Sir Peter MacCallum Department of Oncology - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 17
-
ItemNo Preview AvailableLong-Term Outcomes of TROG 13.01 SAFRON II Randomized Trial of Single- Versus Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases(LIPPINCOTT WILLIAMS & WILKINS, 2023-07-01)Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In a randomized phase II clinical trial, the Trans Tasman Radiation Oncology Group compared single- versus multifraction stereotactic ablative body radiotherapy (SABR) in 90 patients with 133 oligometastases to the lung. The study found no differences in safety, efficacy, systemic immunogenicity, or survival between arms, with single-fraction SABR picked as the winner on the basis of cost-effectiveness. In this article, we report the final updated survival outcome analysis. The protocol mandated no concurrent or post-therapy systemic therapy until progression. Modified disease-free survival (mDFS) was defined as any progression not addressable by local therapy, or death. At a median follow-up of 5.4 years, the 3- and 5-year estimates for overall survival (OS) were 70% (95% CI, 59 to 78) and 51% (95% CI, 39 to 61). There were no significant differences between the multi- and single-fraction arms for OS (hazard ratio [HR], 1.1 [95% CI, 0.6 to 2.0]; P = .81). The 3- and 5-year estimates for disease-free survival were 24% (95% CI, 16 to 33) and 20% (95% CI, 13 to 29), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.6]; P = .92). The 3- and 5-year estimates for mDFS were 39% (95% CI, 29 to 49) and 34% (95% CI, 24 to 44), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.8]; P = .90). In this patient population, where patients receive SABR in lieu of systemic therapy, one-in-three patients are alive without disease in the long term. There were no differences in outcomes by fractionation schedule.
-
ItemNo Preview AvailableEarly circulating tumor DNA dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC(ELSEVIER IRELAND LTD, 2023-11)BACKGROUND: The kinetics of circulating tumor DNA (ctDNA) release following commencement of radiotherapy or chemoradiotherapy may reflect early tumour cell killing. We hypothesised that an increase in ctDNA may be observed after the first fraction of radiotherapy and that this could have clinical significance. MATERIALS AND METHODS: ctDNA analysis was performed as part of a prospective, observational clinical biomarker study of non-small cell lung cancer (NSCLC) patients, treated with curative-intent radiotherapy or chemoradiotherapy. Blood was collected at predefined intervals before, during (including 24 h after fraction 1 of radiotherapy) and after radiotherapy/chemoradiotherapy. Mutation-specific droplet digital PCR assays used to track ctDNA levels during and after treatment. RESULTS: Sequential ctDNA results are available for 14 patients with known tumor-based mutations, including in EGFR, KRAS and TP53, with a median follow-up of 723 days (range 152 to 1110). Treatments delivered were fractionated radiotherapy/chemoradiotherapy, in 2-2.75 Gy fractions (n = 12), or stereotactic ablative body radiotherapy (SABR, n = 2). An increase in ctDNA was observed after fraction 1 in 3/12 patients treated with fractionated radiotherapy with a complete set of results, including in 2 cases where ctDNA was initially undetectable. Neither SABR patient had detectable ctDNA immediately before or after radiotherapy, but one of these later relapsed systemically with a high detected ctDNA concentration. CONCLUSIONS: A rapid increase in ctDNA levels was observed after one fraction of fractionated radiotherapy in three cases. Further molecular characterization will be required to understand if a "spike" in ctDNA levels could represent rapid initial tumor cell destruction and could have clinical value as a surrogate for early treatment response and/or as a means of enriching ctDNA for mutational profiling.
-
ItemPredicting muscle loss during lung cancer treatment (PREDICT): protocol for a mixed methods prospective study(BMJ PUBLISHING GROUP, 2021-09)INTRODUCTION: Low muscle mass and low muscle attenuation (radiodensity), reflecting increased muscle adiposity, are prevalent muscle abnormalities in people with lung cancer receiving curative intent chemoradiation therapy (CRT) or radiation therapy (RT). Currently, there is a limited understanding of the magnitude, determinants and clinical significance of these muscle abnormalities in the lung cancer CRT/RT population. The primary objective of this study is to identify the predictors of muscle abnormalities (low muscle mass and muscle attenuation) and their depletion over time in people with lung cancer receiving CRT/RT. Secondary objectives are to assess the magnitude of change in these parameters and their association with health-related quality of life, treatment completion, toxicities and survival. METHODS AND ANALYSIS: Patients diagnosed with lung cancer and planned for treatment with CRT/RT are invited to participate in this prospective observational study, with a target of 120 participants. The impact and predictors of muscle abnormalities (assessed via CT at the third lumbar vertebra) prior to and 2 months post CRT/RT on the severity of treatment toxicities, treatment completion and survival will be assessed by examining the following variables: demographic and clinical factors, weight loss, malnutrition, muscle strength, physical performance, energy and protein intake, physical activity and sedentary time, risk of sarcopenia (Strength, Assistance in walking, Rise from a chair, Climb stairs, Falls history (SARC-F) score alone and with calf-circumference) and systemic inflammation. A sample of purposively selected participants with muscle abnormalities will be invited to take part in semistructured interviews to understand their ability to cope with treatment and explore preference for treatment strategies focused on nutrition and exercise. ETHICS AND DISSEMINATION: The PREDICT study received ethics approval from the Human Research Ethics Committee at Peter MacCallum Cancer Centre (HREC/53147/PMCC-2019) and Deakin University (2019-320). Findings will be disseminated through peer review publications and conference presentations.
-
Item
-
ItemNo Preview AvailableAn International Expert Survey on the Indications and Practice of Radical Thoracic Reirradiation for Non-Small Cell Lung Cancer(ELSEVIER INC, 2021)PURPOSE: Thoracic reirradiation for non-small cell lung cancer with curative intent is potentially associated with severe toxicity. There are limited prospective data on the best method to deliver this treatment. We sought to develop expert consensus guidance on the safe practice of treating non-small cell lung cancer with radiation therapy in the setting of prior thoracic irradiation. METHODS AND MATERIALS: Twenty-one thoracic radiation oncologists were invited to participate in an international Delphi consensus process. Guideline statements were developed and refined during 4 rounds on the definition of reirradiation, selection of appropriate patients, pretreatment assessments, planning of radiation therapy, and cumulative dose constraints. Consensus was achieved once ≥75% of respondents agreed with a statement. Statements that did not reach consensus in the initial survey rounds were revised based on respondents' comments and re-presented in subsequent rounds. RESULTS: Fifteen radiation oncologists participated in the 4 surveys between September 2019 and March 2020. The first 3 rounds had a 100% response rate, and the final round was completed by 93% of participants. Thirty-three out of 77 statements across all rounds achieved consensus. Key recommendations are as follows: (1) appropriate patients should have a good performance status and can have locally relapsed disease or second primary cancers, and there are no absolute lung function values that preclude reirradiation; (2) a full diagnostic workup should be performed in patients with suspected local recurrence and; (3) any reirradiation should be delivered using optimal image guidance and highly conformal techniques. In addition, consensus cumulative dose for the organs at risk in the thorax are described. CONCLUSIONS: These consensus statements provide practical guidance on appropriate patient selection for reirradiation, appropriate radiation therapy techniques, and cumulative dose constraints.
-
ItemA Deep Learning Model to Automate Skeletal Muscle Area Measurement on Computed Tomography Images(FRONTIERS MEDIA SA, 2021-05-07)BACKGROUND: Muscle wasting (Sarcopenia) is associated with poor outcomes in cancer patients. Early identification of sarcopenia can facilitate nutritional and exercise intervention. Cross-sectional skeletal muscle (SM) area at the third lumbar vertebra (L3) slice of a computed tomography (CT) image is increasingly used to assess body composition and calculate SM index (SMI), a validated surrogate marker for sarcopenia in cancer. Manual segmentation of SM requires multiple steps, which limits use in routine clinical practice. This project aims to develop an automatic method to segment L3 muscle in CT scans. METHODS: Attenuation correction CTs from full body PET-CT scans from patients enrolled in two prospective trials were used. The training set consisted of 66 non-small cell lung cancer (NSCLC) patients who underwent curative intent radiotherapy. An additional 42 NSCLC patients prescribed curative intent chemo-radiotherapy from a second trial were used for testing. Each patient had multiple CT scans taken at different time points prior to and post- treatment (147 CTs in the training and validation set and 116 CTs in the independent testing set). Skeletal muscle at L3 vertebra was manually segmented by two observers, according to the Alberta protocol to serve as ground truth labels. This included 40 images segmented by both observers to measure inter-observer variation. An ensemble of 2.5D fully convolutional neural networks (U-Nets) was used to perform the segmentation. The final layer of U-Net produced the binary classification of the pixels into muscle and non-muscle area. The model performance was calculated using Dice score and absolute percentage error (APE) in skeletal muscle area between manual and automated contours. RESULTS: We trained five 2.5D U-Nets using 5-fold cross validation and used them to predict the contours in the testing set. The model achieved a mean Dice score of 0.92 and an APE of 3.1% on the independent testing set. This was similar to inter-observer variation of 0.96 and 2.9% for mean Dice and APE respectively. We further quantified the performance of sarcopenia classification using computer generated skeletal muscle area. To meet a clinical diagnosis of sarcopenia based on Alberta protocol the model achieved a sensitivity of 84% and a specificity of 95%. CONCLUSIONS: This work demonstrates an automated method for accurate and reproducible segmentation of skeletal muscle area at L3. This is an efficient tool for large scale or routine computation of skeletal muscle area in cancer patients which may have applications on low quality CTs acquired as part of PET/CT studies for staging and surveillance of patients with cancer.
-
ItemAdverse respiratory outcomes following conventional long-course radiotherapy for non-small-cell lung cancer in patients with pre-existing pulmonary fibrosis: A comparative retrospective study(WILEY, 2020-08)INTRODUCTION: There is some evidence to suggest that patients with underlying pulmonary fibrosis (PF) have increased risk of adverse respiratory and survival outcomes, when treated with conventional, long-course radiotherapy (RT) for non-small-cell lung cancer (NSCLC). We performed a retrospective analysis to determine the size of these risks. METHODS: Data from 21 patients with PF (cases) were retrospectively analysed for respiratory toxicity and mortality outcomes, and compared with 84 patients without PF (non-cases). Age and mean lung dose were included as covariates in regression analyses. The additional predictive value of other patient, disease and treatment characteristics on radiation pneumonitis (RP) risk and severity was explored. RESULTS: There was a numerical (though not statistically significant) increase in grade ≥ 2 RP among PF cases (OR 2.74, P = 0.074). Cases were significantly more likely to discontinue radical treatment early (OR 6.10, P = 0.015). There was a significant association between increased RP severity and underlying PF (P = 0.039), with RP strongly implicated in the death in 3 of 21 cases (14.3%) compared to 1 non-case (1.2%). Cases experienced increased grade ≥ 2 respiratory toxicity otherwise (OR 4.35, P = 0.020) and poorer median overall survival (0.6 versus 1.7 years, P < 0.001). Two cases, and no non-cases, died during the proposed RT period. None of the analysed patient, disease or treatment factors, was a significant additional predictor of RP risk/severity. CONCLUSION: Patients with PF are at increased risk of treatment discontinuation, respiratory morbidity and mortality, and poor survival following conventional RT for NSCLC. Caution should be exercised when offering high-dose RT to these patients.
-
ItemSingle-arm prospective interventional study assessing feasibility of using gallium-68 ventilation and perfusion PET/CT to avoid functional lung in patients with stage III non-small cell lung cancer(BMJ PUBLISHING GROUP, 2020)BACKGROUND: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning systems, enabling conformal avoidance of highly functioning regions of lung, thereby facilitating increased doses to tumour while reducing normal tissue doses. METHODS AND ANALYSIS: This prospective interventional study will investigate the use of ventilation and perfusion PET/CT to identify highly functioning lung volumes and avoidance of these using VMAT planning. This single-arm trial will be conducted across two large public teaching hospitals in Australia. Twenty patients with stage III non-small cell lung cancer will be recruited. All patients enrolled will receive dose-escalated (69 Gy) functional avoidance radiation therapy. The primary endpoint is feasibility with this achieved if ≥15 out of 20 patients meet pre-defined feasibility criteria. Patients will be followed for 12 months post-treatment with serial imaging, biomarkers, toxicity assessment and quality of life assessment. DISCUSSION: Using advanced techniques such as VMAT functionally adapted radiation therapy may enable safe moderate dose escalation with an aim of improving local control and concurrently decreasing treatment related toxicity. If this technique is proven feasible, it will inform the design of a prospective randomised trial to assess the clinical benefits of functional lung avoidance radiation therapy. ETHICS AND DISSEMINATION: This study was approved by the Peter MacCallum Human Research Ethics Committee. All participants will provide written informed consent. Results will be disseminated via publications. TRIALS REGISTRATION NUMBER: NCT03569072; Pre-results.
-
ItemNo Preview AvailableSystematic endobronchial ultrasound-guided transbronchial needle aspiration improves radiotherapy planning in non-small cell lung cancer(European Respiratory Society, 2019-07)Objectives: Patients suitable for radical chemoradiotherapy for lung cancer routinely have radiotherapy (planning) volumes based on positron emission tomography (PET)-computed tomography (CT) imaging alone. Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) can identify PET-occult malignancy and benign PET-avid regions. We investigated the impact of EBUS-TBNA on curative-intent radiotherapy in non-small cell lung cancer (NSCLC). Methods: A prospective multicentre trial was undertaken, investigating the impact of systematic EBUS-TBNA in addition to PET-CT for patients considered for radical chemoradiotherapy with NSCLC. A subset analysis of patients with discordant findings between PET-CT and EBUS-TBNA was performed. Radiotherapy plans investigated tumour coverage and dose to critical organs at risk (OARs) using PET-CT alone in comparison to PET-CT and EBUS-TBNA. Results: Of 30 patients enrolled, 10 had discordant findings between PET-CT and EBUS-TBNA. EBUS-TBNA-derived plans allowed for reduction in dose to OARs in patients downstaged by EBUS-TBNA, and reduced the risk of geographic miss in treating PET-occult disease in four patients where EBUS-TBNA identified malignant involvement of PET-negative lymphadenopathy. With the addition of EBUS-TBNA to radiotherapy planning, reductions were noted of 5.7%, 3.7% and 12.5% for the risks of symptomatic pneumonitis, mean heart dose and mean oesophageal dose, respectively. Conclusions: This study demonstrates for the first time that systematic EBUS-TBNA prior to radical-intent radiotherapy significantly improves coverage of subclinical disease through detection of PET-occult metastases. Identification of false-positive lymph node involvement in highly selected cases may reduce radiation dose to critical structures, and risk of organ toxicity.
-
ItemNo Preview AvailableCuring Operable Stage I Non-Small Cell Lung Cancer With Stereotactic Ablative Body Radiotherapy: The Force Awakens(WILEY, 2016-04)In 2016, surgery is the standard of care for peripheral stage I non-small cell lung cancer. However, recent thought-provoking randomized evidence suggests stereotactic ablative body radiotherapy (SABR) has survival outcomes similar to those of surgery. Albeit limited, patient-reported outcomes and quality of life suggest that SABR compares favorably to surgery because it is noninvasive and associated with relatively few treatment-related complications. This article explores the current scientific landscape of surgery and SABR in this patient cohort.