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Background: Biology-guided radiotherapy (BgRT) is a novel treatment where the detection of positron emission originating from a volume called the biological tracking zone (BTZ) initiates dose delivery. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a novel imaging technique that may improve patient selection for metastasis-directed therapy in renal cell carcinoma (RCC). This study aims to determine the feasibility of BgRT treatment for RCC., Material and Methods: All consecutive patients that underwent PSMA PET/CT scan for RCC staging at our institution between 2014 and 2020 were retrospectively considered for inclusion. GTVs were contoured on the CT component of the PET/CT scan. The tumor-to-background ratio was quantified from the normalized standardized uptake value (nSUV), defined as the ratio between SUVmax inside the GTV and SUVmean inside the margin expansion. Tumors were classified suitable for BgRT if (1) nSUV was greater or equal to an nSUV threshold and (2) if the BTZ was free of any PET-avid region other than the tumor., Results: Out of this cohort of 83 patients, 47 had metastatic RCC and were included in this study. In total, 136 tumors were delineated, 1 to 22 tumors per patient, mostly in lung (40%). Using a margin expansion of 5 mm/10 mm/20 mm and nSUV threshold = 3, 66%/63%/41% of tumors were suitable for BgRT treatment. Uptake originating from another tumor, the kidney, or the liver was typically inside the BTZ in tumors judged unsuitable for BgRT., Conclusions: More than 60% of tumors were found to be suitable for BgRT in this cohort of patients with RCC. However, the proximity of PET-avid organs such as the liver or the kidney may affect BgRT delivery., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work is funded in part by the Peter MacCallum Cancer Centre Foundation. This research is partially funded by RefleXion Medical. The funders had no role in study design, analysis or manuscript writing., (© 2023 The Author(s).)

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 cm 3 to 148 cm 3 (median = 52 cm 3 ; IQR = 39 cm 3 - 63 cm 3 ). 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 cm 3 ; IQR = 4.5 cm 3 - 20.0 cm 3 ) and 50%SUVmax (median volume = 1.9 cm 3 ; IQR = 1.1 cm 3 - 3.8 cm 3 ) 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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This research is partially funded by RefleXion Medical., (© 2022 The Author(s).)

Introduction and Background: Choosing the right treatment for the right patient in a setting of metastatic cancer disease remains a challenge. To facilitate clinical decision-making, predictive tools have been developed to personalize treatment. Here, we aim to assess the use of the recently proposed "METSSS score" as a prognostic tool for overall survival of cancer patients after palliative radiotherapy in the last phase of life., Methods: All patients treated with palliative radiotherapy at the end-of-life at the Department of Radiation Oncology of the University Hospital Zurich between January 2010 and December 2019 were included in this study. Data on demographics, diagnosis, treatment and comorbidities was extracted from the treatment planning and the electronical medical records system. To statistically assess the validity of the "METSSS score", the mortality risk score was calculated, followed by stratification of all patients to prognostic risk groups. The prediction of the 1-year overall survival estimates was subsequently calculated., Results: Over the past decade, 274 patients have received palliative radiotherapy during the end-of-life period. One third of patients was female (34%, n = 93). The most frequent primary tumor was lung cancer (n = 121, 44%), and 55% of patients (n = 152) had no comorbidities according to the Charlson-Deyo comorbidity index. The most common radiotherapy site was the brain and eye region (42%, n = 115). The median actual overall survival of all patients was 40 days from the start of radiotherapy. The "METSSS score" survival model predicted that 269 patients (98.1%) belong into the high-risk, four patients (1.5%) into the medium-risk, and one patient (0.4%) into the low-risk group. The predicted median 1-year overall survival was 10%., Discussion: The METSSS score correctly predicted the survival of our end-of-life patient cohort by assigning them into the highest risk category, and it can therefore serve as a decision-making tool when assigning patient to symptomatic radiotherapy., Competing Interests: NA received research support from ViewRay, BrainLab, SNF, the Swiss Cancer League, the Staffanini Foundation, and received honoraria from ViewRay, AstraZeneca, BrainLab, and Debiopharm., (© 2022 The Authors.)

Objectives: The study aimed to assess the suitability of deformable image registration (DIR) software to generate synthetic CT (sCT) scans for dose verification during radiotherapy to the head and neck. Planning and synthetic CT dose volume histograms were compared to evaluate dosimetric changes during the treatment course., Methods: Eligible patients had locally advanced (stage III, IVa and IVb) oropharyngeal cancer treated with primary radiotherapy. Weekly CBCT images were acquired post treatment at fractions 1, 6, 11, 16, 21 and 26 over a 30 fraction treatment course. Each CBCT was deformed with the planning CT to generate a sCT which was used to calculate the dose at that point in the treatment. A repeat planning CT2 was acquired at fraction 16 and deformed with the fraction 16 CBCT to compare differences between the calculations mid-treatment., Results: 20 patients were evaluated generating 138 synthetic CT sets. The single fraction mean dose to PTV_HR between the synthetic and planning CT did not vary, although dose to 95% of PTV_HR was smaller at week 6 compared to planning (difference 2.0%, 95% CI (0.8 to 3.1), p = 0.0). There was no statistically significant difference in PRV_brainstem or PRV_spinal cord maximum dose, although greater variation using the sCT calculations was reported. The mean dose to structures based on the fraction 16 sCT and CT2 scans were similar., Conclusions: Synthetic CT provides comparable dose calculations to those of a repeat planning CT; however the limitations of DIR must be understood before it is applied within the clinical setting., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Purpose: To evaluate different registration methods, setup margins and number of corrections for CBCT-based position verification for oesophageal cancer and to evaluate anatomical changes during the course of radiotherapy treatment., Methods: From 50 patients, 440 CBCT-scans were registered automatically using a soft tissue or bone registration algorithm and compared to the clinical match. Moreover, relevant anatomical changes were monitored. A sub-analysis was performed to evaluate if tumour location influenced setup variations. Margin calculation was performed and the number of setup corrections was estimated. Results were compared to a patient group previously treated with MV-EPID based position verification., Results: CBCT-based setup variations were smaller than EPID-based setup variations, resulting in smaller setup margins of 5.9 mm (RL), 7.5 mm (CC) and 4.7 mm (AP) versus 6.0 mm, 7.8 mm and 5.5 mm, respectively. A reduction in average number of setup corrections per patient was found from 0.75 to 0.36. From all automatically registered CBCT-scans, a clipbox around PTV and vertebras combined with soft tissue registration resulted in the smallest setup margins of 5.9 mm (RL), 7.7 mm (CC), 4.8 mm (AP) and smallest average number of corrections of 0.38. For distally located tumours, a setup margin of 7.7 mm (CC) was required compared to 5.6 mm for proximal tumours. Reduction of GTV volume, heart volume and change in diaphragm position were observed in 16, 10 and 15 patients, respectively., Conclusions: CBCT-based set-up variations are smaller than EPID-based variations and vary according to tumour location. When using kV-CBCT a large variety of anatomical changes is revealed, which cannot be observed with MV-EPID., (© 2017 The Authors. Published by Elsevier Ireland Ltd on behalf of European Society for Radiotherapy & Oncology.)