Introduction:The thorax presents unique challenges in radiotherapy: although stereotactic ablative radiotherapy (SABR) achieves high local control in NSCLC and pulmonary metastases, further improvements are desirable, particularly dose escalation in radioresistant metastases and planning target volume (PTV) margin reduction to minimize toxicity. Online adaptive Magnetic Resonance Imaging-guided Radiotherapy (MRIgART) supports these strategies by ensuring daily dose accuracy through compensation of Electron Density (ED) variations. However, prolonged treatment times remain the main obstacle to clinical implementation. To address this limitation, we introduce Adaptive Skin Radiotherapy (ASRT), a time-efficient MRIgART workflow designed to maintain accuracy while enhancing feasibility. Methods:Lung patients undergoing MRIgART were prospectively enrolled and treated with a biologically effective dose (BED) higher than 100 Gy. The gross tumor volume (GTV) was delineated on a simulation MRI co-registered with the staging CT, and the planning target volume (PTV) was generated by isotropically expanding the GTV by 3  mm. Gross tumor volume (GTV) was delineated on simulation MRI co-registered with staging CT, and planning target volume (PTV) was created by isotropically expanding GTV by 3  mm. ASRT involves a rapid online workflow where only body contour and target are recontoured, minimizing changes to organs at risk (OARs). Physicists update the electron density map to reflect anatomical changes, recalculating the predicted.plan using original beam fluence and re-optimizing it to meet clinical goals. Plans followed ICRU91 guidelines with an isodose line near 80%. Dose differences between predicted, adapted, and original plans were analyzed for target coverage and OARs. Treatment duration and toxicity were recorded. Survival outcomes were assessed using Kaplan-Meier analysis. Results:A total of 41 patients were enrolled, receiving 232 fractions, of which 178 (76.7%) were treated with ASRT. Online adaptation significantly improved target coverage (median V100% change: +0.1%±2.5%) compared to predicted plans (-2.6%±7.3%, p < 0.001), without significant differences in OAR doses. Median total treatment time was 28 min, with an average 5-minute ASRT workflow. No grade ≥ 3 toxicities were reported; grade 2 events occurred in 10.3% of patients. At a median follow-up of 19.8 months, 1-year local control, disease-free survival, and overall survival for the whole cohort were 94%, 80%, and 84%, respectively. Conclusion:Daily changes in the body contour and ED heterogeneity can result in major effects on plan dosimetry which can be quickly corrected with ASRT procedure. ASRT is a safe, effective, and time-efficient alternative for online MRIgRT adaptation in thoracic tumours, with promising clinical outcomes and toxicity profiles.

PURPOSE:Stereotactic ablative body radiation therapy (SABR) is an emerging indication for localized renal cell carcinoma (RCC), yet there is a need for standardizing contouring practices, as accurate target delineation is essential to ensure optimal outcomes. Our objective was to develop consensus guidelines for target volume contouring for RCC SABR. METHODS AND MATERIALS:An international panel of RCC SABR experts affiliated with IROCK was convened. All were asked to contour target volumes for 4 relevant clinical scenarios: a large tumor (>10 cm) with inferior vena cava tumor thrombus; a central tumor abutting the renal hilum; a local recurrence following nephrectomy; and an ablation cavity recurrence after radiofrequency ablation. Participants also contoured 2 investigational renal substructures: renal cortex and renal hilum. Contours by case were analyzed using a Simultaneous Truth and Performance Level Estimation algorithm (95% CI). Consensus contours and guidelines statements were discussed and refined over 2 consensus meetings. Measures of variance and agreement, including dice similarity coefficients (DSCs), Mean Distance to Agreement, and Hausdorff Distance, were measured for each case. RESULTS:In total, 16 radiation oncologists participated. The median DSC was 0.85, and the median Mean Distance to Agreement/Hausdorff Distance were 2.17 mm/9.00 mm, respectively. The median DSC was greater than 0.70 for each case, suggesting "good agreement" among participants. Based on the consensus discussion, any tumor thrombus or ablation cavity should be included in the target volume; organ at risk dose constraints should take priority over target coverage in planning; and the ipsilateral renal cortex should be defined as the ipsilateral renal parenchyma, excluding the target volume, the renal pelvis, renal vasculature, and proximal ureter. CONCLUSIONS:We present the first international consensus contouring guideline for RCC SABR. There was strong agreement among experts, yielding high-fidelity consensus contours and guidance statements for each scenario. These results can be used as a guide for radiation oncologists interested in using SABR to treat patients with localized RCC.

Re-irradiation of adrenal metastases is challenging due to cumulative dose constraints. We present seven patients treated with MR-guided adaptive stereotactic ablative radiotherapy (SABR), leveraging real-time imaging and on-table adaptation for precise dose delivery (5× 10 Gy or 3× 15 Gy). This first report of ablative-dose MR-guided SABR in re-irradiation demonstrates excellent local control and acceptable toxicity, with six patients progression-free at median 8.6 months and no grade ≥3 events (one grade 2 vertebral fracture, one grade 1 nausea). By providing a non-invasive alternative to surgery or palliative radiotherapy, MR-guided adaptive SABR expands therapeutic options for high-risk patients.

Background: Stereotactic Body Radiation Therapy (SBRT) has become an established treatment for several primary and metastatic malignancies; however, considerable heterogeneity remains in its definition, clinical indications, and technical delivery. Methods: In May 2025, the SBRT Focus Group of the European Society for Radiotherapy and Oncology (ESTRO), in collaboration with International Stereotactic Radiosurgery Society (ISRS), the Radiosurgery Society (RSS), and the Japanese Society for Radiation Oncology (JASTRO), conducted a global survey. A 44-item questionnaire explored SBRT indications, technical aspects, dose/fractionation, and barriers to implementation. Descriptive statistics summarized the responses. Results: Overall, 289 professionals from 59 countries participated. Routine use of SBRT was reported by 96.6 % of respondents, with lung, bone, liver and prostate as the most frequent indications. Pancreatic tumor (48.4 %), renal cell carcinoma (46.4 %), and ventricular tachycardia (12.4 %) represented emerging indications. C-arm linacs (89.2 %) and in-room Cone beam CT (CBCT) (92.0 %) were the dominant technologies. Motion man-agement relied mainly on 4D-CT internal target volume (ITV) (88.9 %) and deep inspiration breath-hold (DIBH) (57.8 %). Fractionation was consistent for lung and prostate but heterogeneous for liver, and pancreas. Only 3.5 % reported routine use of online adaptive SBRT, while 61.5 % reported artificial intelligence (AI) use, mainly for organs-at-risk delineation. Key barriers included limited clinical trial funding (35.2 %), high equipment costs (34.2 %), insufficient reimbursement (27.7 %), and workforce shortages (33.9 %). Conclusions: This ESTRO international survey provides the first global overview of SBRT practices. It demon-strates broad adoption but also substantial variability, highlighting the need for consensus guidelines, greater trial access, and expanded education to harmonize SBRT delivery and ensure equitable care worldwide.

Concerns were raised about an observed increase in treatment-related effects in patients treated with proton radiotherapy for glioma. This study compares next-intervention free survival in IDH-mutated WHO grade 2 and 3 glioma patients treated with proton or photon radiotherapy within the same time period. Patients treated consecutively in 2018-2022 with either protons or photons for IDH-mutated WHO grade 2 and 3 glioma were included from eight centers in the Netherlands and one in Belgium. All patients received standard-of-care radiotherapy and adjuvant chemotherapy. The primary outcome was Next Intervention Free Survival (NIFS; new treatment for either tumor progression or therapy effects). Additional endpoints were overall survival (OS), progression free survival (PFS), and pseudoprogression free survival (PsPFS; any new transient contrast-enhancing lesion after radiotherapy). All analyses were corrected for baseline factors in Cox regressions. The total cohort comprised 373 patients with IDH-mutated glioma: 256 WHO grade 2, and 117 WHO grade 3, 216 received proton radiotherapy, and 157 received photon radiotherapy. The median follow-up time is 44.2 months. The NIFS in the entire cohort had an HR of 3.07 (p<0.01), in favor of photons. For WHO grade 2 glioma, no significant differences were seen in any of the outcomes. For WHO grade 3 glioma results were: NIFS HR=5.0 (p<0.01), OS HR=5.0 (p<0.01), PFS HR=4.0 (p<0.01) and PsPFS HR=3.1 (p<0.01), all favoring photons. In WHO grade 3 glioma, 5-year OS and PFS were 59.2% and 34.1% for protons, and 83.9% and 79.1% for photons, respectively. In patients with IDH-mutated WHO grade 3 glioma, proton radiotherapy was associated with a higher rate of subsequent interventions, for either tumor progression or treatment effects, compared to photon radiotherapy. Additionally, we observed poorer OS and PFS, and increased rates of pseudoprogression after proton therapy. Further dosimetric and molecular analyses are warranted and ongoing.

BACKGROUND:Postoperative pancreatic fistula is the main driver of morbidity and mortality after pancreatoduodenectomy. In high-risk patients, the rate of postoperative pancreatic fistula approaches 50%, whereas it is below 5% in patients with pancreatic cancer who receive neoadjuvant chemoradiotherapy. The aim of this study was to evaluate the safety, feasibility, and efficacy of preoperative stereotactic body radiotherapy on the pancreatic neck transection margin in high-risk patients undergoing pancreatoduodenectomy to prevent postoperative pancreatic fistula. METHODS:In this prospective multicentre open-label single-arm trial (progressing from a safety run-in phase to a phase II design), patients undergoing pancreatoduodenectomy for neoplasms other than pancreatic ductal adenocarcinoma received a single preoperative stereotactic body radiotherapy dose of 12 Gy. Primary endpoints included safety (less than or equal to 15% grade 3-5 toxicity), feasibility (a significant change in pancreatic texture measured using a durometer), and efficacy (a 15% reduction in the grade B/C postoperative pancreatic fistula rate compared with patients from the Dutch Pancreatic Cancer Audit who were eligible but not included in this study). Secondary endpoints assessed tissue fibrosis (collagen density). RESULTS:Overall, 38 patients were included, of whom 33 (87%) completed the study protocol and were included in the per-protocol analysis. The safety cut-off was met, with 3% grade 3-5 toxicity. Pancreatic tissue treated with stereotactic body radiotherapy showed increased firmness using a durometer (median of 47 (interquartile range 36-57) versus 37 (interquartile range 30-41) Shore OO units; P < 0.001) and a higher collagen density (median of 6.1% (interquartile range 4.4%-9.5%) versus 4.6% (interquartile range 2.5%-7.4%); P = 0.003). The grade B/C postoperative pancreatic fistula rate with stereotactic body radiotherapy was 57.6% (95% c.i. 41% to 74%), compared with 34% (95% c.i. 27% to 42%) in audit controls (P = 0.011). CONCLUSION:Preoperative stereotactic body radiotherapy is safe in high-risk patients undergoing pancreatoduodenectomy and increases parenchymal firmness and fibrosis, but fails to show evidence of efficacy.

In the vulnerable population of patients with glioblastoma (GBM), there is a strong need for efficient treatment, while maintaining health-related quality of life (HRQoL). Since 2005, the standard of care involves radiotherapy of 2Gy in 30 fractions, with temozolomide (PMID: 15758009). A prior single arm phase II study (n=40) suggests that extreme hypofractionation (6Gyx6) may offer comparable survival with reduced treatment time and costs (PMID: 25107913). A phase III randomized clinical trial was performed to evaluate non-inferiority of a hypofractionated treatment schedule (6Gy times 6, in 2 weeks) versus standard of care (2Gy times 30), in newly diagnosed GBM patients with Karnofsky performance status ≥70. All patients received concurrent treatment and adjuvant temozolomide for six months. The primary endpoint was Overall Survival (OS); secondary outcomes included progression-free survival (PFS), toxicity and HRQoL. Enrollment was halted early, due to poor accrual (n=129 of planned 474). Patients were randomized in the experimental arm (n=65) or standard arm (n=64). At a median follow-up duration of 24 months, median OS was shorter in the experimental arm (13.0 months, 95% confidence interval [CI] 10.2-15.8) versus the standard arm (median OS not reached yet, p=0.002). Cox regression identified treatment arm (Hazard Ratio [HR] 2.19, p=0.001) and age (HR 1.04, p = 0.008) as independent predictors of poor survival. Median PFS was also reduced in the experimental arm (9 versus 10 months, p=0.048). Clinical toxicity analysis showed a significantly higher rate of reported radionecrosis in the experimental arm (58.5% vs 23.1%, p<0.001). Longitudinal HRQoL data is reported separately. In the treatment of newly diagnosed glioblastoma with temozolomide-based chemoradiation, non-inferiority of hypofractionation using 6Gy times 6, compared to the conventional 2Gy times 30 regimen, could not be demonstrated. The hypofractionation schedule is associated with inferior PFS and OS, along with increased reports of radionecrosis.

Introduction:Stereotactic radiosurgery (SRS) is a widely used treatment modality for vestibular schwannomas due to its non-invasive nature and high tumor control rates. However, some patients experience tumor progression after treatment. In this setting, reirradiation with SRS represents a potential treatment option. This systematic review and meta-analysis evaluates the evidence for reirradiation of vestibular schwannomas with SRS. Methods:This systematic literature review and meta-analysis investigates the efficacy and safety of reirradiation with SRS for vestibular schwannoma and was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results:A total of 806 studies were screened and 35 included, comprising 394 reirradiated patients. The median time from first treatment to reirradiation was 45 months (range: 12 - 65 months). Reirradiation with SRS, applying a median marginal/prescription dose of 12 Gy, achieved an estimated local control of 95% (95% confidence interval (CI): 92 - 97%, I2 = 29.62%, p = 0.10). Trigeminal and facial nerve deterioration rates after repeat SRS were 7% (95% CI: 4 - 10%, I2 = 0.0%, p = 0.44) and 6% (95% CI: 3 - 8%, I2 = 0.0%, p = 0.53), respectively. Serviceable hearing after reirradiation with SRS was rare (5%, 95% CI: 2 - 8%, I2 = 0.0%, p = 0.46). Among patients with serviceable hearing before reirradiation, 43% maintained it after treatment (95% CI: 29 - 57%, I2 = 65.71%, p = 0.00). The risk of bias across all studies was high. Conclusion:Reirradiation with SRS appears to be a safe and effective salvage treatment for progressive vestibular schwannomas. Prospective studies are warranted to define the optimal dose, timing, and dose constraints for reirradiation.

Background Irreversible electroporation (IRE) and stereotactic ablative body radiotherapy (SABR) are cytoreductive therapies for locally advanced pancreatic cancer (LAPC). Both may signify immunogenic cell death. We aimed to compare systemic immune responses between the treatments.Methods As part of the randomized phase II CROSSFIRE trial (NCT02791503), comparing the oncological efficacy of IRE to SABR in patients with LAPC, pre- and post-treatment (2 weeks and 3 months) peripheral blood samples were collected. Frequency and activation status of lymphocytic and myeloid subsets were determined using flow cytometry. T cell responses to pancreatic cancer associated with Wilms tumor-1 (WT-1) and survivin tumor antigens were determined by interferon-γ enzyme-linked immunospot assay.Results In total, 20 IRE and 20 SABR-treated participants were analyzed (20 men; median age 65 (IQR 55–70)). IRE induced immediate decreases in systemic regulatory T cell (Treg) and conventional type-1 dendritic cell rates, coinciding with CD4+/CD8+ T cell activation by upregulation of PD-1, which was associated with improved overall survival (OS). SABR similarly induced immediate CD4+/CD8+ T cell activation by upregulation of Ki67 and CD25 but resulted in asynchronously delayed Treg downregulation. SABR also induced a durable increase in CD4+ EM T cells, associated with improved OS. Ablation-induced WT-1 or survivin-specific T cell responses were observed in 9/16 (56%) immune competent participants (IRE n=5, SABR n=4) and were associated with longer OS.Conclusion Distinct immune stimulatory responses associated with improved OS, suggest that SABR might benefit from combined Treg depletion strategies while IRE could benefit from PD-1 checkpoint inhibition.Trial registration number The trial was registered on clinical trials.gov (NCT02791503).

Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiation therapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by 3 cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques such as magnetic resonance imaging guided SBRT, and SBRT response assessment. (c) 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

To evaluate the effectiveness and safety of salvage stereotactic ablative body radiotherapy (SABR) for recurrent renal cell carcinoma (RCC) after thermal ablation (TA). This study was a multi-institutional retrospective analysis of patients with recurrent RCC following TA who received SABR between 2016 and 2020. The primary study outcome was freedom from local failure, evaluated radiographically based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Distant failure, cancer-specific survival (CSS), overall survival (OS), treatment-related toxicity and renal function changes following SABR were the secondary outcomes. The Kaplan–Meier method was used to estimate freedom from local and distant failure, CSS and OS. Seventeen patients with 18 biopsy-confirmed RCCs were included, with a median (interquartile range [IQR]) age at time of SABR of 75.2 (72.6–68.7) years, a median (IQR) tumour size of 3.5 (1.9–4.1) cm and follow-up (reverse Kaplan–Meier method) of 3.36 (95% confidence interval [CI] 1.6–4.1) years. Six of the 17 patients had a solitary kidney. Five patients had failed repeat TA prior to SABR. The median (IQR) time from TA procedure to SABR was 3.03 (1.5–5.1) years. No patient experienced local progression, with a local control rate of 100%. Four patients, two with baseline metastatic disease, experienced distant progression. The distant progression-free survival, CSS and OS at 3 years were 72.1% (95% CI 51.9%–100%), 92.3% (95% CI 78.9%–100%) and 82.1% (95% CI 62.1%–100%), respectively. The median (IQR) glomerular filtration rate before SABR was 58 (40–71) mL/min, and at last follow-up, it was 48 (33–57) mL/min. No patient experienced grade 3+ toxicity or went on to develop end-stage renal disease. The results showed that SABR appears to be an effective and safe salvage strategy in patients with recurrent RCC following TA.

For patients with glioblastoma (GBM), preserving quality of life remains a critical concern alongside pursuing effective therapy. The standard of care is postoperative chemoradiation with temozolomide (PMID: 15758009). A previous single arm phase II study suggests that extreme hypofractionation (6Gyx6) may offer comparable survival to the standard 6-week-schedule with reduced treatment time and costs (PMID: 25107913). Shorter treatment duration may also improve health-related quality of life (HRQoL). Our phase III randomized clinical trial (also to be presented at SNO 2025) in newly diagnosed GBM patients compared hypofractionated radiotherapy (6Gy×6 in 2 weeks) to standard fractionation (2Gy×30 in 6 weeks). All patients had a Karnofsky performance status ≥70 and received concurrent treatment and adjuvant temozolomide for 6 months. As main result of the trial, we could not demonstrate non-inferiority of the experimental hypofractionation schedule, as this schedule resulted in inferior progression-free and overall survival. We now present the HRQoL data from this trial. A key secondary endpoint was HRQoL, assessed via EQ-5D, EORTC QLQ-C30 and QLQ-BN20 at baseline, 1 month, 3 months and every 3 months, up to 24 months after radiation or up to progression. Main analysis of these scales includes comparison of major subscales and overall scores at 6 months, time-to-deterioration and longitudinal modeling. Enrollment was halted early, due to poor accrual (n=129 of planned 474, n=65 experimental arm, n=64 standard arm). Preliminary analyses suggest inferior HRQoL in the experimental arm in several domains at predefined timepoints, including motor dysfunction and communication deficits. Longitudinal analysis of HRQoL is ongoing and will be presented at the SNO 2025 conference. In the treatment of newly diagnosed glioblastoma with temozolomide-based chemoradiation, hypofractionation using 6Gy times 6 is preliminarily associated with inferior HRQoL, which may be due to earlier progression, and/or increased reports of radionecrosis.

BACKGROUND:The PREOPANC-2 trial aimed to evaluate whether neoadjuvant FOLFIRINOX improved overall survival compared with neoadjuvant gemcitabine-based chemoradiotherapy followed by adjuvant gemcitabine in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC). METHODS:In this investigator-initiated, open-label, nationwide, phase 3 randomised trial, patients aged 18 years or older with resectable or borderline resectable PDAC and a WHO performance status of 0 or 1 were enrolled across 19 Dutch centres. Patients in the FOLFIRINOX (FFX) group received FOLFIRINOX (85 mg/m2 intravenous oxaliplatin, 180 mg/m2 intravenous irinotecan, 400 mg/m2 intravenous leucovorin, followed by a 400 mg/m2 intravenous fluorouracil bolus and then continuous infusion at 2400 mg/m2 intravenously over 46 h every 14 days for eight cycles) followed by surgery without adjuvant treatment. Patients in the chemoradiotherapy (CRT) group received three cycles of neoadjuvant gemcitabine (1000 mg/m2 intravenously on days 1, 8, and 15 of each 28-day cycle and on days 1 and 8 only for cycles one and three) combined with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle only, followed by surgery and four cycles of adjuvant gemcitabine. Randomisation (1:1) was done using a minimisation technique and stratified by resectability status (resectable vs borderline resectable disease) and centre. The primary endpoint was overall survival in the modified intention-to-treat population, after excluding ineligible patients. Data on race and ethnicity were not collected. This trial is registered with EudraCT (2017-002036-17) and is complete. FINDINGS:From June 5, 2018, to Jan 28, 2021, 375 patients were randomly assigned to the FFX group (n=188) or the CRT group (n=187). Six patients (three per group) were excluded due to ineligibility (n=4) or immediate withdrawal of informed consent after randomisation (n=2). 208 (56%) of 369 patients were male and 161 (44%) were female. After a median follow-up of 42·3 months (IQR 35·7-48·7), median overall survival was 21·9 months (95% CI 17·7-27·0) in the FFX group versus 21·3 months (16·8-25·5) in the CRT group (HR 0·88 [95% CI 0·69-1·13], p=0·32). The most common grade 3-4 adverse events were neutropenia (43 [25%] of 175 in the FFX group vs 38 [22%] of 176 in the CRT group), diarrhoea (41 [23%] vs two [1%]), and leukopenia (14 [8%] vs 26 [15%]). Serious adverse events occurred in 85 (49%) patients in the FFX group compared with 75 (43%) in the CRT group (p=0·26). Adverse events of grades 3 or worse occurred in 117 (67%) patients in the FFX group versus 106 (60%) patients in the CRT group (p=0·20). Treatment-related deaths occurred in two (1%) patients in the FFX group (multi-organ failure and intestinal mucositis) and one (1%) patient in the CRT group (upper gastrointestinal haemorrhage). INTERPRETATION:This randomised trial did not show a difference in overall survival between neoadjuvant FOLFIRINOX and neoadjuvant gemcitabine-based chemoradiotherapy in patients with resectable or borderline resectable PDAC. Both neoadjuvant treatment regimens may be considered in these patients. FUNDING:Dutch Cancer Society and ZonMw.

Background Pancreatic ductal adenocarcinoma is an aggressive disease with a dismal prognosis. Stage III locally advanced pancreatic cancer is considered unresectable and current palliative chemotherapy regimens only modestly improve survival. Guidelines suggest chemoradiation or stereotactic ablative body radiotherapy (SABR) could be beneficial in certain circumstances. Other local treatments such as irreversible electroporation could enhance patient out comes by extending survival while preserving quality of life. We aimed to compare the efficacy and safety of MRI-guided SABR versus CT-guided percutaneous irreversible electroporation following standard FOLFIRINOX chemotherapy. Methods CROSSFIRE was an open -label, randomised phase 2 superiority trial conducted at the Amsterdam University Medical Centre (Amsterdam, Netherlands). Eligible patients were aged 18 years or older with confirmed histological and radiological stage III locally advanced pancreatic cancer. The maximum tumour diameter was 5 cm and patients had to be pretreated with three to eight cycles of FOLFIRINOX. Patients were randomly assigned (1:1) to MRI-guided SABR (five fractions of 8 Gy delivered on non-consecutive days) or CT-guided percutaneous irreversible electroporation using a computer-generated variable block randomisation model. The primary endpoint was overall survival from randomisation, assessed in the intention-to-treat population. Safety was assessed in the per -protocol population. A prespecified interim futility analysis was done after inclusion of half the original sample size, with a conditional probability of less than 02 resulting in halting of the study. The trial was registered at ClinicalTrials.gov, NCT02791503. Findings Between May 1, 2016, and March 31, 2022, 68 patients were enrolled and randomly assigned to SABR (n=34) or irreversible electroporation (n=34), of whom 64 were treated according to protocol. Of the 68 participants, 36 (53%) were male and 32 (47%) were female, with a median age of 65 years (IQR 57-70). Median overall survival from randomisation was 161 months (95% CI 121-194) in the SABR group versus 125 months (109-170) in the irreversible electroporation group (hazard ratio [HR] 139 [95% CI 084-230]; p=021). The conditional probability to demonstrate superiority of either technique was 013; patient accrual was therefore stopped early for futility. 20 (63%) of 32 patients in the SABR group versus 19 (59%) of 32 patients in the irreversible electroporation group had adverse events (p=08) and five (16%) patients in the SABR group versus eight (25%) in the irreversible electroporation group had grade 3-5 adverse events (p=035). The most common grade 3-4 adverse events were cholangitis (two [6%] in the SABR group vs one [3%] in the irreversible electroporation group), abdominal pain (one [3%] vs two [6%]), and pancreatitis (none vs two [6%]). One (3%) patient in the SABR group and one (3%) in the irreversible electroporation group died from a treatment-related adverse event. Interpretation CROSSFIRE did not identify a difference in overall survival or incidence of adverse events between MRI-guided SABR and CT-guided percutaneous irreversible electroporation after FOLFIRINOX. Future studies should further assess the added value of local ablative treatment over chemotherapy alone. Funding Adessium Foundation, AngioDynamics. Copyright (c) 2024 Elsevier Ltd. All rights reserved.

Purpose: In prostate cancer patients, high radiation doses to the urethra have been associated with an increased risk of severe genitourinary toxicity following dose-escalated radiotherapy. Urethra-sparing techniques have emerged as a promising approach to reduce urinary toxicity. This international survey aims to evaluate current global practices in urethra-sparing and explore future directions for the implementation of this technique in external beam radiotherapy (EBRT) for prostate cancer. Methods and materials: In April 2024, a survey consisting of 20 questions was distributed to 26 international radiation oncology experts in prostate cancer EBRT, with 23 experts participating. The survey focused on clinical scenarios which might take benefit from urethra-sparing, the definition of the urethra and urinary organs-at-risk, and urethral dose constraints. Results: Magnetic resonance imaging with T2-weighted sequences is the preferred method for urethra contouring (83 % consensus). Based on the experts opinion, urethra-sparing should be considered for prostate cancer EBRT, regardless of pelvic irradiation, except in cases where the tumor is located within 2 mm of the urethra and/or transitional zone, or in T4 disease. Most experts would not apply specific dose constraints to the urethra for either conventional or moderate hypofractionation regimens. When delivering stereotactic body radiotherapy (SBRT), urethra-sparing with dose hotspot limitation (urethra steering) is recommended by 70 % of the experts, in particular when combined with focal boosting (91 %). Urethra dose-reduction is also the favored approach for salvage prostate reirradiation with SBRT (70 % agreement). Large variations exists regarding urethral dose constraints. Conclusions: Urethra-sparing is a promising technique for the mitigation of urinary toxicity in prostate cancer patients undergoing EBRT, particularly recommended for ultra-hypofractionation and reirradiation with SBRT. The lack of consensus on specific urethral dose constraints and optimal sparing techniques underscores the need for further research to standardize practices in this field.

Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiation therapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by 3 cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques such as magnetic resonance imaging guided SBRT, and SBRT response assessment.

PurposeThis systematic review provides an overview of literature on the impact of MR-guided radiotherapy (MRgRT) on patient reported outcomes (PROs) in patients with prostate cancer (PC).MethodsA systematic search was performed in October 2023 in PubMed, EMBASE and Cochrane Library. The PICOS framework (i.e., patient, intervention, comparison, outcome, study design) was used to determine eligibility criteria. Included were studies assessing PROs following MRgRT for PC with sample size >10. Methodological quality was assessed using the ROBINS-I and RoB 2. Relevant mean differences (MD) compared to pre-RT were interpreted using minimal important differences (MID). Meta-analyses were performed using random-effects models. Between-study heterogeneity was assessed using the I2-statistic.ResultsEleven observational studies and one randomized controlled trial (n=897) were included. Nine studies included patients with primary PC with MRgRT as first-line treatment (n=813) and three with MRgRT as second-line treatment (n=84). Substantial risk of bias was found in five studies. EORTC QLQ-C30 and EORTC QLQ-PR25 scores were pooled from three studies, and EPIC-26 scores from four studies. Relevant MDs for the urinary domain were found with the EPIC-26 (MD-10.0 [95%CI -12.0 – -8.1]; I20%) and the EORTC QLQ-PR25 (MD8.6 [95%CI -4.7-22.0]; I297%), both at end-RT to one month follow-up. Relevant MDs for the bowel domain were found with the EPIC-26 (MD-4.7 [95%CI -9.2 – -0.2]; I282%), at end-RT or one month follow-up, but not with the EORTC QLQ-PR25. For both domains, no relevant MDs were found after three months of follow-up. No relevant MDs were found in the general QoL domains of the EORTC QLQ-C30.ConclusionMRgRT for PC results in a temporarily worsening of patient-reported urinary and bowel symptoms during the first month after treatment compared to pre-RT, resolving at 3 months. No clinically relevant changes were found for general QoL domains. These results provide important information for patient counseling and can serve as a benchmark for future studies.