Sir Peter MacCallum Department of Oncology - Research Publications
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ItemNo Preview AvailableThe Feasibility of Quality Assurance in the TOPGEAR International Phase 3 Clinical Trial of Neoadjuvant Chemoradiation Therapy for Gastric Cancer (an Intergroup Trial of the AGITG/TROG/NHMRC CTC/EORTC/CCTG)(ELSEVIER SCIENCE INC, 2023-12-01)PURPOSE: The TOPGEAR phase 3 trial hypothesized that adding preoperative chemoradiation therapy (CRT) to perioperative chemotherapy will improve survival in patients with gastric cancer. Owing to the complexity of gastric irradiation, a comprehensive radiation therapy quality assurance (RTQA) program was implemented. Our objective is to describe the RTQA methods and outcomes. METHODS AND MATERIALS: RTQA was undertaken in real time before treatment for the first 5 patients randomized to CRT from each center. Once acceptable quality was achieved, RTQA was completed for one-third of subsequent cases. RTQA consisted of evaluating (1) clinical target volume and organ-at-risk contouring and (2) radiation therapy planning parameters. Protocol violations between high- (20+ patients enrolled) and low-volume centers were compared using the Fisher exact test. RESULTS: TOPGEAR enrolled 574 patients, of whom 286 were randomized to receive preoperative CRT and 203 (71%) were included for RTQA. Of these, 67 (33%) and 136 (67%) patients were from high- and low-volume centers, respectively. The initial RTQA pass rate was 72%. In total, 28% of cases required resubmission. In total, 200 of 203 cases (99%) passed RTQA before treatment. Cases from low-volume centers required resubmission more often (44/136 [33%] vs 13/67 [18%]; P = .078). There was no change in the proportion of cases requiring resubmission over time. Most cases requiring resubmission had multiple protocol violations. At least 1 aspect of the clinical target volume had to be adjusted in all cases. Inadequate coverage of the duodenum was most common (53% major violation, 25% minor violation). For the remaining cases, the resubmission process was triggered secondary to poor contour/plan quality. CONCLUSIONS: In a large multicenter trial, RTQA is feasible and effective in achieving high-quality treatment plans. Ongoing education should be performed to ensure consistent quality during the entire study period.
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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.
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ItemImpact through versatility: Patterns of in vivo dosimetry utilization with TLD across a large multi-site radiotherapy department(FRONTIERS MEDIA SA, 2022-10-18)The complexity of modern radiotherapy treatment pathways necessitate input from different professions to ensure treatment is delivered safely and as planned. In vivo dosimetry is one method of treatment verification providing the opportunity for both in-field verification or out-of-field measurements. It was the aim of this work to review the impact of an in vivo dosimetry programme with t.he view to justify resources and assist in developing a plan for equipment acquisition. Results of 310 (approximately 2 per 1000 treatment fractions) in vivo measurements were reviewed over a two-year time span. The in vivo dosimetry programme using thermoluminescence (TLD) chips was able to detect three significant treatment errors, amongst some 13 000 patients treated. These errors would likely to have been undetected through other quality assurance measures. Increasing demands in workload were found to be associated with commissioning of new equipment and techniques. A skilled operator with knowledge of TLD physics, treatment planning system (TPS) dose calculation algorithms and radiation transport proved to be essential for appropriate interpretation of TLD results particularly in complex radiation delivery scenarios. TLD continues to play a large role in patient safety and quality assurance at our institution.
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ItemTreatment Time Optimization in Single Fraction Stereotactic Ablative Radiation Therapy: A 10-Year Institutional Experience(ELSEVIER INC, 2022)PURPOSE: Stereotactic ablative radiation therapy (SABR) delivered in a single fraction (SF) can be considered to have higher uncertainty given that the error probability is concentrated in a single session. This study aims to report the variation in technology and technique used and its effect on intrafraction motion based on a 10 years of experience in SF SABR. METHODS AND MATERIALS: Records of patients receiving SF SABR delivered at our instruction between 2010 and 2019 were included. Treatment parameters were extracted from the patient management database by using an in-house script. Treatment time was defined as the time difference between the first image acquisition to the last beam off of a single session. The intrafraction variation was measured from the 3-dimensional couch displacement measured after the first cone beam computed tomography (CBCT) acquired during a treatment. RESULTS: The number of SF SABR increased continuously from 2010 to 2019 and were mainly lung treatments. Treatment time was minimized by using volumetric modulated arc therapy, flattening filter-free dose rate, and coplanar field (24 ± 9 min). Treatment time increased as the number of CBCTs per session increased. The most common scenario involved both 2 and 3 CBCTs per session. On the average, a CBCT acquisition added 6 minutes to the treatment time. All treatments considered, the average intrafraction variation was 1.7 ± 1.6 mm. CONCLUSIONS: SF SABR usage increased with time in our institution. The intrafraction motion was acceptable and therefore a single fraction is an efficacious treatment option when considering SABR.
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ItemFirst clinical experience with real-time portal imaging-based breath-hold monitoring in tangential breast radiotherapy(ELSEVIER, 2022-10)BACKGROUND AND PURPOSE: Real-time treatment monitoring with the electronic portal imaging device (EPID) can conceptually provide a more accurate assessment of the quality of deep inspiration breath-hold (DIBH) and patient movement during tangential breast radiotherapy (RT). A system was developed to measure two geometrical parameters, the lung depth (LD) and the irradiated width (named here skin distance, SD), along three user-selected lines in MV EPID images of breast tangents. The purpose of this study was to test the system during tangential breast RT with DIBH. MATERIALS AND METHODS: Measurements of LDs and SDs were carried out in real time. DIBH was guided with a commercial system using a marker block. Results from 17 patients were assessed. Mean midline LDs, , per tangent were compared to the planned mLDs; differences between the largest and smallest observed () per tangent were calculated. RESULTS: For 56% (162/288) of the tangents tested, were outside the tolerance window. All but one patient had at least one fraction showing this behaviour. The largest difference found between an and its planned mLD was -16.9 mm. The accuracy of patient positioning and the quality of marker-block-based DIBH guidance contributed to the differences. Fractions with patient position verification using a single EPID image taken before treatment showed a lower rate (34%), suggesting reassessment of setup procedures. CONCLUSIONS: Real-time treatment monitoring of the internal anatomy during DIBH delivery of tangential breast RT is feasible and useful. The new system requires no additional radiation for the patient.
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ItemThe impact of inter-observer variation in delineation on robustness of radiomics features in non-small cell lung cancer(NATURE PORTFOLIO, 2022-07-27)Artificial intelligence and radiomics have the potential to revolutionise cancer prognostication and personalised treatment. Manual outlining of the tumour volume for extraction of radiomics features (RF) is a subjective process. This study investigates robustness of RF to inter-observer variation (IOV) in contouring in lung cancer. We utilised two public imaging datasets: 'NSCLC-Radiomics' and 'NSCLC-Radiomics-Interobserver1' ('Interobserver'). For 'NSCLC-Radiomics', we created an additional set of manual contours for 92 patients, and for 'Interobserver', there were five manual and five semi-automated contours available for 20 patients. Dice coefficients (DC) were calculated for contours. 1113 RF were extracted including shape, first order and texture features. Intraclass correlation coefficient (ICC) was computed to assess robustness of RF to IOV. Cox regression analysis for overall survival (OS) was performed with a previously published radiomics signature. The median DC ranged from 0.81 ('NSCLC-Radiomics') to 0.85 ('Interobserver'-semi-automated). The median ICC for the 'NSCLC-Radiomics', 'Interobserver' (manual) and 'Interobserver' (semi-automated) were 0.90, 0.88 and 0.93 respectively. The ICC varied by feature type and was lower for first order and gray level co-occurrence matrix (GLCM) features. Shape features had a lower median ICC in the 'NSCLC-Radiomics' dataset compared to the 'Interobserver' dataset. Survival analysis showed similar separation of curves for three of four RF apart from 'original_shape_Compactness2', a feature with low ICC (0.61). The majority of RF are robust to IOV, with first order, GLCM and shape features being the least robust. Semi-automated contouring improves feature stability. Decreased robustness of a feature is significant as it may impact upon the features' prognostic capability.
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ItemAssessing organ at risk position variation and its impact on delivered dose in kidney SABR(BMC, 2022-06-27)BACKGROUND: Delivered organs at risk (OARs) dose may vary from planned dose due to interfraction and intrafraction motion during kidney SABR treatment. Cases of bowel stricture requiring surgery post SABR treatment were reported in our institution. This study aims to provide strategies to reduce dose deposited to OARs during SABR treatment and mitigate risk of gastrointestinal toxicity. METHODS: Small bowel (SB), large bowel (LB) and stomach (STO) were delineated on the last cone beam CT (CBCT) acquired before any dose had been delivered (PRE CBCT) and on the first CBCT acquired after any dose had been delivered (MID CBCT). OAR interfraction and intrafraction motion were estimated from the shortest distance between OAR and the internal target volume (ITV). Adaptive radiation therapy (ART) was used if dose limits were exceeded by projecting the planned dose on the anatomy of the day. RESULTS: In 36 patients, OARs were segmented on 76 PRE CBCTs and 30 MID CBCTs. Interfraction motion was larger than intrafraction motion in STO (p-value = 0.04) but was similar in SB (p-value = 0.8) and LB (p-value = 0.2). LB was inside the planned 100% isodose in all PRE CBCTs and MID CBCTs in the three patients that suffered from bowel stricture. SB D0.03cc was exceeded in 8 fractions (4 patients). LB D1.5cc was exceeded in 4 fractions (2 patients). Doses to OARs were lowered and limits were all met with ART on the anatomy of the day. CONCLUSIONS: Interfraction motion was responsible for OARs overdosage. Dose limits were respected by using ART with the anatomy of the day.
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ItemNo Preview AvailableThe interlace deposition method of bone equivalent material extrusion 3D printing for imaging in radiotherapy(ELSEVIER SCI LTD, 2021-02-01)
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ItemReport dose-to-medium in clinical trials where available; a consensus from the Global Harmonisation Group to maximize consistency(ELSEVIER IRELAND LTD, 2021-06)PURPOSE: To promote consistency in clinical trials by recommending a uniform framework as it relates to radiation transport and dose calculation in water versus in medium. METHODS: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group (GHG; www.rtqaharmonization.org) compared the differences between dose to water in water (Dw,w), dose to water in medium (Dw,m), and dose to medium in medium (Dm,m). This was done based on a review of historical frameworks, existing literature and standards, clinical issues in the context of clinical trials, and the trajectory of radiation dose calculations. Based on these factors, recommendations were developed. RESULTS: No framework was found to be ideal or perfect given the history, complexity, and current status of radiation therapy. Nevertheless, based on the evidence available, the GHG established a recommendation preferring dose to medium in medium (Dm,m). CONCLUSIONS: Dose to medium in medium (Dm,m) is the preferred dose calculation and reporting framework. If an institution's planning system can only calculate dose to water in water (Dw,w), this is acceptable.
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ItemFeasibility of biology-guided radiotherapy using PSMA-PET to boost to dominant intraprostatic tumour(ELSEVIER IRELAND LTD, 2022-07)BACKGROUND: Biology-guided radiotherapy (BgRT) delivers dose to tumours triggered from positron emission tomography (PET) detection. Prostate specific membrane antigen (PSMA) PET uptake is abundant in the dominant intraprostatic lesion (DIL). This study investigates the feasibility of BgRT to PSMA-avid subvolume in the prostate region. METHODS: Patients enrolled in the prospective randomized trial ProPSMA at our institution were included (ID: ANZCTR12617000005358). Gross tumour volumes (GTVs) were delineated on the PET component of a PET/CT scan from a standardized uptake value (SUV) threshold technique. Suitability for BgRT requires a strong signal-to-background ratio with a surrounding tissue free of significant PSMA uptake. The signal-to-background ratio was quantified from the calculation of the normalized SUV (nSUV), defined as the ratio between SUVmax within the GTV and SUVmean inside a 3D margin expansion of the GTV. The PSMA distribution surrounding the tumour was quantified as a function of the distance from the GTV. RESULTS: In this cohort of 84 patients, 83 primary tumours were included. Prostate volume ranged from 19 cm3 to 148 cm3 (median = 52 cm3; IQR = 39 cm3 - 63 cm3). SUVmax inside the prostate was between 2 and 125 (median = 19; IQR = 11 - 30). More than 50% of GTVs generated with threshold between 25%SUVmax (median volume = 10.0 cm3; IQR = 4.5 cm3 - 20.0 cm3) and 50%SUVmax (median volume = 1.9 cm3; IQR = 1.1 cm3 - 3.8 cm3) were suitable for BgRT by using nSUV ≥ 3 and a margin expansion of 5 mm. CONCLUSIONS: It is feasible to identify GTVs suitable for BgRT in the prostate. These GTVs are characterized by a strong signal-to-background ratio and a surrounding tissue free of PSMA uptake.
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