[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.

Adult medulloblastoma in an Australian population.

Medulloblastoma in adult patients is a rare condition with limited contemporary demographic and treatment outcome data available in an Australian population. We conducted a retrospective review of patterns of care and outcomes of adult patients diagnosed with medulloblastoma treated at major neuro-oncology centres across Australia between January 2010 and December 2019. A total of 80 patients were identified and the median follow-up after diagnosis was 59.2 (range 0.5-204) months. A variety of chemotherapy regimens were used in the adjuvant and recurrent settings. The median overall survival (mOS) was 78 months (IQR 17.5-94.8). Patients who had no residual disease post-resection or with SHH-subtype tumours had a numerically longer 5-year survival rate than those with residual disease post resection or non-SHH subtypes respectively. The median time to recurrence from diagnosis was 18.4 months. The median OS from 1st relapse was 22.1 months (95% CI 11.7-31.4) and mOS from second relapse was 10.2 months (95% CI 6.6 - NR). This is the largest dataset examining patterns of care of adult patients with medulloblastoma in an Australian population. Substantial variation existed in the chemotherapy agents used in the adjuvant and recurrent setting. As has been demonstrated in a paediatric population, trials such as the upcoming EORTC 1634-BTG/NOA-23 trial (PersoMed-1 study) which are tailoring treatments to molecular profiles are likely to improve outcome in adult medulloblastoma.

Modified volumetric modulated arc therapy technique with reduced planning and treatment time for craniospinal irradiation utilising two isocentres.

INTRODUCTION: Paediatric patients (individuals below 18 years of age) requiring cranial-spinal irradiation (CSI) at our institution are commonly planned and treated using a three isocentre (3-ISO) volumetric modulated arc therapy (VMAT) technique. A modified two isocentre (2-ISO) VMAT technique was investigated with the aim to improve workflow and reduce planning and treatment time. METHODS: Five CSI paediatric patients previously treated with a 3-ISO VMAT technique were retrospectively replanned using a 2-ISO VMAT technique. The 2-ISO VMAT plans were reviewed and approved by a radiation oncologist (RO) before undergoing patient-specific quality assurance (QA) procedures, performed by a radiation oncology medical physicist (ROMP). Planning target volume (PTV) coverage, organ-at-risk (OAR) dose as well as planning and treatment durations of the first five patients utilising 2-ISO technique were compared with 3-ISO technique. RESULTS: The average percentage difference in PTV coverage by 95% reference dose between the 2-ISO and 3-ISO is 0.14%, and the average difference in OAR median dose is 0.68 Gy. Conformity and homogeneity indices have the same averages at 1.18 and 0.4 respectively. Patient-specific physics QA results were all comparable with the 3-ISO averages at 98.84% and the 2-ISO at 98.71%. Planning duration for the 2-ISO was reduced by up to 75%, and daily treatment duration was reduced by up to 50%. Of all the previously treated CSI patients using a 3-ISO technique, 45% were suitable for the 2-ISO technique. CONCLUSION: The 2-ISO VMAT technique provided comparable dose distribution based on PTV coverage, OAR dose and plan metric indices. Reduced planning and treatment duration with the 2-ISO technique facilitated improved workflow with decreased sedation time for paediatric patients requiring a general anaesthesia.

Considerations and adaptions to the modulated arc total body irradiation technique: dosimetry description.

Total body irradiation (TBI) is a complex treatment technique, which has been slow to transition to a three-dimensional (3D) planning approach. There is limited literature available providing a detailed description on methods to plan TBI on a 3D planning system. 3D planning using the modulated arc TBI (MATBI) technique is a complex process involving a significant number of quality assurance processes and scripts, due to more than 40 treatment beams and two patient positions. This article will focus on the workflow and technical planning aspects of our institution's MATBI technique and identify reasons for modifications made to the developing institution's original MATBI approach. Included is a description of specific simulation equipment, detailed explanation of the four-stage computing process including the role of scripting to standardise and streamline what is otherwise a complex number of steps. The information provided is specific to one centre's approach but shows the fundamental planning process and demonstrates a streamlined method, which can be adapted to other planning systems. Overall, the ability to accurately represent the TBI technique in 3D on a planning system will be shown.

Prospective analysis of the utility of 18-FDG PET in Merkel cell carcinoma of the skin: A Trans Tasman Radiation Oncology Group Study, TROG 09:03.

INTRODUCTION: TROG 09.03 prospectively studied the utility of Fluorine-18 Fluorodeoxyglucose (18-FDG) PET in the management of Merkel cell carcinoma of skin. METHODS: Following consent and registration, a pre-treatment FDG-PET/CT was performed. Sites of avid disease were confirmed by cytology where practicable. Following surgery, patients with AJCCv7 Stages IIA-IIIB disease were treated with chemo-radiotherapy and reassessed with a post-treatment PET. RESULTS: Fifty-eight subjects (45 males and 13 females, median age 68 years) were enrolled between 2011 and 2015, 43 patients of whom went on to receive chemo-radiotherapy. An occult primary was present in 22 (37.9%), T1 in 22 (37.9%) and T2 disease in 14 (24.1%). Nodal disease was present in 69% of cases. Fifty per cent of subjects had gross residual disease at the primary site and/or nodal site at the time of registration. 18-FDG PET/CT had a sensitivity of 94.74% (95% CI 82-99.3%) and a specificity of 88.24% (95% CI 63.56-98.54). The positive predictive value was 94.74% (83.01-98.51) and the negative predictive value was 88.24% (95% CI 65.81-96.69). The pre-treatment PET influenced a treatment decision in 27.6% of cases. Upstaging occurred in 15 (25.9%), with no down staging. Other diseases were identified in 4 (6.9%) patients. Univariate analysis failed to demonstrate that pre-treatment SUV levels or a negative post-treatment PET had any impact on overall survival. PET staged patients had 89% 3-year in-field loco-regional control and 76% 3-year overall survival. CONCLUSION: Staging 18-FDG-PET significantly influenced treatment decisions in approximately one-third of cases of MCC and should be considered in the routine pre-treatment work-up. Post-treatment PET was not found to be prognostic. Funding through the Medicare Benefits Schedule needs to be considered for high risk MCC.

In response to Fogarty et al. and why adjuvant whole brain radiotherapy is not recommended routinely.

The routine use of adjuvant whole brain radiotherapy (AWBRT) after surgery or stereotactic radiosurgery is now discouraged by a number of international expert panels. Three decades of randomised studies have shown that, although AWBRT improves radiological measures of intracranial disease control, the clinical benefit is unclear and it is also associated with inferior quality of life and neurocognitive function. The number of patients with melanoma in these trials was low, but data suggesting that treatment-related side effects should vary according to histology of the primary malignancy are lacking. For metastatic melanoma, the role of AWBRT to control microscopic disease in the brain is also a less relevant concern because systemic therapies with intracranial activity are now available. Whether AWBRT is useful in select patients deemed at high risk of neurologic death remains undefined.

Qualitative Evaluation of a Novel 3D Volumetric Radiotherapy Segmentation Tool.

INTRODUCTION: A novel 3D volumetric segmentation tool allows the user to outline using a small number of points on a range of planes. Unique 3D volumetric "sculpting" tools enable editing of the resulting structures across multiple slices concurrently. This article reports the results of radiation oncologists' preclinical evaluation of the tool. METHODS: Three clinicians outlined prostate and seminal vesicles on 14 data sets using the traditional slice-by-slice method and the new 3D tool. The project gathered focus-group feedback to gather rich data relating to clinician perceptions of the new 3D outlining paradigm. Emergent themes were identified and categorised for discussion. RESULTS: Radiation oncologists reported high levels of satisfaction with the outlines arising from both paradigms. The volumetric sculpting was a challenge, but participants enjoyed using points in orthogonal planes and felt that the paradigm had potential value in terms of speed and smooth volume creation. CONCLUSION: This study has demonstrated that a 3D volumetric outlining system is felt to have potential value by radiation oncologists for accelerating clinician-directed prostate and seminal vesicle segmentation. The new tool was well-received and reported to be capable of producing very rapid and smooth volumes. The novelty of the approach required significant training input and a radically different approach of minimal point placement. Further testing of this software with a less time-poor cohort may be indicated to gain reliable quantitative data relating to the impact on segmentation time.

Clinical implications of the overshoot effect for treatment plan delivery and patient-specific quality assurance for step-and-shoot IMRT.

In this work, overshoot and undershoot effects associated with step-and-shoot IMRT (SSIMRT) delivery on a Varian Clinac 21iX are investigated, and their impact on patient-specific QA point dose measurements and treatment plan delivery are evaluated. Pinnacle3 SSIMRT plans consisting of 5, 10, and 15 identical 5 × 5 cm2 MLC defined segments and MU/segment values of 5 MU, 10 MU, and 20 MU were utilized and delivered at 600/300 MU/min. Independent of the number of segments the overshoot and undershoot at 600 MU/min were approximately ± 10%, ± 5%, and ± 2.5% for 5 MU/segment, 10 MU/segment, and 20 MU/segment, respectively. At 300 MU/min, each of these values is approximately halved. Interfractional variation of these effects (10 fractions), as well as dosimetric variations for intermediate segments, are reduced at the lower dose rate. QA point-dose measurements for a sample (n = 29) of head and neck SSIMRT beams were on average 2.9% (600 MU/min) and 1.7% (300 MU/min) higher than Pinnacle3 planned doses. In comparison for prostate beams (n = 46), measured point doses were 0.8% (600 MU/min) and 0.4% (300 MU/min) higher. The reduction in planned-measured point-dose discrepancies at 300 MU/min can be attributed in part to the inclusion of the first segment (overshoot) in the admixture of segments that deliver measured dose. Pinnacle3 plans for 10/9 head and neck/prostate treatments were adjusted by ± 0.5 MU to include the effects of overshoot and undershoot at 600 MU/min. Comparing original and adjusted plans for each site indicated that the original plan was preferred in 70% and 89% of head and neck and prostate cases, respectively. The disparity between planned and delivered treatment that this suggests can potentially be mitigated by treating SSIMRT at a dose rate below 600 MU/min.

Inter- and intra-fraction motion in stereotactic body radiotherapy for spinal and paraspinal tumours using cone-beam CT and positional correction in six degrees of freedom.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) for spinal tumours delivers high doses per fraction to targets in close proximity to neural tissue. With steep dose gradients, small changes in position can confer significant dosimetric impact on adjacent structures. We analysed positioning error in consecutively treated patients on a strict image-guidance protocol with online correction in 6 degrees of freedom (6-DOF). METHODS: Set-up error, residual error post-correction and intra-fraction motion for 30 courses of spinal SBRT in 27 patients were assessed using cone-beam CT. Positional error was corrected in x, y and z translational planes and rotational axes using a robotic couch, applying 2 mm and 2° action levels. Linear mixed-effects model assessed whether positional error was influenced by factors such as vertebral level, immobilisation device and treatment duration. RESULTS: Sixty-two fractions were delivered with 225 image registrations. Median treatment duration was significantly longer for patients treated with static-field intensity-modulated radiotherapy compared with volumetric-modulated arc treatment--40 min versus 28 min, respectively (P = 0.01). Across all fractions, the median residual positional error after initial correction was greatest in the x translational plane (0.5 mm; 95% confidence interval (CI) 0.3-0.6) and y rotational axis (0.25°; 95% CI 0.1-0.3). Median intra-fraction error was also greatest in the x-plane (0.7 mm; 95% CI 0.5-1.0) and y-axis (0.4°; 95% CI 0.2-0.5). CONCLUSION: With strict immobilisation, image-guidance and 6-DOF correction, our current practice of applying 3-mm planning margins for target volumes and critical structures appears safe. Lower image-guidance action thresholds plus verification with end-to-end testing would be recommended before further reducing margins.

Technique and early clinical outcomes for spinal and paraspinal tumours treated with stereotactic body radiotherapy.

We report technique and early clinical results of stereotactic body radiotherapy (SBRT) from Princess Alexandra Hospital. SBRT involves the precise delivery of highly conformal and image-guided external beam radiotherapy with high doses per fraction. It is increasingly being applied in management of spinal tumours. Thirty-six courses of spine SBRT in 34 patients were delivered between May 2010 and December 2013. Mean patient age was 58 years. Treatment was predominantly for metastatic disease, applied in de novo (n=22), retreatment (n=14) and postoperative (n=8) settings. Prescribed doses included 18-30 Gy in 1-5 fractions. SBRT technique evolved during the study period, resulting in a relative dose escalation. No severe acute toxicities were observed. At median follow-up of 7.4 months (range: 1.7-22.2), no late radiation myelopathy was observed. Risk of new/worsening vertebral compression fractures was 22% (n=8) and was significantly associated with increasing Spinal Instability Neoplastic Scores (p=0.0002). In-field control was 86% with relapse occurring at a median interval of 2.8 months (range: 1.9-4.7). Thirteen patients (36%) died and median overall survival has not been reached. SBRT is an evolving technology with promising early efficacy and safety results. The outcomes of this series are comparable with international literature, and await longer follow-up.

An innovative approach for locally advanced stage III cutaneous melanoma: radiotherapy, followed by nodal dissection.

Patients with advanced nodal melanoma are typically managed with a regional nodal dissection; however, they have a high rate of distant relapse after surgery. This study assesses the role of preoperative radiotherapy to assist with the regional control in this subset of patients. Patients who had histologically confirmed stage III malignant melanoma and were treated with preoperative radiotherapy between 2004 and 2011 were eligible. All patients were staged with computer tomography and most with [F]-fluorodeoxyglucose (FDG) PET. Patients received preoperative radiotherapy, followed by a planned regional dissection at 12-14 weeks from completion with assessment of clinical, radiological and pathological responses. The primary outcome measure was the 1-year actuarial in-field control. There were 12 patients, with nine having disease of the axilla. All patients received radiotherapy up to a median dose of 48 Gy in 20 fractions, with seven patients achieving a partial clinical response. Ten patients proceeded to surgery, with four patients developing minor wound complications. The FDG-PET response did not appear to correlate with the pathological response. The 1-year in-field control rate was 92% (95% confidence interval 54-99) and the 1-year relapse-free survival was 54% (95% confidence interval 21-78). For selected patients with high-volume regional disease, we have successfully used preoperative radiotherapy, followed by a nodal dissection. Whether this type of protocol is of value in a more general group of patients with high-volume regional disease is currently under investigation.

Hypofractionated radiotherapy for the palliation of advanced head and neck cancer in patients unsuitable for curative treatment--"Hypo Trial".

BACKGROUND AND PURPOSE: The primary purpose of the trial was to assess rate of tumour response to a hypofractionated course of radiotherapy in patients with incurable squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives included radiation toxicity, symptom control, quality of life (QoL) and progression-free and overall survival. PATIENTS AND METHODS: Patients were planned to receive 30 Gy in 5 fractions at 2/week, at least 3 days apart, with an additional boost of 6 Gy for small volume disease (< or =3 cm) in suitable patients. Thirty-seven patients were enrolled between August 2004 and March 2006. Median age was 68 (43-87) years, 81% were male and the predominant primary site was oropharynx (32%). The majority (73%) presented with Stage III-IV disease. RESULTS: Thirty-five patients received radiotherapy, 1 died prior to treatment and one refused treatment. Of the 35 patients receiving radiotherapy, 31 (88%) received > or =30 Gy. Of the 35 patients who received treatment the overall objective response was 80%. Grade 3 mucositis and dysphagia were experienced in 9/35 (26%) and 4/35 (11%), respectively. QoL and symptom control were assessable in 21 patients. Thirteen (62%) reported an overall improvement in QoL and 14 (67%) experienced an improvement in pain. The median time to progression and death was 3.9 and 6.1 months, respectively. CONCLUSION: The "Hypo Trial" regimen provided effective palliative treatment in HNSCC unsuitable for curative treatment. Compliance was excellent and resulted in high response rates, symptom control and improvement in QoL with acceptable toxicity. However, progression free and overall survival was short.