model development and reporting. Several models showed reasonable potential but efforts should be increased to improve performance. Baseline symptoms should always be considered as potential features for predictive models.
Publisher: Wiley
Date: 11-1985
DOI: 10.1111/J.1440-1673.1985.TB01733.X
Abstract: Monocyte locomotion inhibitory factor (MLIF) is a pentapeptide produced by Entamoeba histolytica that has a potent anti-inflammatory effect. Either MLIF or phosphate buffered saline (PBS) was administered directly onto the spinal cord (SC) immediately after injury. Motor recovery was evaluated. We also analyzed neuroprotection by quantifying the number of surviving ventral horn motor neurons and the persistence of rubrospinal tract neurons. To evaluate the mechanism through which MLIF improved the outcome of SC injury, we quantified the expression of inducible nitric oxide synthase (iNOS), interleukin-10 (IL-10), and transforming growth factor- β (TGF- β ) genes at the site of injury. Finally, the levels of nitric oxide and of lipid peroxidation were also determined in peripheral blood. Results showed that MLIF improved the rate of motor recovery and this correlated with an increased survival of ventral horn and rubrospinal neurons. These beneficial effects were in turn associated with a reduction in iNOS gene products and a significant upregulation of IL-10 and TGF- β expression. In the same way, MLIF reduced the concentration of nitric oxide and the levels of lipid peroxidation in systemic circulation. The present results demonstrate for the first time the neuroprotective effects endowed by MLIF after SC injury.
Publisher: Springer Science and Business Media LLC
Date: 26-08-2016
DOI: 10.1007/S10555-016-9635-Z
Abstract: Currently used surgical techniques to reconstruct tissue defects after resection of musculoskeletal tumours are associated with high complication rates. This drives a strong demand for innovative therapeutic concepts that are able to improve the clinical outcomes of patients suffering from bone and soft tissue tumours. Tissue engineering and regenerative medicine (TE&RM) provides a technology platform based on biochemical, molecular, cellular and biomaterials modules to selectively direct tissue healing processes for improved defect regeneration. At the same time, precautionary measures have to be taken when these instruments are used in cancer patients to prevent any promotion of tumour growth or metastatic spread. On the other hand, several innovative TE&RM tools are being developed such as multi-functionalized biomaterials, drug-delivering nanomaterials or genetically engineered stem cells that per se have the potential to mediate anti-cancer effects, act synergistically with currently used chemotherapeutics and/or radiotherapy regimens and reduce their side effects. Recently, scientists became conscious that TE&RM strategies may not only be utilized to advance contemporary tissue reconstruction techniques but also to develop personalized diagnostic tools and clinically relevant disease models for cancer patients. Eventually, prospective randomized clinical trials combined with comparative outcome analyses are a conditio sine qua non to shape the benefits of personalized regenerative therapies for the standardized management of patients with musculoskeletal tumours.
Publisher: Wiley
Date: 09-02-2000
DOI: 10.1046/J.1440-1673.2000.00774.X
Abstract: In 1997 the Trans-Tasman Radiation Oncology Group (TROG) performed a quality assurance (QA) audit of its phase III randomized clinical trial investigating the effectiveness of different durations of maximal androgen deprivation prior to and during definitive radiation therapy for locally advanced carcinoma of the prostate (TROG 96.01). The audit reviewed a total of 60 cases from 15 centres across Australia and New Zealand. In addition to verification of technical adherence to the protocol, the audit also incorporated a survey of centre planning techniques and a QA time/cost analysis. The present report builds on TROG's first technical audit conducted in 1996 for the phase III accelerated head and neck trial (TROG 91.01) and highlights the significant progress TROG has made in the interim period. The audit provides a strong validation of the results of the 96.01 trial, as well as valuable budgeting and treatment planning information for future trials. Overall improvements were detected in data quality and quantity, and in protocol compliance, with a reduction in the rate of unacceptable protocol violations from 10 to 4%. Audit design, staff education and increased data management resources were identified as the main contributing factors to these improvements. In addition, a budget estimate of $100 per patient has been proposed for conducting similar technical audits. The next major QA project to be undertaken by TROG during the period 1998-1999 is an intercentre dosimetry study. Trial funding and staff education have been targeted as the key major issues essential to the continued success and expansion of TROG's QA programme.
Publisher: Elsevier BV
Date: 06-1997
DOI: 10.1016/S0748-7983(97)92364-7
Abstract: This study aims to update the experience of multimodality approaches in the management of oesophageal cancer that have been adopted in several Australian and New Zealand hospitals. Between 1984 and 1985, 92 patients received pre-operative radiotherapy (30-36 Gy over 3 weeks) and one of two chemotherapy regimes (one or two courses of i.v. cisplatin 80 mg/m2 plus a 4-5 day continuous i.v. of fluorouracil 5-800 mg/m2/day) concurrently prior to surgery. Eighty-two patients (89%) underwent resection as planned. Operative specimens were microscopically free of residual tumour in 18 patients. Eight patients (9%) had treatment-related deaths: seven from surgery and one due to pre-operative chemoradiation. The Kaplan-Meier 5-year cause-specific survival estimates were 32.9 +/- 7.8% for the 58 patients with squamous cancer and 0% for the 32 with adenocarcinoma. Complete pathological response to the pre-operative regime was more common in females and was associated with a survival advantage. Five-year cause-specific survival expectation in patients who experienced a complete pathological response was 71.5 +/- 12.4%, whereas it was only 15.9 +/- 5.6% in patients who had residual cancer in their surgical specimens. Although less toxic the pre-operative regime utilizing only one cycle of chemotherapy was no less efficacious either in producing a complete pathological response or in terms of survival expectation. This uncontrolled pilot study has produced encouraging long-term results, especially for patients with squamous carcinoma that experienced a complete response to pre-operative synchronous chemoradiotherapy. A randomized controlled study comparing surgery alone with (one cycle) chemoradiation followed by surgery is now underway.
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.IJROBP.2014.11.015
Abstract: To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma. Influential dose-volume histogram regions were to be determined as functions of dose, anatomical location, toxicity, and clinical endpoint. Planning datasets for 754 participants in the TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT) Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a median of 72 months. A rank sum method was used to define dose-volume cut-points as near-continuous functions of dose to 3 GI anatomical regions, together with a comprehensive assessment of significance. Univariate and multivariate ordinal regression was used to assess the importance of cut-points at each dose. Dose ranges providing significant cut-points tended to be consistent with those showing significant univariate regression odds-ratios (representing the probability of a unitary increase in toxicity grade per percent relative volume). Ranges of significant cut-points for rectal bleeding validated previously published results. Separation of the lower GI anatomy into complete anorectum, rectum, and anal canal showed the impact of mid-low doses to the anal canal on urgency and tenesmus, completeness of evacuation and stool frequency, and mid-high doses to the anorectum on bleeding and stool frequency. Derived multivariate models emphasized the importance of the high-dose region of the anorectum and rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency and tenesmus, and low-to-mid doses to the anal canal for stool frequency, diarrhea, evacuation, and bleeding. Results confirm anatomical dependence of specific GI toxicities. They provide an atlas summarizing dose-histogram effects and derived constraints as functions of anatomical region, dose, toxicity, and endpoint for informing future radiation therapy planning.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.CTRV.2014.11.001
Abstract: Active Surveillance (AS) is recommended for the treatment of localised prostate cancer however this option may be under-used, at least in part because of expectations of psychological adverse events in those offered or accepting AS. (1) Determine the impact on psychological wellbeing when treated with AS (non-comparative studies). (2) Compare AS with active treatments for the impact on psychological wellbeing (comparative studies). We used the PRISMA guidelines and searched Medline, PsychInfo, EMBASE, CINHAL, Web of Science, Cochrane Library and Scopus for articles published January 2000-2014. Eligible studies reported original quantitative data on any measures of psychological wellbeing. We identified 34 eligible articles (n=12,497 in iduals) 24 observational, eight RCTs, and two other interventional studies. Studies came from North America (16), Europe (14) Australia (3) and North America/Europe (1). A minority (5/34) were rated as high quality. Most (26/34) used validated instruments, whilst a substantial minority (14/34) used watchful waiting or no active treatment rather than Active Surveillance. There was modest evidence of no adverse impact on psychological wellbeing associated with Active Surveillance and no differences in psychological wellbeing compared to active treatments. Patients can be informed that Active Surveillance involves no greater threat to their psychological wellbeing as part of the informed consent process, and clinicians need not limit access to Active Surveillance based on an expectation of adverse impacts on psychological wellbeing.
Publisher: Wiley
Date: 13-01-2014
Abstract: Procollagen 1 amino-terminal propeptide (P1NP) is a bone formation marker and has been shown to have a strong association with the extent of bone metastases (BM) in patients with advanced prostate cancer. More recently, its levels were found to be affected by androgen deprivation therapies and bisphosphonates. We investigated the role of P1NP as a surrogate marker of sub-radiological skeletal metastases in prostate cancer patients with biochemical failure (BF). BePrepared is a prospective longitudinal substudy of RADAR trial in which serial P1NPs were collected at regular intervals for 123 patients who had completed RADAR protocol treatment. There was no trend identified in P1NP levels prior to diagnosis of BM. We found that there was no difference in P1NP concentrations at the time of diagnosis of BM in the group that developed BM compared with P1NP levels in groups with only nodal metastases or BF. In the group of patients who did not experience BF, P1NP was affected by previous luteinizing hormone-releasing hormone-agonist and bisphosphonate therapy. Hence, patients who received an 18-month course of androgen deprivation without bisphosphonates had significantly higher P1NP values than patients with shorter androgen deprivation therapy (ADT) course combined with a course of bisphosphonates. P1NP is not a sensitive serum marker of early BM in high-risk prostate cancer patients with BF and low prostate-specific antigen levels as its levels are affected by prior history of bone remodelling therapies such as ADT and bisphosphonates.
Publisher: Wiley
Date: 04-04-2016
DOI: 10.1118/1.4944738
Abstract: Given the paucity of available data concerning radiotherapy-induced urinary toxicity, it is important to ensure derivation of the most robust models with superior predictive performance. This work explores multiple statistical-learning strategies for prediction of urinary symptoms following external beam radiotherapy of the prostate. The performance of logistic regression, elastic-net, support-vector machine, random forest, neural network, and multivariate adaptive regression splines (MARS) to predict urinary symptoms was analyzed using data from 754 participants accrued by TROG03.04-RADAR. Predictive features included dose-surface data, comorbidities, and medication-intake. Four symptoms were analyzed: dysuria, haematuria, incontinence, and frequency, each with three definitions (grade ≥ 1, grade ≥ 2 and longitudinal) with event rate between 2.3% and 76.1%. Repeated cross-validations producing matched models were implemented. A synthetic minority overs ling technique was utilized in endpoints with rare events. Parameter optimization was performed on the training data. Area under the receiver operating characteristic curve (AUROC) was used to compare performance using s le size to detect differences of ≥0.05 at the 95% confidence level. Logistic regression, elastic-net, random forest, MARS, and support-vector machine were the highest-performing statistical-learning strategies in 3, 3, 3, 2, and 1 endpoints, respectively. Logistic regression, MARS, elastic-net, random forest, neural network, and support-vector machine were the best, or were not significantly worse than the best, in 7, 7, 5, 5, 3, and 1 endpoints. The best-performing statistical model was for dysuria grade ≥ 1 with AUROC ± standard deviation of 0.649 ± 0.074 using MARS. For longitudinal frequency and dysuria grade ≥ 1, all strategies produced AUROC>0.6 while all haematuria endpoints and longitudinal incontinence models produced AUROC<0.6. Logistic regression and MARS were most likely to be the best-performing strategy for the prediction of urinary symptoms with elastic-net and random forest producing competitive results. The predictive power of the models was modest and endpoint-dependent. New features, including spatial dose maps, may be necessary to achieve better models.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.IJROBP.2009.10.071
Abstract: We sought to compare the prognostic value of early prostate-specific antigen (PSA) test-based variables for the 802 eligible patients treated in the Trans-Tasman Radiation Oncology Group 96.01 randomized trial. Patients in this trial had T2b, T2c, T3, and T4 N0 prostate cancer and were randomized to 0, 3, or 6 months of neoadjuvant androgen deprivation therapy (NADT) prior to and during radiation treatment at 66 Gy to the prostate and seminal vesicles. The early PSA test-based variables evaluated were the pretreatment initial PSA (iPSA) value, PSA values at 2 and 4 months into NADT, the PSA nadir (nPSA) value after radiation in all patients, and PSA response signatures in men receiving radiation. Comparisons of endpoints were made using Cox models of local progression-free survival, distant failure-free survival, biochemical failure-free survival, and prostate cancer-specific survival. The nPSA value was a powerful predictor of all endpoints regardless of whether NADT was given before radiation. PSA response signatures also predicted all endpoints in men treated by radiation alone. iPSA and PSA results at 2 and 4 months into NADT predicted biochemical failure-free survival but not any of the clinical endpoints. nPSA values correlated with those of iPSA, Gleason grade, and T stage and were significantly higher in men receiving radiation alone than in those receiving NADT. The postradiation nPSA value is the strongest prognostic indicator of all early PSA-based variables. However, its use as a surrogate endpoint needs to take into account its dependence on pretreatment variables and treatment method.
Publisher: Elsevier BV
Date: 11-1996
DOI: 10.1016/S0167-8140(96)01830-0
Abstract: Regeneration of the aerodigestive mucosa is known to occur during conventionally fractionated radiotherapy. The circumstances surrounding its time of onset and magnitude are not well understood, however. Mucosal reactions were observed in 100 patients undergoing conventionally fractionated treatment at 2 Gy/day over 7 weeks and 88 receiving accelerated treatment at 1.8 Gy twice daily over 3 1/2 weeks on the Trans Tasman Radiation Oncology Group head and neck cancer trials. Similar observations in 61 patients treated palliatively at dose rates between 0.8 and 240 Gy/h using ten 3.0-4.2 Gy fractions over 2 weeks are compared. Several findings emerged from these studies: 1. Reactions evolved more quickly at oropharyngeal sites than in the hypopharynx. 2. Reactions at both sites evolved more rapidly at greater rates of dose accumulation. 3. The timing of reactions suggested the presence of a strong regenerative mucosal response that started before the manifestation of "patchy' (grade II) mucosal reactions. 4. The regenerative response was strong enough to "make good' damage accumulated at a rate of 2 Gy/day in over a third of cases. 5. The linear quadratic model without time correction failed to provide an adequate prediction of the frequency or intensity of mucosal reactions produced by any of the regimes. A simple model of the regenerative response is presented. This study suggests that the timing and magnitude of the regenerative response vary between sites and in iduals but are linked to the amount of epithelial cellular depletion occurring during treatment.
Publisher: Wiley
Date: 08-1992
DOI: 10.1111/J.1440-1673.1992.TB03170.X
Abstract: The method described in the previous paper was used to induce secondary responses in spleen cells from CBA/H mice, pre-primed with lymphocytic choriomeningitis (LCM) virus by culturing them with LCM-infected peritoneal cells. The cytolytic effector cells thus generated have been characterized. Effector cells were sensitive to treatment with anti-theta ascitic fluid and complement. Separation procedures based on rosetting of certain categories of lymphocytes with sheep red cells through an Isopaque-Ficoll gradient indicated that effector cells lacked surface immunoglobulin and generally did not bear Fc receptors. Cytolytic activity was restricted by the H-2 gene complex. Killing had single-hit characteristics. All these results suggested that the cells from memory cultures mediating cytolysis were T cells. There was evidence for two T cell subsets, a major subpopulation directed against antigens on infected targets and a minor one directed against antigens on uninfected, H-2-compatible targets. Specificity was present at the infected cell:memory responder and killer:target levels between LCM virus (an arenavirus) and ectromelia virus (a poxvirus).
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.EURURO.2013.09.041
Abstract: Long-term prostate cancer (PCa) survivors are at increased risk for comorbidities and physical deconditioning. To determine the effectiveness of a year-long randomised controlled trial of exercise training in PCa survivors >5 yr postdiagnosis on physical functioning. Between 2010 and 2011, 100 long-term PCa survivors from Trans-Tasman Radiation Oncology Group 03.04 Randomised Androgen Deprivation and Radiotherapy previously treated with androgen-deprivation therapy and radiation therapy were randomly assigned to 6 mo of supervised exercise followed by 6 mo of a home-based maintenance programme (n=50) or printed educational material about physical activity (n=50) for 12 mo across 13 university-affiliated exercise clinics in Australia and New Zealand. Supervised resistance and aerobic exercise or printed educational material about physical activity. The primary end point was a 400-m walk as a measure of cardiovascular fitness. Secondary end points were physical function, patient-reported outcomes, muscle strength, body composition, and biomarkers. Analysis of covariance was used to compare outcomes for groups at 6 and 12 mo adjusted for baseline values. Participants undergoing supervised exercise showed improvement in cardiorespiratory fitness performance at 6 mo (-19 s [p=0.029]) and 12 mo (-13 s [p=0.028]) and better lower-body physical function across the 12-mo period (p<0.01). Supervised exercise also improved self-reported physical functioning at 6 (p=.006) and 12 mo (p=0.002), appendicular skeletal muscle at 6 mo (p=0.019), and objective measures of muscle strength at 6 and 12 mo (p<0.050). Limitations included the restricted number of participants undertaking body composition assessment, no blinding to group assignment for physical functioning measures, and inclusion of well-functioning in iduals. Supervised exercise training in long-term PCa survivors is more effective than physical activity educational material for increasing cardiorespiratory fitness, physical function, muscle strength, and self-reported physical functioning at 6 mo. Importantly, these benefits were maintained in the long term with a home-based programme with follow-up at 12 mo. The effect of an exercise intervention on cardiovascular and metabolic risk factors in prostate cancer patients from the RADAR study, ACTRN: ACTRN12609000729224.
Publisher: Wiley
Date: 11-1996
DOI: 10.1111/J.1440-1673.1996.TB00440.X
Abstract: Concurrent chemotherapy and radiation (CT/RT) for localized oesophageal cancer can cause life-threatening myelosuppression. This non-randomized study examines 95 patients from three Australasian centres treated on the Trans-Tasman Radiation Oncology "definitive' chemoradiation study. Duration of fluorouracil infusion and patient age were independently predictive of myelotoxicity after the first cycle of CT/RT. Overall rates of grade III and IV neutropaenia were 23% and of thrombocytopaenia 8% following the first cycle of chemotherapy. Five neutropaenic septic episodes followed the first cycle and six the second. All five patients recovered after the first cycle but there were four treatment-related deaths occurring after the second cycle of CT/RT. Recommendations are made concerning initial dosing, dose reductions and delays to minimize adverse patient outcomes from myelosuppression.
Publisher: Wiley
Date: 10-2008
DOI: 10.1111/J.1440-1673.2008.02005.X
Abstract: The aim of the study was to determine prostate set-up accuracy and set-up margins with off-line bony anatomy-based imaging protocols, compared with online implanted fiducial marker-based imaging with daily corrections. Eleven patients were treated with implanted prostate fiducial markers and online set-up corrections. Pretreatment orthogonal electronic portal images were acquired to determine couch shifts and verification images were acquired during treatment to measure residual set-up error. The prostate set-up errors that would result from skin marker set-up, off-line bony anatomy-based protocols and online fiducial marker-based corrections were determined. Set-up margins were calculated for each set-up technique using the percentage of encompassed isocentres and a margin recipe. The prostate systematic set-up errors in the medial-lateral, superior-inferior and anterior-posterior directions for skin marker set-up were 2.2, 3.6 and 4.5 mm (1 standard deviation). For our bony anatomy-based off-line protocol the prostate systematic set-up errors were 1.6, 2.5 and 4.4 mm. For the online fiducial based set-up the results were 0.5, 1.4 and 1.4 mm. A prostate systematic error of 10.2 mm was uncorrected by the off-line bone protocol in one patient. Set-up margins calculated to encompass 98% of prostate set-up shifts were 11-14 mm with bone off-line set-up and 4-7 mm with online fiducial markers. Margins from the van Herk margin recipe were generally 1-2 mm smaller. Bony anatomy-based set-up protocols improve the group prostate set-up error compared with skin marks however, large prostate systematic errors can remain undetected or systematic errors increased for in idual patients. The margin required for set-up errors was found to be 10-15 mm unless implanted fiducial markers are available for treatment guidance.
Publisher: Elsevier BV
Date: 04-2010
Publisher: Springer Science and Business Media LLC
Date: 14-01-2020
DOI: 10.1038/S41585-019-0274-3
Abstract: Prostate cancer progression has been shown to be dependent on the development of autonomic nerves into the tumour microenvironment. Sympathetic nerves activate adrenergic neurosignalling that is necessary in early stages of tumour progression and for initiating an angiogenic switch, whereas parasympathetic nerves activate cholinergic neurosignalling resulting in tumour dissemination and metastasis. The innervation of prostate cancer seems to be initiated by neurotrophic growth factors, such as the precursor to nerve growth factor secreted by tumour cells, and the contribution of brain-derived neural progenitor cells has also been reported. Current experimental, epidemiological and clinical evidence shows the stimulatory effect of tumour innervation and neurosignalling in prostate cancer. Using nerves and neurosignalling could have value in the management of prostate cancer by predicting aggressive disease, treating localized disease through denervation and relieving cancer-associated pain in bone metastases.
Publisher: Wiley
Date: 10-06-2017
DOI: 10.1002/PON.4182
Publisher: Wiley
Date: 24-08-2011
DOI: 10.1118/1.3626484
Abstract: To assess dose delivery accuracy to clinically significant points in a realistic patient geometry for two separate pelvic radiotherapy scenarios. An inhomogeneous pelvic phantom was transported to 36 radiotherapy centers in Australia and New Zealand. The phantom was treated according to Phase III rectal and prostate trial protocols. Point dose measurements were made with thermoluminescent dosimeters (TLDs) and an ionisation chamber. Comprehensive site-demographic, treatment planning, and physical data were collected for correlation with measurement outcomes. Dose delivery to the prescription point for the rectal treatment was consistent with planned dose (mean difference between planned and measured dose - 0.1 ± 0.3% std err). Dose delivery in the region of the sacral hollow was consistently higher than planned (+1.2 ± 0.2%). For the prostate treatment, dose delivery to the prostate volume was consistent with planned doses (-0.49 ± 0.2%) and planned dose uniformity, though with a tendency to underdose the PTV at the prostate-rectal border. Measured out-of-field doses were significantly higher than planned. A phantom based on realistic anatomy and heterogeneity can be used to comprehensively assess the influence of multiple aspects of the radiotherapy treatment process on dose delivery. The ability to verify dose delivery for two trials with a single phantom was advantageous.
Publisher: Hindawi Limited
Date: 22-12-2017
DOI: 10.1111/ECC.12630
Abstract: To describe the prevalence, severity and nature of depression in a s le of prostate cancer (PCa) survivors 10 years after diagnosis and treatment, 146 Australian patients from the RADAR trial who received their diagnosis 10 years previously completed the Zung Self-rating Depression Scale and a background questionnaire. Prevalence rates for clinically significant depression and severe depression were higher than those reported for the non-PCa men of the same age in Australia. The most common subtype of depression was Anhedonia, followed by Cognitive depression. Change in eating habits was the most powerful depression symptom predicting Anhedonia. By providing the first detailed documentation of major depression prevalence in PCa survivors, plus describing the nature of that depression, these data suggest that there is an ongoing need to provide treatments for these men and that those treatments should be focussed upon loss of previously available sources of enjoyment.
Publisher: Elsevier BV
Date: 07-2010
Publisher: Elsevier BV
Date: 11-1994
DOI: 10.1016/0167-8140(94)90069-8
Abstract: Well-known inadequacies in currently available electron planning systems, and two cases of temporal lobe necrosis following electron therapy of the parotid stimulated a comprehensive head and neck phantom dosimetric study of the use of high energy electrons for parotid treatments. A typical electron field employed for the treatment of parotid malignancy was examined in an anthropomorphic head phantom from which air cavities had been excavated. Thermoluminescent dosimeter measurements were compared with predicted point doses obtained from a Theraplan Treatment planning system (V05). Data was examined for three different electron energies: 12, 16 and 20 MeV and with the addition of contoured bolus for 20 MeV. A number of significant discrepancies between the measured and predicted dose were observed. Measured doses were seen to exceed predicted doses by up to 23% in the temporal lobe. Further under-predictions of dose were found behind the mandible and in the nasal cavity. Over-predictions of dose by the planning algorithm of up to 22% were observed beside the oropharynx. Some of these discrepancies were found to relate to Theraplan under-estimation of the dose in the fall-off region. Other errors are attributable to the difficulties in predicting dose at density interfaces. Localised over- and under-predictions of this magnitude must be accounted for by the clinician prescribing treatment in terms of possible late effects on the temporal lobe and, in particular, the nominated dose specification point.
Publisher: Elsevier BV
Date: 08-2001
Publisher: Wiley
Date: 30-11-2009
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.RADONC.2008.10.002
Abstract: Biological mechanisms underlying radiation induced erythema remain largely unknown, with no simple way to accurately predict or prevent extreme cases. Based on the recent findings in patients suffering from chronic urticaria, we sought to determine if similar mechanisms of hypercoagulation contributed to comparable skin reactions during radiotherapy. Plasma levels of prothrombin factor 1+2 (F1+2), D-dimers and plasminogen activator inhibitor-1 (Pai-1) were tested in 32 women undergoing irradiation following breast conserving surgery for early breast cancer. Reflectance spectrophotometry was used to objectively assess erythema throughout the treatment by measuring the amount of light reflected from the skin surface as a function of wavelength. Correlations between peak levels of erythema and plasma biomarkers were then assessed. In idual peak reflectance readings generally occurred between day 29 of treatment and 2 weeks post radiotherapy, and represented a median increase of 66% (range: 11-146% p<0.001) from baseline. Peak reflectance correlated with F1+2 and Pai-1 levels measured both at baseline and day 29 of treatment, and multivariate analysis indicated that these two baseline measurements were the best predictors of peak reflectance, accounting for 59% of the variability in erythema (p=0.000004). Patients with signs of intravascular thrombin generation are at higher risk of radiotherapy-induced skin reactions, providing a new therapeutic avenue for possibly predicting and preventing this side effect of cancer treatment.
Publisher: Hindawi Limited
Date: 05-2007
DOI: 10.1111/J.1524-4741.2007.00420.X
Abstract: To identify factors that can influence breast edema in women undergoing breast-conserving therapy. Breast edema was assessed clinically and via high frequency ultrasound (HFUS) prior to, during and following radiotherapy. Fifty-four women were assessed. Breast edema was present prior to radiotherapy in patients who had undergone level 2 node dissection or had wound infection after sentinel node dissection. Edema increased during and after radiotherapy and peaked at 4-6 months. The time course of breast edema was related to the extent of nodal dissection, postoperative wound infection and regional radiotherapy. HFUS prior to irradiation was found to be no better than clinical assessment in predicting prolonged parenchymal breast edema but was significantly better at the end of irradiation. Breast edema levels are minimal in patients who do not undergo axillary node dissection or have an uncomplicated sentinel node dissection. Most edema is due to compromise of the draining lymphatics, which relates largely to the extent of axillary node dissection. HFUS appears to be a useful in the research setting in quantifying the effect of techniques that aim to reduce complications such as edema.
Publisher: Elsevier BV
Date: 09-2005
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.RADONC.2008.10.004
Abstract: We sought to determine whether inter-patient variations in pattern of PSA changes after radiation exist and, if so, are they prognostically significant. In the Trans-Tasman Radiation Oncology Group (TROG) 96.01 randomized controlled trial, patients with T2b,c,3,4 N0 prostate cancer (PC) were randomised to 0, 3 or 6months maximal androgen deprivation prior to 66Gy to the prostate and seminal vesicles (XRT). Patterns of anatomical site of failure were one of the trial endpoints. Serial serum PSA's were mandated at all follow-up visits. Pattern recognition software was developed to characterize PSA response "signatures" (PRS) after therapy in in idual patients. By 2000, 270 eligible patients were randomised to radiation alone. In idual patient PSA values were observed to descend after radiation according to one of two characteristic "signatures": single exponential (PRS Type 1), non-exponential (PRS Type 2). Compared to PRS Type 1, men with PRS Type 2 (50% of the group) had lower PSA nadir (nPSA) levels (p<.0001), longer doubling times on relapse (p=.006) and significantly lower rates of local (hazard ratio [HR]: 0.47, 95% confidence interval [0.30-0.75], p=.0014) and distant failure (HR: 0.25[0.13-0.46], p<.0001), death due to PC (HR: 0.20[0.10-0.42], p<.0001) and death due to any cause (HR: 0.37 [0.23-0.60], p<.0001). PRS retained its powerful prognostic significance in Cox models that incorporated all key pre-treatment covariates and nPSA. PRS reflect the presence of tumor phenotypes that vary substantially in their clinical behavior and response to XRT. Molecular characterization is now necessary.
Publisher: Elsevier BV
Date: 02-2002
DOI: 10.1016/S0360-3016(01)02682-7
Abstract: Many different factors can affect the accurate delivery of dose to the clinical target volume in radiotherapy. This is particularly important in the context of multicenter clinical trials where different equipment and techniques may be used for supposedly identical treatments. A dosimetric intercomparison employing an anthropomorphic phantom (level III dosimetric intercomparison) can be used to check many of the factors that could affect treatment by mimicking the radiotherapy pathway of a patient as closely as possible. An anthropomorphic phantom (ART) was taken to 18 radiotherapy centers in Australia and New Zealand and treated for two different treatment scenarios based on current clinical trials of the Trans-Tasman Radiation Oncology Group (TROG): a two-field treatment of a carcinoma of the tonsil (TROG 91.01), and a four-field prostate treatment (TROG 96.01). The dose distribution was assessed in two consecutive treatments using thermoluminescence dosimeters (TLDs) placed throughout the target volume and in "critical" structures such as the lens of the eye or the rectum. The study also included a check of absolute dose calibration in a slab phantom (level I dosimetric intercomparison). The influence of a variety of treatment parameters on the dose homogeneity in the target and the measured dose in the target and the critical organs was evaluated. The dose measurements confirmed that in all participating centers the correct dose was delivered to the ICRU reference point (tonsil: 99.8 +/- 2.3% prostate: 100.9 +/- 1.9% [1 SD]). Also the absolute dose calibration and the mean dose in the target volume were within the specified action levels of plus minus 5% for all participating centers. No influence of shielding, beam modifiers, beam weighting, treatment planning approach (CT, 2D, 3D), and type of equipment used on the dose in the target and its homogeneity could be demonstrated. However, treatment technique and energy used influenced the dose to the critical organs. It was shown that the interpretation of results could be improved by including two complementary treatment scenarios and a level I intercomparison with the level III dosimetric intercomparison. The study demonstrated the feasibility of a level III dosimetric intercomparison service at a cost of approximately $1000(US) per center in Australasia. It confirmed that the dose delivered by all participating centers was as intended in the two treatment scenarios chosen. While this provides reassurance to the oncology community and the general public, the service must be extended to all centers and other potentially more complex treatment scenarios. The present study has built the foundation for this by establishing a baseline and action levels and suggesting improvements in phantom design which will be included in future TROG quality assurance exercises.
Publisher: Oxford University Press (OUP)
Date: 09-1990
Abstract: Twenty-nine evaluable patients with adenocarcinoma of the cardia were treated with synchronously administered chemotherapy (two cycles of 5-fluorouradl and cisplatin and 30–36 Gy of radiation to determine whether these tumours are responsive to such treatment. Complete regression of tumour was observed endoscopically in 19 patients, and partial regression in four. Fourteen patients had their tumours resected and in six no microscopic tumour was found in the specimen. Nine patients received additional radiotherapy to a total dose of 54–60 Gy instead of surgery. Tumour response was associated with rapid reversal of dysphagia. Only one patient required subsequent intervention for relief of dysphagia due to fibrous stricture. Enhanced survival was associated with a complete endoscopic response to initial chemotherapy and radiotherapy, and a tumour of & 5 cm in length. The median survival of responding patients was 15 months. Synchronous chemotherapy and radiotherapy was of major palliative benefit in this series and merits further evaluation.
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.SEMRADONC.2013.01.008
Abstract: The optimal duration of hormonal therapy when combined with radiation for men with high-risk and locally advanced prostate cancer remains under active study. Based on the results of randomized controlled trials, durations of androgen suppression therapy of at least 6 months have been shown to prolong survival in men with Gleason score 7 prostate cancer, irrespective of clinical stage. For men with locally advanced prostate cancer and 2 high-risk factors (particularly Gleason 8-10 tumors with evidence of extracapsular extension or seminal vesicle invasion on digital rectal examination) or pelvic nodal involvement, longer durations of 28-36 months appear best, although shorter durations (eg, 18 months) remain under study. Trials are also ongoing to determine whether radiation dose escalation and/or nonhormonal agents, such as zoledronic acid and docetaxel, will reduce the need for supplementary androgen suppression therapy.
Publisher: Wiley
Date: 08-1987
DOI: 10.1111/J.1440-1673.1987.TB01841.X
Abstract: Chagas disease is a neglected tropical disease endemic in Latin America. The first-line treatment option is benznidazole, but stocks are expected to run out in the coming months. Spain would need around 5 million benznidazole tablets. This drug shortage could make Chagas disease a neglected tropical disease also in developed countries.
Publisher: Elsevier BV
Date: 03-1996
DOI: 10.1016/0959-8049(95)00635-4
Abstract: The Ann Arbor staging classification has long been recognised to have shortcomings when used to stage the follicular lymphomas. To date, the identification of important prognostic variables has not succeeded in producing a superior staging classification that reflects the stages of dissemination of these processes in a way that can be used in the testing of new therapeutic strategies. A fresh look is taken at these factors. Data from 398 patients entered into the British National Lymphoma Investigation trials between 1974 and 1980, were analysed to evaluate the performance of the Ann Arbor staging classification. Multiple regression and proportional hazards techniques were used to determine what factors independently influence response to initial treatment, the durability of that response and ultimate survival, and to isolate factors that relate to disease progression from those that have other mechanisms of action. The Ann Arbor staging classification fared poorly, minimally separating relapse-free and cause-specific survival probabilities in patients with the largest staging groupings, III and IV. Significant prognostic heterogeneity was seen in both of these stage groupings, with 22% of patients with stage IV disease on the basis of marrow involvement having slightly better outcomes than patients with stage III disease. Significant differences in outcome were also observed between patients of different age and sex in each Ann Arbor stage grouping. Increasing number of lymph node regions involved, constitutional symptoms, the presence of splenomegaly and increasing age were observed to have powerfully independent adverse influence on probability of complete response to treatment and cause-specific survival. The evolution of the follicular lymphomas is reflected at the clinical level by an increase in the number of lymph node regions involved and splenomegaly. Simple classifications based on simple counts of lymph node regions involved and splenomegaly are more successful than the Ann Arbor staging classification in sub iding the series into patient subgroups that, regardless of gender or age, experience significantly different probabilities of responding completely to therapy and, as a consequence, relapse-free and cause-specific survival expectations. The definition of poor prognosis in subgroups may be of value in selecting patients for newer and more intensive therapeutic approaches.
Publisher: Wiley
Date: 07-10-2014
Abstract: Aging skeletal muscle is associated with not only a reduction in muscle size and strength but also in muscle quality which reflects an increase in fatty infiltration of muscle. In men with prostate cancer, androgen deprivation therapy (ADT) accelerates this loss of muscle size and strength, but it is unknown if muscle quality is also adversely affected. Therefore, we examined the effects of ADT on muscle attenuation, an indirect measure of intramuscular lipid content, as well as the muscle cross-sectional area (CSA) in men with prostate cancer. Pre- and post-CT scans of the pelvis in 39 men aged 49-78 years receiving leuprorelin were examined. The time between baseline and follow-up scans was 14.6-20 weeks after the commencement of ADT. Changes in skeletal muscle attenuation in Hounsfield units of the rectus femoris and the CSA of the rectus femoris, sartorius and quadricep muscles were assessed. Muscle attenuation of the rectus femoris muscle was significantly reduced following the initiation of ADT by 18.9% (P < 0.001). In addition, there was a significant decrease (P < 0.001) in the CSA for the sartorius, quadriceps and rectus femoris muscles. There was no effect of Zometa on muscle attenuation or muscle CSA. Our results indicate that not only muscle size but also muscle quality may be adversely affected by the undertaking of ADT in men with prostate cancer. Consequently, interventions to counteract deteriorations to both muscle mass and possibly muscle quality should be considered in men receiving ADT.
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.3109/00313021003787924
Abstract: To compare the distribution and predictive performance of Gleason grade and scores derived using classical and modified (International Society of Urological Pathology) criteria. Classical and modified Gleason grades and scores were assigned to cases of prostate carcinoma accessioned by the Trans-Tasman Radiation Oncology Group RADAR trial. Separate scores were derived for each grading system based on the percentage of each Gleason grade per case (area-based score) and the score of the highest scoring core. The predictive performance of each of the four Gleason scores assigned to each case was evaluated using nadir prostate specific antigen (nPSA) as a clinical end point. Modified Gleason scoring resulted in an upward shift of scores, primarily resulting from the reclassification of classical pattern 3 to modified pattern 4. On re-grading classical Gleason score 7 cores, there was a 64% decrease in the number of cores with < 25% Gleason pattern 4 tumour, while the number of cores with 75-100% Gleason pattern 4 tumour increased by 96%. All four scoring models performed reasonably well as predictors of nPSA however, on comparison of the prognostic gradients of the grade groupings, classical Gleason scoring outperformed modified Gleason scoring. The overlap of the predictive performance of Gleason pattern 3 with Gleason pattern 4, suggests that review of the defining features of modified pattern 4 may improve the prognostic prediction of modified Gleason scoring.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.RADONC.2015.06.011
Abstract: To identify dosimetry, clinical factors and medication intake impacting urinary symptoms after prostate radiotherapy. Data describing clinical factors and bladder dosimetry (reduced with principal component (PC) analysis) for 754 patients treated with external beam radiotherapy accrued by TROG 03.04 RADAR prostate radiotherapy trial were available for analysis. Urinary symptoms (frequency, incontinence, dysuria and haematuria) were prospectively assessed using LENT-SOMA to a median of 72months. The endpoints assessed were prevalence (grade ⩾1) at the end of radiotherapy (representing acute symptoms), at 18-, 36- and 54-month follow-ups (representing late symptoms) and peak late incidence including only grade ⩾2. Impact of factors was assessed using multivariate logistic regression models with correction for over-optimism. Baseline symptoms, non-insulin dependent diabetes mellitus, age and PC1 (correlated to the mean dose) impact symptoms at >1 timepoints. Associations at a single timepoint were found for cerebrovascular condition, ECOG status and non-steroidal anti-inflammatory drug intake. Peak incidence analysis shows the impact of baseline, bowel and cerebrovascular condition and smoking status. The prevalence and incidence analysis provide a complementary view for urinary symptom prediction. Sustained impacts across time points were found for several factors while some associations were not repeated at different time points suggesting poorer or transient impact.
Publisher: Elsevier BV
Date: 08-1997
DOI: 10.1016/S0167-8140(97)00086-8
Abstract: Oligodeoxynucleotides (ODNs) are typically purified and analysed with HPLC equipped with a UV-Vis detector. Quantities of ODNs are usually determined using a UV-Vis spectrometer separately after HPLC, and are reported as optical density at 260 nm (OD
Publisher: Elsevier BV
Date: 11-2005
Publisher: Elsevier BV
Date: 10-2015
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.RADONC.2013.03.025
Abstract: In the TROG 96.01 trial 6 month neo-adjuvant androgen suppression (NAS) and radiotherapy (RT) for locally advanced prostate cancer prevented distant progressions (DPs) when compared to RT alone, but 3 months did not. We ask why? Between 1996 and 2000, 802 men with T2-4 N0 M0 prostate cancers received RT alone (0 month NAS) to 66 Gy, 3 months or 6 months NAS before RT. Interval hazards and cumulative incidences of DP were compared using competing risks methodology. In the first 4 follow-up years 39, 40 and 26 DPs were diagnosed in subjects treated with 0, 3 and 6 month NAS, respectively. Compared with 0 month, significant reductions in PSA doubling time in subjects with DP occurred following 3 month NAS (p=0.01), but a significant reduction (p=0.01) and a near significant delay in DPs (p=0.06) occurred after 6 month NAS. Subsequently 25, 20 and 11 DPs occurred in the three trial arms. After early secondary therapy for PSA or local progression 34, 19 and 12 DPs were diagnosed after median delays of almost 4 years. The data are consistent with the failure of 3 month NAS to prevent the progression of sub-clinical metastatic deposits already present before treatment.
Publisher: Elsevier BV
Date: 07-2000
Publisher: Wiley
Date: 2000
DOI: 10.1002/1097-0215(20001020)90:5<295::AID-IJC7>3.0.CO;2-B
Publisher: Elsevier BV
Date: 2004
DOI: 10.1016/S0360-3016(03)01445-7
Abstract: To describe the natural history of mucosal changes, in particular the development of telangiectases in the rectum, after radiotherapy (RT) for prostate cancer. Twenty patients undergoing local-field, nonconformal RT for prostate cancer underwent flexible sigmoidoscopy every 6 months for up to 3 years after RT completion. Telangiectasis was scored as absent, single, multiple, or multiple confluent. The site and circumferential extent were also documented. The patients filled in a diary to document the symptoms they were experiencing, including rectal bleeding. Of the 20 patients, 12 developed multiple telangiectases, and 10 of these had rectal bleeding, which in all cases was mild. Telangiectasis was most commonly seen between 4 (anorectal junction) and 8 cm from the anal verge. In 5 patients, 4 of whom had multiple telangiectases, spontaneous resolution occurred. Late radiation effects in the rectum do not appear to be permanent in all cases. This first prospective prolonged evaluation may provide an explanation for the observation that rectal bleeding resolves in a large proportion of patients with mild symptoms after RT. The reasons for improvement in the late radiation changes in the rectum compared with the permanent changes seen in organs such as the skin are unknown.
Publisher: Wiley
Date: 08-1990
DOI: 10.1111/J.1440-1673.1990.TB02640.X
Abstract: Low dose rate teletherapy aims to combine the supposedly superior results obtained with low dose rate implants with the convenience and staff protection characteristics of external beam therapy. Previous investigators have used telecobalt units to produce dose rates of 1.1 to 1.8 Gy/hr to treat in daily sessions lasting 6-10 hours to total doses of 60-70 Gy. These studies have not discounted the possibility that much of the advantage of interstitial implants results from the low dose rates used per se, and from the fact that the total dose is delivered in a short overall time. The relationship between total dose, dose rate and volume giving normal tissue and anit-tumour effects, however, remains ill-defined. At the Newcastle Mater Misericordiae Hospital a Caesium teletherapy unit has been modified to treat at low dose rates and a study has been designed with a view to establish which permutations of total dose and dose rate are isoeffective for acute mucosal and acute skin reactions in the dose rate range between 0.8 and 9.6 Gy/hr (1.3 and 16 cGy/min).
Publisher: Elsevier BV
Date: 04-1999
DOI: 10.1016/S0167-8140(99)00027-4
Abstract: To investigate the significance of the various late rectal symptoms that appear after radical prostatic irradiation. Patients with localised prostate cancer treated between 1987 and 1994 at the Mater Hospital, Newcastle with radical megavoltage irradiation were recalled for examination and to complete a detailed questionnaire concerning late radiation-induced symptoms and their effects on normal daily life. The influence of patient age treatment related variables and acute proctitis symptoms occurring during therapy or the late symptoms recorded were assessed and the relationship between late symptoms and late EORTC/RTOG score and impact on normal daily life were studied. The presence of symptoms of acute proctitis was the only factor to predict any of three late symptoms (urgency, frequency and diarrhoea) and late EORTC/RTOG score in this series (odds ratios: 1.7-2.57, P-values: 0.009-0.0007). Cluster and discriminant function analyses revealed the presence of five subgroups of patients with varying permutations of different late rectal symptoms, including one group with minimal symptoms (P < 0.0001). While bleeding and rectal discharge were the major contributors to late EORTC/RTOG score (P < 0.0001 and 0.04), faecal urgency and bleeding were the most important factors to impact on normal daily life (P < 0.0001 and P < 0.0003). A relatively low concordance was found between late EORTC/RTOG score and the patients' self assessment on the effect of their symptoms on their normal daily lives. Some late symptoms, including bleeding and rectal discharge become less prevalent after 3 years of follow-up with a resulting improvement in EORTC/RTOG score. There may be more than one late (chronic) proctitis syndrome which may be linked in greater or lesser degrees to acute proctitis symptoms occurring during therapy. Urgency is a common late symptom which often has an important impact on normal daily life and deserves recognition in late normal tissue scoring systems. Assessment of the incidence of bleeding as a measure of late rectal morbidity following prostate irradiation may underestimate the impact of these chronic effects. Confirmatory studies are necessary.
Publisher: Elsevier BV
Date: 07-1996
DOI: 10.1016/0167-8140(96)01762-8
Abstract: To define new directions, the Trans Tasman Radiation Oncology Group (TROG) has conducted a detailed analysis of its unrandomised experience with radio-chemotherapy in oesophageal cancer. Since 1984, 373 patients with oesophageal cancer have been treated on three prospective, but unrandomised, protocols involving radiation with concurrent cisplatin and infusional fluorouracil. Centres in Australia and New Zealand have contributed patients. Reasons for case selection have been examined in detail and prognostic models have been examined in the light of biases exposed. Cause specific survival in 92 patients treated pre-operatively with 35 Gy, infusional fluorouracil and cisplatin was 25.5 +/- 6.0% at 5 years and similar to the 5 year expectations of 169 patients treated with 60 Gy and two courses of the same chemotherapy (23.8 +/- 4.7%). Analysis of failure in these groups suggests that local relapse precedes the development of metastases and competes as a cause for ultimate failure. Although patients treated surgically were less likely to relapse locally, survival was no better because more developed metastases. Some of the 112 patients treated "palliatively" with 30-35 Gy concurrent with chemotherapy without surgery have become long-term survivors with 5 year survival figure in this group 7.7 +/- 3.4%. Apart from variables related to disease stage and performance status at presentation, tumour site emerged as a strong predictor of outcome. Prognosis worsens the nearer the tumour is to the stomach. In addition, indications of a radiation dose response relationship emerged. Concurrent radio-chemotherapy protocols can improve outcome in patients fit enough to tolerate these approaches. New strategies remain necessary, however.
Publisher: Elsevier BV
Date: 11-1997
DOI: 10.1016/S0167-8140(97)00146-1
Abstract: A limited number of studies have suggested that oral sucralfate reduces the acute and late gastro-intestinal side-effects of pelvic radiotherapy and sucralfate enemas ameliorate symptoms of chronic proctitis. Sucralfate may act via local bFGF at the mucosal level in promoting angiogenesis and reducing epithelial associated microvascular injury. This multi-institutional study was designed to test the hypothesis that sucralfate given as an enema would have a significant protective effect against acute radiation induced rectal injury by direct application to the mucosa. Eighty-six patients having radiotherapy for localised carcinoma of the prostate were randomised in a double-blind placebo-controlled study to receive either 15 ml of placebo suspension or 3 g of sucralfate in 15 ml suspension, given as a once daily enema during and for 2 weeks following radiotherapy. Assessment was based on the EORTC/RTOG acute toxicity criteria and a patient self-assessment diary. There was no significant difference between placebo and sucralfate for peak incidences of EORTC/RTOG proctitis. For the placebo and sucralfate arms 95 and 88% (difference 7 +/- 11%) suffered some degree of proctitis, with 71 and 61% (difference 10 +/- 19%) reaching grade 2, respectively. The median period to onset of grade 2 proctitis was 33.5 and 36 days, with the median duration being 9.5 and 15 days, respectively, again these difference being non-significant. Thirty-five and 37% of patients rated the effect of radiotherapy on bowel habit as 'a lot' with a moderate or severe effect on normal daily living in 52 and 49%, respectively. This study suggests that sucralfate given as a once daily enema does not substantially reduce the incidence of symptoms associated with acute radiation proctitis and its routine clinical use cannot be recommended. This cohort of patients will be followed to determine if any difference develops in relation to late toxicity.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.CLINBIOCHEM.2010.10.002
Abstract: To examine altered amino acid homeostasis as a predisposing factor of fatigue in female radiotherapy breast cancer patients. Participants underwent breast-conserving surgery and adjuvant breast irradiation and were free from significant fatigue pre-radiotherapy. The Functional Assessment of Cancer Therapy fatigue subscale was used to assess fatigue pre- and post-radiotherapy. Blood biochemistry factors and urinary and plasma amino acid levels were measured. One third of 27 patients developed fatigue and were designated as the fatigued cohort. It was possible to differentiate between fatigued subjects pre- and post-radiotherapy based upon their urinary amino acid profiles. Univariate analysis supported altered amino acid homeostasis within the fatigued cohort. Urinary levels of histidine and alanine were increased pre-radiotherapy whilst threonine, methionine, alanine, serine, asparagine and glutamine levels were higher after 5weeks of radiotherapy for the fatigued cohort. Fatigue was accompanied by altered amino acid homeostasis with increased amino acid excretion suggestive of a catabolic response.
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.RADONC.2008.10.011
Abstract: A multi-centre clinical trial for prostate cancer patients provided an opportunity to introduce conformal radiotherapy with dose escalation. To verify adequate treatment accuracy prior to patient recruitment, centres submitted details of a set-up accuracy study (SUAS). We report the results of the SUAS, the variation in clinical practice and the strategies used to help centres improve treatment accuracy. The SUAS required each of the 24 participating centres to collect data on at least 10 pelvic patients imaged on a minimum of 20 occasions. Software was provided for data collection and analysis. Support to centres was provided through educational lectures, the trial quality assurance team and an information booklet. Only two centres had recently carried out a SUAS prior to the trial opening. Systematic errors were generally smaller than those previously reported in the literature. The questionnaire identified many differences in patient set-up protocols. As a result of participating in this QA activity more than 65% of centres improved their treatment delivery accuracy. Conducting a pre-trial SUAS has led to improvement in treatment delivery accuracy in many centres. Treatment techniques and set-up accuracy varied greatly, demonstrating a need to ensure an on-going awareness for such studies in future trials and with the introduction of dose escalation or new technologies.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-09-2017
Abstract: Adjuvant therapy for intermediate-risk and high-risk localized prostate cancer decreases the number of deaths from this disease. Surrogates for overall survival (OS) could expedite the evaluation of new adjuvant therapies. By June 2013, 102 completed or ongoing randomized trials were identified and in idual patient data were collected from 28 trials with 28,905 patients. Disease-free survival (DFS) and metastasis-free survival (MFS) were determined for 21,140 patients from 24 trials and 12,712 patients from 19 trials, respectively. We evaluated the surrogacy of DFS and MFS for OS by using a two-stage meta-analytic validation model by determining the correlation of an intermediate clinical end point with OS and the correlation of treatment effects on both the intermediate clinical end point and OS. Trials enrolled patients from 1987 to 2011. After a median follow-up of 10 years, 45% of 21,140 men and 45% of 12,712 men experienced a DFS and MFS event, respectively. For DFS and MFS, 61% and 90% of the patients, respectively, were from radiation trials, and 63% and 66%, respectively, had high-risk disease. At the patient level, Kendall’s τ correlation with OS was 0.85 and 0.91 for DFS and MFS, respectively. At the trial level, R 2 was 0.86 (95% CI, 0.78 to 0.90) and 0.83 (95% CI, 0.71 to 0.88) from weighted linear regression of 8-year OS rates versus 5-year DFS and MFS rates, respectively. Treatment effects—measured by log hazard ratios—for the surrogates and OS were well correlated ( R 2 , 0.73 [95% CI, 0.53 to 0.82] for DFS and 0.92 [95% CI, 0.81 to 0.95] for MFS). MFS is a strong surrogate for OS for localized prostate cancer that is associated with a significant risk of death from prostate cancer.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2007
End Date: 2012
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2007
End Date: 2012
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2005
End Date: 2009
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2005
End Date: 2007
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2002
End Date: 2006
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2004
End Date: 2008
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 1999
End Date: 2001
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 1999
End Date: 2000
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2009
End Date: 2011
Funder: Cancer Australia
View Funded ActivityStart Date: 2006
End Date: 2006
Funder: Cancer Council NSW
View Funded ActivityStart Date: 2008
End Date: 2008
Funder: Cancer Institute NSW
View Funded ActivityStart Date: 1991
End Date: 1992
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 1997
End Date: 1999
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2009
End Date: 2009
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 1999
End Date: 2001
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2016
End Date: 2017
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2009
End Date: 2012
Funder: Prostate Cancer Foundation of Australia
View Funded ActivityStart Date: 2011
End Date: 2013
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2005
End Date: 2007
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2015
End Date: 2018
Funder: National Health and Medical Research Council
View Funded Activity