Sir Peter MacCallum Department of Oncology - Research Publications
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ItemLarge variation in radiation therapy fractionation for multiple myeloma in Australia(WILEY, 2023-02)AIM: To evaluate the patterns of use of different radiation therapy (RT) fractionation for multiple myeloma (MM) bone disease. METHODS: 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. RESULTS: 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. CONCLUSION: There is increasing use of shorter course RT (2-5 fractions) for MM over time. SFRT use remains low, with large variation in practice.
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ItemVariations in whole brain radiation therapy fractionation for brain metastases in Victoria(WILEY, 2022-12)INTRODUCTION: We aim to evaluate the use of different whole brain radiation therapy (WBRT) fractionation schedules for brain metastases (BM) in Victoria, and the factors associated with it. METHODS: This is a population-based cohort of patients who received radiation therapy for BM between 2012 and 2017, as captured in the Victorian Radiotherapy Minimum Dataset. We excluded patients with primary brain tumour and those who had 'prophylactic' intent treatment. The Cochran-Armitage test was used to evaluate changing trend in WBRT fractionation. Multivariate multinomial logistic regressions were used to evaluate factors associated with WBRT fractionation. RESULTS: Of the 3111 patients who had WBRT, 1048 (45%), 1291 (42%) and 312 (13%) had ≤5, 6-10 and >10 fractions WBRT respectively. There was progressive increase in ≤5 fractions WBRT use over time, from 37% in 2012 to 50% in 2017 (P-trend < 0.001). In multivariate analyses, increasing age, patients with gastrointestinal cancer, patients living in remote/regional areas and more recent treatment were associated with the use of shorter WBRT fractionation (≤5 fractions), while patients who had WBRT plus stereotactic radiosurgery, and those treated in private institutions were associated with the use of prolonged WBRT fractionation (≥6 fractions). Three hundred eighty-nine (13%) patients died within 30 days of WBRT, of which 241 (64%), 119 (32%) and 17 (5%) had ≤5, 6-10 and > 10 fractions WBRT respectively. CONCLUSION: We observed large variations in WBRT fractionation that are associated with patient, tumour, treatment and institutional factors. It is important to continuously monitor and benchmark our practice in order to reduce potentially unwarranted variations.
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ItemDisparities in radiation therapy utilization for cancer patients in Victoria(WILEY, 2022-09)INTRODUCTION: To evaluate the proportion of cancer patients who received radiation therapy (RT) within 12 months of cancer diagnosis (RTU12) and identify factors associated with RTU12. METHODS: This is a population-based cohort of individuals with incident cancer, diagnosed between 2013 and 2017 in Victoria. Data linkages were performed between the Victorian Cancer Registry and Victorian Radiotherapy Minimum Dataset. The primary outcome was the proportion of patients who had RTU12. For the three most common cancers (i.e., prostate, breast and lung cancer), the time trend in RTU12 and factors associated with RTU12 were evaluated. RESULTS: The overall RTU12 in our study cohort was 26-20% radical RT and 6% palliative RT. Of the 21,735 men with prostate cancer, RTU12 was 17%, with no significant change over time (P-trend = 0.53). In multivariate analyses, increasing age and lower socioeconomic status were independently associated with higher RTU12 for prostate cancer. Of the 20,883 women with breast cancer, RTU12 was 64%, which increased from 62% in 2013 to 65% in 2017 (P-trend < 0.05). In multivariate analyses, age, socioeconomic status and area of residency were independently associated with RTU12 for breast cancer. Of the 13,093 patients with lung cancer, RTU12 was 42%, with no significant change over time (P-trend = 0.16). In multivariate analyses, younger age, male and lower socioeconomic status were independently associated with higher RTU12. CONCLUSION: In this large population-based state-wide cohort of cancer patients, only 1 in 4 had RT within 12 months of diagnosis. There were marked sociodemographic disparities in RTU12 for prostate, breast and lung cancer patients.
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ItemImportance of quality in radiation oncology(WILEY, 2017-10)
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ItemPatterns of health services utilization in the last two weeks of life among cancer patients: Experience in an Australian academic cancer center(WILEY, 2017-12)AIM: To report the trend in end-of-life health services (HS) utilization among cancer patients treated in a large Australian academic cancer center over a 12-year period. METHODS: This is a retrospective study of cancer patients treated at the Peter MacCallum Cancer Centre (PMCC), who had documented death between January 2002 and December 2013. Using administrative and billing database, we report on the utilization of different categories of HS within two weeks of death: diagnostic investigations (pathology and radiology), inpatient and outpatient services, and potentially futile interventions (PFI, which include radiotherapy, chemotherapy and surgery). RESULTS: Of the 27 926 "active" cancer patients in the study (i.e. those with medical contact at PMCC in the last year of life), 6368 (23%) had documented HS utilization within two weeks of death. 11% and 9% had pathology and radiology investigations respectively, 14% had outpatient clinic appointments, and 7% had hospital admissions. There were 2654 patients (10%) who had PFI within two weeks of death - 2198 (8%) had radiotherapy, 287 (1%) chemotherapy and 267 (1%) surgery. We observed peak HS and PFI utilization in 2004, which then dropped to its lowest in 2009/2010. CONCLUSION: Experience in an Australian cancer center suggests approximately one in four "active" cancer patients had HS utilization, and one in ten had PFI, within two weeks of death. The implementation of palliative care guidelines may reduce some of these potentially wasteful and futile interventions.
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ItemStereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial(WILEY, 2017-11)OBJECTIVE: To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess oncological and functional outcomes. MATERIALS AND METHODS: This was a prospective interventional clinical trial with institutional ethics board approval. Inoperable patients were enrolled, after multidisciplinary consensus, for intervention with informed consent. Tumour response was defined using Response Evaluation Criteria In Solid Tumors v1.1. Toxicities were recorded using Common Terminology Criteria for Adverse Events v4.0. Time-to-event outcomes were described using the Kaplan-Meier method, and associations of baseline variables with tumour shrinkage was assessed using linear regression. Patients received either single fraction of 26 Gy or three fractions of 14 Gy, dependent on tumour size. RESULTS: Of 37 patients (median age 78 years), 62% had T1b, 35% had T1a and 3% had T2a disease. One patient presented with bilateral primaries. Histology was confirmed in 92%. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). The median follow-up was 24 months. Treatment-related grade 1-2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4-5 toxicities were recorded and six patients (18%) reported no toxicity. Freedom from local progression, distant progression and overall survival rates at 2 years were 100%, 89% and 92%, respectively. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (P < 0.001). Neutrophil:lymphocyte ratio correlated to % change in tumour size at 1 year, r2 = 0.45 (P < 0.001). CONCLUSION: The study results show that SABR for primary RCC was feasible and well tolerated. We observed encouraging cancer control, functional preservation and early survival outcomes in an inoperable cohort. Baseline neutrophil:lymphocyte ratio may be predictive of immune-mediated response and warrants further investigation.
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ItemA retrospective review of the long-term outcomes of online adaptive radiation therapy and conventional radiation therapy for muscle invasive bladder cancer(ELSEVIER IRELAND LTD, 2021-09)BACKGROUND AND PURPOSE: To report long-term outcomes of online image-guided (IG) adaptive radiation therapy (aRT) versus conventional IG radiation therapy (cRT) for bladder preservation in muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: A retrospective review of patients with histologically proven MIBC who were prescribed radical intent radiation therapy (RT) following trans-urethral resection of bladder tumour (TURBT) was conducted. There were three groups based on their RT treatment modality: conventional RT (cRT), margin 5 mm adaptive RT (aRT5mm) and margin 7 mm adaptive RT (aRT7mm). RESULTS: 171 patients were included in this study, with median age of 79.4 years (41-90). Approximately half of all patients received concurrent chemotherapy. N = 57 underwent cRT, n = 39 underwent aRT5mm, and n = 75 underwent aRT7mm. Response evaluable patients in all three groups (n = 133) had high rates of complete response (CR, 83%) on first post-RT cystoscopy with no significant differences between the groups. At a median follow-up of 54 months, the 5-year freedom from muscle-invasive failure survival (FFMIFS) in the cRT, aRT5mm, and aRT7mm groups were 75%, 59%, and 98%, respectively. The estimated cancer specific survival (CSS) at 5 years were 60%, 30%, and 59%, respectively. The estimated overall survival (OS) at 5 years were 43%, 26%, and 38%, respectively. The incidence of late grade 3 or 4 toxicity was n = 5 in aRT5mm, n = 2 in cRT group, and n = 1 in aRT7mm. CONCLUSION: IG aRT with 7 mm expansion for MIBC provides higher rates of FFMIFS, similar 5-year CSS and OS, as well as toxicity outcomes when compared to cRT. aRT with 5 mm expansion with this RT protocol is not recommended for treatment.
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ItemPersonalising treatment plan quality review with knowledge-based planning in the TROG 15.03 trial for stereotactic ablative body radiotherapy in primary kidney cancer(BMC, 2021-08-03)INTRODUCTION: Quality assurance (QA) of treatment plans in clinical trials improves protocol compliance and patient outcomes. Retrospective use of knowledge-based-planning (KBP) in clinical trials has demonstrated improved treatment plan quality and consistency. We report the results of prospective use of KBP for real-time QA of treatment plan quality in the TROG 15.03 FASTRACK II trial, which evaluates efficacy of stereotactic ablative body radiotherapy (SABR) for kidney cancer. METHODS: A KBP model was generated based on single institution data. For each patient in the KBP phase (open to the last 31 patients in the trial), the treating centre submitted treatment plans 7 days prior to treatment. A treatment plan was created by using the KBP model, which was compared with the submitted plan for each organ-at-risk (OAR) dose constraint. A report comparing each plan for each OAR constraint was provided to the submitting centre within 24 h of receiving the plan. The centre could then modify the plan based on the KBP report, or continue with the existing plan. RESULTS: Real-time feedback using KBP was provided in 24/31 cases. Consistent plan quality was in general achieved between KBP and the submitted plan. KBP review resulted in replan and improvement of OAR dosimetry in two patients. All centres indicated that the feedback was a useful QA check of their treatment plan. CONCLUSION: KBP for real-time treatment plan review was feasible for 24/31 cases, and demonstrated ability to improve treatment plan quality in two cases. Challenges include integration of KBP feedback into clinical timelines, interpretation of KBP results with respect to clinical trade-offs, and determination of appropriate plan quality improvement criteria.
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ItemProximal seminal vesicle displacement and margins for prostate cancer radiotherapy(WILEY, 2021-09)INTRODUCTION: Guidelines recommend that the proximal seminal vesicles (PrSV) should be included in the clinical target volume for locally advanced prostate cancer patients undergoing radiotherapy. Verification and margins for the prostate may not necessarily account for PrSV displacement. The purpose was to determine the inter-fraction displacement of the PrSV relative to the prostate during radiotherapy. METHODS: Fiducials were inserted into the prostate, and right and left PrSV (RSV and LSV) in 30 prostate cancer patients. Correctional shifts for the prostate, right and left PrSV and pelvic bones were determined from each patient's 39 daily orthogonal portal images relative to reference digitally reconstructed radiographs. RESULTS: There was a significant displacement of the RSV relative to the prostate in all directions: on average 0.38 mm (95% confidence interval (CI) 0.26 to 0.50) to the left, 0.80-0.81 mm (CI 0.68 to 0.93) superiorly and 1.51 mm (CI 1.36 to 1.65) posteriorly. The LSV was significantly displaced superiorly to the prostate 1.09-1.13 mm (CI 0.97 to 1.25) and posteriorly 1.81 mm (CI 1.67 to 1.96), but not laterally (mean 0.06, CI -0.06 to 0.18). The calculated PTV margins (left-right, superior-inferior, posterior-anterior) were 4.9, 5.3-5.6 and 4.8 mm for the prostate, 5.2, 7.1-8.0 and 9.7 mm for the RSV, and 7.2, 7.5-7.6 and 8.6 mm for the LSV. CONCLUSION: There is a significant displacement of the PrSV relative to the prostate during radiotherapy. Greater margins are recommended for the PrSV compared to the prostate.
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