ORCID Profile
0000-0002-0900-5815
Current Organisation
Peter MacCallum Cancer Centre
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Publisher: Elsevier BV
Date: 02-2002
DOI: 10.1016/S0360-3016(01)02673-6
Abstract: At our center, approximately 30% of radical radiotherapy (RRT) candidates become ineligible for RRT for non-small-cell lung cancer (NSCLC) after positron emission tomography (PET). We hypothesized that early cancer death rates would be lower in patients receiving RRT after PET staging compared with conventionally staged patients. Two prospective cohorts were compared. Cohort 1 consisted of all participants in an Australian randomized trial from our center given 60 Gy conventionally fractionated RRT with or without concurrent carboplatin from 1989 to 1995. Eligible patients had Stage I--III, Eastern Cooperative Oncology Group status 0 or 1, <10% weight loss, and had not undergone PET. Cohort 2 included all RRT candidates between November 1996 and April 1999 who received RRT after PET staging and fulfilled the above criteria for stage, Eastern Cooperative Oncology Group status, and weight loss. Eighty and 77 eligible patients comprised the PET and non-PET groups, respectively. The PET-selected patients had significantly less weight loss 73% and 49% of the PET and non-PET patients, respectively, received chemotherapy. The median survival was 31 months for PET patients and 16 months for non-PET patients. Mortality from NSCLC and other causes in the first year was 17% and 8% for PET patients and 32% and 4% for non-PET patients, respectively. The hazard ratio for NSCLC mortality for PET vs. non-PET patients was 0.49 (p = 0.0016) on unifactorial analysis and was 0.55 (p = 0.0075) after adjusting for chemotherapy, which significantly improved survival. Patients selected for RRT after PET have lower early cancer mortality than those selected using conventional imaging.
Publisher: Springer Science and Business Media LLC
Date: 20-11-2018
DOI: 10.1007/S10585-017-9867-5
Abstract: Radiation therapy is an effective means of achieving local control in a wide range of primary tumours, with the reduction in the size of the tumour(s) thought to mediate the observed reductions in metastatic spread in clinical trials. However, there is evidence to suggest that the complex changes induced by radiation in the tumour environment can also present metastatic risks that may counteract the long-term efficacy of the treatment. More than 25 years ago, several largely theoretical mechanisms by which radiation exposure might increase metastatic risk were postulated. These include the direct release of tumour cells into the circulation, systemic effects of tumour and normal tissue irradiation and radiation-induced changes in tumour cell phenotype. Here, we review the data that has since emerged to either support or refute these putative mechanisms focusing on how the unique radiobiology underlying modern radiotherapy modalities might alter these risks.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.RADONC.2015.04.013
Abstract: To assess the utility of functional lung avoidance using IMRT informed by four-dimensional (4D) ventilation erfusion (V/Q) PET/CT. In a prospective clinical trial, patients with non-small cell lung cancer (NSCLC) underwent 4D-V/Q PET/CT scanning before 60Gy of definitive chemoradiation. Both "highly perfused" (HPLung) and "highly ventilated" (HVLung) lung volumes were delineated using a 70th centile SUV threshold, and a "ventilated lung volume" (VLung) was created using a 50th centile SUV threshold. For each patient four IMRT plans were created, optimised to the anatomical lung, HPLung, HVLung and VLung volumes, respectively. Improvements in functional dose volumetrics when optimising to functional volumes were assessed using mean lung dose (MLD), V5, V10, V20, V30, V40, V50 and V60 parameters. The study cohort consisted of 20 patients with 80 IMRT plans. Plans optimised to HPLung resulted in a significant reduction of functional MLD by a mean of 13.0% (1.7Gy), p=0.02. Functional V5, V10 and V20 were improved by 13.2%, 7.3% and 3.8% respectively (p-values<0.04). There was no significant sparing of dose to functional lung when adapting to VLung or HVLung. Plan quality was highly consistent with a mean PTV D95 and D5 ranging from 60.8Gy to 61.0Gy and 63.4Gy to 64.5Gy, respectively, and mean conformity and heterogeneity index ranging from 1.11 to 1.17 and 0.94 to 0.95, respectively. IMRT plans adapted to perfused but not ventilated lung on 4D-V/Q PET/CT allowed for reduced dose to functional lung whilst maintaining consistent plan quality.
Publisher: Wiley
Date: 16-09-2013
Abstract: The purpose of this study is to assess the impact of a vacuum immobilisation system on reproducibility of patient set-up, interfraction stability and tumour motion litude. From February 2010 to February 2012 as part of a prospective clinical trial 12 patients with solitary pulmonary metastases had consecutive four-dimensional computed tomography (4DCT) scans performed with and without vacuum immobilisation. The displacement of the tumour centroid position was recorded in each of the 10 phases of the 4DCT reconstruction. A further six patients with seven metastases underwent single fraction stereotactic ablative body radiotherapy (SABR) during this period (a total of 19 targets) and were included in an analysis of positional reproducibility and intrafraction immobilisation. Couch shifts recorded in the medio-lateral (X), cranio-caudal (Y) and ventero-dorsal (Z) planes. For the 19 treatments delivered, the median (0-90% range) shift required immediately pretreatment was 1 mm (0-3) in the X-plane, 2 mm (0-6) in the Y-plane and 4 mm (0-8) in the Z-plane, respectively. The mean (+/- standard deviation) of mid-treatment shifts were 0.3 mm (+/- 0.7), 1.1 mm (+/- 2) and 0.8 mm (+/- 1.5) in the X, Y and Z planes, respectively. Mid-treatment shifts were <2 mm in all directions (P = < 0.001). The length of treatment time correlated to the required shifts in the Z plane (r(2) = 0.377, P = 0.005), but not in the X or Y planes (P = 0.198 and P = 0.653, respectively). In the subset of 12 patients who had two 4DCTs, the median (range) litude of tumour displacements in the X, Y and Z planes when immobilised were 0.9 mm (0.3-2.9), 2.6 mm (0.2-10.6) and 1.6 mm (0.5-5.5), respectively. Immobilisation reduced the volume of tumour displacement during respiration by a median of 52.6% (P = 0.021). Vacuum immobilisation reduces total tumour excursion, facilitates reproducible positioning and provides robust intrafractional immobilisation during SABR treatments for pulmonary metastases.
Publisher: Public Library of Science (PLoS)
Date: 07-10-2014
Publisher: Wiley
Date: 13-06-2017
Abstract: Acute radiation oesophagitis (ARO) is frequently experienced by patients receiving concurrent chemo-radiation therapy (cCRT) for non-small-cell lung cancer (NSCLC). We investigated ARO symptoms (CTCAE v3.0), radiation dose and oesophageal FDG PET/CT uptake. Candidates received cCRT (60 Gy, 2 Gy/fx) and sequential FDG PET/CT (baseline FDG Forty-four patients underwent FDG FDG
Publisher: Wiley
Date: 04-2011
DOI: 10.1111/J.1754-9485.2011.02257.X
Abstract: Fused positron emission tomography/computed tomography (PET-CT) images are increasingly being used to assist radiation oncologists in the definition of treatment volumes for patients with metabolically active tumours. This is the first report in which baseline fluorodeoxyglucose-PET-CT images were acquired in the treatment position in a case of diffuse large B-cell lymphoma and incorporated directly into the radiotherapy treatment planning process. It highlights the potential benefits of using combined 3-D functional and structural imaging for the design of radiation target volumes in patients with aggressive lymphomas that are managed with combined chemo and radiotherapy.
Publisher: AME Publishing Company
Date: 11-2019
Publisher: Springer Berlin Heidelberg
Publisher: British Institute of Radiology
Date: 02-2002
DOI: 10.1259/BJR.75.890.750114
Abstract: The purpose of this study was to document the accuracy of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) with sodium iodide detectors in characterizing indeterminate lung nodules or masses and in identifying additional extra-lesional findings. 50 consecutive patients without a confident diagnosis of malignancy on CT underwent (18)FDG PET with and without attenuation correction. The diagnosis of malignancy was made using visual diagnostic criteria, and tumour-to-blood pool ratios were calculated. The final diagnosis was established by surgery, biopsy or long-term follow-up. Any additional findings made at PET were recorded and similarly verified. Using blinded visual diagnostic criteria for the differentiation of malignant from benign nodules, sodium iodide PET achieved a sensitivity of 91% (30 of 33 cases), a specificity of 88% (15 of 17 cases), a positive predictive value for malignancy of 94% (30 of 32 cases) and a negative predictive value of 83% (15 of 18 cases). False positives occurred with active tuberculosis and sarcoidosis. False negatives were a 3 cm bronchoalveolar carcinoma, a 1.3 cm sarcoma metastasis and a 1 cm carcinoma. Use of tumour-to-blood pool ratios did not improve performance. PET suggested the presence of nodal or distant metastases in 13 of 33 patients with a malignant pulmonary lesion. These PET findings were confirmed in 11 patients. These results indicate that sodium iodide PET is an accurate tool for the characterization of indeterminate pulmonary masses or nodules and simultaneously provides non-invasive staging information that can alter patient management in up to one-third of such patients. Performance of sodium iodide PET is comparable with reported results for PET scanners using other detector materials.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.RADONC.2012.12.018
Abstract: This prospective study investigated the impact of radiotherapy (RT)-planning FDG-PET/CT on management of non-small cell lung cancer (NSCLC). Patients still eligible for radical RT after conventional staging underwent RT-planning PET/CT and, if disease was still treatable to 60 Gy, they entered our planning study, where visually-contoured tumour volumes derived with and without PET information were compared. If PET/CT detected advanced disease, palliative therapy was given. Overall survival (OS) for palliative and curative patients was compared. Of 76 eligible patients, only 50 (66%) received radical chemoRT after PET/CT while 26 (34%) received palliative therapies because PET/CT detected advanced disease. Without PET, FDG-avid tumour would reside outside the planning target volume (PTV) in 36% of radical cases and in 25% 95% prescribed dose. OS for all patients was 56.8% and 24.9% at 1 and 4 years, respectively. OS for patients given chemoRT was 77.5% and 35.6% at 1 and 4 years, respectively and was 32% for stage IIIA patients at 4 years. OS for patients treated palliatively was inferior (P<0.001) 16.3% and 4.1% at 1 and 4 years, respectively. Planning PET/CT frequently changed management and was associated with excellent survival. Survival data from this study were presented in part at the 2011 World Lung Cancer Conference, Amsterdam and planning data at the 2010 Annual Scientific Meeting of the American Society for Therapeutic Radiology and Oncology, Chicago.
Publisher: Elsevier BV
Date: 03-2020
Publisher: BMJ
Date: 12-2020
DOI: 10.1136/BMJOPEN-2020-042465
Abstract: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning systems, enabling conformal avoidance of highly functioning regions of lung, thereby facilitating increased doses to tumour while reducing normal tissue doses. This prospective interventional study will investigate the use of ventilation and perfusion PET/CT to identify highly functioning lung volumes and avoidance of these using VMAT planning. This single-arm trial will be conducted across two large public teaching hospitals in Australia. Twenty patients with stage III non-small cell lung cancer will be recruited. All patients enrolled will receive dose-escalated (69 Gy) functional avoidance radiation therapy. The primary endpoint is feasibility with this achieved if ≥15 out of 20 patients meet pre-defined feasibility criteria. Patients will be followed for 12 months post-treatment with serial imaging, biomarkers, toxicity assessment and quality of life assessment. Using advanced techniques such as VMAT functionally adapted radiation therapy may enable safe moderate dose escalation with an aim of improving local control and concurrently decreasing treatment related toxicity. If this technique is proven feasible, it will inform the design of a prospective randomised trial to assess the clinical benefits of functional lung avoidance radiation therapy. This study was approved by the Peter MacCallum Human Research Ethics Committee. All participants will provide written informed consent. Results will be disseminated via publications. NCT03569072 Pre-results
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-01-2019
Publisher: Elsevier BV
Date: 08-2023
Publisher: Wiley
Date: 25-05-2006
DOI: 10.1111/J.1440-1673.2006.01566.X
Abstract: Low-dose radiotherapy over the last decade has been reported to provide effective palliation for patients with low-grade non-Hodgkin's lymphoma. In this retrospective case series of 10 patients, we report our early experience using low-dose radiotherapy (usually 2 x 2 Gy) for patients with advanced-stage follicular, mucosal associated lymphoid tissue, mantle cell and small lymphocytic lymphomas. Median follow up was 27 weeks. Response rates were high (complete response, 70% partial response, 20%), the response durable and the toxicity was minimal (no toxicity greater than grade 1). Low-dose irradiation is an effective treatment option for patients with low-grade lymphomas with local symptoms.
Publisher: Society of Nuclear Medicine
Date: 10-06-2013
DOI: 10.2967/JNUMED.112.116814
Abstract: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with limited evidence on the role of PET scanning. The primary aim of this study was to assess the impact of (18)F-FDG PET in the staging and management of MCC. A single-institution review using clinical outcome data collected until February 2012 was performed of patients with MCC who underwent staging PET scanning between January 1997 and October 2010. Management plans were recorded prospectively at the time of the PET request, and follow-up outcomes were recorded retrospectively. The clinical impact of PET was scored using our previously published criteria: "high" if the PET scan changed the primary treatment modality or intent "medium" if the treatment modality was unchanged but the radiation therapy technique or dose was altered. The primary objective was to test the hypothesis that the true proportion of patients who have a high- or medium-impact scan would be greater than 25%. The median follow-up of 102 consecutive patients was 4.8 y. The results of staging PET had an impact on patient management in 37% of patients (P < 0.003). High- and medium-impact scans were recorded for 22% and 15% of patients, respectively. PET staging results differed from conventional staging results in 22% of patients, with PET upstaging 17% and downstaging 5%. The 3- and 5-y overall survival was 60% (95% confidence interval, 50%-71%) and 51% (95% confidence interval, 41%-64%), respectively. In stratification by PET-defined stage, the 5-y overall survival was 67% for patients with stage I/II disease but only 31% for patients with stage III disease (log-rank P < 0.001). The 5-y cumulative incidence of locoregional failure, distant failure, and death was 16.6%, 22.3% and 14.3%, respectively. On multivariate analysis, only PET stage (P < 0.001) and primary treatment modality (P = 0.050) were significantly associated with overall survival. The primary treatment modality was not associated with progression-free survival when stratification was by tumor stage. The use of (18)F-FDG PET scans had a great impact on patients and may play an important role in the prognostic stratification and treatment of this disease.
Publisher: Elsevier BV
Date: 05-2011
Abstract: Chemotherapy plus radiotherapy is the standard of care for patients with limited stage Hodgkin lymphoma (HL). Radiotherapy is evolving from involved field radiotherapy (IFRT) to involved node radiotherapy (INRT) to decrease radiotherapy-related morbidity. In the absence of long-term toxicity data, dose-volume metrics of organs at risk (OAR) provide a surrogate measure of toxicity risk. Ten female patients with stage I-IIA supradiaphragmatic HL were randomly selected. All patients had pre-chemotherapy computerised tomography (CT) and CT-positron emission tomography staging. Using CT planning, three radiotherapy plans were produced per patient: (i) IFRT, (ii) INRT using parallel-opposed beams and (iii) INRT using volumetric modulated arc therapy (VMAT). Radiotherapy dose was 30.6 Gy in 1.8 Gy fractions. OAR evaluated were lungs, breasts, thyroid, heart and coronary arteries. Compared with IFRT, INRT significantly reduced mean doses to lungs (P < 0.01), breasts (P < 0.01), thyroid (P < 0.01) and heart (P < 0.01), on Wilcoxon testing. Compared with conventional INRT, VMAT improved dose conformality but increased low-dose radiation exposure to lungs and breasts. VMAT reduced the heart volume receiving 30 Gy (V30) by 85%. Reduction from IFRT to INRT decreased the volumes of lungs, breasts and thyroid receiving high-dose radiation, suggesting the potential to reduce long-term second malignancy risks. VMAT may be useful for patients with pre-existing heart disease by minimising further cardiac toxicity risks.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 04-2003
Abstract: Purpose: To prospectively study the capacity of positron emission tomography (PET) and computed tomography (CT) to determine response soon after radical radiotherapy or chemoradiotherapy and, thereby, predict survival. PET is known to provide a more accurate estimate of true extent of disease than CT when used to stage non–small-cell lung cancer (NSCLC). Patients and Methods: Seventy-three patients with NSCLC underwent [ 18 F]fluorodeoxyglucose PET and CT scans before and after radical radiotherapy (n = 10) or chemoradiotherapy (n = 63). Follow-up PET scans were performed at a median of 70 days after radiotherapy. The median PET-CT interval was 1 day. Each patient had determinations of response to therapy made with PET and CT, categorized as complete response, partial response, no response, progressive disease, or nonassessable. Responses were correlated with subsequent survival. Results: Median survival after follow-up PET was 24 months. There was poor agreement between PET and CT responses (weighted kappa = 0.35), which were identical in only 40% of patients. There were significantly more complete responders on PET (n = 34) than CT (n = 10), whereas fewer patients were judged to be nonresponders (12 patients on PET v 20 on CT) or nonassessable (zero patients on PET v six on CT) by PET. Both CT and PET responses were in idually significantly associated with survival duration but on multifactor analysis that included the known prognostic factors of CT response, performance status, weight loss, and stage, only PET response was significantly associated with survival duration (P .0001). Conclusion: In NSCLC, a single, early, posttreatment PET scan is a better predictor of survival than CT response, stage, or pretreatment performance status.
Publisher: Wiley
Date: 28-07-2021
Abstract: This study aims to investigate whether nodal metabolic tumour volume (nMTV) and nodal total lesion glycolysis (nTLG) on Fluorine‐18 fluoro‐deoxy‐glucose positron emission tomography–computed tomography ( 18 F‐FDG PET/CT) in inoperable node‐positive stage II and III non‐small cell lung cancer (NSCLC) are independent predictors of overall survival (OS) in patients undergoing curative‐intent chemoradiotherapy/radiotherapy (CRT/RT). Data from two prospective trials between 2004 and 2016 were analysed retrospectively. Primary, nodal and total metabolic tumour volume and total lesion glycolysis (pMTV, nMTV, tMTV, pTLG, nTLG and tTLG, respectively) were derived from baseline 18 F‐FDG PET/CT. Cox regressions were used to model OS by 18 F‐FDG PET/CT parameters adjusting for overall stage. 89 patients with stage II (8%) and stage III (92%) were included. The median age at diagnosis was 67 years 62% were male. The median follow‐up was 6.9 years the median OS was 2.2 years (95% CI 1.7–3.1). The median pMTV, nMTV and tMTV were 14 mL (range 0–360), 8 mL (range 0–250) and 34 mL (range 3–384), respectively. In 3 patients, the primary lesion could not be delineated from the central hilar mass. There was no association between nMTV (adjusted HR 1.04, 95% CI 0.95–1.15, P ‐value 0.43), pMTV (adjusted HR 1.0, 95% CI 0.96–1.04, P ‐value 0.92), tMTV (adjusted HR 1.0, 95% CI 0.97–1.04, P ‐value 0.88), nTLG, pTLG or tTLG and OS. Consistent results were noted when patients with central hilar lesions were excluded from analysis. In node‐positive stage II and III NSCLC patients who underwent 18 F‐FDG PET/CT‐guided target delineation curative‐intent concurrent CRT/RT, metabolic parameters did not appear to provide independent prognostication.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Springer Science and Business Media LLC
Date: 02-10-2014
Publisher: Springer Science and Business Media LLC
Date: 18-01-2023
DOI: 10.1038/S42003-022-04350-4
Abstract: Despite significant therapeutic advances, lung cancer remains the leading cause of cancer-related death worldwide 1 . Non-small cell lung cancer (NSCLC) patients have a very poor overall five-year survival rate of only 10–20%. Currently, TNM staging is the gold standard for predicting overall survival and selecting optimal initial treatment options for NSCLC patients, including those with curable stages of disease. However, many patients with locoregionally-confined NSCLC relapse and die despite curative-intent interventions, indicating a need for intensified, in idualised therapies. Epithelial-to-mesenchymal transition (EMT), the phenotypic depolarisation of epithelial cells to elongated, mesenchymal cells, is associated with metastatic and treatment-refractive cancer. We demonstrate here that EMT-induced protein changes in small extracellular vesicles are detectable in NSCLC patients and have prognostic significance. Overall, this work describes a novel prognostic biomarker signature that identifies potentially-curable NSCLC patients at risk of developing metastatic NSCLC, thereby enabling implementation of personalised treatment decisions.
Publisher: Wiley
Date: 14-06-2013
Abstract: For many cancers, tumour hypoxia is an adverse prognostic factor, and increases chemoradiation resistance its importance in non-small cell lung cancer (NSCLC) is unproven. This study evaluated tumoural hypoxia using fluoroazomycin arabinoside ((18) F-FAZA) positron emission tomography (PET) scans among patients with locoregionally advanced NSCLC treated with definitive chemoradiation. Patients with stage IIIA-IIIB NSCLC underwent (18) F-FAZA PET scans and (18) F-2-deoxyglucose (FDG)-PET scans within 4 weeks of commencing and 8 weeks following conventionally-fractionated concurrent platinum-based chemoradiation (60 Gy). Intra-lesional hypoxic volumes of the primary and nodal masses were compared with FDG-PET metabolic volumes. Baseline tumoural hypoxia was correlated with disease free survival (DFS). Seventeen patients underwent pre-treatment (18) F-FAZA PET and FDG-PET scans. Intra-lesional hypoxia was identified on 11 scans (65%). Baseline lesional hypoxic volumes were consistently smaller than FDG-PET volumes (P = 0.012). There was no statistical difference between the mean FDG-PET volumes in patients with or without baseline hypoxia (P = 0.38). Eight patients with baseline hypoxia had post treatment (18) F-FAZA scans and 6 of these (75%) had resolution of imageable hypoxia following chemoradiation. The DFS was not significantly different between the hypoxic or non-hypoxic groups (median 0.8 years and 1.3 years respectively, P = 0.42). Intra-lesional hypoxia, as detected by (18) F-FAZA PET, was present in 65% of patients with locally-advanced NSCLC and resolved in the majority of patients following chemoradiation. Larger studies are required to evaluate the prognostic significance of the presence and resolution of hypoxia assessed by PET in NSCLC.
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1016/J.IJROBP.2007.09.051
Abstract: Accurate staging is critical to select patients with early-stage (I-II) follicular lymphoma (ESFL) suitable for involved-field radiotherapy (IFRT) and to define the radiotherapy portal. We evaluated the impact of fluorodeoxyglucose (FDG) PET on staging, treatment, and outcome for patients with ESFL on conventional staging. Forty-two patients with untreated ESFL (World Health Organization Grade I-IIIa, or "low grade") following a minimum of physical examination, computerized tomography, and bone marrow examination (conventional assessment) and who had staging PET from June 1997 to June 2006 were studied retrospectively. Stage allocation was based on routine imaging reports. Disease sites, stage, and management plan were recorded based on conventional assessment or conventional assessment plus PET. FDG avidity was demonstrated in 97% of patients in whom disease was evident on conventional assessment after biopsy. PET findings suggested a change of stage or management in 19 patients: 13 (31%) who were upstaged to Stage III-IV, altering ideal management from IFRT to systemic therapy, and 6 (14%) who had the involved field enlarged, including 4 upstaged from Stage I to II. Of these 19 cases, PET findings were considered true positive in 8 patients, indeterminate in 10, and false positive in only 1 patient. Our data confirm that ESFL is usually FDG-avid. In routine practice, PET has the potential to upstage and thereby alter management in a high proportion of patients with apparent ESFL.
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1016/S0169-5002(03)00235-6
Abstract: The optimal chemoradiation regimen for stage III non-small cell lung cancer (NSCLC) has not been determined. In this phase I/II study, the use of twice-weekly paclitaxel concomitant with weekly cisplatin and thoracic radiotherapy (RT) was evaluated. Patients with stage III NSCLC (without pleural effusion or cervical lymphadenopathy) were treated with thoracic RT (60 Gy in 30 fractions over 6 weeks) with concurrent weekly cisplatin 20 mg/m(2) and escalating doses of twice-weekly paclitaxel (starting dose of paclitaxel of 20 mg/m(2) increased in increments of 5 mg/m(2)) in successive cohorts of three to six patients until two or more patients experienced dose limiting toxicities (DLTs) at a particular dose level. All patients were planned to be given a further two cycles of consolidation chemotherapy consisting of paclitaxel 175 mg/m(2) and carboplatin AUC 5 after completion of RT. Twenty-five patients were enrolled in this study from two institutions. At a dose of paclitaxel 35 mg/m(2), two of four treated patients had DLTs (1 grade 3 oesophagitis and pulmonary toxicity 1 grade 3 oesophagitis and infection). The recommended dose was therefore determined to be 30 mg/m(2) and a total of 15 patients were enrolled in an expanded cohort at this level. The overall response rate for all patients was 64% (95% CI: 43-82%). The estimated median survival was 23.6 months with an estimated 1-year and 2-year survival of 72 and 49%, respectively. Paclitaxel can be safely given twice-weekly at a dose of 30 mg/m(2) in combination with weekly cisplatin (20 mg/m(2)) and thoracic RT (60 Gy), and this regimen has significant activity in stage III NSCLC.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.RADONC.2016.09.002
Abstract: To assess the impact of a standardized delineation protocol and training interventions on PET/CT-based target volume delineation (TVD) in NSCLC in a multicenter setting. Over a one-year period, 11 pairs, comprised each of a radiation oncologist and nuclear medicine physician with limited experience in PET/CT-based TVD for NSCLC from nine different countries took part in a training program through an International Atomic Energy Agency (IAEA) study (NCT02247713). Teams delineated gross tumor volume of the primary tumor, during and after training interventions, according to a provided delineation protocol. In-house developed software recorded the performed delineations, to allow visual inspection of strategies and to assess delineation accuracy. Following the first training, overall concordance indices for 3 repetitive cases increased from 0.57±0.07 to 0.66±0.07. The overall mean surface distance between observer and expert contours decreased from -0.40±0.03cm to -0.01±0.33cm. After further training overall concordance indices for another 3 repetitive cases further increased from 0.64±0.06 to 0.80±0.05 (p=0.01). Mean surface distances decreased from -0.34±0.16cm to -0.05±0.20cm (p=0.01). Multiple training interventions improve PET/CT-based TVD delineation accuracy in NSCLC and reduce interobserver variation.
Publisher: Springer Berlin Heidelberg
Date: 2011
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.RADONC.2013.02.010
Abstract: To investigate the impact of treatment delays on radiation therapy (RT) target volumes and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) who underwent two baseline FDG PET/CT scans. Patients underwent a staging (PET1) and RT planning (PET2) FDG PET/CT scan. At PET1 all patients were eligible for radical chemo-RT. OS and progression-free survival (PFS) were compared for patients remaining eligible for radical RT and those treated palliatively because PET2 showed progression. RT target volumes were contoured using PET1 and PET2. Normal tissue doses were compared for patients remaining eligible for radical RT. Eighty-two patients underwent PET2 scans between October 2004 and February 2007. Of these, 21 had a prior PET1 scan, median 23 days apart (range 8-176 days). Six patients (29%) were unsuitable for radical RT after PET2 five received palliative treatment and one received no treatment. Patients treated palliatively had significantly worse OS and PFS than patients treated radically p<0.001. Mean RT tumour volume increased from 105cc to 198cc (p<0.005) between scans. Disease progression while awaiting initiation of curative RT in NSCLC is associated with larger treatment volumes and worse survival.
Publisher: Wiley
Date: 10-04-2012
DOI: 10.1111/J.1754-9485.2012.02369.X
Abstract: Primary gastric extramedullary plasmacytoma is an extremely rare condition and there is scant information in the literature concerning its natural history or therapy. There have been anecdotal reports of surgical resection, with or without Helicobacter pylori eradication, but there are no useful reports of the role of radiotherapy. We report the clinicopathologic outcome of radical radiotherapy as a primary treatment modality. We identified two patients with biopsy-proven primary gastric extramedullary plasmacytoma. Routine staging investigations were performed and H. pylori status was determined. Radical radiotherapy to 41.4 Gy in 23 fractions was delivered using conformal techniques. The target volume was the stomach with a 1-cm margin. Prophylactic anti-emetic was administered prior to each fraction. Post-treatment endoscopies and biopsies were performed at 3-monthly intervals to assess clinicopathological response. Treatment-related toxicities were documented. Both patients achieved durable (>12 months) pathologically confirmed complete remissions without significant toxicities. Radical radiotherapy offers the potential for cure and organ preservation with low toxicity. It should be considered a favourable alternative to surgery in the management of this rare disease entity.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.CANLET.2013.09.018
Abstract: An "abscopal" effect occurs when localized irradiation perturbs the organism as a whole, with consequences that can be either beneficial or detrimental. Mechanistic explanations of this effect are challenging. From the oncologist's perspective, the term refers to distant tumor regression after localized irradiation. On the other hand, from a biologist's point of view, abscopal effects include induction of genomic instability, cell death, and oncogenic transformation in normal tissues. This conceptual dichotomy is explored in this review, with a focus on clinically documented cases of anti-tumor abscopal effects and abscopal effects in normal tissues. This review also outlines several suggested mechanisms for abscopal effects.
Publisher: Wiley
Date: 10-2015
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.CPET.2014.12.002
Abstract: (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) plays a key role in the evaluation of undiagnosed lung nodules, when primary lung cancer is strongly suspected, or when it has already been diagnosed by other techniques. Although technical factors may compromise characterization of small or highly mobile lesions, lesions without apparent FDG uptake can generally be safely observed, whereas FDG-avid lung nodules almost always need further evaluation. FDG-PET/CT is now the primary staging imaging modality for patients with lung cancer who are being considered for curative therapy with either surgery or definitive radiation therapy.
Publisher: American Association for Cancer Research (AACR)
Date: 10-2016
DOI: 10.1158/1078-0432.CCR-16-0138
Abstract: Purpose: To study the response of irradiated and out-of-field normal tissues during localized curative intent radiotherapy. Experimental Design: Sixteen patients with non–small cell lung carcinoma (NSCLC) received 60 Gy in 30 fractions of definitive thoracic radiotherapy with or without concurrent chemotherapy. Peripheral blood lymphocytes (PBL) and eyebrow hairs were s led prior, during, and after radiotherapy. Clinical variables of radiotherapy dose/volume, patient age, and use of chemoradiotherapy were tested for association with γ-H2AX foci, a biomarker of DNA damage that underlies cellular response to irradiation. Results: Radiotherapy induced an elevation of γ-H2AX foci in PBL, representing normal tissues in the irradiated volume, 1 hour after fraction one. The changes correlated directly with mean lung dose and inversely with age. γ-H2AX foci numbers returned to near baseline values in 24 hours and were not significantly different from controls at 4 weeks during radiotherapy or 12 weeks after treatment completion. In contrast, unirradiated hair follicles, a surrogate model for out-of-field normal tissues, exhibited delayed “abscopal” DNA damage response. γ-H2AX foci significantly increased at 24 hours post-fraction one and remained elevated during treatment, in a dose-independent manner. This observed abscopal effect was associated with changes in plasma levels of MDC/CCL22 and MIP-1α/CCL3 cytokines. No concordant changes in size and concentration of circulating plasma exosomes were observed. Conclusions: Both localized thoracic radiotherapy and chemoradiotherapy induce pronounced systemic DNA damage in normal tissues. In idual assessment of biologic response to dose delivered during radiotherapy may allow for therapeutic personalization for patients with NSCLC. Clin Cancer Res 22(19) 4817–26. ©2016 AACR. See related commentary by Verma and Lin, p. 4763
Publisher: Springer Berlin Heidelberg
Date: 2011
DOI: 10.1007/174_2011_300
Publisher: Elsevier BV
Date: 03-2011
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.IJROBP.2015.06.005
Abstract: To investigate (68)Ga-ventilation erfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r(2)=0.99, P<.01), with ventilation strongly negatively linear (r(2)=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.CANLET.2015.01.009
Abstract: Over the last decade there has been a dramatic shift in the focus of cancer research toward understanding how the body's immune defenses can be harnessed to promote the effectiveness of cytotoxic anti-cancer therapies. The ability of ionizing radiation to elicit anti-cancer immune responses capable of controlling tumor growth has led to the emergence of promising combination-based radio-immunotherapeutic strategies for the treatment of cancer. Herein we review the immunoadjuvant properties of localized radiation therapy and discuss how technological advances in radio-oncology and developments in the field of tumor-immunotherapy have started to revolutionize the therapeutic application of radiotherapy.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 03-2002
Publisher: Springer Science and Business Media LLC
Date: 10-1994
DOI: 10.1007/BF02940567
Publisher: MDPI AG
Date: 17-04-2020
Abstract: Advanced-stage follicular lymphoma (FL) is generally considered incurable with conventional systemic therapies, but historic series describe long-term disease-free survival in stage III disease treated with wide-field radiation therapy (WFRT), encompassing all known disease sites. We report outcomes for patients staged with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and treated with CT-planned WFRT, given as either comprehensive lymphatic irradiation (CLI) or total nodal irradiation (TNI). This analysis of a prospective cohort includes PET-staged patients given curative-intent WFRT as a component of initial therapy, or as sole treatment for stage III FL. Thirty-three PET-staged patients with stage III FL received WFRT to 24–30Gy between 1999 and 2017. Fifteen patients also received planned systemic therapy (containing rituximab in 11 cases) as part of their primary treatment. At 10 years, overall survival and freedom from progression (FFP) were 100% and 75%, respectively. None of the 11 rituximab-treated patients have relapsed. Nine relapses occurred seven patients required treatment, and all responded to salvage therapies. A single death occurred at 16 years. The principal acute toxicity was transient hematologic one patient had residual grade two toxicity at one year. With FDG-PET staging, most patients with stage III FL experience prolonged FFP after WFRT, especially when combined with rituximab.
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.LUNGCAN.2014.02.009
Abstract: Thromboembolism is common in lung cancer. Current thromboprophylaxis guidelines lack specific recommendations for appropriate strategies in this high thrombotic risk patient cohort. We profiled lung cancer patients receiving anti-cancer therapy. Thromboembolism incidence and thromboembolism-related mortality rates are reported and we explored patient, disease, and treatment-related risk factors associated with higher thrombotic rates. Retrospective review of lung cancer patients referred to a Comprehensive Cancer Centre between 01/07/2011 and 30/06/2012 for anti-cancer therapy. Data were collected from medical, pharmacy, pathology and diagnostic imaging electronic records. After a median follow up of 10 months (range: 0.03-32 months), 24/222 patients (10.8%) had developed radiologically confirmed thromboembolism 131 events per 1000 person-years (95%CI 87-195). Thromboembolism occurred equally in patients with non-small cell and small cell lung cancer (10.8% and 10.5% respectively), and more frequently among patients with adenocarcinoma compared to squamous cell carcinoma (14.7% and 5.3% respectively). Chemotherapy-treated patients experienced thromboembolism more often than patients who did not receive chemotherapy (HR 5.7 95%CI 2.2-14.8). Radiotherapy was also associated with more frequent thromboembolism (HR 5.2 95%CI 2.0-13.2). New lung cancer diagnosis, presence of metastatic disease, second primary malignancy and Charlson Index ≥ 5 were also associated with higher rates of thromboembolism. Importantly, pharmacological thromboprophylaxis (P-TP) was not routinely or systematically prescribed for ambulant lung cancer patients during any treatment phase, at this institution. The majority (83%) of thromboembolic events occurred in the ambulatory care setting. Morbidity and mortality from thromboembolism occurs frequently in lung cancer. Thromboprophylaxis guidelines should be developed for the ambulatory care setting.
Publisher: Springer Science and Business Media LLC
Date: 28-02-2018
DOI: 10.1007/S10585-018-9875-0
Abstract: Patients with cancer are at high risk of both thromboembolic and haemorrhagic events during the course of their disease. The pathogenesis of haemostatic dysfunction in cancer is complex and involves the interplay of multiple factors. There is growing evidence that interactions between malignancies and the coagulation system are not random but can represent coordinated and clinically-significant adaptations that enhance tumour cell survival, proliferation and metastatic potential. A detailed understanding of the interactions between the haemostatic systems and the pathophysiology of metastasis may not only provide insight into strategies that could potentially reduce the incidence of thrombohaemorrhagic events and complications, but could also help design strategies that are capable of modifying tumour biology, progression and metastatic potential in ways that could enhance anticancer therapies and thereby improve overall survival.
Publisher: Department of Biomedical Imaging, University of Malaya, Malaysia
Date: 2007
DOI: 10.2349/BIIJ.3.1.E3
Publisher: Department of Biomedical Imaging, University of Malaya, Malaysia
Date: 2007
DOI: 10.2349/BIIJ.3.1.E4
Publisher: Wiley
Date: 04-04-2023
DOI: 10.1111/BJH.18644
Abstract: Positron emission tomography (PET) response assessment using the Deauville score has prognostic utility in relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) undergoing autologous stem‐cell transplantation (ASCT). Improved predictive methods are required to identify patients with poor outcomes who may be better considered for other salvage options. We investigated the prognostic value of mean tumour volume (MTV) and maximum standardised uptake value (SUVmax) at pre‐salvage and pre‐ASCT time‐points, and the quantitative changes between scans (∆MTV and ∆SUVmax). One hundred and twenty‐five patients with R/R DLBCL underwent salvage immunochemotherapy and ASCT: 80 patients had pre‐salvage PET and 90 had pre‐ASCT PET available. With a median follow‐up of 5.6 years, 5‐year progression‐free survival (PFS) and overall survival (OS) were 52% and 65%, respectively. For patients with PET‐positive residual disease after salvage therapy, pre‐ASCT MTV was a significant negative prognosticator for PFS (HR 1.19 per 100 ml, p 0.001) and OS (HR 1.78 per 100 ml, p 0.001). Similarly, pre‐ASCT SUVmax was negatively associated with PFS (HR 1.08, p 0.001) and OS (HR 1.08, p 0.001). Notably, pre‐salvage MTV and SUVmax and ∆MTV and ∆SUVmax were not associated with PFS or OS. In conclusion, pre‐ASCT MTV and SUVmax appear to be of greater predictive value than the degree of response. Potential application may exist for PET‐directed management of R/R DLBCL patients.
Publisher: Elsevier BV
Date: 07-2010
Publisher: Wiley
Date: 18-11-2001
DOI: 10.1046/J.1440-1673.2001.00960.X
Abstract: Thallium-201 (Tl-201) single photon emission computed tomography (SPECT) is funded for evaluation of malignancy in Australia and may have utility for staging of non-small cell lung cancer (NSCLC) if CT results are equivocal. Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) is superior to CT for staging NSCLC but is more expensive and less widely available than Tl-201 SPECT. Therefore, these techniques were prospectively compared in 27 radical radiation therapy candidates. Patients were allocated a conventional, PET and Tl-201 stage. Tumour to background ratios (TBR) were recorded for the primary on both techniques. Metastatic disease was confirmed by surgical pathology, serial imaging or clinical follow up. Tumour to background ratios were consistently higher for FDG PET than Tl-201 SPECT (P < 0.0001). Positron emission tomography detected all known primary tumours but Tl-201 failed to image four primary tumours (15%). In 10 of 18 cases of discordance between PET and Tl-201 SPECT regarding stage, corroboration was available from pathology or disease progression. Positron emission tomography was shown to have a 100% positive predictive value, including all three patients with PET-detected distant metastases (P=0.002). Results indicate that PET is superior to Tl-201 SPECT scanning in the staging of NSCLC for radical radiation therapy, and that the low sensitivity for detection of local and metastatic disease is likely to limit the clinical impact and cost-effectiveness of this technique despite its lower cost.
Publisher: Elsevier BV
Date: 07-1994
Publisher: American Society of Hematology
Date: 17-01-2019
DOI: 10.1182/BLOOD-2018-04-843540
Abstract: Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis median age was 58 years (range, 20-90) 410 patients (80.1%) had stage I disease median RT dose was 30 Gy (24-52) and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 96%. For stage I, FFP was 74.1% vs 49.1% for stage II (P & .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.
Publisher: Public Library of Science (PLoS)
Date: 24-11-2015
Publisher: Springer Science and Business Media LLC
Date: 19-09-2018
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.RADONC.2017.06.004
Abstract: Primary non-small cell lung cancer cavitation and central photopenia, detected by radiology and FDG-PET scanning respectively, are thought to be the result of tumor necrosis. Such regions may contain hypoxic but viable carcinoma cells which may be relatively radioresistant compared with fully oxygenated regions. We hypothesized that photopenic tumors treated with radiotherapy with or without chemotherapy would be associated with worse survival compared with tumors not showing central photopenia. The data were from a prospective trial (TROG 99-05) investigating the prognostic significance of primary tumor volume in patients receiving radical radiotherapy for locoregional non-small cell lung cancer (NSCLC). A subset of patients who had a pre-treatment FDG-PET scan formed the study population. The scans were evaluated by two observers for central photopenia in the primary tumor using a visual scoring system. The relationship of photopenia with survival was determined after adjusting for other prognostic factors. There were 172 eligible patients. The two observers agreed on the presence of photopenia in 90% of cases (Kappa=0.822, p<0.001). Seventy-three patients were scored as having photopenia. Photopenia was not associated with worse survival, either on univariate analysis, or after adjusting for sex, performance status and nodal status (HR=1.20, 95% CI 0.78-1.87, p=0.4) Photopenia was however significantly associated with larger tumor volume and weight loss. This study failed to demonstrate a significantly worse survival associated with central photopenia in patients treated with radiotherapy for NSCLC.
Publisher: Research Square Platform LLC
Date: 03-10-2023
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1016/J.IJROBP.2005.05.006
Abstract: To evaluate the long-term results of salvage radiotherapy (SRT) for Hodgkin's lymphoma after chemotherapy failure. We reviewed 81 patients undergoing SRT for persistent or recurrent Hodgkin's lymphoma after chemotherapy 19 also received conventional-dose salvage chemotherapy. At SRT, the median patient age was 31 years. Of the 81 patients, 81% had Stage I-II, 25.9% had B symptoms, 14.8% had bulky disease, and 7.4% had extranodal disease. A less than a complete response (CR) to the last chemotherapy regimen occurred in 47%. SRT was generally limited to one side of the diaphragm, and the median dose was 36 Gy. After SRT, 75% of patients achieved a CR, with 82% retaining durable in-field control. In-field failure was associated with less than a CR to the last chemotherapy regimen (p = 0.0287). Most failures were at distant sites, with 60% in previously involved sites. The 10-year freedom from treatment failure and overall survival rates were 32.8% and 45.7%, respectively. The adverse prognostic factors for freedom from treatment failure were age >50 years (p < 0.001), B symptoms (p 50 years (p < 0.001), B symptoms (p = 0.002), and less than a CR to the last chemotherapy regimen (p = 0.002). Favorable cohorts had a 10-year freedom from treatment failure rate of 51% and overall survival rate of 92%. Salvage radiotherapy is effective for selected patients with Hodgkin's lymphoma after chemotherapy failure and should be considered for incorporation into salvage programs.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.IJROBP.2017.07.035
Abstract: To investigate the associations between interim tumor responses on Patients with FDG-PET/computed tomography stage I-III NSCLC were prescribed concurrent chemotherapy and radiation therapy (60 Gy in 30 fractions). Scans were acquired at baseline (FDG-PET/computed tomography [FDG Between 2009 and 2013, 60 patients were recruited. Thirty-seven (62%) were male, and the median age was 66 years (range, 31-86 years). Two-year OS and PFS were 0.51 and 0.26, respectively. Unexpectedly, SD on FLT Stable uptake of
Publisher: Wiley
Date: 28-10-2022
DOI: 10.1002/PBC.29415
Abstract: The aim of this study was to evaluate the diagnostic accuracy of PubMed, Cochrane, Scopus, and Web of Science were searched for relevant studies. Data concerning Thirty-one studies with a total of 735 patients were included in this meta-analysis. The sensitivity and specificity of
Publisher: Wiley
Date: 13-11-2019
DOI: 10.1111/AJCO.13099
Publisher: American Medical Association (AMA)
Date: 10-2021
Publisher: Elsevier BV
Date: 11-1989
DOI: 10.1016/0016-5085(89)91703-4
Abstract: The hepatic microcirculation is believed to cause variable cellular oxygenation within the organ. In this study a marker of cellular hypoxia was used to demonstrate liver oxygen tension gradients in vivo. Covalent binding of misonidazole adducts to cellular macromolecules is enhanced by hypoxia. Autoradiographs of liver from mice treated with radiolabeled misonidazole demonstrated enhanced binding of adducts within hepatocytes surrounding hepatic veins. Livers from both hypoxic and normal mice had characteristic autoradiographic grain patterns reflecting regional oxygen tension variation in vivo. Differential binding of misonidazole adducts formed in hypoxic cells could have an application in studies of liver physiology and biochemistry.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.RADONC.2008.11.008
Abstract: Positron Emission Tomography (PET) is a significant advance in cancer imaging with great potential for optimizing radiation therapy (RT) treatment planning and thereby improving outcomes for patients. The use of PET and PET/CT in RT planning was reviewed by an international panel. The International Atomic Energy Agency (IAEA) organized two synchronized and overlapping consultants' meetings with experts from different regions of the world in Vienna in July 2006. Nine experts and three IAEA staff evaluated the available data on the use of PET in RT planning, and considered practical methods for integrating it into routine practice. For RT planning, (18)F fluorodeoxyglucose (FDG) was the most valuable pharmaceutical. Numerous studies supported the routine use of FDG-PET for RT target volume determination in non-small cell lung cancer (NSCLC). There was also evidence for utility of PET in head and neck cancers, lymphoma and in esophageal cancers, with promising preliminary data in many other cancers. The best available approach employs integrated PET/CT images, acquired on a dual scanner in the radiotherapy treatment position after administration of tracer according to a standardized protocol, with careful optimization of images within the RT planning system and carefully considered rules for contouring tumor volumes. PET scans that are not recent or were acquired without proper patient positioning should be repeated for RT planning. PET will play an increasing valuable role in RT planning for a wide range of cancers. When requesting PET scans, physicians should be aware of their potential role in RT planning.
Publisher: Elsevier BV
Date: 12-1999
Publisher: Wiley
Date: 02-1999
DOI: 10.1046/J.1440-1673.1999.00600.X
Abstract: A case of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma treated with radiotherapy alone is reported here. This case highlights treatment issues related to the variability in size and position of the stomach, and the substantial reduction in the size of the irradiated volume achieved by treating the patient in a fasting state.
Publisher: Wiley
Date: 23-01-2006
DOI: 10.1002/CNCR.21704
Abstract: Many experienced oncologists have encountered patients with proven non-small cell lung cancer (NCLC) who received modest doses of palliative radiotherapy (RT) and who unexpectedly survived for > 5 years some were apparently cured. We used a very large prospective database to estimate the frequency of this phenomenon and to look for correlative prognostic factors. Patients with histologically or cytologically proven NSCLC, treated with palliative RT to a dose of 5 years after palliative RT, and many of these patients appeared to have been cured by a treatment usually considered to be without curative potential. Because of the potential for long-term survival, doses to late-reacting normal tissues should be kept within tolerance when prescribing palliative RT in NSCLC.
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.IJROBP.2010.04.021
Abstract: To study the relationship between fluorodeoxyglucose (FDG) uptake in pulmonary tissue after radical radiation therapy (RT) and the presence and severity of radiation pneumonitis. In 88 consecutive patients, (18)F-FDG-positron emission tomography was performed at a median of 70 days after completion of RT. Patients received 60 Gy in 30 fractions, and all but 15 had concurrent platinum-based chemotherapy. RT-induced pulmonary inflammatory changes occurring within the radiation treatment volume were scored, using a visual (0 to 3) radiotoxicity grading scale, by an observer blinded to the presence or absence of clinical radiation pneumonitis. Radiation pneumonitis was retrospectively graded using the Radiation Therapy Oncology Group (RTOG) scale by an observer blinded to the PET radiotoxicity score. There was a significant association between the worst RTOG pneumonitis grade occurring at any time after RT and the positron emission tomograph (PET) radiotoxicity grade (one-sided p = 0.033). The worst RTOG pneumonitis grade occurring after the PET scan was also associated with the PET radiotoxicity grade (one-sided p = 0.035). For every one-level increase in the PET toxicity scale, the risk of a higher RTOG radiation pneumonitis score increased by approximately 40%. The PET radiotoxicity score showed no significant correlation with the duration of radiation pneumonitis. The intensity of FDG uptake in pulmonary tissue after RT determined using a simple visual scoring system showed significant correlation with the presence and severity of radiation pneumonitis. (18)F-FDG-PET may be useful in the prediction, diagnosis and therapeutic monitoring of radiation pneumonitis.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 05-2017
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 12-2008
Publisher: Elsevier BV
Date: 08-2010
Publisher: MDPI AG
Date: 08-01-2019
Abstract: Prevention of cancer-associated thromboembolism (TE) remains a significant clinical challenge and priority world-wide safety initiative. In this prospective non-small cell lung cancer (NSCLC) cohort, longitudinal TE risk profiling (clinical and biomarker) was undertaken to develop risk stratification models for targeted TE prevention. These were compared with published models from Khorana, CATS, PROTECHT, CONKO, and CATS/MICA. The NSCLC cohort of 129 patients, median follow-up 22.0 months (range 5.6—31.3), demonstrated a hypercoagulable profile in % patients and TE incidence of 19%. High TE risk patients were those receiving chemotherapy with baseline fibrinogen ≥ 4 g/L and d-dimer ≥ 0.5 mg/L or baseline d-dimer ≥ 1.5 mg/L or month 1 d-dimer ≥ 1.5 mg/L. The model predicted TE with 100% sensitivity and 34% specificity (c-index 0.67), with TE incidence 27% vs. 0% for high vs. low-risk. A comparison using the Khorana, PROTECHT, and CONKO methods were not discriminatory TE incidence 17–25% vs. 14–19% for high vs. low-risk (c-index 0.51–0.59). Continuous d-dimer (CATS/MICA model) was also not predictive of TE. Independent of tumour stage, high TE risk was associated with cancer progression (HR 1.9, p = 0.01) and mortality (HR 2.2, p = 0.02). The model was tested for scalability in a prospective gastrointestinal cancer cohort with equipotency demonstrated 80% sensitivity and 39% specificity. This proposed TE risk prediction model is simple, practical, potent and can be used in the clinic for real-time, decision-making for targeted thromboprophylaxis. Validation in a multicentre randomised interventional study is underway (ACTRN12618000811202).
Publisher: Springer Science and Business Media LLC
Date: 23-08-2016
DOI: 10.1038/NRCLINONC.2016.128
Abstract: Despite progressive improvements in the management of patients with locoregionally confined, advanced-stage solid tumours, distant metastasis remains a very common - and usually fatal - mode of failure after attempted curative treatment. Surgery and radiotherapy are the primary curative modalities for these patients, often combined with each other and/or with chemotherapy. Distant metastasis occurring after treatment can arise from previously undetected micrometastases or, alternatively, from persistent locoregional disease. Another possibility is that treatment itself might sometimes cause or promote metastasis. Surgical interventions in patients with cancer, including biopsies, are commonly associated with increased concentrations of circulating tumour cells (CTCs). High CTC numbers are associated with an unfavourable prognosis in many cancers. Radiotherapy and systemic antitumour therapies might also mobilize CTCs. We review the preclinical and clinical data concerning cancer treatments, CTC mobilization and other factors that might promote metastasis. Contemporary treatment regimens represent the best available curative options for patients who might otherwise die from locally confined, advanced-stage cancers however, if such treatments can promote metastasis, this process must be understood and addressed therapeutically to improve patient survival.
Publisher: Wiley
Date: 29-05-2013
DOI: 10.1111/IJN.12095
Abstract: The aim of this study was to explore the motivations of student nurses enrolled in nursing courses across a variety of Pacific Island countries. The image of nursing, the desire to help others, family and friends in the profession, personal experience, security, travel opportunities and flexibility have all been identified as motivators for people to enter nursing. To date, what motivates students in Pacific Island countries to enrol in a nursing course has not been investigated. An exploratory qualitative approach using focus group interviews with 152 nursing students was undertaken. Data were analysed using thematic content analysis, revealing four themes: (i) helping others (ii) 'making a difference for my people' (iii) following in the footsteps of others and (iv) financial and professional gain. In a time of health and nursing workforce shortages, developing a deeper understanding of what drives people can be used to improve recruitment strategies in the future.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2004
DOI: 10.1097/01.COC.0000054889.58718.6F
Abstract: Accurate staging is important in small-cell lung cancer (SCLC). Patients with limited stage may benefit from chemoradiation, whereas those with extensive stage conventionally receive chemotherapy. Prophylactic cranial irradiation may benefit those attaining complete remission (CR). 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) enhances accuracy of staging in non-SCLC. Its role in SCLC remains unclear. We reviewed 36 consecutive SCLC patients who underwent 47 PET studies between December 1996 and January 2001, for either staging (n = 11), restaging after therapy (n = 21), or both (n = 4). Conventional imaging was also performed. Of 15 patients who had PET for staging, 5 (33%) were upstaged from limited to extensive disease and treated without thoracic radiotherapy. Twenty-five patients underwent 32 restaging PET scans, of which 20 (63%) were discordant with conventional imaging. In 8 cases PET showed more extensive disease than conventional imaging, and in 12 cases PET-apparent disease appeared less extensive. In 13 patients, 14 untreated discordant lesions were evaluable PET was confirmed accurate in 11 (79%) sites by last follow-up. Restaging PET influenced management in 13 cases (52%). PET-CR conferred longer median time to progression (13.7 months) than no CR (9.7 months). FDG-PET for SCLC was often discordant with conventional assessment and frequently influenced management.
Publisher: Elsevier BV
Date: 08-2013
Publisher: Future Medicine Ltd
Date: 12-2017
Abstract: Surgery is the main curative therapy for patients with localized non-small-cell lung cancer while radiotherapy (RT), alone or with concurrent platinum-based chemotherapy, remains the primary curative modality for locoregionally advanced non-small-cell lung cancer. The risk of distant metastasis is high after curative-intent treatment, largely attributable to the presence of undetected micrometastases, but which could also be related to treatment-related increases in circulating tumor cells (CTCs). CTC mobilization by RT or systemic therapies might either reflect efficient tumor destruction with improved prognosis, or might promote metastasis and thus represent a potential therapeutic target. RT may induce prometastatic biological alterations in CTC at the cellular level, which are detectable by ‘liquid biopsies’, though their rarity represents a major challenge. Improved methods of isolation and ex vivo propagation will be essential for the future of CTC research.
Publisher: MDPI AG
Date: 05-01-2022
Abstract: With five-year survival rates as low as 3%, lung cancer is the most common cause of cancer-related mortality worldwide. The severity of the disease at presentation is accredited to the lack of early detection capacities, resulting in the reliance on low-throughput diagnostic measures, such as tissue biopsy and imaging. Interest in the development and use of liquid biopsies has risen, due to non-invasive s le collection, and the depth of information it can provide on a disease. Small extracellular vesicles (sEVs) as viable liquid biopsies are of particular interest due to their potential as cancer biomarkers. To validate the use of sEVs as cancer biomarkers, we characterised cancer sEVs using miRNA sequencing analysis. We found that miRNA-3182 was highly enriched in sEVs derived from the blood of patients with invasive breast carcinoma and NSCLC. The enrichment of sEV miR-3182 was confirmed in oncogenic, transformed lung cells in comparison to isogenic, untransformed lung cells. Most importantly, miR-3182 can successfully distinguish early-stage NSCLC patients from those with benign lung conditions. Therefore, miR-3182 provides potential to be used for the detection of NSCLC in blood s les, which could result in earlier therapy and thus improved outcomes and survival for patients.
Publisher: Society of Nuclear Medicine
Date: 15-05-2014
DOI: 10.2967/JNUMED.113.131631
Abstract: We aimed to prospectively observe cellular metabolism and proliferation in patients with non-small-cell lung cancer (NSCLC) during radical chemoradiation therapy using serial PET/CT with (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT). Twenty patients with stage I-III NSCLC and candidates for radical chemoradiation therapy (60 Gy in 30 fractions over 6 wk) were recruited. (18)F-FDG and (18)F-FLT PET/CT were performed at baseline and during therapy (weeks 2 and 4). Tumor response was assessed semiquantitatively and using visual response criteria. The median and range for primary tumor volume (cm(3)) at baseline on (18)F-FDG were 28 and 2-241, respectively, and on (18)F-FLT 31 and 2-184, respectively. At week 2, (18)F-FDG was 26 (range, 2-164), and (18)F-FLT was 11 (range, 0-111). At week 4, (18)F-FDG was 19 (1-147), and (18)F-FLT was 7 (0-48). The median and range of maximum standardized uptake value (SUVmax) at baseline on (18)F-FDG were 14 and 4-31, respectively, and on (18)F-FLT 6 and 2-12, respectively. Week 2 (18)F-FDG median SUVmax was 10 (2-31), and (18)F-FLT median SUVmax was 3 (1-15) week 4 (18)F-FDG median SUVmax was 10 (2-15), and (18)F-FLT median SUVmax was 2 (2-9). There was fair agreement between visual tumor response on (18)F-FDG and (18)F-FLT during therapy (Cohen's unweighted κ statistic, 0.27 at week 2 and 0.355 at week 4). Cerebral metastases were detected on 1 baseline (18)F-FLT scan, resulting in palliative management. Progressive disease was detected on week 2 scans in 3 patients, resulting in changes to radiation therapy (2 patients) and treatment intent (1 patient). This study demonstrates that (18)F-FLT PET/CT is a more sensitive tracer of early treatment response than (18)F-FDG PET/CT. The ability of these tracers to detect distinct biologic processes may lead to their use as biomarkers for personalized radiation therapy and prognosis in the future.
Publisher: Springer Science and Business Media LLC
Date: 11-03-2014
DOI: 10.1007/S00066-014-0644-Y
Abstract: The integration of positron emission tomography (PET) information for target volume delineation in radiation treatment planning is routine in many centers. In contrast to automatic contouring, research on visual-manual delineation is scarce. The present study investigates the dependency of manual delineation on experience and qualification. A total of 44 international interdisciplinary observers each defined a [(18)F]fluorodeoxyglucose (FDG)-PET based gross tumor volume (GTV) using the same PET/CT scan from a patient with lung cancer. The observers were "experts" (E n = 3), "experienced interdisciplinary pairs" (EP 9 teams of radiation oncologist (RO) + nuclear medicine physician (NP)), "single field specialists" (SFS n = 13), and "students" (S n = 10). Five automatic delineation methods (AM) were also included. Volume sizes and concordance indices within the groups (pCI) and relative to the experts (eCI) were calculated. E (pCI = 0.67) and EP (pCI = 0.53) showed a significantly higher agreement within the groups as compared to SFS (pCI = 0.43, p = 0.03, and p = 0.006). In relation to the experts, EP (eCI = 0.55) showed better concordance compared to SFS (eCI = 0.49) or S (eCI = 0.47). The intermethod variability of the AM (pCI = 0.44) was similar to that of SFS and S, showing poorer agreement with the experts (eCI = 0.35). The results suggest that interdisciplinary cooperation could be beneficial for consistent contouring. Joint delineation by a radiation oncologist and a nuclear medicine physician showed remarkable agreement and better concordance with the experts compared to other specialists. The relevant intermethod variability of the automatic algorithms underlines the need for further standardization and optimization in this field.
Publisher: Society of Nuclear Medicine
Date: 27-05-2014
DOI: 10.2967/JNUMED.113.136127
Abstract: Historically, it has been difficult to monitor the acute impact of anticancer therapies on hematopoietic organs on a whole-body scale. Deeper understanding of the effect of treatments on bone marrow would be of great potential value in the rational design of intensive treatment regimens. 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a functional radiotracer used to study cellular proliferation. It is trapped in cells in proportion to thymidine-kinase 1 enzyme expression, which is upregulated during DNA synthesis. This study investigates the potential of (18)F-FLT to monitor acute effects of chemotherapy on cellular proliferation and its recovery in bone marrow, spleen, and liver during treatment with 2 different chemotherapy regimens. Sixty patients with non-small cell lung cancer underwent concurrent radical chemoradiotherapy to 60 Gy in 6 wk with either cisplatin/etoposide (C/E, n = 28) weeks 1 and 5 or weekly carboplatin aclitaxel (C/P, n = 32) regimens. (18)F-FLT and (18)F-FDG PET with CT were performed at baseline, week 2 (day 9 for (18)F-FLT and day 10 for (18)F-FDG PET), and week 4 (day 23 for (18)F-FLT and day 24 for (18)F-FDG PET). Visual and semiquantitative standardized uptake value (SUV) measurements were performed in bone marrow outside the radiotherapy field, liver, spleen, and small bowel. These were correlated to blood counts and smears in a subset of patients. The C/E group exhibited a drop in bone marrow (18)F-FLT uptake at week 2 (median SUVmax [maximum SUV] decrease to 31%, 8.7-6.0, P 0.05). Spleen uptake in both cohorts decreased at week 2, with intense rebound activity at week 4 (SUVmax week 4 at 58% above baseline: 2.4-3.8, for C/E, respectively, 30% for C/P: 2.7-3.5, P < 0.001). Liver uptake changed little. (18)F-FLT changes preceded neutrophil count reductions. (18)F-FDG uptake in marrow liver and spleen changed much less than (18)F-FLT. (18)F-FLT imaging may be used to quantify impairment and recovery of bone marrow by specific chemotherapy regimens and may also enable imaging of organ-specific processes such as spleen activation. (18)F-FLT is superior to (18)F-FDG for this purpose. This technology may support novel treatment planning and monitoring approaches in oncology patients.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.IJROBP.2015.04.027
Abstract: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)-positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Fifty-one patients were studied: 67% male median age 68 (range, 31-87) years 8% never smokers 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interin idual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow in such cases, in idual FLT-PET scans may be required.
Publisher: Wiley
Date: 15-08-2001
DOI: 10.1046/J.1440-1673.2001.00930.X
Abstract: Long-term follow-up data from Stanford and other centres suggest that 40-50% of patients with clinical stages I and II follicular low-grade lymphoma can be cured by radiotherapy (RT). Relapse generally occurs outside radiation fields and most relapsed patients ultimately die from lymphoma. No randomized data exist to support adjuvant chemotherapy but only one trial of low-intensity chemotherapy was sufficiently powerful to address the question. Nevertheless, data from a large phase-II study from MD Anderson suggest that combined chemotherapy and RT can produce progression-free survival results that are far superior to historical series, with survival at 10 years to be approximately 20% superior to radiation alone. These results have encouraged the development of a joint phase III study by the Trans Tasman Radiation Oncology Group (TROG) and the Australasian Leukaemia and Lymphoma Group (ALLG) in which patients with clinical stage I/II follicular lymphoma are randomized to involved field RT with or without six cycles of cytotoxic chemotherapy. In an era of rapid development in immunological and molecular therapies the potential for improved results with new combinations of more established treatment modalities should not be forgotten. This report reviews the literature on the management of localized low-grade lymphoma and discusses the rationale for the TROG/ALLG study, which began recruitment in early 2000.
Publisher: Society of Nuclear Medicine
Date: 07-06-2012
DOI: 10.2967/JNUMED.111.099713
Abstract: We investigated the incremental management impact and prognostic value of staging with (18)F-FDG PET/CT in patients with non-small cell lung cancer (NSCLC) being considered for potentially curative therapies. Information on 168 consecutive patients with NSCLC being considered for surgery or definitive radiotherapy with curative intent before PET/CT was entered into a prospective database. The pre-PET/CT management plan, based on conventional imaging (conventional CT, appropriately supplemented by bone scintigraphy or other modalities), was defined prospectively by referring clinicians before PET/CT results became available. After PET/CT, actual clinical management was recorded, and patients were followed up until 5 y or death. The appropriateness of PET/CT management plans was assessed by biopsy when available, clinical follow-up, and survival analysis. Stage was discordant on PET/CT and conventional imaging in 50.6% of patients (41.1% upstaged, 9.5% downstaged), with high management impact (change in treatment modality or curative intent) in 42.3% of patients. Both conventional imaging stage and PET/CT stage were strongly predictive of overall survival (OS) but there were greater differences between hazard rates and separations in the OS curves for stage groupings determined using PET/CT. OS was also strongly predicted by PET/CT-directed choice of therapy (P < 0.0001). PET/CT frequently affects patient management and strongly predicts OS in NSCLC, supporting the appropriateness of such changes.
Publisher: Springer Science and Business Media LLC
Date: 20-07-2017
DOI: 10.1038/BJC.2017.232
Publisher: Elsevier BV
Date: 07-2015
Publisher: Elsevier BV
Date: 11-2001
DOI: 10.1016/S0360-3016(01)01699-6
Abstract: To determine the long-term outcome of radiotherapy (RT) in patients with progressively symptomatic thyroid eye disease and to evaluate the potential long-term sequelae. Four hundred fifty-three patients provided written informed consent and received retrobulbar RT for Graves' ophthalmopathy at Stanford University Medical Center 197 with 1 year of follow-up were retrospectively analyzed. Of the 197 patients, 189 received RT to the bilateral retrobulbar regions, and 4 received unilateral RT. The technical information was unavailable for 4 patients. Patients were assessed by chart review, telephone interview, questionnaire, and multidisciplinary physician examination. Eye impairment was scored using the SPECS system. The end point review included the before and after treatment SPECS score, surgical intervention, and patient satisfaction. Potential complications, including cataract development, retinopathy, and tumor formation, were investigated. Multivariate analyses were performed to assess the prognostic variables. Improvement or resolution was 89% for soft-tissue findings 70% for proptosis 85% for extraocular muscle dysfunction 96% for corneal abnormalities and 67% for sight loss. The response to RT may take >6 months to stabilize. Factors predictive of response varied in the in idual SPECS categories but included the initial SPECS score, pretreatment thyroid status, female gender, a 20-Gy RT dose, and a history of hypertension. Nonpredictive factors included a history of tobacco use, diabetes mellitus, steroids, and prior cataracts. Only 16% required surgical intervention to preserve their vision or restore binocular vision. Twenty-two patients (12%) developed cataracts after irradiation (median 11 years). No patient developed a tumor within the RT field during the follow-up period (range 1-29 years). Ninety-eight percent of patients were pleased with their results, and 2% believed their symptoms progressed despite RT. Retrobulbar irradiation (20 Gy) is safe and effective treatment for progressive Graves' ophthalmopathy, with a 96% overall response rate, 98% patient satisfaction rate, and no irreparable long-term sequelae, with follow-up extending 29 years. The most common late effect observed was cataract development, which occurred more frequently in older patients and was reversible with extraction. Elective surgical intervention after RT should be withheld until patients have demonstrated a plateau in response.
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1016/J.IJROBP.2004.08.025
Abstract: To determine the relationship between various parameters derived from lung dose-volume histogram analysis and the risk of symptomatic radiation pneumonitis (RP) in patients undergoing radical radiotherapy for primary lung cancer. The records of 156 patients with lung cancer who had been treated with radical radiotherapy (>/=45 Gy) and for whom dose-volume histogram data were available were reviewed. The incidence of symptomatic RP was correlated with a variety of parameters derived from the dose-volume histogram data, including the volume of lung receiving 10 Gy (V(10)) through 50 Gy (V(50)) and the mean lung dose (MLD). The rate of RP at 6 months was 15% (95% confidence interval 9-22%). On univariate analysis, only V(30) (p = 0.036) and MLD (p = 0.043) were statistically significantly related to RP. V(30) correlated highly positively with MLD (r = 0.96, p < 0.001). V(30) and MLD can be used to predict the risk of RP in lung cancer patients undergoing radical radiotherapy.
Publisher: Wiley
Date: 2018
DOI: 10.1111/IMJ.13491
Abstract: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease comprising not only different histological subtypes but also different molecular subtypes. To describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. Metastatic NSCLC patients enrolled in a prospective Thoracic Malignancies Cohort Study between July 2012 and August 2016 were selected. Patients underwent molecular testing for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene rearrangements, Kirsten rat sarcoma (KRAS), B-Raf proto-oncogene (BRAF) mutations and ROS1 gene rearrangements. Survival was calculated using the Kaplan-Meier method for groups of interest, and comparisons were made using the log-rank test. A total of 392 patients were included, 43% of whom were female with median age of 64 years (28-92). Of 296 patients tested, 172 patients (58%) were positive for an oncogenic driver: 81 patients (27%) were EGFR positive, 25 patients (9%) were ALK positive, 57 patients (19%) had KRAS mutation and 9 patients (3%) were ROS1 or BRAF positive. Patients with an actionable mutation (EGFR/ALK) had a survival advantage when compared with patients who were mutation negative (hazard ratio (HR) 0.49 95% confidence interval (CI) 0.33-0.71 P < 0.01). Survival difference between mutation negative and mutation status unknown was not statistically significant when adjusted for confounding factors in a multivariate analysis (HR 1.29 95% CI 0.97-1.78, P = 0.08). In this prospective cohort, the presence of an actionable mutation was the strongest predictor of overall survival. These results confirm the importance of molecular testing and suggest likely survival benefit of identification and treatment of actionable oncogenes.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2014
DOI: 10.1007/S00520-014-2170-Y
Abstract: The purpose of this study was to report the opinions and self-reported practices of clinicians, as well as the availability of decision support tools, regarding appropriate thromboprophylaxis for patients with lung cancer to identify variation in practice and/or ergence from evidence-based clinical practice guidelines (CPG). A computer-generated survey (SurveyMonkey software) was distributed to surgical, radiation and medical oncologists with lung cancer specialisation, via membership of the Australian Lung Cancer Trials Group (ALTG) from May to September 2013. Seventy-two clinicians, from public, private, specialist and general hospitals, completed the survey (46% response rate). Hospital-endorsed CPG were widely available (91%) however, these routinely lacked robust recommendations for the ambulatory care setting (98%) and risk stratification tools (65%). Clinicians consistently identified ambulatory care treatment modalities (chemotherapy, alone or in combination with radiotherapy) as having similar (high) thrombotic risk as surgery. Timing and duration of pharmacological thromboprophylaxis prescribing among surgical oncologists varied and were ergent from guideline recommendations. Fifty-eight percent of surveyed clinicians cited a lack of high-quality data to guide preventative strategies in lung cancer patients. Clinicians consistently identified patients with lung cancer as having a high thromboembolic risk in both ambulatory and surgical settings, but with differences in recommendations and variation in practice. CPG lacked robust recommendations for the ambulatory care setting, the main arena for the multimodality lung cancer treatment paradigm.
Publisher: Elsevier BV
Date: 02-2022
Publisher: Elsevier BV
Date: 05-2008
Publisher: Public Library of Science (PLoS)
Date: 25-02-2020
Publisher: AMPCo
Date: 11-2008
DOI: 10.5694/J.1326-5377.2008.TB02179.X
Abstract: To measure long-term survival following combined chemotherapy and radiotherapy for inoperable non-small cell lung cancer. Two prospective Phase I/II studies in the multidisciplinary Lung Service of a dedicated cancer hospital in Victoria, commencing in 1996 and 1997-1998. 33 patients referred for treatment of histologically or cytologically proven inoperable non-small cell lung cancer, who had no evidence of distant metastases, Karnofsky performance status > 70%, weight loss < 10%, and no prior treatment for lung cancer. Patients were followed until death or for a minimum of 9 years. Patients in both studies were treated concomitantly with chemotherapy and radiotherapy 60 Gy in 30 fractions over 6 weeks. Chemotherapy in the first study (LURTCE) consisted of cisplatin and etoposide in the second study (LURTCF), chemotherapy consisted of escalating doses of carboplatin and fluorouracil. Overall survival. Six of 33 patients were still alive 9 years after commencement of treatment. Median survival for the whole group was 2.1 years (95% CI, 1.3-3.1 years), with 18% (95% CI, 8%-35%) of patients still alive at 5 years (plateau). Long-term survival can be achieved in some patients with inoperable non-small cell lung cancer treated by radical chemoradiation alone, suggesting the possibility of cure.
Publisher: Elsevier BV
Date: 10-2006
Publisher: Elsevier BV
Date: 08-2003
Publisher: Springer Science and Business Media LLC
Date: 31-07-2019
Publisher: Elsevier BV
Date: 2006
Publisher: Springer Science and Business Media LLC
Date: 07-04-2022
DOI: 10.1038/S41698-022-00263-X
Abstract: Immune checkpoint inhibitors and related molecules can achieve tumour regression, and even prolonged survival, for a subset of cancer patients with an otherwise dire prognosis. However, it remains unclear why some patients respond to immunotherapy and others do not. PET imaging has the potential to characterise the spatial and temporal heterogeneity of both immunotherapy target molecules and the tumor immune microenvironment, suggesting a tantalising vision of personally-adapted immunomodulatory treatment regimens. Personalised combinations of immunotherapy with local therapies and other systemic therapies, would be informed by immune imaging and subsequently modified in accordance with therapeutically induced immune environmental changes. An ideal PET imaging biomarker would facilitate the choice of initial therapy and would permit sequential imaging in time-frames that could provide actionable information to guide subsequent therapy. Such imaging should provide either prognostic or predictive measures of responsiveness relevant to key immunotherapy types but, most importantly, guide key decisions on initiation, continuation, change or cessation of treatment to reduce the cost and morbidity of treatment while enhancing survival outcomes. We survey the current literature, focusing on clinically relevant immune checkpoint immunotherapies, for which novel PET tracers are being developed, and discuss what steps are needed to make this vision a reality.
Publisher: Elsevier BV
Date: 05-2023
Publisher: Springer Science and Business Media LLC
Date: 09-2005
Publisher: Frontiers Media SA
Date: 07-05-2021
Abstract: Muscle wasting (Sarcopenia) is associated with poor outcomes in cancer patients. Early identification of sarcopenia can facilitate nutritional and exercise intervention. Cross-sectional skeletal muscle (SM) area at the third lumbar vertebra (L3) slice of a computed tomography (CT) image is increasingly used to assess body composition and calculate SM index (SMI), a validated surrogate marker for sarcopenia in cancer. Manual segmentation of SM requires multiple steps, which limits use in routine clinical practice. This project aims to develop an automatic method to segment L3 muscle in CT scans. Attenuation correction CTs from full body PET-CT scans from patients enrolled in two prospective trials were used. The training set consisted of 66 non-small cell lung cancer (NSCLC) patients who underwent curative intent radiotherapy. An additional 42 NSCLC patients prescribed curative intent chemo-radiotherapy from a second trial were used for testing. Each patient had multiple CT scans taken at different time points prior to and post- treatment (147 CTs in the training and validation set and 116 CTs in the independent testing set). Skeletal muscle at L3 vertebra was manually segmented by two observers, according to the Alberta protocol to serve as ground truth labels. This included 40 images segmented by both observers to measure inter-observer variation. An ensemble of 2.5D fully convolutional neural networks (U-Nets) was used to perform the segmentation. The final layer of U-Net produced the binary classification of the pixels into muscle and non-muscle area. The model performance was calculated using Dice score and absolute percentage error (APE) in skeletal muscle area between manual and automated contours. We trained five 2.5D U-Nets using 5-fold cross validation and used them to predict the contours in the testing set. The model achieved a mean Dice score of 0.92 and an APE of 3.1% on the independent testing set. This was similar to inter-observer variation of 0.96 and 2.9% for mean Dice and APE respectively. We further quantified the performance of sarcopenia classification using computer generated skeletal muscle area. To meet a clinical diagnosis of sarcopenia based on Alberta protocol the model achieved a sensitivity of 84% and a specificity of 95%. This work demonstrates an automated method for accurate and reproducible segmentation of skeletal muscle area at L3. This is an efficient tool for large scale or routine computation of skeletal muscle area in cancer patients which may have applications on low quality CTs acquired as part of PET/CT studies for staging and surveillance of patients with cancer.
Publisher: Springer Science and Business Media LLC
Date: 07-08-2018
DOI: 10.1007/S00259-018-4112-2
Abstract: To evaluate the impact of positron emission tomography (PET) staging on overall survival (OS) and progression-free survival (PFS) in patients with early-stage (stages I and II) follicular lymphoma (ESFL) treated with radiation therapy alone. Eighty-five patients with ESFL treated with curative-intent radiation therapy (RT) between December 2000 and May 2011 were identified. Of those, 13 who had no PET staging and 25 who received additional systemic therapy were excluded from the analysis. Thus, we analyzed 47 patients with PET-staged ESFL treated with definitive radiation therapy alone (dose > 23Gy). Tumour features, pre-treatment computed tomography (CT) and PET stage, dose fractionation, and radiation therapy field extent were recorded. The Kaplan-Meier method was used to estimate the OS and PFS. Patterns of failure were assessed as cumulative incidences assuming competing risks. Median age was 57 years (range 24-83) 43% were females. Most were PET stage 1 (76.6%). Median maximum nodal diameter was 3 cm. Median pre-treatment lactate dehydrogenase (LDH) was 327.5 (range 123-607, upper normal limit = 220). Twenty-six patients (55.3%) had infra-diaphragmatic disease. All received 30-36Gy in 15-24 fractions, with 59.6% treated with involved-field radiation therapy (IFRT) techniques. There was no significant difference in PFS between CT stage I and stage II (HR 1.30 95% CI [0.25-6.72], p = 0.75) with a 5-year PFS of 77% and 78% respectively. However, stage I on PET staging had a significantly better PFS than stage II (HR 4.66 95% CI [1.15-18.8], p = 0.038), with 5-year PFS of 84% and 60% respectively. Ten patients had recurrent disease, with distant disease being the first site of failure in seven patients. Seven-year OS was 91% (95% CI 79-100) for the whole cohort. FDG-PET should be considered an essential element in the evaluation of patients with ESFL being considered for RT.
Publisher: Wiley
Date: 04-2010
DOI: 10.1111/J.1754-9485.2010.02146.X
Abstract: The aim of this study was to retrospectively evaluate the value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in extrapulmonary small-cell cancer (EPSCC). Patients with EPSCC who underwent PET for staging or response assessment between 1996 and 2007 were identified from a database. Patient records were reviewed. PET-based, and conventional staging and restaging results were compared. The binary staging classification of limited disease (LD) versus extensive disease (ED) was used. Patients with LD had tumours that could be encompassed within a tolerable radiation therapy (RT) volume. Of 33 eligible patients, 12 had staging PET scans, 11 had restaging scans and 10 had both. All known gross disease sites were FDG-avid. PET and conventional stage groupings were concordant in 21 of 22 cases. One patient was appropriately upstaged from LD to ED by PET. PET detected additional disease sites, without causing upstaging in three further patients. Restaging PET scans identified previously unrecognised persistent or progressive disease in 4 of 21 cases. In four further cases, persistent FDG uptake after treatment was either false positive (n = 2) or of uncertain (n = 2) aetiology. PPV was 100% for staging and 82% for restaging. In 8 of 43 imaging episodes (19%), PET appropriately influenced management in five cases by changing treatment intent from radical to palliative, and in three cases by altering the RT volume. PET has incremental value compared to conventional imaging for staging EPSCC, and may also be useful for restaging after therapy. PET influenced patient management in 19% of 43 imaging episodes.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1053/J.SEMNUCLMED.2012.04.003
Abstract: Positron emission tomography (PET)/computed tomography (CT) has rapidly assumed a critical role in the management of patients with locoregionally advanced lung cancers who are candidates for definitive radiation therapy (RT). Definitive RT is given with curative intent, but can only be successful in patients without distant metastasis and if all gross tumor is contained within the treated volume. An increasing body of evidence supports the use of PET-based imaging for selection of patients for both surgery and definitive RT. Similarly, the use of PET/CT images for accurate target volume definition in lung cancer is a dynamic area of research. Most available evidence on PET staging of lung cancer relates to non-small cell lung cancer (NSCLC). In general clinical use, (18)F-fluorodeoxyglucose (FDG) is the primary radiopharmaceutical useful in NSCLC. Other tracers, including proliferation markers and hypoxia tracers, may have significant roles in future. Much of the FDG-PET literature describing the impact of PET on actual patient management has concerned candidates for surgical resection. In the few prospective studies where PET was used for staging and patient selection in NSCLC candidates for definitive RT, 25%-30% of patients were denied definitive RT, generally because PET detected unsuspected advanced locoregional or distant metastatic disease. PET/CT and CT findings are often discordant in NSCLC but studies with clinical-pathological correlation always show that PET-assisted staging is more accurate than conventional assessment. In all studies in which "PET-defined" and "non-PET-defined" RT target volumes were compared, there were major differences between PET and non-PET volumes. Therefore, in cases where PET-assisted and non-PET staging are different and biopsy confirmation is unavailable, it is rational to use the most accurate modality (namely PET/CT) to define the target volume. The use of PET/CT in patient selection and target volume definition is likely to lead to improvements in outcome for patients with NSCLC.
Publisher: Springer Science and Business Media LLC
Date: 12-06-2019
DOI: 10.1007/S00259-019-04388-3
Abstract: Inflammatory FDG uptake in the lung (PET-pneumonitis) following curative-intent radiotherapy (RT)/chemo-RT (CRT) in non-small cell lung cancer (NSCLC) can pose a challenge in FDG-PET/CT response assessment. The aim of this study is to describe different patterns of PET-pneumonitis to guide the interpretation of FDG-PET/CT and investigate its association with tumor response and overall survival (OS). Retrospective analysis was performed on 87 NSCLC patients in three prospective trials who were treated with radical RT (n = 7) or CRT (n = 80), with baseline and post-treatment FDG-PET/CT. Visual criteria were performed for post-treatment FDG-PET/CT response assessment. The grading of PET-pneumonitis was based on relative lung uptake intensity compared to organs of reference and classified as per Deauville score from grade 1-5. Distribution patterns of PET-pneumonitis were defined as follows: A) patchy/sub-pleural B) diffuse (involving more than a segment) and C) peripheral (diffusely surrounding a photopenic region). Follow-up FDG-PET/CT scans were performed approximately 3 months (median, 89 days interquartile range, 79-93) after RT. Overall, PET-pneumonitis was present in 62/87 (71%) of patients, with Deauville 2 or 3 in 12/62 (19%) and 4 or 5 in 50/62 (81%) of patients. The frequency of patterns A, B and C of PET-pneumonitis was 19/62 (31%), 20/62 (32%) and 23/62 (37%), respectively. No association was found between grade or pattern of PET-pneumonitis and overall response at follow-up PET/CT (p = 0.27 and p = 0.56, respectively). There was also no significant association between PET-pneumonitis and OS (hazard ratio [HR], 1.3 95% confidence interval [CI], 0.6-2.5 p = 0.45). Early FDG-PET/CT response assessment, however, was prognostic for OS (HR, 1.7 95% CI, 1.2-2.2 p < 0.001). PET-pneumonitis is common in early post-CRT/RT, but pattern recognition may assist in response assessment by FDG-PET/CT. While FDG-PET/CT is a powerful tool for response assessment and prognostication, PET-pneumonitis does not appear to confound early response assessment or to independently predict OS.
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.IJROBP.2013.10.033
Abstract: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood s les immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Twenty-seven RT-treated NSCLC patients had blood s les analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood s les signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies.
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.IJROBP.2009.06.032
Abstract: Positron emission tomography/computed tomography (PET/CT) is increasingly used for delineating gross tumor volume (GTV) in non-small-cell lung cancer (NSCLC). The methodology for contouring tumor margins remains controversial. We developed a rigorous visual protocol for contouring GTV that uses all available clinical information and studied its reproducibility in patients from a prospective PET/CT planning trial. Planning PET/CT scans from 6 consecutive patients were selected. Six "observers" (two radiation oncologists, two nuclear medicine physicians, and two radiologists) contoured GTVs for each patient using a predefined protocol and subsequently recontoured 2 patients. For the estimated GTVs and axial distances, least-squares means for each observer and for each case were calculated and compared, using the F test and pairwise t-tests. In five cases, tumor margins were also autocontoured using standardized uptake value (SUV) cutoffs of 2.5 and 3.5 and 40% SUV(max). The magnitude of variation between observers was small relative to the mean (coefficient of variation [CV] = 3%), and the total variation (intraclass correlation coefficient [ICC] = 3%). For estimation of superior/inferior (SI), left/right (LR), and anterior osterior (AP) borders of the GTV, differences between observers were also small (AP, CV = 2%, ICC = 0.4% LR, CV = 6%, ICC = 2% SI, CV 4%, ICC = 2%). GTVs autocontoured generated using SUV 2.5, 3.5, and 40% SUV(max) differed widely in each case. An SUV contour of 2.5 was most closely correlated with the mean GTV defined by the human observers. Observer variation contributed little to total variation in the GTV and axial distances. A visual contouring protocol gave reproducible results for contouring GTV in NSCLC.
Publisher: BMJ
Date: 11-2022
DOI: 10.1136/BMJOPEN-2021-056708
Abstract: ImmunoPET is a multicentre, single arm, phase 0–1 study that aims to establish if 89 Zr-durvalumab PET/CT can be used to interrogate the expression of PD-L1 in larger, multicentre clinical trials. The phase 0 study recruited 5 PD-L1+ patients with metastatic non-small cell lung cancer (NSCLC). Patients received 60MBq/70 kg 89 Zr-durva up to a maximum of 74 MBq, with scan acquisition at days 0, 1, 3 or 5±1 day. Data on (1) Percentage of injected 89 Zr-durva dose found in organs of interest (2) Absorbed organ doses (µSv/MBq of administered 89 Zr-durva) and (3) whole-body dose expressed as mSv/100MBq of administered dose was collected to characterise biodistribution. The phase 1 study will recruit 20 patients undergoing concurrent chemoradiotherapy for stage III NSCLC. Patients will have 89 Zr-durva and FDG-PET/CT before, during and after chemoradiation. In order to establish the feasibility of 89 Zr-durva PET/CT for larger multicentre trials, we will collect both imaging and toxicity data. Feasibility will be deemed to have been met if more than 80% of patients are able complete all trial requirements with no significant toxicity. This phase 0 study has ethics approval (HREC/65450/PMCC 20/100) and is registered on the Australian Clinical Trials Network (ACTRN12621000171819). The protocol, technical and clinical data will be disseminated by conference presentations and publications. Any modifications to the protocol will be formally documented by administrative letters and must be submitted to the approving HREC for review and approval. Australian Clinical Trials Network ACTRN12621000171819.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.RADONC.2015.03.014
Abstract: This document describes best practice and evidence based recommendations for the use of FDG-PET/CT for the purposes of radiotherapy target volume delineation (TVD) for curative intent treatment of non-small cell lung cancer (NSCLC). These recommendations have been written by an expert advisory group, convened by the International Atomic Energy Agency (IAEA) to facilitate a Coordinated Research Project (CRP) aiming to improve the applications of PET based radiation treatment planning (RTP) in low and middle income countries. These guidelines can be applied in routine clinical practice of radiotherapy TVD, for NSCLC patients treated with concurrent chemoradiation or radiotherapy alone, where FDG is used, and where a calibrated PET camera system equipped for RTP patient positioning is available. Recommendations are provided for PET and CT image visualization and interpretation, and for tumor delineation using planning CT with and without breathing motion compensation.
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.SEMRADONC.2014.12.001
Abstract: Molecular imaging with positron emission tomography (PET) has dramatically changed the management of patients with lung cancer who are treated with radiotherapy. Uptake of the most widely used PET radiopharmaceutical (18)F-fluorodeoxyglucose identifies lung nodules or intrathoracic lymph nodes as likely to be malignant and frequently identifies previously unsuspected sites of malignant disease outside the thorax. Patients with non-small cell lung cancer, especially those with apparently more advanced locoregional disease to start with, are often upstaged, and this has a profound effect on their subsequent management. Better patient selection, primarily by excluding patients with PET-detected advanced disease, and better targeting of radiotherapy to avoid geographic miss have contributed significantly to improvements in outcome in recent series of patients treated with definitive chemoradiation. Advances in motion management with 4-dimensional PET/computed tomography and research into sequential imaging during treatment to permit response-adapted therapy hold promise for further improvements in treatment outcomes. Research involving novel PET tracers that can characterize biological properties of tumors, such as proliferation or hypoxia, may help develop more personalized approaches to patient management in the future.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.JTHO.2016.01.016
Abstract: We addressed the uncertainty of comorbidity as a prognosticator by evaluating comorbidity and the Simplified Comorbidity Score (SCS) as predictors of overall survival in non-small cell lung cancer (NSCLC). A prospective study included patients in whom NSCLC was diagnosed at an Australian cancer hospital between 2012 and 2014. Patients were assessed for SCS at recruitment and followed up every 3 months until death. The cohort included 633 patients their median age was 67 years (range 28-93), 63% were male, and 86% were ever-smokers. The median SCS at enrolment was 8 (range 0-19) 20% had an SCS higher than 9, and 11% had an SCS of 0. An SCS higher than 9 was associated with male sex, age older than 75 years, an Eastern Cooperative Oncology Group performance status of 2 or higher, and fewer cancer treatments. The 1-year overall survival rate was 62% (95% confidence interval: 58-66). In multivariate analysis, the strongest associations with mortality were metastatic disease (hazard ratio [HR] = 2.8, p < 0.01), Eastern Cooperative Oncology Group performance status of 2 or higher (HR = 2.0, p < 0.01), male sex (HR = 1.6, p < 0.01), more than 10% weight loss at diagnosis (HR = 1.5, p < 0.01), and age older than 75 years (HR = 1.5, p = 0.01). An SCS higher than 9 was not associated with overall survival (HR = 1.0, p = 0.8), and the effect of continuous SCS (HR = 1.1, p < 0.01) was explained by smoking status. In this cohort of patients with NSCLC the SCS was not a clinically significant predictor of overall survival over and above basic patient and disease factors.
Publisher: Wiley
Date: 10-04-2012
DOI: 10.1111/J.1754-9485.2012.02367.X
Abstract: The Peter MacCallum Cancer Centre has established a stereotactic lung radiosurgery program for the treatment of isolated lung metastases. The aim of this study was to critically assess the technical feasibility of performing stereotactic lung radiosurgery in an Australian institution. A single 26-Gy fraction of radiotherapy was delivered to patients with positron emission tomography (PET) staged solitary lung metastases. Motion management was addressed using four-dimensional computed tomographic simulation, and cone beam CT (CBCT) online soft-tissue matching. Treatments were with multiple coplanar and non-coplanar asymmetric beams. Patients were immobilised in a dedicated stereotactic body cradle. Quality assurance (QA) of treatment plans with both ion chamber and film measurements was performed accounting for patient-specific respiratory motion. Between February 2010 and February 2011, nine patients received stereotactic lung radiosurgery. One grade 1 toxicity and one grade 2 toxicity were recorded after treatment. The mean planning target volume was 22.6 cc. A median of eight beams were delivered per treatment plan (range 7-10) with a median of two non-coplanar beams (range 0-6). At treatment plan QA, the difference between planned and delivered dose was ≤1.76% in all static and dynamic ion chamber recordings. A mid-treatment CBCT was performed at a median time of 21 min, with the mean displacement discrepancy from initial set-up being 0.4 mm (range 0-2 mm). Stereotactic radiosurgery to the lung was both feasible and tolerable at our institution. Intrafractional immobilisation within 2 mm was reproducible. Excellent concordance between planned and delivered treatments was achieved in the phantom QA.
Publisher: Springer Science and Business Media LLC
Date: 07-2020
Publisher: Elsevier BV
Date: 10-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-03-2021
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.CLON.2015.01.004
Abstract: To compare outcomes of single-fraction and multi-fraction stereotactic ablative body radiotherapy (SABR) for pulmonary metastases. A retrospective review from two academic institutions of patients with one to three pulmonary metastases staged with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans. For single-fraction SABR, 26 Gy was prescribed for peripheral targets and 18 Gy for central targets. In the multi-fraction cohort, 48 Gy/4 or 50 Gy/5 was prescribed for peripheral targets and 50 Gy/5 was prescribed for central targets. Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were delivered using heterogeneity corrections. Conformity indices at an intermediate dose (R50%) and at a high dose (R100%) were used to assess a relationship with the planning target volume (PTV). Overall survival, local and distant progression and toxicity rates were analysed from the date of treatment completion. Between February 2010 and June 2013, 65 patients with 85 pulmonary metastases were reviewed. The median follow-up was 2.1 years. Metastases most commonly originated from colorectal cancer (31%), followed by non-small cell lung cancer (25%). 3D-CRT was used in 52 targets, IMRT in 21 and VMAT in 12. 3D-CRT showed a lower median R50% (P=0.01), but a higher median R100% than IMRT/VMAT (P=0.04). The R50% index was inversely correlated to the PTV with all techniques (P=0.01). Overall survival at 1 and 2 years in all patients was 93% (95% confidence interval 87-100%) and 71% (95% confidence interval 58-86%), respectively. The 2 year freedom from local and distant progression was 93% (95% confidence interval 86-100%) and 38% (95% confidence interval 27-55%), respectively. There were no significant differences between overall survival (P=0 .14), time to distant progression (P=0.06) or toxicity rates (P=0.75) between single- and multi-fraction cohorts. We report comparable local control, overall survival and toxicity rates between single-fraction and multi-fraction SABR treatments in patients with FDG-PET-staged pulmonary oligometastases. We propose a guideline for R50% conformity incorporating 3D-CRT/IMRT/VMAT techniques with heterogeneity corrected planning algorithms.
Publisher: Wiley
Date: 12-07-2007
DOI: 10.1111/J.1440-1673.2007.01755.X
Abstract: Imaging with F-18 fluorodeoxyglucose positron emission tomography (PET) significantly improves lung cancer staging, especially when PET and CT information are combined. We describe a method for obtaining CT and PET images at separate acquisitions, which allows coregistration and incorporation of PET information into the radiotherapy (RT) planning process for non-small-cell lung cancer. The influence of PET information on RT planning was analysed for 10 consecutive patients. Computed tomography and PET images were acquired with the patient in an immobilization device, in the treatment position. Using specially written software, PET and CT data were coregistered using fiducial markers and imported into our RT planning system (Cadplan version 6). Treatment plans were prepared with and without access to PET/CT coregistered images and then compared. PET influenced the treatment plan in all cases. In three cases, geographic misses (gross tumour outside planning target volume) would have occurred had PET not been used. In a further three cases, better planning target volume marginal coverage was achieved with PET. In four patients, three with atelectasis, there were significant reductions in V20 (percentage of the total lung volume receiving 20 Gy or more). Use of coregistered PET/CT images significantly altered treatment plans in a majority of cases. This method could be used in routine practice at centres without access to a combined PET/CT scanner .
Publisher: Informa UK Limited
Date: 02-04-2015
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/10428190601099965
Abstract: Residual 2-fluoro-2-deoxyglucose (FDG) - positron emission tomography (PET) positivity during treatment of patients with diffuse large B-cell lymphoma (DLBLC) prospectively identifies a subgroup at high likelihood of subsequent treatment failure. A single institution clinical audit of FDG-PET performance for this indication was undertaken for patients with DLBCL treated with anthracycline-based chemotherapy +/- radiotherapy. Of 45 eligible patients, 14 (31%) were PET-positive after a median of three chemotherapy cycles (range 1 - 5), of which 10 (71%) progressed at a median of 6.5 months. An interim positive PET was a statistically significant adverse prognostic factor for treatment failure (P < 0.0001, log-rank analysis) with a hazard ratio for a positive interim-treatment PET of 9 (95% confidence interval = 4 - 55) and positive predictive value of 71% and negative predictive value of 90%. Notably, four patients with low-grade FDG-avidity limited to sites previously involved by biopsy-proven osseous lymphoma, remain progression-free (median follow-up 62 months). Low-grade FDG-avidity on interim restaging at sites of bone involvement by DLBCL at diagnosis, appears to be less predictive of disease progression than residual nodal or extra-nodal soft tissue abnormality by PET.
Publisher: American Society of Hematology
Date: 30-09-2019
DOI: 10.1182/BLOODADVANCES.2019000458
Abstract: Practices in early-stage FL are variable and include radiation alone, systemic therapy, CMT, or observation. Each practice resulted in similar excellent outcomes randomized trials are required to determine the optimal treatment.
Publisher: Springer Berlin Heidelberg
Date: 2015
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.RADONC.2006.02.014
Abstract: This prospective study sought to determine how the use of combined PET/CT for radiotherapy treatment planning of oesophageal cancer would alter the delineation of tumour volumes compared to CT alone if PET/CT is assumed to more accurately represent true disease extent. All patients underwent FDG-PET/CT scanning in the radiotherapy treatment position. For each patient, two separate gross tumour volumes (GTV) were defined, one based on CT images alone (GTV-CT) and another based on combined PET/CT data (GTV-PET). Corresponding planning target volumes (PTV) were generated, and separate treatment plans were then produced. For each patient, volumetric analysis of GTV-CT, PTV-CT and GTV-PET was performed to quantify the proportion of PET-avid disease that was not included in the GTV and PTV (geographic miss) if CT data alone were used for radiotherapy planning. Assessment of the cranial and caudal extent of the primary oesophageal tumour as defined by CT alone vs PET/CT was also compared. The addition of PET information altered the clinical stage in 8 of 21 eligible patients enrolled on the study (38%) 4 patients had distant metastatic disease and 4 had unsuspected regional nodal disease. Sixteen patients proceeded to the radiotherapy planning phase of the study and received definitive chemoradiation planned with the PET/CT data set. The GTV based on CT information alone excluded PET-avid disease in 11 patients (69%), and in five patients (31%) this would have resulted in a geographic miss of gross tumour. The discordance between CT and PET/CT was due mainly to differences in defining the longitudinal extent of disease in the oesophagus. The cranial extent of the primary tumour as defined by CT vs PET/CT differed in 75% of cases, while the caudal extent differed in 81%. This study demonstrates that if combined PET/CT is used for radiotherapy treatment planning, there may be alterations to the delineation of tumour volumes when compared to CT alone, with the potential to avoid a geographic miss of tumour.
Publisher: Wiley
Date: 22-05-2023
DOI: 10.1111/AJCO.13783
Abstract: To evaluate the patterns of use of different radiation therapy (RT) fractionation for multiple myeloma (MM) bone disease. This is a population‐based cohort of patients with MM who had RT between 2012 and 2017 as captured in the statewide Victorian Radiotherapy Minimum Data Set in Australia. Data linkage was performed to identify subsets of RT delivered within 3 months of death. RT fractionation was classified into four groups: single‐fraction (SFRT), 2–5, 6–10, and 10 fractions. Changes in RT fractionation use over time were evaluated with the Cochran–Armitage test for trend. Factors associated with RT fractionation were evaluated using multivariate logistic regressions. Nine hundred and sixty‐seven courses of RT were delivered in 623 patients. The proportion of SFRT, 2–5, 6–10 and 10 fractions RT was 18%, 47%, 28%, and 7%, respectively. There was an increase in the use of 2–5 fractions, from 48% in 2012 to 60% in 2017 ( p ‐trend .001), with corresponding decrease in the use of 6–10 fractions, from 26% in 2012 to 20% in 2017 ( p ‐trend = .003). Nine percent (40/430) of RT courses at private institutions were SFRT, compared to 25% (135/537) in public institutions ( p .001). In multivariate analyses, treatment in private institution was the strongest predictor of multifraction RT use. SFRT use was more common closer to the end of life–18%, 14%, and 33% of RT within 2–3, 1–2, 1 month of death, respectively. There is increasing use of shorter course RT (2–5 fractions) for MM over time. SFRT use remains low, with large variation in practice.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.IJROBP.2015.05.011
Abstract: Measuring changes in lung perfusion resulting from radiation therapy dose requires registration of the functional imaging to the radiation therapy treatment planning scan. This study investigates registration accuracy and utility for positron emission tomography (PET)/computed tomography (CT) perfusion imaging in radiation therapy for non-small cell lung cancer. (68)Ga 4-dimensional PET/CT ventilation-perfusion imaging was performed before, during, and after radiation therapy for 5 patients. Rigid registration and deformable image registration (DIR) using B-splines and Demons algorithms was performed with the CT data to obtain a deformation map between the functional images and planning CT. Contour propagation accuracy and correspondence of anatomic features were used to assess registration accuracy. Wilcoxon signed-rank test was used to determine statistical significance. Changes in lung perfusion resulting from radiation therapy dose were calculated for each registration method for each patient and averaged over all patients. With B-splines/Demons DIR, median distance to agreement between lung contours reduced modestly by 0.9/1.1 mm, 1.3/1.6 mm, and 1.3/1.6 mm for pretreatment, midtreatment, and posttreatment (P < .01 for all), and median Dice score between lung contours improved by 0.04/0.04, 0.05/0.05, and 0.05/0.05 for pretreatment, midtreatment, and posttreatment (P .2). Poorer posttreatment results were likely caused by posttreatment pneumonitis and tumor regression. Up to 80% standardized uptake value loss in perfusion scans was observed. There was limited change in the loss in lung perfusion between registration methods however, Demons resulted in larger interpatient variation compared with rigid and B-splines registration. DIR accuracy in the data sets studied was variable depending on anatomic changes resulting from radiation therapy caution must be exercised when using DIR in regions of low contrast or radiation pneumonitis. Lung perfusion reduces with increasing radiation therapy dose however, DIR did not translate into significant changes in dose-response assessment.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-02-2013
Publisher: Springer Science and Business Media LLC
Date: 06-2002
DOI: 10.1007/BF03178468
Publisher: Elsevier BV
Date: 07-2002
DOI: 10.1016/S0360-3016(02)02783-9
Abstract: To examine the interclinician variation in the definition of gross tumor volume (GTV) in patients undergoing radiotherapy for non-small-cell lung cancer (NSCLC), develop methods to minimize this variation, and test these methods. The radiotherapy planning computed tomography (CT) scans of 6 consecutive patients with NSCLC in which the radiologist was able to define and outline the GTV were used. Six oncologists independently contoured the tumors with the radiologist's markings as a guide using a three-dimensional treatment planning system. Separate contours were prepared using only mediastinal window settings and using both mediastinal and lung window settings. The volumes were calculated using the planning system software (series 1). Factors that resulted in interclinician variation were determined, and, after a 3-year interval, 5 of the 6 clinicians redefined the GTVs using a revised protocol aimed at minimizing variation (series 2). For series 1, the interclinician variation in the measurement of volumes ranged from 5%, in the most tightly measured tumor, to 42%, in the most variable, but was, on average, 20%. Statistically significant differences were noted among the clinicians (p = 0.002), that is, some clinicians tended to record relatively small and some relatively large volumes. The reasons for the variation among the oncologists included a tendency to include regions with a low probability of containing tumor, as if the oncologist were contouring a target volume inclusion of adjacent atelectasis (ignoring the radiologist's outline) and variable treatment of spicules. When the exercise was repeated using the revised protocol (series 2), the degree of interclinician variation was reduced, with a range of 7-22% (average 13%). In series 2, the differences among the clinicians were not statistically significant (p = 0.25). Despite major radiologic input, significant variation occurred in the delineation of the three-dimensional GTVs of NSCLC among oncologists. Standardization of the approach with guidelines resulted in a reduction in this variation.
Publisher: Wiley
Date: 22-02-2007
DOI: 10.1111/J.1445-5994.2006.01291.X
Abstract: We evaluated the efficacy and toxicity of radiotherapy (RT) in patients with low-grade gastric marginal zone lymphoma. A retrospective review of consecutive cases of gastric marginal zone lymphoma treated by radical RT at the Peter MacCallum Cancer Centre and Radiation Oncology Victoria between January 1980 and September 2003 was carried out. Eighteen patients (11 men and 7 women) were identified. The median age at commencement of RT was 65 years (range 42-84 years). Prior treatment included Helicobacter pylori eradication in 12 patients, chemotherapy in 7 and surgery in 2, whereas 2 patients had no prior therapy. The median time to progression after commencement of last treatment before RT was 4.8 months (range 0-129.4 months). The radiation fields included the stomach plus perigastric and coeliac nodes in 15 patients (83%), stomach plus spleen in 2 patients (11%) and stomach plus para-aortic nodes in 1 patient (6%). The median RT dose was 30 Gy (range 30-36 Gy) in a median 20 fractions (range 17-24 fractions). One patient required treatment interruption for acute toxicity. A complete response on post-RT biopsies was achieved in 17 of 18 patients (94%). With a median follow up of 4.5 years after RT, 3 of these 17 patients (18%) have had a recurrence. At the last follow up, 11 patients were alive in continuous complete histological remission. No late renal toxicity was identified. Radiotherapy is an effective, well-tolerated treatment for patients with low-grade gastric marginal zone lymphoma, including those who have had prior therapy.
Publisher: Elsevier BV
Date: 11-2004
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.IJROBP.2008.12.039
Abstract: To establish whether (18)F-3'-deoxy-3'-fluoro-L-thymidine ((18)F-FLT) can monitor changes in cellular proliferation of non-small-cell lung cancer (NSCLC) during radical chemo-radiotherapy (chemo-RT). As part of a prospective pilot study, 5 patients with locally advanced NSCLC underwent serial (18)F-FLT positron emission tomography (PET)/computed tomography (CT) scans during treatment. Baseline (18)F-FLT PET/CT scans were compared with routine staging (18)F-FDG PET/CT scans. Two on-treatment (18)F-FLT scans were performed for each patient on Days 2, 8, 15 or 29, providing a range of time points for response assessment. In all 5 patients, baseline lesional uptake of (18)F-FLT on PET/CT corresponded to staging (18)F-FDG PET/CT abnormalities. (18)F-FLT uptake in tumor was observed on five of nine (55%) on-treatment scans, on Days 2, 8 and 29, but not Day 15. A "flare" of (18)F-FLT uptake in the primary tumor of one case was observed after 2 Gy of radiation (1.22 x baseline). The remaining eight on-treatment scans demonstrated a mean reduction in (18)F-FLT tumor uptake of 0.58 x baseline. A marked reduction of (18)F-FLT uptake in irradiated bone marrow was observed for all cases. This reduction was observed even after only 2 Gy, and all patients demonstrated a complete absence of proliferating marrow after 10 Gy. This proof of concept study indicates that (18)F-FLT uptake can monitor the distinctive biologic responses of epithelial cancers and highly radiosensitive normal tissue changes during radical chemo-RT. Further studies of (18)F-FLT PET/CT imaging during therapy may suggest that this tracer is useful in developing response-adapted RT for NSCLC.
Publisher: Elsevier BV
Date: 03-2014
Publisher: Elsevier BV
Date: 05-2005
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.IJROBP.2008.08.037
Abstract: To evaluate the impact of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) on management of patients with apparently isolated plasmacytoma. Twenty-one patients with apparently solitary plasmacytoma who underwent FDG-PET for staging or restaging were identified from a central PET database. They were either candidates for or had received definitive radiation therapy (RT). Seventeen patients had initial staging scans for bone (n = 11) or soft tissue (n = 6) plasmacytomas, and 11 had PET scans after RT. Only 1 of 14 known untreated sites of plasmacytoma was not identified on staging PET (lesion sensitivity = 93%). Three plasmacytomas were excised before PET. Staging PET influenced management in 6 of 17 patients (35%) by showing multiple myeloma (n = 1), discouraging RT after complete resection (n = 1), excluding plasmacytoma at a second site (n = 1), by increasing RT fields (n = 2), or by suggesting sarcoidosis (n = 1). Fifteen of 17 patients with initial staging PET scans received definitive RT. Restaging PET scans after RT showed complete metabolic response in 8 of 11 cases and progressive disease in 2. Two patients with either no response or partial metabolic response had late responses. Staging sestamibi and PET scans were concordant in five of six occasions (one sestamibi scan was false negative). FDG-PET has value for staging and RT planning in plasmacytoma and potentially could have a role in response-assessment after RT. Slow resolution of FDG uptake posttreatment does not necessarily imply an adverse prognosis.
Publisher: Elsevier BV
Date: 1992
DOI: 10.1016/0360-3016(92)90010-F
Abstract: Hypobaric hypoxia has been used to induce tumor hypoxia for in vivo comparison of the anti-tumor effects of the bioreductive agents SR 4233 (3-amino-1,2,4-benzotriazine-1,4-dioxide), RSU 1069 (1(2-nitro-1-imidazolyl)-3-aziridino-2-propanol), and Nitromin (methylbis(2-chloroethyl)amine N-oxide). BDF mice bearing the T50/80 mammary carcinoma were treated with these agents over a range of doses under normobaric (oxic) and hypobaric (hypoxic) conditions. The time taken for the tumor to double treatment volume (volume doubling time) was used as a measure of anti-tumor effect. Volume doubling time was plotted against log dose and dose response curves were fitted. A dose enhancement ratio (the ratio of drug doses required to give an equivalent anti-tumor effect under oxic and hypoxic conditions) was determined. The dose enhancement ratios for SR 4233 and RSU 1069 were 8.8 and 8.5, respectively, showing that these agents had an equivalent and substantial enhancement of their cytotoxicity when combined with hypobaric hypoxia. For Nitromin, no significant dose response effect was obtained under oxic conditions precluding the calculation of the dose enhancement ratio. SR 4233 was found to have increased systemic toxicity when combined with hypobaric hypoxia, suggesting that it is more readily activated than the other drugs tested. This in vivo test system will allow determination of the dose enhancement ratio for novel bioreductive agents and facilitate their comparison.
Publisher: Springer Science and Business Media LLC
Date: 16-10-2014
Publisher: MDPI AG
Date: 31-08-2022
DOI: 10.3390/CURRONCOL29090495
Abstract: Background: The PREDICT-HN study aimed to systematically assess the kinetics of imaging MR biomarkers during head and neck radiotherapy. Methods: Patients with intact squamous cell carcinoma of the head and neck were enrolled. Pre-, during, and post-treatment MRI were obtained. Serial GTV and ADC measurements were recorded. The correlation between each feature and the GTV was calculated using Spearman’s correlation coefficient. The linear mixed model was used to evaluate the change in GTV over time. Results: A total of 41 patients completed the study. The majority (76%) had oropharyngeal cancer. A total of 36 patients had intact primary tumours that can be assessed on MRI, and 31 patients had nodal disease with 46 nodes assessed. Median primary GTV (GTVp) size was 14.1cc. The rate of GTVp shrinkage was highest between pre-treatment and week 4. Patients with T3-T4 tumours had a 3.8-fold decrease in GTVp compared to T1-T2 tumours. The ADC values correlated with residual GTVp. The median nodal volume (GTVn) was 12.4cc. No clinical features were found to correlate with GTVn reduction. The overall change in ADC for GTVn from pre-treatment was significant for 35th–95th percentiles in weeks 1–4 (p 0.001). Conclusion: A discrepancy in the trajectory of ADC between primary and nodal sites suggested that they exhibit different treatment responses and should be analysed separately in future studies.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 2001
DOI: 10.1200/JCO.2001.19.1.111
Abstract: PURPOSE: To prospectively study the impact of 18 F fluorodeoxyglucose (FDG) positron emission tomography (PET) on clinical management of patients with non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred five consecutive patients with NSCLC undergoing 18 F FDG PET were analyzed. Before PET, referring physicians recorded scan indication, conventional clinical stage, and proposed treatment plan. PET scan results were reported in conjunction with available clinical and imaging data, including results of computed tomography (CT). Subsequent management and appropriateness of PET-induced changes were assessed by follow-up for at least 6 months or until the patient’s death. RESULTS: Indications for PET were primary staging (n = 59), restaging (n = 34), and suspected malignancy subsequently proven to be NSCLC (n = 12). In 27 (26%) of 105 of cases, PET results led to a change from curative to palliative therapy by upstaging disease extent. Validity of the PET result was established in all but one case. PET appropriately downstaged 10 of 16 patients initially planned for palliative therapy, allowing either potentially curative treatment (four patients) or no treatment (six patients). PET influenced the radiation delivery in 22 (65%) of 34 patients who subsequently received radical radiotherapy. Twelve patients considered probably inoperable on conventional imaging studies were downstaged by PET and underwent potentially curative surgery. PET missed only one primary tumor (5-mm scar carcinoma). CT and PET understaged three of 20 surgical patients (two with N1 lesions 5 mm and one with unrecognized atrial involvement), and PET missed one small intrapulmonary metastasis apparent on CT. No pathological N2 disease was missed on PET. CONCLUSION: FDG PET scanning changed or influenced management decisions in 70 patients (67%) with NSCLC. Patients were frequently spared unnecessary treatment, and management was more appropriately targeted.
Publisher: Cold Spring Harbor Laboratory
Date: 14-10-2020
DOI: 10.1101/2020.10.13.20211516
Abstract: Head and neck squamous cell carcinoma (HNSCC) treatment response relies heavily on macroscopic clinical findings. Blood monitoring of circulating markers during treatment may improve earlier detection of responders versus non-responders during radiotherapy. In this study, patients with intact tumour of HNSCC were enrolled in the prospective PREDICT-HN study. Pre-, after first treatment, weekly, and post-treatment blood s les were collected. CTC was enumerated using the CellSearch system. cfDNA was quantified from cfNA isolated at pre-, mid- and post-treatment timepoints. Blood s les were collected from 45 patients. Of the 339 s les analysed for CTC, 31% had detectable CTCs. Nine patients had detectable CTCs (1-3/7.5ml blood) in pre-treatment s les. After 1 fraction, 16 patients had CTCs detected, with 12 who had no pre-treatment CTC. Sixteen (36%) patients had detectable CTC in final week of treatment. There was no correlation between cancer stage, nodal status and tumour burden with CTC. cfDNA levels increased during treatment, with its highest level in the final week and lowest at post-treatment. Our results showed in HNSCC that CTCs can be detected during radiotherapy, suggesting mobilization into circulation during treatment, with as-yet-unknown viability. cfDNA kinetics during treatment correlated with CTC release, and may indicate apoptotic change. Head and neck squamous cell carcinoma (HNSCC) treatment response relies heavily on macroscopic clinical findings. Blood monitoring of circulating markers such as circulating tumour cell (CTC) and cell-free DNA (cfDNA) during treatment may improve earlier detection of responders versus non-responders during definitive radiotherapy. Although the detection of CTCs and cfDNA in patients with HNSCC has been described, there is minimal data on the kinetics of CTC counts and cfDNA levels during radiotherapy in patients with HNSCC. Here, our study prospectively describes the changes in CTC and cfDNA enumeration during radiotherapy in patients with HNSCC. Our results showed, for the first time to our knowledge, in HNSCC, that CTCs can be detected during radiotherapy, suggesting mobilization into peripheral circulation during treatment, with as-yet-unknown viability. cfDNA kinetics during treatment correlated with CTC release, may indicate apoptotic change during radiotherapy. Combined cfDNA-CTC as an early marker of treatment response should be investigated further.
Publisher: Elsevier BV
Date: 1983
DOI: 10.1016/S0009-9260(83)80153-6
Abstract: Forty-five cases of neuroblastoma were reviewed to assess the value of current diagnostic methods. Urinary catecholamine and 3-methoxy-4-hydroxymandelic acid levels were elevated in only 48% and 60% of cases, respectively. All abdominal or pelvic tumour masses were detected by intravenous urography, ultrasound or computed tomography (CT): CT was the best single investigation but the two less expensive techniques detected most of the tumours. Trephine biopsy was more successful than aspiration in detecting bone marrow metastases. Liver scintigraphy was positive in six of seven cases with hepatic secondaries.
Publisher: Springer Science and Business Media LLC
Date: 22-04-2014
Publisher: Elsevier BV
Date: 10-2004
Publisher: Elsevier BV
Date: 09-2008
Publisher: Elsevier BV
Date: 06-2001
DOI: 10.1016/S0360-3016(01)01477-8
Abstract: Most radical radiotherapy (RT) candidates with non-small-cell lung cancer (NSCLC) have Stage III disease and ultimately die with distant metastases. We tested the hypothesis that positron emission tomography (PET) using 18-F fluorodeoxyglucose (FDG) would detect more unsuspected metastases in apparent Stage III disease than in Stages I-II. Staging FDG-PET was performed for 167 NSCLC patients, with Stage I-III by conventional workup, who were candidates for curative therapy with surgery (n = 8), radical chemo/RT or RT (n = 156), or preoperative chemo/RT (n = 3). Each patient was allocated a conventional "pre-PET stage" and a "post-PET stage" that relied on PET when discordance with conventional staging occurred. Stage distribution pre-PET was n = 39 (Stage I), n = 28 (Stage II), and n = 100 (Stage III). In 32 patients (19%), PET detected distant metastasis, most commonly abdominal with 17 cases (adrenal, n = 7 liver, n = 4 other, n = 6). Other sites included lung (n = 10) and bone (n = 6). PET-detected metastasis increased with increasing pre-PET stage from I (7.5%) through II (18%) to III (24%, p = 0.016), and, in particular, was significantly higher in Stage III (p = 0.039). Biopsy confirmation was not routine, but progression occurred at PET-detected metastatic sites or other metastatic sites in all but 3 of the 32 patients by last review. PET staging is recommended for radical RT candidates with NSCLC. The highest yield of unexpected distant metastases is observed in Stage III.
Publisher: E-MED LTD
Date: 2007
Publisher: Wiley
Date: 18-05-2017
DOI: 10.1002/MP.12124
Publisher: Department of Biomedical Imaging, University of Malaya, Malaysia
Date: 2006
DOI: 10.2349/BIIJ.2.1.E2
Publisher: Informa UK Limited
Date: 28-09-2012
DOI: 10.3109/10428194.2012.717279
Abstract: Marginal zone lymphoma (MZL) is a radiosensitive tumor, with high local control (LC) rates with moderate dose radiotherapy (RT). This retrospective study, performed at the Peter MacCallum Cancer Centre, evaluated the efficacy and toxicity of patients with orbital MZL treated to 24-25 Gy. Twenty-four patients (27 orbits) were identified, with median follow-up of 41 months. Disease was conjunctival in 16 orbits (59%), lacrimal in seven (26%), in the eyelid in one (4%) and elsewhere in three (11%). All patients attained a complete response. Three patients had treatment failures: one local relapse, one contralateral and one distant relapse. Freedom from local failure, freedom from progression, progression-free survival and overall survival were 100%, 90%, 90% and 100% at 2 years and 92%, 81%, 81% and 100% at 5 years, respectively. Aside from cataractogenesis, there was no significant late toxicity. Our study shows that RT doses of 24-25 Gy provide high rates of LC for orbital MZL with acceptable morbidity.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-10-2018
Abstract: Follicular lymphoma (FL) is curable by involved-field radiotherapy (IFRT) in 50% of patients with stage I to II disease. We hypothesized that adding systemic therapy to IFRT would improve long-term progression-free survival (PFS). A multicenter randomized controlled trial enrolled patients with stage I to II low-grade FL after staging computed tomography scans and bone marrow biopsies. 18 F-labeled fluorodeoxyglucose–positron emission tomography (PET) was not mandatory. Patients were randomly assigned to either arm A (30 Gy IFRT alone) or arm B (IFRT plus six cycles of cyclophosphamide, vincristine, and prednisolone [CVP]). From 2006, rituximab was added to arm B (R-CVP). Between 2000 and 2012, 150 patients were enrolled, 75 per arm. In arm B, 44 patients were allocated to receive CVP and 31 were allocated to receive R-CVP. At randomization, 75% had stage I, the median age was 57 years, 52% were male, and 48% were PET staged. With a median follow-up of 9.6 years (range, 3.1 to 15.8 years), PFS was superior in arm B (hazard ratio, 0.57 95% CI, 0.34 to 0.95 P = .033). Ten-year PFS rates were 59% (95% CI, 46% to 74%) and 41% (95% CI, 30% to 57%) for arms B and A, respectively. Patients in arm B who received R-CVP had markedly superior PFS compared with contemporaneous patients in arm A (hazard ratio, 0.26 95% CI, 0.07 to 0.97 P = .045). Fewer involved regions ( P = .047) and PET staging ( P = .056) were associated with better PFS. Histologic transformation occurred in four and 10 patients in arms B and A, respectively ( P = .1). Ten deaths occurred in arm A versus five in arm B, but overall survival was not significantly different ( P = .40 87% and 95% at 10 years, respectively). Systemic therapy with R-CVP after IFRT reduced relapse outside radiation fields and significantly improved PFS. IFRT followed by immunochemotherapy is more effective than IFRT in early-stage FL.
Publisher: Wiley
Date: 15-02-2010
DOI: 10.1002/CNCR.24858
Abstract: The aim of this study was to determine if extrapulmonary small cell carcinomas (EPSCC) should be managed using protocols similar to those for small cell lung cancer (SCLC). Treatment strategies, survival, patterns of failure, and prognostic factors for patients with EPSCC were analyzed retrospectively at a large cancer center. SCLC was excluded by thoracic computed tomography (75%) or chest radiography (25%). Of 120 eligible patients, 70% had limited disease (LD). Treatment modalities included chemotherapy (n = 82 68%), radiotherapy (RT) (n = 80 67%), and surgery (n = 41, 34%). The median survival for patients with LD and extensive disease was 1.4 years and 0.7 years, respectively. Gynecologic (n = 31) and gastrointestinal (n = 28) were the most common primary tumor sites. Gynecologic and head and neck primary tumor sites had better 1-year survival than other sites (P = .019 and 0.005, respectively). Brain metastasis was the site of first distant failure in 4.1% of patients versus 35% for soft tissue metastases. The lifetime risk of brain metastasis was 13%. Definitive RT (P = .004), LD (P = .028), and prophylactic cranial irradiation (PCI) (P = .022) were found to be positive prognostic factors and weight loss (P < .001) was a negative prognostic factor on multivariate analysis. Patients with EPSCC usually experienced short survival, often with early distant metastasis. Although PCI was associated with improved overall survival, brain metastasis was less frequent than in patients with SCLC, and therefore the potential benefit of PCI was less than in patients with SCLC. Definitive chemoradiotherapy was associated with better outcomes and should be delivered whenever feasible.
Publisher: Springer Science and Business Media LLC
Date: 03-1989
DOI: 10.1038/BJC.1989.69
Abstract: The effect of hypobaric hypoxia on the in vivo binding of misonidazole was investigated in normal mice and mice bearing T50/80 or CA NT mammary carcinomas. After the intraperitoneal injection of radiolabelled misonidazole, mice were randomised to breathe either room air or air at 0.5 atmospheres. The distribution of misonidazole in liver, kidney, heart, spleen and tumour tissue, 24 h later, was studied by scintillation counting and by autoradiography. Significantly higher misonidazole binding occurred in the livers (x2.5), kidneys (x2.4), spleens (x2.9) and hearts (x1.8) of hypoxic mice compared to controls. Hypobaric hypoxia was associated with a greater than four-fold increase in misonidazole binding within T50/80 tumours. However, significantly higher binding was not demonstrated within CA NT tumours after exposure of tumour-bearing animals to hypoxic conditions. In autoradiographs of hypoxic liver, labelling was intense in regions near to hepatic veins but sparse in areas surrounding portal tracts. This pattern was striking and consistent. In hypoxic kidney, labelling was most intense over tubular cells, less intense over glomeruli and sparse in the renal medulla. It is likely that the hepatic and renal cortical distributions of misonidazole binding reflect local oxygen gradients.
Publisher: Elsevier BV
Date: 1995
DOI: 10.1016/0959-8049(94)00488-Q
Abstract: We report the effect of granulocyte colony stimulating factor (G-CSF) on neutropenia occurring during extended field radiotherapy in two groups of patients. The first group comprised 8 patients receiving craniospinal irradiation for a variety of central nervous system (CNS) neoplasms. None of these patients received cytotoxic chemotherapy. G-CSF was administered when the absolute neutrophil count (ANC) approached 1.5 x 10(9)/l. Neutropenia was promptly corrected in all cases, thereby avoiding unscheduled interruptions in radiotherapy. Following each G-CSF administration, ANC reached a peak on the following day and then declined steadily. Mean ANC rose from 1.33 x 10(9)/l on the day of G-CSF treatment to 7.07 x 10(9)/l the next day. Patients received 2-6 G-CSF injections during radiotherapy. Experiments were carried out in vitro to assess the risk of G-CSF causing increased CNS tumour cell proliferation. 11 human CNS tumour cultures (2 medulloblastomas, 2 primitive neuroectodermal tumours and 7 astrocytic tumours) were cultured in the presence of G-CSF at a range of concentrations up to 100 ng/ml. Their proliferation was compared with that of a G-CSF dependent murine leukemia cell line (NFS-60). None of the human tumour cultures demonstrated a significant increase in proliferation in response to G-CSF. 4 patients undergoing "mantle" type radiotherapy for Hodgkin's Disease or Non-Hodgkin's Lymphoma also received G-CSF treatment for neutropenia. All 4 had previously received cytotoxic chemotherapy. The number of G-CSF injections given per patient during radiotherapy ranged from 3-6. Mean ANC rose from 1.76 x 10(9)/l to 10.8 x 10(9)/l the next day. These results suggest that G-CSF is a reliable treatment for radiotherapy induced neutropenia and that an intermittent dosage schedule is effective.
Publisher: Elsevier BV
Date: 06-2007
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.RCL.2007.05.002
Abstract: The superiority of PET imaging to structural imaging in many cancers is rapidly transforming the practice of radiotherapy planning, especially in lung cancer. Although most lung cancers are potentially treatable with radiation therapy, only patients who have truly locoregionally confined disease can be cured by this modality. PET improves selection for high-dose radiation therapy by excluding many patients who have incurable distant metastasis or extensive locoregional spread. In those patients suitable for definitive treatment, PET can help shape the treatment fields to avoid geographic miss and minimize unnecessary irradiation of normal tissues. PET will allow for more accurately targeted dose escalation studies in the future and could potentially lead to better long-term survival.
Publisher: Society of Nuclear Medicine
Date: 20-07-2018
DOI: 10.2967/JNUMED.118.214148
Abstract: The optimal methodology for defining response with
Publisher: SAGE Publications
Date: 09-01-2016
Abstract: Ga-68-macroaggregated albumin ( 68 Ga-perfusion) positron emission tomography/computed tomography (PET/CT) is a novel imaging technique for the assessment of functional lung volumes. The purpose of this study was to use this imaging technique for functional adaptation of definitive radiotherapy plans in patients with non-small cell lung cancer (NSCLC). This was a prospective clinical trial of patients with NSCLC who received definitive 3-dimensional (3D) conformal radiotherapy to 60 Gy in 30 fx and underwent pretreatment respiratory-gated (4-dimensional [4D]) perfusion PET/CT. The “perfused” lung volume was defined as all lung parenchyma taking up radiotracer, and the “well-perfused” lung volume was contoured using a visually adapted threshold of 30% maximum standardized uptake value (SUVmax). Alternate 3D conformal plans were subsequently created and optimized to avoid perfused and well-perfused lung volumes. Functional dose volumetrics were compared using mean lung dose (MLD), V5 (volume receiving 5 Gy or more), V10, V20, V30, V40, V50, and V60 parameters. Fourteen consecutive patients had alternate radiotherapy plans created based on functional lung volumes. When considering the original treatment plan, the dose to perfused and well-perfused functional lung volumes was similar to that of the conventional anatomical lung volumes with an average MLD of 12.15, 12.67, and 12.11 Gy, respectively. Plans optimized for well-perfused lung improved functional V30, V40, V50, and V60 metrics (all P values .05). The functional MLD of well-perfused lung was improved by a median of 0.86 Gy, P .01. However, plans optimized for perfused lung only showed significant improvement in the functional V60 dose parameter (median 1.00%, P = .04) but at a detriment of a worse functional V5 (median 3.33%, P = .05). This study demonstrates proof of principle that 4D-perfusion PET/CT may enable functional lung avoidance during treatment planning of patients with NSCLC. Radiotherapy plans adapted to well-perfused but not perfused functional lung volumes allow for reduction in dose to functional lung using 3D conformal radiotherapy.
Publisher: Elsevier BV
Date: 08-1993
Publisher: Elsevier BV
Date: 10-2023
Publisher: Elsevier BV
Date: 10-1997
DOI: 10.1016/S0889-8588(05)70469-X
Abstract: The results of treatment of localized low-grade lymphoma have been reviewed with particular emphasis on the results of long-term follow-up of patients treated with radiation therapy at Stanford University. These data and results from numerous other centers suggest that 40% to 50% of patients with stage I and II follicular low-grade lymphomas can expect to achieve clinical cure of their disease with radiation therapy. Randomized trials published to date do not support the use of adjuvant chemotherapy. Although a policy of initial observation with deferral of treatment until the occurrence of disease progression is a well established approach to patients with advanced disease, no randomized studies exist that support this as a safe alternative to radiation therapy for early stage disease. New systemic therapies are required for the treatment of occult disease to prevent the occurrence of relapse outside of irradiated volumes.
Publisher: Department of Biomedical Imaging, University of Malaya, Malaysia
Date: 07-2008
DOI: 10.2349/BIIJ.4.3.E25
Publisher: Wiley
Date: 09-07-2010
DOI: 10.1002/CNCR.25392
Abstract: The authors studied growth and progression of untreated nonsmall cell lung cancer (NSCLC) by comparing diagnostic and radiotherapy (RT) planning fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scans before proposed radical chemo-RT. Patients enrolled on a prospective clinical trial were eligible for this analysis if they underwent 2 pretreatment whole body FDG-PET/CT scans, >7 days apart. Scan 1 was performed for diagnosis/disease staging and scan 2 for RT planning. Interscan comparisons included disease stage, metabolic characteristics, tumor doubling times, and change in treatment intent. Eighty-two patients underwent planning PET/CT scans between October 2004 and February 2007. Of these, 28 patients (61% stage III, 18% stage II) had undergone prior staging PET/CT scans. The median interscan period was 24 days (range, 8-176 days). Interscan disease progression (TNM stage) was detected in 11 (39%) patients. The probability of upstaging within 24 days was calculated to be 32% (95% confidence interval [CI], 18%-49%). Treatment intent changed from curative to palliative in 8 (29%) cases, in 7 because of PET. For 17 patients who underwent serial PET/CT scans under standardized conditions, there was a mean relative interscan increase of 19% in tumor maximum standardized uptake value (SUV) (P=.022), 16% in average SUV (P=.004), and 116% in percentage injected dose (P=.002). Estimated doubling time of FDG avid tumor was 66 days (95% CI, 51-95 days). Rapid tumor progression was detected in patients with untreated, predominantly stage III, NSCLC on serial FDG-PET/CT imaging, highlighting the need for prompt diagnosis, staging, and initiation of therapy in patients who are candidates for potentially curative therapy.
Publisher: AME Publishing Company
Date: 12-2017
Publisher: Royal College of Psychiatrists
Date: 04-1988
Abstract: Patients with multiple myeloma are often treated surgically as though they have bone metastases. Due to major differences in oncological therapy and comparatively long survival times these patients should be considered separately. Seventy-five multiple myeloma patients were treated surgically (83 interventions) for skeletal complications of the disease. Location and dissemination, symptoms, method of surgery, complications, recurrence and survival time were evaluated retrospectively. Most of the lesions were in the axial skeleton or the proximal extremities apart from one distal lesion of the fibula, and most surgery was performed in the spine (35 patients). The mean follow-up of patients was 5.4 years (range 1-25 years). Survival proved to be very favourable (37% at five years). Patients with a single bone lesion, a negative bone marrow biopsy, no paraproteinaemia in serum or a Salmon-Durie-stage I had a better survival probability. Surgical treatment in patients with multiple myeloma was mostly limited to a palliative approach but survival time was better (37% at five years) than in patients with metastatic bone disease which has to be considered in their surgical treatment.
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.LUNGCAN.2011.07.018
Abstract: Accurate delineation of the primary tumor and of involved lymph nodes is a key requisite for successful curative radiotherapy in non-small cell lung cancer (NSCLC). In recent years, it has become clear that the incorporation of FDG PET-CT scan information into the related processes of patient selection and radiotherapy planning has lead to significant improvements for patients with NSCLC. The use of FDG PET-CT information in radiotherapy planning allows better target volume definition, reduces inter-observer variability and encourages selective irradiation of involved mediastinal lymph nodes. PET-CT also opens the door for innovative radiotherapy delivery and the development of new concepts. However, care must be taken to avoid a variety of technical pitfalls and specific education is necessary, for clinicians and physicists alike.
Publisher: American Society of Hematology
Date: 06-12-2021
Publisher: Elsevier BV
Date: 06-2003
Abstract: [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is useful in staging aggressive non-Hodgkin's lymphoma (NHL). However, its role in indolent NHL has not been established. This retrospective study assessed the sensitivity and clinical impact of PET findings in patients with indolent NHL. Patients with indolent NHL who underwent FDG-PET scanning between May 1997 and August 2001 were identified. Case records were reviewed for FDG-PET and conventional staging/restaging results and compared for concordance. Forty-seven patients were identified. Twelve staging FDG-PET scans and 37 restaging FDG-PET scans were obtained. The FDG-PET case sensitivity rate was 98%. Forty-two percent of staging FDG-PET scans were concordant with conventional staging, with the remaining patients exhibiting more extensive disease on PET. At progression, FDG-PET and conventional assessments were discordant in 46% of cases. Positron emission tomography findings downstaged disease in 30% of these patients and upstaged disease in 16%. Computed tomography (CT) and FDG-PET identified 150 and 146 in idual sites of disease, respectively. Among "definite" sites on structural imaging, 74% were also seen on PET. For equivocal lesions, only 19% were seen on both modalities. Clinical management was changed in 34% of patients as a result of FDG-PET findings. Of 22 discordant lesions in which true disease status could be evaluated, the PET findings were confirmed to be correct in 21 (95% P < 0.0001). These findings demonstrate that FDG-PET has a high sensitivity for indolent NHL and often leads to alteration of disease staging and management. This high accuracy of FDG-PET in assessing discordant lesions suggests a greater diagnostic utility compared with CT.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.CPET.2017.08.005
Abstract: PET scanning plays key roles in planning the management of patients with lung cancer who are candidates for curative-intent treatment with radiotherapy and has contributed to improvements in survival.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Elsevier BV
Date: 11-2021
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.IJROBP.2008.10.067
Abstract: Concomitant chemoradiotherapy (CRT) increases survival rates compared with radical radiotherapy alone (RT) in Stage III non-small-cell lung cancer (NSCLC), as a result of improved local control. The effect of CRT on local control in Stage I NSCLC is less well documented. We retrospectively reviewed local control and survival following CRT or RT for inoperable Stage I NSCLC patients. Eligible patients had histologically/cytologically proved inoperable Stage I NSCLC and had undergone complete staging investigations including an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Radiotherapy was planned as (1) 60 Gy in 30 fractions over 6 weeks with or without concomitant chemotherapy or (2) 50-55 Gy in 20 fractions without chemotherapy. Between 2000 and 2005, 73 patients met the eligibility criteria and were treated as follows: CRT (60 Gy)-39 RT (60 Gy)-23 RT (50-55 Gy)-11. The median follow-up time for all patients was 18 months (range, 1-81 months). Survival analysis was based on intent to treat. Local progression-free survival (PFS) at 2 years was 66% with CRT and 55% with RT. The 2-year distant PFS was 60% following CRT and 63% after RT. The 2-year PFS rates were 57% and 50%, respectively. The 2-year survival rate for patients treated with CRT was 57% and 33% in patients receiving RT. Despite the use of CRT and routine staging with FDG-PET, both local and distant recurrences remain important causes of treatment failure in patients with inoperable stage I NSCLC.
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.IJROBP.2022.05.034
Abstract: Medical operability is prognostic for survival after SABR in primary malignancies. This study investigated the prognostic significance of medical operability and total versus subtotal ablation of all oligometastatic disease sites. Consecutive patients with 1 to 5 sites of active extracranial oligometastases had medical operability status and presence of subtotal versus total metastatic ablation recorded prospectively in an institutional database. We retrospectively compared overall survival (OS) and progression-free survival (PFS) for medically operable or inoperable patients and patients undergoing total or subtotal metastatic ablation. Secondary endpoints were patterns of failure, high-grade treatment toxic effects (Common Terminology Criteria for Adverse Events version 4.0), and freedom from systemic therapy. The threshold dose per fraction considered ablative was 8 Gy. A total of 401 patients with 530 treated oligometastases were included, with a median follow-up of 3 years. Three hundred and two and 99 patients had metachronous and synchronous presentations of oligometastatic disease, respectively. Common histologies included prostate (24%), lung (18%), gastrointestinal (19%), and breast (11%). More than 90% of doses delivered were Biologically Effective Dose [BED Medical operability was not prognostic in patients with oligometastatic disease treated with SABR. Total metastatic ablation was associated with superior OS and PFS compared with subtotal metastatic ablation. Our data support ablation of all sites of oligometastases wherever feasible.
Publisher: Society of Nuclear Medicine
Date: 09-07-2015
DOI: 10.2967/JNUMED.115.158261
Abstract: The objective of this study was to evaluate the utility of (18)F-FDG PET in restaging and response assessment of patients who underwent definitive treatment for Merkel cell carcinoma (MCC). A retrospective review of patients undergoing (18)F-FDG PET imaging for MCC between January 1997 and October 2010 at the Peter MacCallum Cancer Centre with follow-up until February 2015 was performed. Data analysis was performed on patients who were treated definitively and underwent post-treatment PET imaging performed either as a restaging scan for ongoing monitoring, suspicion of recurrence, or assessment for suitability of salvage treatment or as response assessment within 1-6 mo of treatment. Management plans were recorded prospectively before (18)F-FDG PET imaging and compared with post-imaging management to assess the impact of the study as per our previously defined categories: high if the primary treatment modality or intent was changed and medium if the radiotherapy technique or dose was altered. In total, 62 patients were included in the analysis. Thirty-six patients underwent 53 restaging scans, and 37 patients underwent a response-assessment scan. The median follow-up of patients in the restaging group was 5.3 y (95% confidence interval [CI], 4.6-9.4), and it was 5.7 y (95% CI, 4.3-10.8) in the response-assessment group. Restaging (18)F-FDG PET scans had a high impact in 24 of 53 cases (45%) and a medium impact in 6 of 53 cases (11%). In the response-assessment group, 24 of 37 patients had a complete metabolic response (CMR). Patients without a CMR had a 15% 1-y overall survival (95% CI, 0.04-0.55). Those with a CMR had an 88% 2-y overall survival (95% CI, 0.75-1.00) and a 68% 5-y overall survival (95% CI, 0.49-0.95). The presence of a CMR (P < 0.001) and nodal involvement (P = 0.016) were statistically significant prognostic factors for overall survival. (18)F-FDG PET imaging had a high impact on restaging after definitive treatment in patients with MCC. Metabolic response was significantly associated with overall survival. (18)F-FDG PET may play an important role in ongoing post-treatment management of MCC.
Publisher: American Society of Hematology
Date: 04-1997
Abstract: Risk factors for unscheduled interruptions in radiotherapy courses completed between June 1989 and August 1995, lasting ≥2 days, and associated with World Health Organization grade III-IV neutropenia or thrombocytopenia were studied retrospectively. A group of controls was randomly selected. Potential risk factors for myelosuppression were analyzed using univariate and multivariate analyses. The most important risk factors for treatment interruption with thrombocytopenia were concurrent chemotherapy (odds ratio [OR], 45.5 P & .001), increasing percentage of marrow irradiated (OR, 4.1 for each 20% P & .001), and brain metastases (OR, 7.3 P = .01). Other significant (P & .05) factors were leukemia/lymphoma, bone or bone marrow metastases, and prior chemotherapy. The most important risk factors for treatment interruptions with neutropenia were concurrent chemotherapy (OR, 42.1 P & .001) and increasing percentage of marrow irradiated (OR, 3.3 for each 20% P & .001). Similarly, the most important risk factors for treatment interruptions with both thrombocytopenia and neutropenia were concurrent chemotherapy (OR, 48.6 P & .001) and increasing percentage of marrow irradiated (OR, 3.9 for each 20% P & .001). Other significant (P & .05) factors in these groups were bone marrow or brain metastases and previous chemotherapy. These data were used to create a model, assigning patients to groups at high, intermediate, or low risk for treatment interruption with thrombocytopenia. High-risk patients may be candidates for clinical trials of a platelet growth factor.
Publisher: Elsevier BV
Date: 03-2002
DOI: 10.1016/S0002-9343(01)01117-2
Abstract: To compare fluorine-18 fluorodeoxyglucose positron emission tomography (PET) and gallium scanning with each other and with conventional staging, for patients with Hodgkin's disease or non-Hodgkin's lymphoma. Fifty patients had PET, gallium scanning, and conventional staging of newly diagnosed or progressive Hodgkin's disease or non-Hodgkin's lymphoma. Disease sites, stage, and treatment plans were assessed retrospectively. Positron emission tomography and gallium scanning each upstaged 14% of patients (n = 7). Management was altered by PET in 9 cases (18%) and by gallium scanning in 7 (14%, P = 0.6). Disease was evident in 117 sites in 42 patients. The case positivity rate for conventional assessment was 90% for PET, 95% for gallium scanning, 88% for conventional assessment plus PET, 100% and for conventional assessment plus gallium scanning, 98%. Site positivity rates for conventional assessment were 68% for PET, 82% for gallium scanning, 69% (conventional vs. PET, P = 0.01 conventional vs. gallium scanning, P = 0.9 PET vs. gallium scanning, P = 0.01) for conventional assessment plus PET, 96% and for conventional assessment plus gallium scanning, 94%. Positron emission tomography and gallium scanning were entirely concordant in 31 patients in the other 19 patients, PET identified 25 sites missed by gallium scanning, whereas gallium scanning identified 10 sites missed by PET. In this retrospective study, PET demonstrated a higher site positivity rate than did gallium scanning, with similar case positivity rates. These data support the use of PET in place of gallium scanning for the staging of patients with Hodgkin's disease or non-Hodgkin's lymphoma.
Publisher: Elsevier BV
Date: 11-2004
Publisher: Elsevier BV
Date: 08-2007
Publisher: Informa UK Limited
Date: 2003
Abstract: The prognostic significance of extracranial distant metastasis detected by positron emission tomography (PET) was investigated in patients with non-small cell lung cancer (NSCLC). Forty-two patients staged with 18F-fluorodeoxyglucose-PET-detected distant metastasis before planned surgery (n = 7) or radical radiotherapy (RT)/chemoradiotherapy (n = 35) for NSCLC were identified from a prospective database. The influence of metastasis number and other prognostic factors was investigated using Cox's regression analysis. Treatment after PET included surgery (n = 2), radical RT (n = 5), palliative RT (n = 25), chemotherapy (n = 8) or supportive care (n = 2). All but 4 patients had died by the last follow-up. Median survival was 9 months overall, 12 months for 27 patients with single PET-detected metastasis and 5 months for 15 patients with > 1 metastasis (p = 0.009). It was found that the Eastern Cooperative Oncology Group performance status (p = 0.027) but not pre-PET stage, weight loss or metastasis site correlated with survival. PET-detected metastatic tumor burden appeared to influence survival and should be evaluated as a prognostic factor in NSCLC.
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.LUNGCAN.2004.11.024
Abstract: We previously reported that F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) response correlated strongly with survival after radical radiotherapy (RT)/chemoradiotherapy for non-small cell lung cancer (NSCLC). PET-response, survival and patterns of failure data are presented with long-term follow-up. Pre- and post-treatment FDG-PET scans were performed for 88 patients after concurrent platinum-based radical chemo/RT (n = 73) or radical RT alone (n = 15). PET responses were prospectively assessed as either complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD). RT was 60 Gy in 30 fractions in 6 weeks. Follow-up PET was performed at a median of 70 days after treatment. PET responses were: CMR, n = 40 (45%) PMR, n = 32 (36%) SMD, n = 5 (6%) and PMD 11 (13%). Estimated median survival after follow-up PET was 23 months median follow-up duration 35 months. One and 2 year survival after follow-up PET was 68% and 45%, respectively. Median survival for CMR and non-CMR patients was 31 and 11 months, respectively (p = 0.0001). One-year survival for CMR and non-CMR patients was 93% and 47%, respectively and 2 years survival was 62% and 30%, respectively. Excluding PMD patients, non-CMR patients had higher rates of local failure (HR 2.15, p = 0.009) and distant metastasis (HR 2.05, p = 0.041) than CMR patients. By last follow-up, 20 of 40 CR patients (50%) had PMD, with local failure (n = 8), distant metastasis (n = 2) or both (n = 10). Attainment of CMR after radical RT/chemoRT for NSCLC bestows superior freedom from local and distant relapse late local relapse is common.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.IJROBP.2009.11.040
Abstract: Given that proliferating hematopoietic stem cells are especially radiosensitive, the bone marrow is a potential organ at risk, particularly with the use of concurrent chemotherapy and radiotherapy. Existing data on bone marrow distribution have been determined from the weight and visual appearance of the marrow in cadavers. 18F-fluoro-L-deoxythymidine concentrates in bone marrow, and we used its intensity on positron emission tomography imaging to quantify the location of the proliferating bone marrow. The 18F-fluoro-L-deoxythymidine positron emission/computed tomography scans performed at the Peter MacCallum Cancer Centre between 2006 and 2009 on adult cancer patients were analyzed. At a minimum, the scans included the mid-skull through the proximal femurs. A software program developed at our institution was used to calculate the percentage of administered activity in 11 separately defined bony regions. The study population consisted of 13 patients, 6 of whom were men. Their median age was 61 years. Of the 13 patients, 9 had lung cancer, 2 had colon cancer, and 1 each had melanoma and leiomyosarcoma 6 had received previous, but not recent, chemotherapy. The mean percentage of proliferating bone marrow by anatomic site was 2.9%±2.1% at the skull, 1.9%±1.2% at the proximal humeri, 2.9%±1.3% at the sternum, 8.8%±4.7% at the ribs and clavicles, 3.8%±0.9% at the scapulas, 4.3%±1.6% at the cervical spine, 19.9%±2.6% at the thoracic spine, 16.6%±2.2% at the lumbar spine, 9.2%±2.3% at the sacrum, 25.3%±4.9% at the pelvis, and 4.5%±2.5% at the proximal femurs. Our modern estimates of bone marrow distribution in actual cancer patients using molecular imaging of the proliferating marrow provide updated data for optimizing normal tissue sparing during external beam radiotherapy planning.
Publisher: Wiley
Date: 09-2003
DOI: 10.1002/SSU.10032
Abstract: Positron emission tomography (PET) represents a dramatic advance in the imaging of lung cancer. It is valuable for the diagnosis, staging, prognosis, and restaging of disease, and is most useful in patients considered for potentially curative therapy for non-small-cell lung cancer (NSCLC). In this work the current status and potential future applications of PET scanning in lung cancer are discussed. The relevant literature is also discussed, with an emphasis on studies with clinical applicability. Most of these studies involved the use of 18F-fluorodeoxyglucose (FDG). Numerous studies of the use of PET to assess undiagnosed pulmonary nodules have reported significant improvements in accurate diagnosis or exclusion of malignancy compared to conventional structural imaging alone. All of these studies, including metaanalysis, have shown that PET is more accurate than CT-based structural imaging in staging the mediastinum in surgical candidates. PET may have value in radiotherapy planning, and PET-based staging more accurately predicts survival in radiotherapy-treated patients than conventional staging. The rate of unsuspected distant metastasis detection in stage III disease exceeds 20%. PET also facilitates an accurate assessment of response in patients treated with radical chemoradiation or neoadjuvant therapy prior to surgery. PET has rapidly become an indispensable part of the evaluation of patients with potentially curable lung cancer however, more work is required to define its role.
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1053/J.SEMNUCLMED.2005.02.003
Abstract: Lymphomas represent a erse range of diseases with manifold presentations, outlook, and therapeutic approaches. Key to the modern management of lymphoma is accurate delineation of the extent of disease. The inability of computed tomography (CT) to identify the involvement of nonenlarged nodes and its relatively poor sensitivity in the detection of extra-nodal sites of involvement limit the performance of noninvasive staging techniques. Functional imaging techniques such as Ga-67 scintigraphy have been used for many years to improve the evaluation of patients with lymphoma. While providing complementary information to CT in many clinical settings, functional imaging has never had sufficient accuracy or localizing ability to seriously challenge conventional primary staging paradigms. (18)F-Fluorodeoxyglucose positron emission tomography (FDG PET), however, has been demonstrated to have both higher sensitivity and specificity than CT in many comparative series. Now that this technology also can be performed at the same time as structural imaging in the form of hybrid PET/CT devices, clinicians are rethinking the methods used to select, plan, and monitor therapy of lymphoma patients. In our institution, FDG PET/CT has become the preferred initial staging tool for patients with lymphoma.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Elsevier BV
Date: 07-1998
DOI: 10.1016/S0360-3016(98)00107-2
Abstract: Combined modality therapy with chemotherapy and radiotherapy has become increasingly popular in the management of solid malignancies. However, unexpected toxicities may arise from their interactions. We report the case of a young woman with a large mediastinal non-Hodgkin's lymphoma who underwent high-dose chemotherapy with autologous bone marrow transplantation and involved field radiotherapy, and who developed radiation myelopathy after a latent period of only 3 months. The spinal cord dose did not exceed 40.3 Gy in 22 fractions over 4.5 weeks, which is well within accepted tolerance limits. She had no other identifiable risk factors for radiation myelopathy, suggesting an adverse drug-radiation interaction as the most likely cause of her injury. This represents the first report of radiation myelopathy at accepted safe radiation doses following high-dose chemotherapy with autologous bone marrow transplantation, and we recommend caution in the choice of radiotherapeutic dose in this setting.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Wiley
Date: 06-2008
DOI: 10.1111/J.1440-1673.2008.01957.X
Abstract: This study evaluated the variability among six radiation therapy planners in planning radiation treatment for four patients with lung cancer using two treatment protocols. The interplanner variability for target conformity and homogeneity was smaller than the variability among the patients and planning approaches. The same was found for the dose volume indices achieved for most critical structures, indicating that interplanner variability is not likely to be an important source of variation in radiotherapy studies if concise treatment protocols are followed.
Location: United States of America
No related grants have been discovered for Michael MacManus.