ORCID Profile
0000-0003-2506-4871
Current Organisation
University of Sydney
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Publisher: Elsevier BV
Date: 04-2013
Abstract: Patients with platinum-sensitive recurrent ovarian cancer have variable prognosis and survival. We extend previous work on prediction of progression-free survival by developing a nomogram to predict overall survival (OS) in these patients treated with platinum-based chemotherapy. The nomogram was developed using data from the CAELYX in Platinum-Sensitive Ovarian Patients (CALYPSO) trial. Multivariate proportional hazards models were generated based on pre-treatment characteristics to develop a nomogram that classifies patient prognosis based on OS outcome. We also developed two simpler models with fewer variables and conducted model validations in independent datasets from AGO-OVAR Study 2.5 and ICON 4. We compare the performance of the nomogram with the simpler models by examining the differences in the C-statistics and net reclassification index (NRI). The nomogram included six significant predictors: interval from last platinum chemotherapy, performance status, size of the largest tumour, CA-125, haemoglobin and the number of organ sites of metastasis (C-statistic 0.67 95% confidence interval 0.65-0.69). Among the CALPYSO patients, the median OS for good, intermediate and poor prognosis groups was 56.2, 31.0 and 20.8 months, respectively. When CA-125 was not included in the model, the C-statistics were 0.65 (CALYPSO) and 0.64 (AGO-OVAR 2.5). A simpler model (interval from last platinum chemotherapy, performance status and CA-125) produced a significant decrease of the C-statistic (0.63) and NRI (26.4%, P < 0.0001). This nomogram with six pre-treatment characteristics improves OS prediction in patients with platinum-sensitive ovarian cancer and is superior to models with fewer prognostic factors or platinum chemotherapy free interval alone. With independent validation, this nomogram could potentially be useful for improved stratification of patients in clinical trials and also for counselling patients.
Publisher: Elsevier BV
Date: 11-2011
Abstract: CALYPSO (CAeLYx in Platinum Sensitive Ovarian) patients compared carboplatin-pegylated liposomal doxorubicin (C-PLD) with carboplatin-paclitaxel (C-P) in patients with late-relapsing recurrent ovarian cancer (ROC). We analyzed outcomes in patients ≥70 years. Nine hundred and seventy-six patients with taxane-pretreated ROC relapsing >6 months after first- or second-line platinum-based therapy were randomly assigned to 4-weekly C area under the curve (AUC) 5 plus PLD 30 mg/m(2) or 3-weekly C AUC 5 plus P 175 mg/m(2) for six or more cycles. One hundred and fifty-seven (16%) patients ≥70 years (median: 74 years, C-PLD 73 years, C-P range 70-82 years) were included (n = 71, C-PLD n = 86, C-P). In comparing elderly and younger, elderly patients experienced fewer grade ≥2 allergic reactions (P = 0.005) but more grade ≥2 sensory neuropathy (P = 0.007). Myelosuppression did not differ with age. Elderly patients completed planned treatment as frequently as younger (79%, C-PLD 82%, C-P). In comparing arms within elderly patients, C-P was associated with more grade ≥2 alopecia, sensory neuropathy, arthralgia/myalgia (P < 0.001 for all), severe leukopenia plus febrile neutropenia C-PLD was associated with more grade ≥2 hand-foot syndrome (P = 0.005). Median progression-free survival was 11.6 months (C-PLD) and 10.3 months (C-P P = 0.44). Patients ≥70 years experienced more neuropathy, with a higher incidence in the C-P arm. Similar to all study patients, C-PLD provided a better therapeutic index with less toxicity than C-P in elderly women with platinum-sensitive ROC.
Publisher: Elsevier BV
Date: 05-2012
Abstract: To perform a subset analysis of patients with partially platinum-sensitive recurrent ovarian cancer (ROC) who received either CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) in the CALYPSO trial. CALYPSO, an international phase III, non-inferiority trial, enrolled women with ROC that relapsed >6 months following first- or second-line therapy. Patients were randomized to CD or CP. Patients with a treatment-free interval of >6 and ≤ 12 months were evaluated for progression-free survival (PFS), the primary end point of CALYPSO trial, and safety. A total of 344 partially platinum-sensitive patients were included (N = 161, CD and N = 183, CP). The hazard ratio for PFS was 0.73 (95% confidence interval: 0.58-0.90 P = 0.004 for superiority) in favor of CD. Median PFS times were 9.4 months (CD) and 8.8 months (CP). Toxicities more common with CP versus CD included grade 3/4 neutropenia (50% versus 39% P = 0.015), grade 2 alopecia (86% versus 9% P < 0.001), neuropathy and hypersensitivity reactions. Hand-foot syndrome was more common with CD however, grade 3/4 reactions were low (one patient in each arm). Carboplatin-PLD has a more favorable risk-benefit profile than CP in patients with partially platinum-sensitive ROC and should be considered an effective treatment option for these patients.
Publisher: Wiley
Date: 17-12-2013
Publisher: Springer Science and Business Media LLC
Date: 18-06-2013
DOI: 10.1038/BJC.2013.300
Publisher: Springer Science and Business Media LLC
Date: 19-05-2022
DOI: 10.1186/S13063-022-06355-0
Abstract: Kidney failure prevalence is increasing worldwide. Haemodialysis, peritoneal dialysis or kidney transplantation are undertaken to extend life with kidney failure. People receiving haemodialysis commonly experience fatigue, pain, nausea, cr ing, itching, sleeping difficulties, anxiety and depression. This symptom burden contributes to poor health-related quality of life (QOL) and is a major reason for treatment withdrawal and death. The Symptom monitoring WIth Feedback Trial (SWIFT) will test the hypothesis that regular symptom monitoring with feedback to people receiving haemodialysis and their treating clinical team can improve QOL. We are conducting an Australia and New Zealand Dialysis and Transplant (ANZDATA) registry-based cluster randomised controlled trial to determine the clinical- and cost-effectiveness at 12 months, of 3-monthly symptom monitoring using the Integrated Palliative Outcome Scale-Renal (IPOS-Renal) survey with clinician feedback, compared with usual care among adults treated with haemodialysis. Participants complete symptom scoring using a tablet, which are provided to participants and to clinicians. The trial aims to recruit 143 satellite haemodialysis centres, (up to 2400 participants). The primary outcome is change in health-related QOL, as measured by EuroQol 5-Dimension, 5-Level (EQ-5D-5L) instrument. Secondary outcomes include overall survival, symptom severity (including haemodialysis-associated fatigue), healthcare utilisation and cost-effectiveness. SWIFT is the first registry-based trial in the Australian haemodialysis population to investigate whether regular symptom monitoring with feedback to participants and clinicians improves QOL. SWIFT is embedded in the ANZDATA Registry facilitating pragmatic recruitment from public and private dialysis clinics, throughout Australia. SWIFT will inform future collection, storage and reporting of patient-reported outcome measures (PROMs) within a clinical quality registry. As the first trial to rigorously estimate the efficacy and cost-effectiveness of routine PROMs collection and reporting in haemodialysis units, SWIFT will provide invaluable information to health services, clinicians and researchers working to improve the lives of those with kidney failure. Australian New Zealand Clinical Trials Registry ACTRN12620001061921 . Registered on 16 October 2020
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.COMPPSYCH.2017.04.002
Abstract: To collate data from multiple obsessive-compulsive disorder (OCD) treatment centers across seven countries and five continents, and to report findings in relation to OCD comorbidity, age of onset of OCD and comorbid disorders, and suicidality, in a large clinical and ethnically erse s le, with the aim of investigating cultural variation and the utility of the psychiatric diagnostic classification of obsessive-compulsive and related disorders. Researchers in the field of OCD were invited to contribute summary statistics on current and lifetime psychiatric comorbidity, age of onset of OCD and comorbid disorders and suicidality in their patients with OCD. Data from 3711 adult patients with primary OCD came from Brazil (n=955), India (n=802), Italy (n=750), South Africa (n=565), Japan (n=322), Australia (n=219), and Spain (n=98). The most common current comorbid disorders were major depressive disorder (28.4% n=1055), obsessive-compulsive personality disorder (24.5%, n=478), generalized anxiety disorder (19.3%, n=716), specific phobia (19.2%, n=714) and social phobia (18.5%, n=686). Major depression was also the most commonly co-occurring lifetime diagnosis, with a rate of 50.5% (n=1874). OCD generally had an age of onset in late adolescence (mean=17.9years, SD=1.9). Social phobia, specific phobia and body dysmorphic disorder also had an early age of onset. Co-occurring major depressive disorder, generalized anxiety disorder and psychotic disorders tended to have a later age of onset than OCD. Suicidal ideation within the last month was reported by 6.4% (n=200) of patients with OCD and 9.0% (n=314) reported a lifetime history of suicide attempt. In this large cross-continental study, comorbidity in OCD was common. The high rates of comorbid major depression and anxiety disorders emphasize the need for clinicians to assess and monitor for these disorders. Earlier ages of onset of OCD, specific phobia and social phobia may indicate some relatedness between these disorders, but this requires further study. Although there do not appear to be significant cultural variations in rates or patterns of comorbidity and suicidality, further research using similar recruitment strategies and controlling for demographic and clinical variables may help to determine whether any sociocultural factors protect against suicidal ideation or psychiatric comorbidity in patients with OCD.
Publisher: figshare
Date: 2019
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.LUNGCAN.2010.08.007
Abstract: We sought (i) lung cancer clinicians' judgements about the smallest survival benefits that would make the harms of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) worthwhile, (ii) factors associated with their judgements, and (iii) comparisons with breast cancer and colon cancer clinicians surveyed similarly in 2002-2003. Delegates at the Australian Lung Cancer Conference 2008 were invited to complete a validated, self-administered questionnaire that used the time trade-off method to determine the minimum survival benefits judged sufficient to make adjuvant chemotherapy worthwhile. The baseline survival times were 3 and 5 years, and the baseline 5-year survival rates were 50% and 65%. Chemotherapy was 4 cycles of cisplatin and vinorelbine. Characteristics of the 156 respondents were: median age 41 years (range 23-62), female 55%, married 83%, with dependent children 62%, respiratory physician 28%, nurse 24%, medical oncologist 14%, radiation oncologist 12%, trial nurse/coordinator 12%, thoracic surgeon 4%. Moderate survival benefits were judged sufficient to make chemotherapy worthwhile. The median benefit judged sufficient was an extra 9 months beyond a baseline survival time of 3 or 5 years. The median benefit judged sufficient was an extra 5% for a baseline survival rate of 65%, versus an extra 10% for a baseline survival rate of 50% (p<0.001). Smaller benefits were judged sufficient by clinicians who were married (p=0.02) or had dependants (p=0.04). Lung cancer clinicians judged smaller benefits sufficient than breast cancer (n=89) and colon cancer (n=72) clinicians in similar prior studies (median required benefit of 9 months versus 12 months, p<0.001). Most lung cancer clinicians attending a national lung cancer conference judged moderate improvements in survival sufficient to make adjuvant chemotherapy worthwhile. Smaller benefits were judged sufficient by lung cancer clinicians in 2008 than by breast cancer and colon cancer clinicians 5-6 years earlier. Clinicians should be aware of their own preferences, and explore their patients' preferences, when discussing adjuvant chemotherapy.
Publisher: BMJ
Date: 24-08-2017
DOI: 10.1136/BMJSPCARE-2017-001370
Abstract: The aim of this study was to evaluate the influence of an approaching cancer death on end-of-life aspirin use, a frequently prescribed medication for cardiovascular disease prevention. This study was conducted using linked cancer registry and prescribing data. Breast (n=1151) and colorectal (n=1859) cancer decedents were matched to cancer survivors and the probability of either initiating aspirin, or continuing established aspirin use, was estimated in consecutive periods over the 5 years approaching a cancer-specific death (decedents) or matched index date (survivors). Using the linked data sets, we identified patients who died of their cancer (decedents) between 1 January 2001 and 31 December 2009. In the 5 years prior to death, we compared (1) the probability of initiating aspirin use for the first time, and (2) the probability of continuing aspirin use. In comparison to matched cancer survivors, an approaching cancer death was not associated with a reduction in aspirin initiation by breast or colorectal cancer decedents. However, the probability of continuing established aspirin use declined considerably in the 24 months approaching death and at the time of a death was significantly lower for breast (risk difference (RD) −0.26, 95% CI −0.33 to −0.20) and colorectal (RD −0.38, 95% CI −0.46 to −0.30) cancer decedents versus matched survivors. A significant proportion of patients discontinue their aspirin in the time approaching a breast or colorectal cancer-specific death. The safety and benefits of this are unclear and empirical data are needed to guide decisions about aspirin use in the end of life.
Publisher: Public Library of Science (PLoS)
Date: 03-02-2015
Publisher: Elsevier BV
Date: 09-2020
Publisher: BMJ
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 02-08-2021
Publisher: Springer Science and Business Media LLC
Date: 26-07-2012
DOI: 10.1038/BJC.2012.307
Publisher: Mary Ann Liebert Inc
Date: 03-2012
Abstract: Increasing demand for palliative care unit (PCU) beds has led to shorter inpatient stays and a requirement to transfer some patients from a PCU to a residential aged care facility (RACF). Concerns have been raised regarding this move with suggestion that patients often die shortly after transfer. Published data investigating this patient group are limited. The aim of the current study was to audit discharges from a PCU to RACFs specifically looking at predictive factors for survival following discharge. A retrospective audit was undertaken of all discharges from the Barwon Health PCU to RACFs between July 2007 and July 2010. Data on patient demographics, clinical and functional status, admission and discharge details, and survival times were examined. Factors influencing survival were evaluated by Cox proportional-hazards regression analysis. Sixty-two discharges from a PCU to an RACF were included in the analysis. The mean age at discharge was 76 and the majority of patients had malignant disease. Mean and median survival times post-transfer were 106 and 42.5 days, respectively, and 16% of subjects survived more than 100 days. From univariate analyses age, PCU length of stay, admission Resource Utilization Groups-Activities of Daily Living (RUG-ADL) score, dependent mobility, having lung cancer or cancer of unknown primary, and living alone or in an RACF pre PCU admission affected survival. Multivariate analyses showed age, PCU length of stay, RUG-ADL score, and living situation prior to PCU admission together were associated with postdischarge survival times. This study is one of the largest investigating this cohort and suggests a number of factors that may predict survival for patients after discharge from a PCU to an RACF.
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.EJCA.2011.04.024
Abstract: Second-line treatment with irinotecan for advanced or metastatic colorectal cancer prolongs survival. It is uncertain whether irinotecan is better administered with 5-fluorouracil or alone in patients previously treated with a fluoropyrimidine. We compared toxicity (particularly diarrhoea), quality of life, and efficacy of combination chemotherapy and irinotecan in these patients. In DaVINCI, a randomised phase II trial, patients with advanced colorectal cancer were randomly allocated to: Combination therapy (FOLFIRI), irinotecan (180 mg/m(2) IV over 90 min, day 1), 5-fluorouracil (400mg/m(2) IV bolus and 2400 mg/m(2) by 46-hour infusion from day 1) and folinic acid (20mg/m(2) IV bolus, day 1), 2-weekly or Single-agent, irinotecan (350 mg/m(2) IV over 90 min), 3-weekly. Toxicity was evaluated every treatment cycle QOL and response 6-weekly. Analysis was by intention to treat. The trial, amended from a larger factorial design, was terminated early due to slow recruitment. Results were also combined with other second-line irinotecan trials. We randomised 44 patients to combination and 45 to single agent. Eight patients in the irinotecan arm and 4 in the combination arm had grade 3/4 diarrhoea (P=0.24). Treatment groups did not differ significantly in overall QOL changes, response rate or progression free or overall-survival. In a systematic review of 29 trials of second-line irinotecan-based treatment, single-agent irinotecan was associated with more diarrhoea and alopecia than the combination but efficacy was similar. Combination treatment compared with single-agent irinotecan reduces alopecia and diarrhoea without compromising efficacy on clinical outcomes. Both regimens remain as reasonable treatment options. Research grant (Pfizer).
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.LUNGCAN.2013.05.006
Abstract: BNC105P is a tubulin polymerisation inhibitor that selectively disrupts tumour vasculature and suppresses cancer cell proliferation. This agent has exhibited preclinical and phase I activity in Malignant Pleural Mesothelioma (MPM). This phase II, single arm trial investigated the efficacy and safety of BNC105P as second line therapy in MPM. Participants had progressive MPM after first line pemetrexed latinum chemotherapy, ECOG PS 0-1, adequate organ function, and measurable disease. BNC105P 16 mg/m(2) was administered intravenously on day 1 and 8 every 21 days until progression or undue toxicity. The primary endpoint was centrally reviewed objective response rate (RR). Tumour response was assessed every two cycles using modified RECIST. 30 patients were enrolled in 10 months, predominantly male (90%), ECOG PS 1 (77%), epithelioid histology (67%), and non-metastatic disease (67%). All patients received at least one dose of study drug, with a median of 2 cycles. No significant haematologic, biochemical, or cardiac adverse events (AEs) were observed. Grade 3 or 4 AEs occurred in 10 patients (33%). There were 2 deaths on study: 1 cardiorespiratory, the other to pneumonia. We observed 1 partial response (3%) 13 patients had stable disease (43%). Median progression free survival was 1.5 months (95% CI 1.4-2.4) median overall survival was 8.2 months (95% CI 3.8-11.9). BNC105P was safe and tolerable. The sole response was insufficient to warrant further research as a single agent.
Publisher: Oxford University Press (OUP)
Date: 30-06-2015
Publisher: Wiley
Date: 07-2020
DOI: 10.1111/JHN.12788
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-07-2021
Publisher: Informa UK Limited
Date: 08-09-2017
DOI: 10.1080/13651501.2017.1374413
Abstract: To examine the psychometric characteristics of the Nepean Belief Scale (NBS), a short clinician-administered scale that assesses the characteristics and intensity of beliefs in obsessive-compulsive disorder (OCD). The NBS was administered by two clinicians to 27 subjects with OCD as part of a larger study that included a comprehensive assessment using the Yale-Brown Obsessive Compulsive Symptom Scale (Y-BOCS), the Overvalued Ideas Scale (OVIS) and the Symptom Checklist 90-Revised (SCL-90R). Test-retest reliability of the NBS was assessed by administering the scale 5 days after initial administration. The 5-item NBS proved easy to use with an assessment time of less than 5 min. Its interrater reliability revealed 99.5% concordance, while the kappa for test-retest reliability was 0.98 (95% CI = 0.95-1.00). Cronbach alpha coefficient for internal consistency was 0.87. The NBS was found to have excellent convergent and discriminant validity. Preliminary results suggest that the NBS could be a useful shorter alternative to the currently more widely used instruments for assessing beliefs such as the OVIS and the Brown Assessment of Belief Scale. The NBS has clear instructions and definitions, excellent interrater reliability and convergent validity, and it more accurately measures belief-related insight.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.EJCA.2014.11.017
Abstract: To perform a subset analysis of patients with very platinum-sensitive recurrent ovarian cancer (ROC) enrolled in the phase III CALYPSO trial. The international non-inferiority trial enrolled women with ROC that relapsed >6 months following first- or second-line platinum- and paclitaxel-based therapies. Patients were randomised to CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) and stratified by treatment-free interval (TFI). In this analysis, patients with a TFI>24 months were analysed separately for progression free survival (PFS), the primary endpoint of CALYPSO, overall survival (OS) and safety. A total of 259 very platinum-sensitive patients were included (n=131, CD n=128, CP). Median PFS was 12.0 months for the CD arm and 12.3 months for CP [HR=1.05 (95% CI, 0.79-1.40) P=0.73 for superiority] and median OS was 40.2 months for CD and 43.9 for CP [HR=1.18 (95% CI 0.85-1.63) P=0.33 for superiority]. Overall response rates were 42% and 38%, respectively (P=0.46). Toxicities were more common with CP versus CD, including grade 3/4 neutropenia (40.8% versus 27.5% P=0.025), nausea (4.8% versus 3.1% P=0.47), allergic reaction (8% versus 3.1% P=0.082) sensory neuropathy (4.8% versus 2.3% P=0.27) and grade 2 alopecia (88% versus 9.2% P<0.001). Grade 3/4 thrombocytopenia (12.2% versus 3.2% P=0.007) and mucositis (2.3% versus 0% P=0.089) were more common with CD. Grade 3/4 hand-foot syndrome occurred rarely with CD (3 patients versus 0 in CP arm P=0.089). CP and CD were equally effective treatment regimens for patients with very platinum-sensitive ROC. The favourable risk-benefit profile suggests carboplatin-PLD as treatment of choice for these patients.
Publisher: Wiley
Date: 03-09-2020
DOI: 10.1002/JMRS.420
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.ORCP.2017.10.003
Abstract: Abdominal adiposity and subcutaneous fat (SF), an important endocrine organ for health outcomes, can be ided into two layers, superficial (SSAT) and deep subcutaneous adipose tissue (DSAT) each with a different histological and metabolic function. The aim was to investigate longitudinal changes in maternal abdominal SF thickness and its layers throughout pregnancy and post-partum within body mass index (BMI) categories. A prospective longitudinal study of 214 women was performed measuring abdominal SF using ultrasound at 12-14(M1), 18-20(M2), 26-29(M3) and 33-36 weeks' gestation (M4) and 6-8 weeks post-partum. SF thickness (SFT), SSAT and DSAT were measured. A ratio of DSAT/SSAT (D/S) was calculated. Measurements were compared to baseline and BMI evaluating for interaction with changes over time. Of the 214 women, 43.5%(93) were normal weight, 25.7%(55) overweight and 30.8%(66) obese. SFT and SSAT decreased from M1 to M4 for the overweight and obese whilst remaining stable for normal weight women. For all BMI categories SFT and SSAT increased post-partum. DSAT decreased significantly in the obese and overweight and increased significantly in the normal weight. Obese women had a higher D/S at M1 that decreased at M2 and remained constant to post-partum. D/S increased at M2 then decreased in the overweight. Normal weight women increased D/S at M2-M4. The results indicate a difference in distribution and mobilisation of fat in SSAT, and DSAT abdominal subcutaneous compartments within the different BMI categories in pregnancy. Understanding how fat mobilises during pregnancy may be fundamental to understanding obesity related complications.
Publisher: Springer Science and Business Media LLC
Date: 26-04-2019
DOI: 10.1007/S00066-019-01467-0
Abstract: The current study aimed to assess patterns of failure (PoF) in anaplastic glioma (AG) patients managed with intensity-modulated radiation therapy (IMRT) and their relationship to molecular subtype. The outcomes of AG patients managed between 2008 and 2014 and entered into a prospective database were assessed, including PoF. AG was initially defined using the WHO 2007 classification, but for analysis, patients were subsequently recategorised based on WHO 2016 as anaplastic oligodendroglioma (AOD), astrocytoma isocitrate dehydrogenase (IDH) mutant (AAmut) or astrocytoma IDH wildtype (AAwt). Management involved IMRT and temozolomide (TMZ), including from 2011 patients with an IDH mutation (IDHmut) planned with 18F-fluoroethyltyrosine (FET) and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET). PoF was local, marginal or distant in relation to the IMRT volume. Relapse-free survival (RFS) was calculated from the start of IMRT. A total of 156 patients were assessed, with median follow-up of 5.1 years. Of these patients, 75% were IDHmut, 44% were managed at first or later relapse and 73% received TMZ. Relapse occurred in 68 patients, with 6‑year RFS of 75.0, 48.8 and 2.5% for AOD, AAmut and AAwt, respectively (p < 0.001). There was a component of local relapse in 63%, of marginal relapse in 19% and of distant relapse in 37% of relapses. Isolated local, marginal and distant relapse was evident in 51, 9 and 22%, respectively. A distant relapse pattern was more frequent in IDHmut compared to IDHwt patients (26% vs. 45%, p = 0.005), especially within the first 2 years post-IMRT. In multivariate analysis, distant relapse remained associated with AAmut (p < 0.002) and delayed IMRT until the second relapse (p < 0.001). Although patients with IDH-mutated AG have improved outcomes, there was a higher proportion of distant relapses occurring during the 2 years after IMRT.
Publisher: Springer Science and Business Media LLC
Date: 02-06-2021
Publisher: Springer Science and Business Media LLC
Date: 12-01-2012
DOI: 10.1038/BJC.2011.593
Publisher: Elsevier BV
Date: 12-2020
Publisher: BMJ
Date: 2012
Publisher: Research Square Platform LLC
Date: 19-03-2021
DOI: 10.21203/RS.3.RS-270052/V1
Abstract: Purpose: Scan-associated anxiety (‘scanxiety’) in people with advanced cancer is a common clinical problem. This study aims to explore the experiences of scans and scanxiety in people with advanced cancer, including their strategies to reduce scanxiety. Methods: Semi-structured qualitative interviews were conducted with people with advanced cancers who had a computed tomography scan for monitoring of their cancer. Data was analysed with an interpretivist approach using framework analysis. Results: Interviews with 16 participants identified three key themes: the scan experience, the scanxiety experience and coping with scans. Scans and scanxiety were viewed as a routine and normal part of cancer care, though this was experienced differently by each person. Scanxiety often related to the scan result rather than the scan, and lead to psycho-cognitive manifestations. Adaptive coping strategies were often self-derived. Conclusion: People with advanced cancer experience scanxiety, but often accept scanxiety as a normal part of the cancer process. The findings fit within a transactional model of stress and coping, which influences the level of scanxiety for each in idual. Quantitative research to determine the scope of scanxiety will be useful to develop formal approaches to reduce scanxiety.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1053/J.AJKD.2021.12.007
Abstract: Patients receiving hemodialysis experience high symptom burden and low quality of life (QOL). Electronic patient-reported outcome measures (e-PROMs) monitoring with feedback to clinicians may be an acceptable intervention to improve health-related QOL for patients receiving hemodialysis. This study explored patient and clinician perspectives on e-PROMs monitoring with feedback to clinicians. Qualitative study. 41 participants (12 patients, 13 nephrologists, 16 dialysis nurses) who participated in a 6-month feasibility pilot study of adults receiving facility-based hemodialysis across 4 Australian units. The intervention consisted of electronic symptom monitoring with feedback to clinicians, who also received evidence-based symptom management recommendations to improve health-related QOL. Semistructured interviews and focus group discussions explored the feasibility and acceptability of e-PROMs monitoring with feedback to clinicians. We conducted a thematic analysis of transcripts. We identified 4 themes: enabling efficient, systematic, and multidisciplinary patient-centered care experiencing limited data and options for symptom management requiring familiarity with technology and processes and identifying barriers and competing priorities. While insufficient patient engagement, logistic/technical challenges, and delayed symptom feedback emerged as barriers to implementation, active engagement by nurses in encouraging and supporting patients during survey completion and clinicians' prompt action after symptom feedback were considered to be facilitators to implementation. Limited generalizability due to inclusion of English-speaking participants only. Patients, nurses, and nephrologists considered e-PROMs monitoring with feedback to clinicians feasible for symptom management in hemodialysis. Clinician engagement, patient support, reliable technology, timely symptom feedback, and interventions to address symptom burden are likely to improve its implementation within research and clinical settings.
Publisher: Oxford University Press (OUP)
Date: 11-08-2011
DOI: 10.1093/JNCI/DJR282
Abstract: We used data from 886 patients from the CAELYX in Platinum Sensitive Ovarian Patients (CALYPSO) trial, recruited between April 2005 and September 2007, to examine the role of early decline in cancer antigen 125 (CA125) and early tumor response as prognostic factors and surrogates for superiority of treatment with carboplatin-pegylated liposomal doxorubicin (CPLD) compared with carboplatin-paclitaxel (CP) in a landmark analysis. Progression-free survival (PFS) was estimated by Kaplan-Meier analyses. We used univariate and multivariable Cox proportional hazards analyses to assess early decline and early response as surrogates for CPLD treatment benefit compared with CP. All statistical tests were two-sided. Early decline (defined as rate of CA125 decrease of at least 50% per month) was associated with improved PFS (adjusted hazard ratio [HR] for progression = 0.81, 95% confidence interval [CI] = 0.67 to 0.97, P = .02) but early response (complete or partial responses) was not. CPLD was associated with improved PFS compared with CP (HR = 0.82, 95% CI = 0.69 to 0.96, P = .01). However, fewer CPLD patients had an early decline (161 [37.4%] vs 233 [51.2%], P < .001) or an early response (146 [33.9%] vs 176 [38.7%], P = .14) compared with CP patients. The PFS for CPLD patients did not change statistically significantly after adjustment for early decline (adjusted HR = 0.80, 95% CI = 0.68 to 0.94, P = .007). These findings are opposite to what would be expected if these markers were good surrogates for treatment benefit.
Publisher: Wiley
Date: 06-12-2021
DOI: 10.1002/CAM4.3623
Publisher: American Academy of Pediatrics (AAP)
Date: 03-2011
Abstract: For singletons with cerebral palsy (CP) who were born at term, the goals were (1) to determine the proportion not admitted to a Special Care Unit/NICU (NICU), (2) to compare clinical descriptions of those admitted to NICUs and those not admitted, and (3) to identify neonatal predictors of CP among those not admitted to a NICU. A total-population case- (N = 442) control (N = 468) study of, singleton, term-born infants with CP, as ascertained from the Western Australian Cerebral Palsy Register, was performed. All types of CP were represented among the 67% of term infants with CP (N = 295) who were not admitted to a NICU, which also included 54% of the subjects with the most severe impairments. Independent neonatal predictors were abnormalities of tone (odds ratio [OR]: 7.3 [95% confidence interval [CI]: 2–26.8]), temperature regulation (OR: 4.1 [95% CI: 1.2–14]), consciousness (OR: 3.7 [95% CI: 2–7]), and fontanelles (OR: 4.4 [95% CI: 0.8–23]), requirement for resuscitation (OR: 2.9 [95% CI: 2.2–12.9]), and birth defects (OR: 5.1 [95% CI: 2.4–10]). The risk of CP increased with the number of factors, but 58% of subjects who were not admitted to a NICU exhibited none of these factors. Neonatal predictors of CP among term infants not admitted to a NICU were identified. However, 39% of all term singletons with CP were not admitted to a NICU and exhibited none of these predictors.
Publisher: Springer Science and Business Media LLC
Date: 08-2023
DOI: 10.1186/S13014-023-02302-8
Abstract: Oligometastatic disease in prostate cancer (PCa) is a challenging clinical scenario encountered more frequently with the widespread adoption of PSMA-PET. SBRT aims to defer androgen deprivation and may deliver sustained biochemical failure (BF) free survival in selected patients. Little long-term data is currently available regarding the effectiveness of this approach. A retrospective single institution study of PSMA-PET directed SBRT without initial ADT for oligo-metachronous PCa. Median dose/fractionation was 24 Gy in 2# to bones and 30 Gy in 3# to lymph nodes. The primary endpoint was time to BF (PSA + 0.2 ug/L above nadir). Secondary endpoints included time to ADT for relapse (i.e. palliative ADT), BF defined as PSA nadir + 2 ug/L, toxicity, patterns of failure and survival. Patients were excluded if they received ADT with their SBRT, had short disease-free interval, or 3 metastases on PSMA-PET. 103 patients treated from November-2014 to December-2019 were analysed from our prospective database. Median follow-up was 5 years. 64 patients were treated for nodal only disease, 35 bone only and 4 mixed. 15% were free of any BF at 5 years with median time to BF of 1.1 years. 32% (33/103) of patients had further curative-intent radiation treatment following their first BF after SBRT, including subsequent SBRT. Eight patients underwent potentially curative treatment for their second or third relapse. Allowing for salvage treatment, 29/103 (28%) were biochemically disease free at last follow up. At 5 years, 39% of patients had never received any ADT and 55% had not started ADT for relapse with a median time to ADT for relapse of 5.5 years. There were 2 grade 3 toxicities (rib fracture and lymphoedema), and no local failures. PSMA-PET guided SBRT for oligo-metachronous PCa recurrence in appropriately triaged patients results in excellent local control, low toxicity and over 50% ADT free at 5 years.
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.JOCN.2011.02.026
Abstract: Concurrent and post-radiotherapy temozolomide (T) significantly improves survival in patient with newly diagnosed glioblastoma multiforme. We aimed to assess the activity of the combination of T and pegylated liposomal doxorubicin (PLD) in this population. A combination of T (days 1-5, 200mg/m(2) orally) and PLD (day 1, 40 mg/m(2) intravenous) was given every 4 weeks for six cycles following chemo-radiotherapy as a post-operative treatment. The primary endpoint was 6-month progression free survival (6PFS). Of the 40 patients who enrolled (53 years median age, 73% male), the 6PFS was 58% (95% confidence interval [CI], 41-72%). The median time to progression was 6.2 months (95% CI, 5.6-8.0 months) and overall survival (OS) was 13.4 months (95% CI, 12.7-15.8 months). Thirty-four patients had measurable disease: one had a complete response (3%), 28 had stable disease (82%), and five had progressive disease (15%). Treatment was well tolerated: hematological toxicity included grade 3 neutropenia (8%). Grade 3 non-hematologic toxicity included nausea and vomiting (8%) and palmar-plantar toxicity (5%). We concluded that combination T and PLD is well tolerated but does not add significant clinical benefit regarding 6PFS and OS.
Publisher: Future Medicine Ltd
Date: 28-09-2023
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.CLLC.2022.07.016
Abstract: There are limited real world data on the IMpower150 regimen in oncogene driven tumors and central nervous system metastases this study aims to address this gap. Retrospective analysis of patients with advanced non-small cell lung cancer treated with the IMpower150 regimen across 12 Australian sites between July 2018 and April 2021. Clinicopathologic and treatment parameters were correlated with efficacy and toxicity. A total of 106 patients identified with median follow up of 8 months (range 0-72). Median age was 61 years (range 33-83), 34% Asian and 58% never-smokers. An oncogene was reported in 94 (89%) patients, EGFR in 72 (68%). At treatment commencement, 50 (47%) patients had brain metastases, 21 (20%) leptomeningeal disease (LMD) and 47 (44%) liver metastases. 27% were treatment-naïve and pemetrexed was substituted for paclitaxel in 44 (42%). The overall response rate was 51% for all patients 52% in patients with EGFR mutations. Patients with untreated brain metastases prior to commencing IMpower150 had a similar intracranial response as those with treated brain metastases (55% vs. 53%). The median time to treatment failure and overall survival from commencement of IMpower150 was 5.7 and 11.4 months respectively for the entire cohort and 5.2 and 10.5 months in those with an EGFR sensitizing mutation. Overall survival in patients with liver, brain metastases and LMD was 11.0, 11.4, and 7.1 months respectively. No new safety signals seen. In this largely oncogene positive, pre-treated population the IMpower150 regimen demonstrated clinically-meaningful responses, including in patients with CNS disease.
Publisher: figshare
Date: 2020
Publisher: Elsevier BV
Date: 08-2012
Abstract: In the CALYPSO trial, carboplatin-pegylated liposomal doxorubicin (CD) demonstrated superior therapeutic index versus carboplatin-paclitaxel (CP) in patients with recurrent ovarian cancer. This paper reports the health-related quality of life (HRQoL) findings. HRQoL was measured with the EORTC QoL-QC30 questionnaire and OV28 ovarian cancer module. Mean change scores from baseline in HRQoL subscales (five functional scales and global health status) in each arm and the proportion of patients improved or worsened were calculated every 3 months until 12 months. Compliance was 90% at baseline and 76%, 64%, 57% at 3, 6, and 9 months, respectively. Baseline HRQoL showed already impaired global scores (mean 62/100) and considerable symptom burden (90% of patients reporting nonzero scores). Global QoL and abdominal symptom scores improved over time in both arms at 6 months, 36% of patients met criteria for improved symptoms. Treatment with CD resulted in less peripheral neuropathy (9.8 versus 24.2), fewer other chemotherapy side-effects (9.5 versus 16.2), and less impact on body image (3.8 versus 10.4) versus CP (all P<0.02) at 6 months. These patient-reported outcomes confirm the overall lower toxicity of CD versus CP. The improved disease-related outcomes achieved with CD were not at the expense of QoL.
Publisher: Springer Science and Business Media LLC
Date: 13-01-2022
DOI: 10.1186/S12883-021-02548-3
Abstract: The impact of near-total resection of IDH-mutated anaplastic glioma (IDHmutAG) is well-established but there remains uncertainty of benefit in tumours of the insular cortex where the extent of safe resection may be limited. This study aimed to assess tumour volume reduction in patients following IMRT and impact of residual post-surgical volume. Patients with IDHmutAG involving insular cortex managed with IMRT from 2008 to 2019 had baseline patient, tumour and treatment factors recorded. Volumetric assessment of residual disease on MRI was performed at baseline, month+ 3 and month+ 12 post-IMRT. Potential prognostic factors were analysed for tumour reduction and relapse-free survival, and assessed by log-rank and Cox regression analyses. Thirty two patients with IDHmutAG of the insular cortex were managed with median follow-up post-IMRT of 67.2 months. Pathology was anaplastic astrocytoma (AAmut) in 20, and anaplastic oligodendroglioma (AOD) in 12 patients. Median pre-IMRT volume on T1 and T2Flair was 24.3cm 3 and 52.2cm 3 . Twenty-seven patients were alive with 5-year relapse-free survival of 80%. There was a median 67 and 64% reduction from baseline occurring at 3 months post-IMRT for T1 and T2Flair respectively and subsequent median 78 and 73% at 12 months. At 12 months AOD patients had median 83% T1 volume reduction compared to 63% in AAmut ( p 0.01). There was no difference on T2Flair volume ( p = 0.64). No other pathological factors influenced volume reduction at 12 months. No factors were associated with relapse-free survival including baseline T1 ( p = 0.52) and T2Flair ( p = 0.93) volume. IMRT provides large tumour volume reduction in IDHmutAG of the insular cortex. While maximal safe debulking remains standard of care when feasible, this patient cohort reported no significant negative impact of residual disease volume on relapse-free survival.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2014
DOI: 10.1007/S11060-014-1525-Z
Abstract: The literature on medulloblastoma in adults is generally limited to case reports and retrospective series, and there is no accepted standard of care. The Cooperative Trials Group for Neuro-Oncology (COGNO) sought to determine the range and consistency of clinicians' approaches to management as a basis for future trials. We aimed to identify current treatment strategies for adult medulloblastoma through an online survey launched at the 2012 Society of Neuro-Oncology meeting and by email invitation. Clinicians who had treated at least one adult patient with medulloblastoma, primitive neuroectodermal tumor (PNET), or pineoblastoma in the preceding year were asked about their most recent patient and invited to discuss their approach to a typical clinical scenario. Between November 2012 and January 2013, 45 clinicians (11 medical oncologists, 8 radiation oncologists, 5 pediatric oncologists, and 21 others) from Australia (24), United States (3), Europe (4) and other countries (14) completed the survey. Responding clinicians had treated 54 cases in the past 12 months. The most common histological type was medulloblastoma (64%), then PNET (20%). Most patients were male (68%), and had high-risk disease (65%). Complete surgical resection in 56 and 32% had molecular testing. Radiotherapy was predominantly cranio-spinal (92%) and given mostly post-resection (80%). Combination chemotherapy was more common than single-agent chemotherapy. The choice of chemotherapy varied considerably. There is substantial variation in the treatment of adult medulloblastoma, most pronounced in the choice of chemotherapeutic agents, highlighting the need for further collaborative research to guide evidence-based treatment strategies.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2013
Publisher: Public Library of Science (PLoS)
Date: 10-10-2017
Publisher: Public Library of Science (PLoS)
Date: 14-04-2016
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 2023
Publisher: Elsevier BV
Date: 12-2020
Publisher: Research Square Platform LLC
Date: 18-06-2021
DOI: 10.21203/RS.3.RS-598305/V1
Abstract: Background: In IDH-mutated anaplastic glioma (IDHmutAG) of the insular cortex there remains uncertainty of benefit with near-total resection compared to limited surgery with radiation therapy (IMRT). This study aimed to assess tumour volume reduction in patients following IMRT and impact of residual post-surgical volume. Methods and Materials: Patients with IDHmutAG involving insular cortex managed with IMRT from 2008-2019 had baseline patient, tumour and treatment factors recorded. Volumetric assessment of residual disease on MRI was performed at baseline, month+3 and month+12 post-IMRT. Potential prognostic factors were analysed for tumour reduction and relapse-free survival, and assessed by log-rank and Cox regression analyses. Results: 32 patients with IDHmutAG of the insular cortex were managed with median follow-up post-IMRT of 67.2 months. Pathology was anaplastic astrocytoma (AAmut) in 20, and anaplastic oligodendroglioma (AOD) in 12 patients. Median pre-IMRT volume on T1 and T2Flair was 24.3cm 3 and 52.2cm 3 . Twenty-seven patients were alive with 5-year relapse-free survival of 80%. There was a median 67% and 64% reduction from baseline occurring at 3 months post-IMRT for T1 and T2Flair respectively and subsequent median 78% and 73% at 12 months. At 12 months AOD patients had median 83% T1 volume reduction compared to 63% in AAmut (p .01). There was no difference on T2Flair volume (p=0.64). No other pathological factors influenced volume reduction at 12 months. No factors were associated with relapse-free survival including baseline T1 (p=0.52) and T2Flair (p=0.93) volume. Conclusion: IMRT provides large tumour volume reduction in IDHmutAG of the insular cortex with no significant negative impact of residual disease volume on relapse-free survival.
Publisher: Springer Science and Business Media LLC
Date: 13-09-2011
DOI: 10.1038/BJC.2011.364
Publisher: Wiley
Date: 12-12-2017
DOI: 10.1002/AJUM.12081
Publisher: Springer Science and Business Media LLC
Date: 21-10-2020
Publisher: American Medical Association (AMA)
Date: 07-2020
Publisher: Oxford University Press (OUP)
Date: 17-04-2013
DOI: 10.1093/JNCI/DJT072
Abstract: The epidermal growth factor receptor (EGFR) signaling pathway is crucial for regulating tumorigenesis and cell survival and may be important in the development and progression of non-small cell lung cancer (NSCLC). We examined the impact of EGFR-tyrosine kinase inhibitors (TKIs) on progression-free survival (PFS) and overall survival (OS) in advanced NSCLC patients with and without EGFR mutations. Randomized trials that compared EGFR-TKIs monotherapy or combination EGFR-TKIs-chemotherapy with chemotherapy or placebo were included. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of EGFR-TKIs for the EGFR mutation-positive (EGFRmut(+)) and EGFR mutation-negative (EGFRmut(-)) subgroups were calculated with the fixed-effects inverse variance weighted method. All statistical tests were two-sided. We included 23 eligible trials (13 front-line, 7 second-line, 3 maintenance n = 14570). EGFR mutation status was known in 31% of patients. EGFR-TKIs treatment prolonged PFS in EGFRmut(+) patients, and EGFR mutation was predictive of PFS in all settings: The front-line hazard ratio for EGFRmut(+) was 0.43 (95% confidence interval [CI] = 0.38 to 0.49 P < .001), and the front-line hazard ratio for EGFRmut(-) was 1.06 (95% CI = 0.94 to 1.19 P = .35 P interaction < .001). The second-line hazard ratio for EGFRmut(+) was 0.34 (95% CI = 0.20 to 0.60 P < .001), and the second-line hazard ratio for EGFRmut(-) was 1.23 (95% CI = 1.05 to 1.46 P = .01 P interaction < .001). The maintenance hazard ratio for EGFRmut(+) was 0.15 (95% CI = 0.08 to 0.27 P < .001), and the maintenance hazard ratio for EGFRmut(-) was 0.81 (95% CI = 0.68 to 0.97 P = .02 P interaction < .001). EGFR-TKIs treatment had no impact on OS for EGFRmut(+) and EGFRmut(-) patients. EGFR-TKIs therapy statistically significantly delays disease progression in EGFRmut(+) patients but has no demonstrable impact on OS. EGFR mutation is a predictive biomarker of PFS benefit with EGFR-TKIs treatment in all settings. These findings support EGFR mutation assessment before initiation of treatment. EGFR-TKIs should be considered as front-line therapy in EGFRmut(+) advanced NSCLC patients.
Publisher: Oxford University Press (OUP)
Date: 09-06-2021
DOI: 10.1093/NOP/NPAB034
Abstract: There is minimal evidence to support decision making for symptomatic steroid-refractory pseudoprogression or true progression occurring after intensity-modulated radiation therapy (IMRT) for glioblastoma (GBM). This study audited the survival outcome of patients managed with redo craniotomy (RedoSx) or bevacizumab (BEV) for steroid-refractory mass effect after IMRT for GBM. Patients with GBM managed between 2008 and 2019 with the EORTC-NCIC Protocol were entered into a prospective database. Patients with symptomatic steroid-refractory mass effect within 6 months of IMRT managed with either RedoSx or BEV were identified for analysis. For the primary endpoint of median overall survival (OS) postintervention, outcome was analyzed in regards to potential prognostic factors, and differences between groups were assessed by log-rank analyses. Of the 399 patients managed with the EORTC-NCIC Protocol, 78 required an intervention within 6 months of IMRT completion for either true or pseudoprogression (49 with RedoSx and 29 with BEV). Subsequently, 20 of the 43 patients managed with RedoSx when BEV was clinically available, required salvage with BEV within 6 months after RedoSx. Median OS postintervention was 8.7 months (95% CI: 7.84-11.61) for the total group and 8.7 months (95% CI: 6.8-13.1) for RedoSx and 9.4 months (95% CI: 7.8-13.6) for BEV (P = .38). Subsequent use of BEV in RedoSx patients was not associated with improved survival compared with RedoSx alone (P = .10). Age, time from IMRT, and ECOG performance status were not associated with OS. In the RedoSx patients, immunohistochemical features such as Ki-67% reduction correlated with survival. The presence of pure necrosis and residual tumor cells only had improved survival compared with the presence of gross tumor (P & .001). At time of symptomatic steroid-refractory true or pseudoprogression following IMRT for GBM, BEV was equivalent to RedoSx in terms of OS. Pseudoprogression with residual cells at RedoSx was not associated with worse outcome compared to pure necrosis.
Publisher: Hindawi Limited
Date: 17-07-2018
DOI: 10.1111/ECC.12875
Abstract: While burden in cancer caregivers is high and associated with poor outcomes, little is known about significance of specific supportive care needs' domains in determining survivors' or caregivers' perceived caregiver burden. This cross-sectional study explored which domains of survivor- and caregiver-reported supportive care needs were most associated with survivor- and caregiver-reported caregiver burden, in breast cancer survivor-caregiver dyads. Cancer survivors (N = 55) and their caregivers (N = 44) completed measures of supportive care needs, anxiety, depression, functional well-being and perceived caregiver burden. Correlation and linear regression analyses were used to determine relative significance of survivor and caregiver supportive care needs in accounting for variance in survivor and caregiver perceptions of burden. Higher survivor-perceived caregiver burden and higher caregiver-perceived difficulty of caregiving were associated with higher levels of survivor and caregiver supportive care needs. Survivors' psychological needs uniquely contributed to survivors' self-perceived burden, and survivors' sexual needs and caregivers' work and social needs uniquely contributed to caregivers' perceived difficulty of caregiving. Caregiver's perceived time spent caregiving was associated with access to services needs but not other needs. Survivor and caregiver supportive care needs and burden appear interdependent. Longitudinal research with larger s les is warranted to examine these relationships.
Publisher: Springer Science and Business Media LLC
Date: 12-05-2011
DOI: 10.1007/S00280-010-1351-8
Abstract: Biliary tract cancers (BTC) have a poor prognosis, and there is no consensus on the best chemotherapy regimen. This study determined the response rate for fixed-dose-rate (FDR) gemcitabine combined with cisplatin. This multicentre phase II trial enrolled 50 patients with inoperable locally advanced or metastatic BTC. Treatment consisted of FDR gemcitabine 1,000 mg/m² (10 mg/m²/min) and cisplatin 20 mg/m² on days 1 and 8 of a 21-day cycle. The primary endpoint was response rate. Secondary endpoints included safety, response duration (RD), progression-free (PFS) and overall survival (OS), and cancer antigen 19-9 response. Thirteen patients (26%, 95% CI 14.6-40.4) had a partial response, and 12 (24%) had stable disease. The median RD was 8.3 months (95% CI 6.91-9.99) median PFS 4 months (95% CI 2.5-6.77) and median OS 6.8 months (95% CI 5.0-8.7). Treatment was well tolerated. Grade 3 and grade 4 nausea, vomiting, and fatigue were uncommon. Thirty-eight per cent of patients discontinued treatment because of toxicity, patient or clinician preference. This treatment combination had moderate activity with acceptable toxicity, supporting previous results that this combination has a role to play. The study does not suggest that FDR gemcitabine is superior to bolus infusion.
Publisher: BMJ
Date: 05-2021
DOI: 10.1136/BMJOPEN-2020-043215
Abstract: To identify available literature on prevalence, severity and contributing factors of scan-associated anxiety (‘scanxiety’) and interventions to reduce it. Systematic scoping review. Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, Ovid Cochrane Central Register of Controlled Trials, Scopus, EBSCO CINAHL and PubMed up to July 2020. Eligible studies recruited people having cancer-related non-invasive scans (including screening) and contained a quantitative assessment of scanxiety. Demographics and scanxiety outcomes were recorded, and data were summarised by descriptive statistics. Of 26 693 citations, 57 studies were included across a range of scan types (mammogram: 26/57, 46% positron-emission tomography: 14/57, 25% CT: 14/57, 25%) and designs (observation: 47/57, 82% intervention: 10/57, 18%). Eighty-one measurement tools were used to quantify prevalence and/or severity of scanxiety, including purpose-designed Likert scales (17/81, 21%) the State Trait Anxiety Inventory (14/81, 17%) and the Hospital Anxiety and Depression Scale (9/81, 11%). Scanxiety prevalence ranged from 0% to 64% (above prespecified thresholds) or from 13% to 83% (‘any’ anxiety, if no threshold). Mean severity scores appeared low in almost all measures that quantitatively measured scanxiety (54/62, 87%), regardless of whether anxiety thresholds were prespecified. Moderate to severe scanxiety occurred in 4%–28% of people in studies using descriptive measures. Nine of 20 studies assessing scanxiety prescan and postscan reported significant postscan reduction in scanxiety. Lower education, smoking, higher levels of pain, higher perceived risk of cancer and diagnostic scans (vs screening scans) consistently correlated with higher scanxiety severity but not age, gender, ethnicity or marital status. Interventions included relaxation, distraction, education and psychological support. Six of 10 interventions showed a reduction in scanxiety. Prevalence and severity of scanxiety varied widely likely due to heterogeneous methods of measurement. A uniform approach to evaluating scanxiety will improve understanding of the phenomenon and help guide interventions.
Publisher: Springer Science and Business Media LLC
Date: 12-2011
DOI: 10.1038/BJC.2011.526
Publisher: Elsevier BV
Date: 02-2012
Publisher: MDPI AG
Date: 20-09-2021
DOI: 10.3390/NU13093284
Abstract: Background: Sarcopenia is associated with significant morbidity and mortality in patients with chronic kidney disease. The prevalence of sarcopenia in the dialysis population varies from 4% to 63%. However, the prevalence and risk factors of sarcopenia in the Australian dialysis population remain uncertain. Aim: To study the prevalence of sarcopenia in patients on maintenance dialysis by using the European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic criteria of sarcopenia and to identify associated risk factors. Methods: We evaluated adult patients on maintenance haemodialysis and peritoneal dialysis in this single-centre cross-sectional study in Australia. Patient’s clinical (age, gender, dialysis modality and diabetic status) and laboratory parameters (serum albumin, calcium, phosphate, 25-hydroxy-vitamin D and parathyroid hormone levels) were investigated. We employed bioimpedance spectroscopy, hand grip dynamometer and the timed up and go test (TUG) to evaluate muscle mass, strength and function, respectively. Results: We evaluated 39 dialysis patients with a median age of 69 years old. The prevalence of sarcopenia was 18%. Sarcopenia was associated with low serum albumin (p = 0.02) and low serum phosphate level (p = 0.04). Increasing age and female sex were potential risk factors for sarcopenia (p = 0.05 and 0.08, respectively). Low lean muscle mass, reduced hand grip strength and prolonged TUG were present in 23.1%, 41% and 40.5%, respectively, of the cohort. The hand grip test had good correlation with lean muscle evaluation and the TUG. Conclusions: Sarcopenia was prevalent in 18% of maintenance haemodialysis patients from an Australian single-centre cohort, with low serum albumin and phosphate as significant risk factors.
Publisher: figshare
Date: 2019
Publisher: Elsevier BV
Date: 10-2020
Publisher: BMJ
Date: 05-2014
Publisher: BMJ
Date: 2022
DOI: 10.1136/BMJOPEN-2021-057663
Abstract: There is a strong theoretical rationale for combining checkpoint blockade with cytotoxic chemotherapy in pleural mesothelioma and other cancers. Two recent single-arm, phase 2 trials [DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (PrE0505)] combining the programmed death ligand-1 (PD-L1) inhibitor durvalumab with standard first-line chemotherapy exceeded prespecified safety and activity criteria to proceed to a phase 3 confirmatory trial to assess this combination. We present the protocol of the DREAM3R trial. This multicentre open-label randomised trial will recruit 480 treatment-naïve adults with advanced pleural mesothelioma, randomised (2:1) to either 3-weekly durvalumab 1500 mg plus 3-weekly doublet chemotherapy (cisplatin 75 mg/m 2 or carboplatin, Area Under the Curve,AUC 5 and pemetrexed 500 mg/m 2 ) 4–6 cycles, followed by 4-weekly durvalumab 1500 mg until disease progression, unacceptable toxicity or patient withdrawal OR doublet chemotherapy alone for 4–6 cycles, followed by observation. The target accrual time is 27 months, with follow-up for an additional 24 months. This provides over 85% power if the true HR for overall survival (OS) is 0.70, with two-sided alpha of 0.05, assuming a median OS of 15 months in the control group. Randomisation is stratified by age (18–70 years vs ), sex, histology (epithelioid vs non-epithelioid), platinum agent (cisplatin vs carboplatin) and region (USA vs Australia/New Zealand vs Other). The primary endpoint is OS. Secondary endpoints include progression-free survival, objective tumour response (by mRECIST V.1.1 and iRECIST), adverse events, health-related quality of life and healthcare resource use. Tertiary correlative objectives are to explore and validate potential prognostic and/or predictive biomarkers (including features identified in the DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and PrE0505 studies, PD-L1 expression, tumour mutational burden, genomic characteristics and human leukocyte antigen subtypes) in tissue and serial blood s les. An imaging databank will be assembled for validation of radiological measures of response, and studies of possible radiomic biomarkers in mesothelioma. The protocol was approved by human research ethics review committees for all participating sites. Results will be disseminated in peer-reviewed journals and at scientific conferences. AstraZeneca. CTC 0231 / TOGA 18/001 / PrE0506 3.0, 29 July 2021. ClinicalTrials.gov Identifier: NCT04334759 ACTRN 12620001199909.
Publisher: The Endocrine Society
Date: 12-2012
DOI: 10.1210/JC.2012-2267
Abstract: Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α agonist that showed beneficial effects on total cardiovascular risk in patients with type 2 diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. This study aimed to investigate the long-term effect of fenofibrate therapy on three novel biomarkers of cardiovascular risk, namely adipocyte-fatty acid-binding protein (A-FABP), fibroblast growth factor 21 (FGF21), and retinol-binding protein 4 (RBP4), which are all downstream targets of PPAR-α or PPAR-γ, in patients with type 2 diabetes. A total of 216 patients (108 in the fenofibrate group and 108 in the placebo group) were randomly selected from the FIELD study cohort. A-FABP, FGF21, and RBP4 levels were measured in serum s les at both baseline and the fifth year of the study. Relative to the placebo group, the changes of serum FGF21 and RBP4 levels were 85% (P 0.05). The effect of fenofibrate treatment on serum FGF21, but not RBP4, remained significant after adjusting for fenofibrate-induced changes in glycosylated hemoglobin, total cholesterol, triglycerides, apolipoprotein A-II, fibrinogen, plasma creatinine, and homocysteine (P = 0.002). Long-term fenofibrate treatment could increase serum FGF21 levels over 5 yr in patients with type 2 diabetes. Additional studies are needed to investigate the potential role of FGF21 in the fenofibrate-mediated reduction of cardiovascular risk.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Wiley
Date: 08-10-2019
DOI: 10.1002/HED.25969
Abstract: Elderly patients with mucosal squamous cell carcinomas of the head and neck (mHNSCC) represent a challenging clinical dilemma. A retrospective review was performed of patients ≥75 years, treated with curative-intent radiotherapy for mHNSCC in two quaternary Sydney hospitals between 2007 and 2017. Ninety-five patients met inclusion criteria. The median age was 79 years (75-94). Patients received radiotherapy alone (n = 24), concurrent chemoradiotherapy (n = 22), surgery and adjuvant radiotherapy (n = 45), or surgery with adjuvant chemoradiotherapy (n = 4). Median follow-up was 4.5 years, median overall survival (OS) was 3.8 years, and 2-year and 5-year OS were 56% and 43%, respectively. Eastern Cooperative Oncology Group performance status of ≥2 (P < .001) was a statistically significant predictor of reduced OS. Thirty-four patients (36%) required hospitalization, 5 (5%) did not complete radiotherapy, and 9 (9%) were feeding tube dependent beyond 6 months. Appropriately selected elderly patients can achieve durable outcomes from curative intent radiotherapy with acceptable treatment toxicity.
Publisher: Wiley
Date: 05-03-2018
DOI: 10.1111/AOGS.13315
Abstract: Levator trauma is a risk factor for the development of pelvic organ prolapse. We aimed to identify antenatal predictors for significant damage to the levator ani muscle during a first vaginal delivery. A retrospective observational study utilizing data from two studies with identical inclusion criteria and assessment protocols between 2005 and 2014. A total of 1148 primiparae with an uncomplicated singleton pregnancy were recruited and assessed with translabial ultrasound at 36 weeks antepartum and 871 (76%) returned for reassessment 3-6 months postpartum. The ultrasound data of vaginally parous women were analyzed for levator avulsion and microtrauma. The former was diagnosed if the muscle insertion at the inferior pubic ramus in the plane of minimal hiatal dimensions and within 5 mm above were abnormal on tomographic ultrasound imaging. Microtrauma was diagnosed in women with an intact levator and if there was a postpartum increase in hiatal area on Valsalva by >20% with the resultant area ≥25 cm The complete datasets of 844 women were analyzed. Among them, 609 delivered vaginally: by normal vaginal delivery in 452 (54%), a vacuum birth in 102 (12%) and a forceps delivery in 55 (6%). Levator avulsion was diagnosed in 98 and microtrauma in 97. On multivariate analysis, increasing maternal age, lower body mass index and lower bladder neck descent were associated with avulsion. Increased bladder neck descent and a family history of cesarean section (CS) were associcated with microtrauma. Maternal age, body mass index, bladder neck descent and family history of CS are antenatal predictors for levator trauma.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-07-2010
Abstract: This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC). Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m 2 ) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m 2 ) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS) secondary end points were toxicity, quality of life, and overall survival. Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821 95% CI, 0.72 to 0.94 P = .005) median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4% P .01) leading to early discontinuation (15% v 6% P .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm. To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.
Publisher: Wiley
Date: 28-06-2019
DOI: 10.1002/CNCR.32352
Abstract: Patients with anaplastic glioma (AG) harboring an isocitrate dehydrogenase mutation have potential durable survival after intensity-modulated radiotherapy (IMRT) and chemotherapy. Understanding long-term functioning, and the factors that have an impact on later effects, is important for decision making. Consecutive patients with AG who received IMRT were reviewed with regard to 6 survivorship domains, including Eastern Cooperative Oncology Group (ECOG) performance status, Medical Research Council (MRC) neurological status, late toxicity, comorbidity, functional status (employment/driving), and psychosocial events. Assessments were performed at baseline before RT at month +6 and at years +1, +3, and +5 after RT. The primary endpoints were ECOG at year +3 and employment at year +3. A total of 146 patients were included, with a median follow-up of 5.1 years. The 6-year overall survival rate was 78.7% (95% CI, 71.1%-87.0%). Baseline ECOG performance status was 0 to 1 in 82.2% of patients but improved at year +1 (95.7%) and year +3 (97.2%). Employment rates at year +3 and year +5 were 70.1% and 76.5%, respectively, compared with 61.6% at baseline. Worse ECOG performance status at year +3 was related to the anaplastic astrocytoma subtype (P = .001), delayed RT (P = .081), multiple craniotomies performed before RT (P = .002), worse ECOG performance status before RT (P < .001), worse MRC neurological status before RT (P < .001), seizures (P = .038), neurocognitive disturbance (P < .001), and the presence of recurrent disease (P = .004). Absent or impaired employment at year +3 was found to be related to older age (P = .007), delayed timing of RT (P = .023), multiple craniotomies prior to RT (P = .005), worse ECOG performance status before RT (P < .001), worse MRC neurological status before RT (P < .001), and neurocognitive disturbance (P 95% of patients having high ECOG performance status and >75% being employed.
Publisher: Wiley
Date: 26-07-2021
DOI: 10.1002/JMRS.526
Abstract: This study aimed to develop a single-isocentre volumetric modulated arc therapy (si-VMAT) technique for multiple brain metastases using knowledge-based planning software, comparing it with a multiple-isocentre stereotactic radiosurgery (mi-SRS) planning approach. Twenty-six si-VMAT plans were created and uploaded into RapidPlan There was a significant difference in the PCI scores for the mi-SRS plans (M = 0.667, SD = 0.114) and si-VMAT plans (M = 0.728, SD = 0.088), with PCI values suggesting better prescription dose conformity with the si-VMAT technique (P = 0.014). Percentage of total brain volume receiving low-dose wash at four of the five different dose levels was significantly less (P < 0.05) with mi-SRS. Average time to treat a single met with current mi-SRS technique is 25.7 min, with each additional met requiring this same amount of time. The average time to treat 2-3 mets using si-VMAT would be 25.3 min and 4+ metastases 33.5 min. A knowledge-based si-VMAT approach was efficient in planning and treating multi metastases while achieving clinically acceptable dosimetry with respect to dose conformity and low-dose fall off.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1111/AJT.13366
Abstract: Islet beta cells in situ express intracellular heparan sulfate (HS), a property previously shown in vitro to be important for their survival. We report that HS levels inside islet beta cells correlate with the novel intracellular localization of the HSPG core proteins for collagen type XVIII (Col18), a conventional extracellular matrix component. Syndecan-1 (Sdc1) and CD44 core proteins were similarly localized inside beta cells. During isolation, mouse islets selectively lose HS to 11-27% of normal levels but retain their HSPG core proteins. Intra-islet HS failed to recover substantially during culture for 4 days and was not reconstituted in vitro using HS mimetics. In contrast, significant recovery of intra-islet HS to ∼40-50% of normal levels occurred by 5-10 days after isotransplantation. Loss of islet HS during the isolation procedure is independent of heparanase (a HS-degrading endoglycosidase) and due, in part, to oxidative damage. Treatment with antioxidants reduced islet cell death by ∼60% and increased the HS content of isolated islets by ∼twofold compared to untreated islets, preserving intra-islet HS to ∼60% of the normal HS content of islets in situ. These findings suggest that the preservation of islet HS during the islet isolation process may optimize islet survival posttransplant.
Publisher: Springer Science and Business Media LLC
Date: 07-2011
DOI: 10.1038/BJC.2011.256
Publisher: MDPI AG
Date: 19-05-2020
DOI: 10.3390/NU12051465
Abstract: Malnutrition is prevalent in patients with head and neck cancer (HNC), impacting outcomes. Despite publication of nutrition care evidence-based guidelines (EBGs), evidence–practice gaps exist. This study aimed to implement and evaluate the integration of a patient-centred, best-practice dietetic model of care into an HNC multidisciplinary team (MDT) to minimise the detrimental sequelae of malnutrition. A mixed-methods, pre–post study design was used to deliver key interventions underpinned by evidence-based implementation strategies to address identified barriers and facilitators to change at in idual, team and system levels. A data audit of medical records established baseline adherence to EBGs and clinical parameters prior to implementation in a prospective cohort. Key interventions included a weekly Supportive Care-Led Pre-Treatment Clinic and a Nutrition Care Dashboard highlighting nutrition outcome data integrated into MDT meetings. Focus groups provided team-level evaluation of the new model of care. Economic analysis determined system-level impact. The baseline clinical audit (n = 98) revealed barriers including reactive nutrition care, lack of familiarity with EBGs or awareness of intensive nutrition care needs as well as infrastructure and dietetic resource limitations. Post-implementation data (n = 34) demonstrated improved process and clinical outcomes: pre-treatment dietitian assessment use of a validated nutrition assessment tool before, during and after treatment. Patients receiving the new model of care were significantly more likely to complete prescribed radiotherapy and systemic therapy. Differences in mean percentage weight change were clinically relevant. At the system level, the new model of care avoided 3.92 unplanned admissions and related costs of $AUD121K per annum. Focus groups confirmed clear support at the multidisciplinary team level for continuing the new model of care. Implementing an evidence-based nutrition model of care in patients with HNC is feasible and can improve outcomes. Benefits of this model of care may be transferrable to other patient groups within cancer settings.
Publisher: Wiley
Date: 07-03-2018
DOI: 10.1111/ANS.14398
Abstract: Loco-regional failure is the predominant cause of death in anal squamous cell carcinoma. We assessed patterns of loco-regional recurrence to determine the impact of radiotherapy (RT) volumes on patient outcome. Retrospective clinical study, including patients treated curatively with RT or chemo-radiotherapy between 1994 and 2007. RT fields/volumes were reviewed and compared with patterns of failure. Patients were classified as having whole pelvic radiotherapy (WPRT) if RT extended to L5/S1 or lower pelvic radiotherapy (LPRT) if it extended to the lower sacroiliac joints or below. Patients with negative inguinal nodes either underwent prophylactic inguinal radiotherapy (PIRT) or had inguinal observation (IO). Patterns of failure were compared. Twenty-seven patients (53%) had WPRT and 24 (47%) had LPRT. Forty-two patients had negative inguinal nodes: 29 (69%) had PIRT and 13 (31%) had IO. Median follow-up was 5.8 years. Twelve regional failures occurred in eight patients: three pelvic, one inguinal and four pelvic and inguinal. All patients with regional failure died of disease. Pelvic nodal failure was 7.7% in N0 and 33% in N1-3 patients (P = 0.012). There was no difference in pelvic regional failure between WPRT and LPRT (11% versus 16%, P = 0.64). There was only one possible regional failure above LPRT in this group (4%). Inguinal failure was 0% in the PIRT group compared with 23% in IO group (P = 0.009). There was no difference in pelvic regional failure between WPRT and LPRT. LPRT is likely to be safe in N0 patients. Inguinal nodes should be treated in all patients.
Publisher: Elsevier BV
Date: 05-2021
DOI: 10.1016/J.PRRO.2021.09.008
Abstract: Stereotactic body radiation therapy (SBRT) is a recognized treatment for low- and intermediate-risk prostate cancer, with 36.25 Gy in 5 fractions the most commonly used regimen. We explored the preliminary efficacy, patient recorded toxicity, and decision regret in intermediate- and high-risk prostate cancer receiving SBRT with prostate-specific membrane antigen (PSMA)/magnetic resonance imaging (MRI) guided focal gross tumor volume boost to 45 Gy. Between July 2015 and June 2019, 120 patients received SBRT across 2 institutions with a uniform protocol. All patients had fiducial markers and hydrogel, MRI and PSMA positron emission tomography (PET) scan. All patients received a questionnaire asking the degree of urinary, bowel, and sexual bother experienced at set time points, including questions about treatment choice and decision regret. One hundred twelve of 120 patients consented. Their median age was 72 years and median follow-up was 2.3 years. As per National Comprehensive Cancer Network guidelines, 78% had intermediate risk and 20% high risk. Androgen deprivation was combined with radiation in 6 patients. Most patients (74%) reported that receiving SBRT significantly influenced their choice of treatment. Five men (4%) expressed "quite a lot" (n = 4) or "very much" regret (n = 1) regarding their choice of treatment, while 89% expressed "no regret." Similar to pretreatment levels, "quite a lot" or "very much" urinary or bowel bother was expressed in 8% and 6% of patients, respectively. Two patients experienced nadir +2 biochemical failure, both found to have bone metastases. A third patient underwent PSMA PET at nadir +1.7 and had disease at the penile bulb, which was out of field. Three year estimated freedom from biochemical failure was 99% for intermediate and 85% for high-risk groups. We have demonstrated promising efficacy and low toxicity with PSMA/MRI-guided SBRT focal boost. Less than 5% of patients expressed significant decision regret for their choice of treatment.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2019
Publisher: Springer Science and Business Media LLC
Date: 08-2021
DOI: 10.1007/S00520-021-06454-9
Abstract: Scan-associated anxiety ('scanxiety') is a problem for people with advanced cancer. We aimed to determine the prevalence, severity and associations of scanxiety in this population. People with advanced cancer and a computed tomography scan within the last 4 months completed a multicentre survey including self-rated presence (yes/no) and severity (distress thermometer, 0-10) of scanxiety, state anxiety (STAI-6), clinical anxiety and depression (HADS), and fear of progression (FOP-Q-SF). Associations with scanxiety were evaluated. There were 222 participants: mean age 64 years (range 26 to 91), female (61%), most common cancer types (breast 37%, lung 19%, colorectal 16%) and > 1 year since cancer diagnosis (82%). Sixty-two percent had a scan within the last month, and 70% reported waiting > 2 days for the result. Over half (55%) of participants experienced scanxiety. On multivariable analysis, scanxiety was more prevalent in participants who were younger (mean age 62 years with v 66 years without scanxiety, p = 0.02) and more remote (v major city, OR 2.6, p = 0.04). Among participants with scanxiety, the mean severity score was 6 (range 1-10) with peak severity occurring when waiting for scan results. On multivariable analysis, scanxiety was 1.2 points higher in participants who had been diagnosed within the past year (v > 1 year, p = 0.04) and was higher in participants who had higher STAI-6 scores (β = 0.06, p = 0.004). Scanxiety is common and can be severe. Strategies to reduce scanxiety are needed.
Publisher: Springer Science and Business Media LLC
Date: 15-09-2023
Publisher: Wiley
Date: 21-10-2021
DOI: 10.1002/JCSM.12829
Abstract: Computed tomography (CT)‐defined skeletal muscle depletion and malnutrition are demonstrated as poor prognostic factors in patients with head and neck cancer (HNC), however to date, have only been explored in isolation. We aimed to describe body composition profile and examine the impact of nutritional status as well as independently and concurrently occurring body composition features on overall survival, treatment completion, unplanned admissions and length of stay (LOS) in patients undergoing radiotherapy (RT) or chemoradiotherapy (CRT) of curative intent for HNC. This work is a retrospective, observational study of patients who had completed treatment of curative intent for HNC. Scored Patient‐Generated Subjective Global Assessment (PG‐SGA) was used to determine nutritional status. Tissue‐density data were derived at the third lumbar vertebra (L3) with sarcopenia and myosteatosis defined by published, sex‐specific threshold values stratified by body mass index for skeletal muscle index (cm 2 /m 2 ) and skeletal muscle radiodensity (SMR, Hounsfield Unit). Pre‐treatment data ( n = 277: 78% male, mean (SD) age 60 (13) years) revealed the prevalence of malnutrition (24.9%), sarcopenia (52.3%), myosteatosis (82.3%), and concurrently occurring sarcopenia and myosteatosis (39.7%). Malnutrition was independently associated with reduced OS for patients with moderate [hazard ratio (HR) 2.57 95% confidence interval (CI) 1.45–4.55, P = 0.001] and severe (HR 3.19 95% CI 1.44–7.07, P = 0.004) malnutrition on multivariable analysis but not sarcopenia (HR 1.09 95% CI 0.70–1.71), P = 0.700 or myosteatosis (HR 1.28 95% CI 0.57–2.84), P = 0.500). Malnutrition was associated with treatment discontinuation ( P 0.001), not completing RT as planned ( P 0.001), unplanned hospital admission ( P = 0.021), and greater LOS ( P 0.001). Skeletal muscle status features were associated with unplanned hospital admissions for those with no features (32%), with sarcopenia only (50%), myosteatosis only (25%), and concurrent sarcopenia and myosteatosis (50%), P 0.001. Similarly, a clinically relevant greater median (Q1, Q3) LOS was observed for those with sarcopenia only [5 (3, 32)], myosteatosis only [10 (5, 30)], concurrent sarcopenia, and myosteatosis [14 (4, 33)] days vs. those with no features [3 (2, 11)] days, P = 0.2. Malnutrition was a more powerful prognostic indicator than CT‐defined skeletal muscle depletion and was independently associated with reduced OS in patients undergoing RT or CRT of curative intent for HNC. CT‐defined skeletal muscle depletion studies should recognize the multifaceted nature of human body composition and also measure nutritional status using validated methods in order to move towards developing a typology of high risk criteria for this complex patient group.
No related grants have been discovered for Chris Brown.