[18]F-fluoroethyl-l-tyrosine positron emission tomography for radiotherapy target delineation: Results from a Radiation Oncology credentialing program.

Background and purpose: The [18]F-fluoroethyl-l-tyrosine (FET) PET in Glioblastoma (FIG) study is an Australian prospective, multi-centre trial evaluating FET PET for newly diagnosed glioblastoma management. The Radiation Oncology credentialing program aimed to assess the feasibility in Radiation Oncologist (RO) derivation of standard-of-care target volumes (TVMR) and hybrid target volumes (TVMR+FET) incorporating pre-defined FET PET biological tumour volumes (BTVs). Materials and methods: Central review and analysis of TVMR and TVMR+FET was undertaken across three benchmarking cases. BTVs were pre-defined by a sole nuclear medicine expert. Intraclass correlation coefficient (ICC) confidence intervals (CIs) evaluated volume agreement. RO contour spatial and boundary agreement were evaluated (Dice similarity coefficient [DSC], Jaccard index [JAC], overlap volume [OV], Hausdorff distance [HD] and mean absolute surface distance [MASD]). Dose plan generation (one case per site) was assessed. Results: Data from 19 ROs across 10 trial sites (54 initial submissions, 8 resubmissions requested, 4 conditional passes) was assessed with an initial pass rate of 77.8 %; all resubmissions passed. TVMR+FET were significantly larger than TVMR (p < 0.001) for all cases. RO gross tumour volume (GTV) agreement was moderate-to-excellent for GTVMR (ICC = 0.910; 95 % CI, 0.708-0.997) and good-to-excellent for GTVMR+FET (ICC = 0.965; 95 % CI, 0.871-0.999). GTVMR+FET showed greater spatial overlap and boundary agreement compared to GTVMR. For the clinical target volume (CTV), CTVMR+FET showed lower average boundary agreement versus CTVMR (MASD: 1.73 mm vs. 1.61 mm, p = 0.042). All sites passed the planning exercise. Conclusions: The credentialing program demonstrated feasibility in successful credentialing of 19 ROs across 10 sites, increasing national expertise in TVMR+FET delineation.

The safety, feasibility, and efficacy of an 18-week exercise intervention for adults with primary brain cancer - the BRACE study.

PURPOSE: To determine the safety, feasibility, and potential effect of an 18-week exercise intervention for adults with primary brain cancer. MATERIALS AND METHODS: Eligible patients were 12-26-weeks post-radiotherapy for brain cancer. The individually-prescribed weekly exercise was ≥150-minutes of moderate-intensity exercise, including two resistance-training sessions. The intervention was deemed "safe" if exercise-related, serious adverse events (SAE) were experienced by <10% of participants, and feasible if recruitment, retention, and adherence rates were ≥75%, and ≥75% compliance rates were achieved in ≥75% of weeks. Patient-reported and objectively-measured outcomes were assessed at baseline, mid-intervention, end-intervention, and 6-month follow-up, using generalized estimating equations. RESULTS: Twelve participants enrolled (51 ± 19.5 years, 5 females). There were no exercise-related SAEs. The intervention was feasible (recruitment:80%, retention:92%, adherence:83%). Participants completed a median of 172.8 (min:77.5, max:560.8) minutes of physical activity per week. 17% met the compliance outcome threshold for ≥75% of the intervention. Improvements in quality of life (mean change (95% CI): 7.9 units (1.9, 13.8)), functional well-being (4.3 units (1.4, 7.2)), depression (-2.0 units (-3.8, -0.2)), activity (112.8 min (42.1, 183.4)), fitness (56.4 meters (20.4, 92.5)), balance (4.9 s (0.9, 9.0)), and lower-body strength (15.2 kg (9.3, 21.1)) were observed end-intervention. CONCLUSION: Preliminary evidence support that exercise is safe and beneficial to the quality of life and functional outcomes for people with brain cancer.Registration: ACTRN12617001577303.

The BRAin Cancer and Exercise (BRACE) study highlights the need for regular monitoring of disease- and treatment-related side effects which may present as barriers to exercise.Exercise prescription should be modified according to the presence and severity of disease- and treatment-related barriers.Adverse events observed, such as dizziness, highlight the importance of supervised exercise for people with brain cancer.If supervision is not possible, then exercise modes with low risk of harm from falls are recommended (e.g., walking, machine-based resistance training).

Long-Term Outcomes of TROG 13.01 SAFRON II Randomized Trial of Single- Versus Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases.

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.

Impact of radiopacified bone cement on radiotherapy dose calculation.

BACKGROUND AND PURPOSE: Radiopacifiers are introduced to bone cements to provide the appearance of bone in kilovoltage (kV) radiographic images. For higher energy megavoltage (MV) radiotherapy treatment beams, however, these radiopacifiers do not cause a bone-like perturbation of dose. This study therefore aimed to determine the impact of the barium-contrasted plastic-based cement materials on radiotherapy dose calculations. MATERIALS AND METHODS: The radiological properties of a physical sample of bone cement were characterised by computed tomography (CT) imaging and transmission measurements. Monte Carlo simulations of percentage depth-dose profiles were performed to determine the possible dose error for MV treatment beams. Dose differences were then investigated for clinical volumetric modulated radiotherapy treatment plans, with and without density overrides applied. RESULTS: Differences of up to 7% were observed at the downstream interface of a 0.6 cm thick bone cement layer, compared to bone. Differences in planning target volume dose-volume metrics varied between -0.5% and 2.0%. CONCLUSION: Before planning radiotherapy treatments for patients who have undergone cranioplasty, every effort should be made to identify whether a radiopacified bone cement has been implanted. Density overrides should be applied to minimise dose calculation errors, whenever bone cement is used.

Re-irradiation for recurrent high-grade gliomas: a systematic review and analysis of treatment technique with respect to survival and risk of radionecrosis.

BACKGROUND: Re-irradiation may be considered for select patients with recurrent high-grade glioma. Treatment techniques include conformal radiotherapy employing conventional fractionation, hypofractionated stereotactic radiotherapy (FSRT), and single-fraction stereotactic radiosurgery (SRS). METHODS: A pooled, population-weighted, multiple linear regression analysis of publications from 1992 to 2016 was performed to evaluate the relationships between re-irradiation technique and median overall survival (OS) and radionecrosis outcomes. RESULTS: Seventy published articles were analyzed, yielding a total of 3302 patients. Across all studies, initial treatment was external beam radiotherapy to a median dose of 60 Gy in 30 fractions, with or without concurrent chemotherapy. On multivariate analysis, there was a significant correlation between OS and radiotherapy technique after adjusting for age, re-irradiation biologically equivalent dose (EQD2), interval between initial and repeat radiotherapy, and treatment volume (P < .0001). Adjusted mean OS was 12.2 months (95% CI, 11.8-12.5) after SRS, 10.1 months (95% CI, 9.7-10.5) after FSRT, and 8.9 months (95% CI, 8.4-9.4) after conventional fractionation. There was also a significant association between radionecrosis and treatment technique after adjusting for age, re-irradiation EQD2, interval, and volume (P < .0001). Radionecrosis rate was 7.1% (95% CI, 6.6-7.7) after FSRT, 6.1% (95% CI, 5.6-6.6) after SRS, and 1.1% (95% CI, 0.5-1.7) after conventional fractionation. CONCLUSIONS: The published literature suggests that OS is highest after re-irradiation using SRS, followed by FSRT and conventionally fractionated radiotherapy. Whether this represents superiority of the treatment technique or an uncontrolled selection bias is uncertain. The risk of radionecrosis was low for all modalities overall. Re-irradiation is a feasible option in appropriately selected patients.

Non-small cell lung cancer brain metastasis screening in the era of positron emission tomography-CT staging: Current practice and outcomes.

INTRODUCTION: Several clinical guidelines indicate that brain metastasis screening (BMS) should be guided by disease stage in non-small cell lung cancer (NSCLC). We estimate that screening is performed more broadly in practice, and patients undergo brain imaging at considerable cost with questionable benefit. Our aim was to quantify the use and detection rate of BMS in a contemporary cohort staged with 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT). METHODS: We conducted a retrospective review of prospectively collected data from three major lung cancer referral centres in Brisbane between January 2011 and December 2015. Patients included had a new diagnosis of NSCLC and had undergone a PET-CT to stage extra-cranial disease. BMS was defined as dedicated brain imaging with contrast-enhanced computed tomography (CE-CT) or magnetic resonance (MR), in the absence of clinically apparent neurological deficits. RESULTS: A total of 1751 eligible cases were identified and of these 718 (41%) underwent BMS. The majority had CE-CT imaging (n = 703). Asymptomatic brain metastases (BM) were detected in 18 patients (2.5%). Of these patients, 12 had concurrent non-brain metastases. Only six patients (0.8%) had BM alone. The rate of detection increased with N-stage (P = 0.02) and overall stage (P < 0.001). It was 0.5%, 1%, 1.6% and 7.3% for stage I, II, III and IV respectively. The overall screening rate increased with T-stage (P = 0.001), N-Stage (P < 0.001) and overall stage (P < 0.001). CONCLUSIONS: Non-small cell lung cancer BMS practices remain at odds with published guidelines. The low number of occult BMs detected supports the existing international recommendations. Rationalising BMS would minimise the burden on patients and the health care system.

A retrospective analysis of survival outcomes for two different radiotherapy fractionation schedules given in the same overall time for limited stage small cell lung cancer.

PURPOSE: To compare survival outcomes for two fractionation schedules of thoracic radiotherapy, both given over 3 weeks, in patients with limited stage small cell lung cancer (LS-SCLC). METHODS AND MATERIALS: At Radiation Oncology Mater Centre (ROMC) and the Royal Brisbane & Women's Hospital (RBWH), patients with LS-SCLC treated with curative intent are given radiotherapy (with concurrent chemotherapy) to a dose of either 40 Gy in 15 fractions ('the 40 Gy/15# group') or 45 Gy in 30 fractions ('the 45 Gy/30# group'). The choice largely depends on institutional preference. Both these schedules are given over 3 weeks, using daily and twice-daily fractionation respectively. The records of all such patients treated from January 2000 to July 2009 were retrospectively reviewed and survival outcomes between the two groups compared. RESULTS: Of 118 eligible patients, there were 38 patients in the 40 Gy/15# group and 41 patients in the 45 Gy/30# group. The median relapse-free survival time was 12 months in both groups. Median overall survival was 21 months (95% CI 2-37 months) in the 40 Gy/15# group and 26 months (95% CI 1-48 months) in the 45 Gy/30# group. The 5-year overall survival rates were 20% and 25%, respectively (P = 0.24). On multivariate analysis, factors influencing overall survival were: whether prophylactic cranial irradiation (PCI) was given (P = 0.01) and whether salvage chemotherapy was given at the time of relapse (P = 0.057). CONCLUSIONS: Given the small sample size, the potential for selection bias and the retrospective nature of our study it is not possible to draw firm conclusions regarding the efficacy of hypofractionated thoracic radiotherapy compared with hyperfractionated accelerated thoracic radiotherapy however hypofractionated radiotherapy may result in equivalent relapse-free survival.

Emerging understanding of dosimetric factors impacting on dysphagia and nutrition following radiotherapy for oropharyngeal cancer.

BACKGROUND: Research has reported relationships between 3-dimensional (3D) radiation dose to head and neck structures and consequential swallowing/nutritional outcomes. However, this evidence is preliminary. The current study aimed to identify which reported dose constraints identified functional impairment at 6 months posttreatment. METHODS: Dose constraints with reported relationships to swallowing and nutrition were identified through a systematic literature review. Dose-volume histograms for 12 patients with T1-T3 oropharyngeal cancer treated with 3D conformal radiotherapy determined dosages delivered to specific structures. Doses were examined in relation to published dose constraints and the swallowing and nutritional outcomes at 6 months posttreatment. RESULTS: In all, 66% of the reported mean, maximum, and partial doses to 8 structures correctly identified swallowing and nutrition outcomes at 6 months. CONCLUSION: The relationships observed between known dosimetric constraints and functional outcomes highlight the potential for dosimetric data to assist in prognosis and treatment. Systematic research is required to refine dosimetric parameters and the impact on functional outcomes.