Purpose Given the complexity of SABR to the pelvis in prostate cancer (PCa), it was important to establish the safety and feasibility in a multicentric setting. We report the outcomes of a multicenter, phase II study of SABR with elective nodal irradiation (ENI) and an optional prostate focal boost. Methods Patients had unfavorable-intermediate or high-risk PCa. All patients received 5 fractions SABR weekly delivering 25Gy ENI and 40Gy to prostate simultaneously, with an optional 50Gy focal prostate boost. All patients had ADT. Primary endpoint was acute GI and GU adverse events (AE). Results 76 patients were accrued at 4 hospitals with a median follow-up of 62.8 months. 63% of patients had high-risk PCa. 41% of patients had a focal boost. Acute grade ≥ 2 GI and GU AE was 4.1% and 18%. At 5 years, 2.9% and 4.3% of patients had grade 2 GI and GU AE, and no grade 3+ GI/GU AE was observed at the last follow-up. 5-year cumulative biochemical failure was 10.5%. The median PSA nadir was 0.2 ng/ml. 84% of patients recovered their testosterone level, with a median time of 14.3 months. 2.9%, 5.9% and 4.6% of patients had a large change in QOL (SD*2) in the EPIC urinary, bowel, and sexual domains. Conclusions 5-fraction SABR to prostate and pelvis for unfavorable-risk PCa was safe and feasible in a multicentric setting with or without a focal boost. There were few significant AE, encouraging PSA kinetics and biochemical control. The results are currently being validated in randomized trials.

Traditionally, androgen deprivation therapy (ADT) alone was the standard treatment for oligometastatic prostate cancer. However, stereotactic body radiotherapy (SBRT) for metastasis-directed therapy (MDT) in the hormone sensitive setting is demonstrating improved outcomes. Despite this, not all patients will experience a durable response to MDT. The discovery of pre-treatment biomarkers to predict patient outcomes are needed to further improve management in this setting. In this randomized study, peripheral blood mononuclear cells were collected and analyzed using flow cytometry from 26 hormone sensitive oligometastatic prostate cancer patients that were recruited and randomly assigned to receive either intermittent androgen deprivation therapy (iADT) alone or MDT in the form of iADT+SBRT as part of a larger clinical trial. In patients treated with MDT, a high peripheral ratio of CD14high (classical) to CD14low (non-classical) monocytes at pre-treatment was significantly associated with complete biochemical response (PSA becoming ≤ 0.02 ng/mL) and freedom from biochemical progression (PSA nadir + 2 ng/mL). In contrast, the association was absent in patients treated with iADT alone, suggesting that SBRT may play a significant role in mounting an immune response, resulting in improved oncological outcomes. Furthermore, single-cell RNA sequencing of prostate cancer metastases suggested that classical monocytes from early responder patients may exhibit an elevated pro-inflammatory and chemokine-responsive transcriptional program. Together, these preliminary findings suggest the potential of monocyte ratios as an early predictive biomarker for MDT. If validated, this could potentially identify poor responders to MDT for consideration of additional systemic treatments.

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.

Importance:Stereotactic body radiotherapy (SBRT) and high-dose-rate brachytherapy monotherapy (HDR-BT) are options for intermediate-risk prostate cancer. However, no prospective evidence is available to compare these modalities. Objective:To compare the biochemical failure (BCF), late patient-reported quality of life (PR-QoL), and acute and late adverse events (AEs) associated with SBRT and HDR-BT using prospective data. Data Sources:This was an individual patient data post hoc pooled analysis of 5 prospective trials with recruitment from 2010 to 2018. Statistical analyses were performed in September 2024. Study Selection:This was a post hoc analysis of these 5 sprospective trials. Eligibility criteria comprised men with intermediate-risk prostate cancer undergoing 5- or 2-fraction SBRT or 2-fraction HDR-BT. No androgen deprivation therapy was permitted. Data Extraction and Synthesis:Baseline patient and clinicopathological characteristics were requested. Main Outcomes and Measures:BCF, a minimal clinically important change on the PR-QoL, and clinician-reported AEs were the main outcomes. Results:After a median (IQR) follow-up of 9.5 (5.5-10.6) years, 247 men met the eligibility criteria, including 180 men undergoing SBRT (72.8%; mean [SD] age, 69.5 [6.7] years) and 67 men undergoing HDR-BT (27.1%; mean [SD] age, 66.0 [6.5] years). HDR-BT was associated with increased BCF. At 5 years, BCF was 7.8% (95% CI, 1.0%-14.6%) for HDR compared with 3.0% (95% CI, 0.4%-5.6%) for SBRT. At 10 years, BCF was 38.0% (95% CI, 19.8%-56.1%) for HDR compared with 10.4% (95% CI, 4.3%-16.6%) for SBRT (P < .001). The HDR-BT cohort had a significantly higher incidence of acute grade 2 or greater genitourinary AEs compared with SBRT (50 men [74.6%] vs 31 men [51.7%]; P = .007). There were no significant differences in any other acute or late AEs or late PR-QoL. Conclusions and Relevance:This post hoc pooled analysis reports a long-term comparison of SBRT and HDR-BT using prospective data. SBRT had significantly lower BCF and acute genitourinary AEs, and there was no significant difference in late PR-QoL.

Purpose Most prostate SABR trials with pelvic elective nodal irradiation (ENI) applied dose constraints to individual bowel loops. There is no evidence-based data to guide bowel bag dose constraints in ultrahypofractionated ENI for prostate cancer. We aimed to correlate bowel bag dosimetric parameters with gastrointestinal toxicities and bowel quality of life (QOL). Methods and Materials We included 59 men enrolled in the SATURN and 5STAR trials. The prescribed dose of ENI was 25 Gy in 5 fractions delivered in weekly fractionation. The bowel bag was retrospectively contoured as per the Radiation Therapy Oncology Group guidelines. Gastrointestinal toxicities and bowel QOL data were prospectively collected up to 5 years after the trial using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 and the Expanded Prostate Cancer Index questionnaire. Dosimetric parameters for the bowel bag based on delivered treatment plans were extracted. Logistic regressions were performed to identify dosimetric parameters associated with gastrointestinal toxicities and bowel QOL. Results Of the 59 men included in this analysis, 7 of 59 men (12%) and 12 of 59 men (20%) had acute and late grade 2 gastrointestinal toxicities, respectively, with no grade 3+ gastrointestinal toxicities. There were 21 of 55 men (38%) and 10 of 55 men (18%) who had minimal clinically important changes in acute and late bowel QOL. No bowel bag dosimetric parameters were identified to be associated with acute/late grade 2+ gastrointestinal toxicities or minimal clinically important changes in bowel QOL. Based on bowel bag dosimetry of the delivered treatment plans, we propose bowel bag dose constraints for ultrahypofractionated ENI, applying the median and IQR upper limit as optimal and mandatory constraints: V20 Gy (optimal <320 cc; mandatory <380 cc), V24 Gy (optimal <150 cc; mandatory <200 cc), V25 Gy (optimal <80 cc; mandatory <100 cc), and maximum point dose (optimal <27 Gy; mandatory <35 Gy). Conclusions Using individual patient data from prospective trials, we did not identify bowel bag dosimetric parameters associated with gastrointestinal toxicities and bowel QOL; however, this provided us with data that suggested dose constraints for future practice.

BACKGROUND AND OBJECTIVE:The PROFIT trial was designed to compare moderately hypofractionated (HF) radiotherapy versus conventional fractionation (CF) for patients with intermediate-risk prostate cancer (IR-PC). Similar efficacy and toxicity outcomes were previously reported. The aim of the current analysis was to evaluate differences in long-term patient-reported outcomes (PROs) between the HF and CF arms in PROFIT. METHODS:For the PROFIT phase 3 randomized clinical trial, patients with IR-PC (n = 1206) were enrolled from 14 sites in Canada, 12 in Australia, and one in France and randomized to receive 78 Gy in 39 fractions over 8 wk (CF) or 60 Gy in 20 fractions over 4 wk (HF). PROs were evaluated at baseline and 24 and 48 mo using the Expanded Prostate Cancer Index Composite, American Urological Association Symptom Score (AUASS), and the 12-item Short Form Health Survey (SF-12) comprising a physical component summary (PCS) and a mental component summary (MCS). A minimally important difference (MID) was defined as a deterioration in domain- or subdomain-specific health-related quality of life (HRQoL) score by ≥0.5 times the standard deviation at each time point in comparison to baseline. Statistical significance was set at p < 0.01. KEY FINDINGS AND LIMITATIONS:AUASS results were similar and stable over time in both arms (median 5 points, interquartile range 2-9; p > 0.2). There were no significant differences in scores for urinary, bowel, sexual, and hormonal domains or subdomains between the arms at any time point (p > 0.02). The greatest decline over time occurred in sexual domain, with a decrease of ≥10 points from baseline to 24 mo in both arms. SF-12 mean scores for both PSC and MSC were similar in the two arms and remained stable at all time points. The only significant differences in the proportion of patients reporting MIDs were for the bowel subdomains at 48 mo, with significant MID reductions favoring HF for both the bowel summary score (53% vs 44%; p = 0.01) and bowel function score (51% vs 39%; p = 0.001). Overall treatment satisfaction was high in both arms: ≥88% of patients were either satisfied or extremely satisfied with their treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS:PRO results from the PROFIT trial suggest no significant differences in urinary, bowel, sexual, hormonal, and general HRQoL between CF and HF radiotherapy schedules. This study provides level 1 evidence supporting the use of moderate HF radiotherapy as standard treatment in patients with IR-PC. This trial is registered on ClinicalTrials.gov as NCT00304759.

BACKGROUND AND OBJECTIVE:The PATRIOT multicentre phase 2 trial showed that prolongation of overall treatment time (OTT) for prostate stereotactic ablative body radiotherapy (SABR) was associated with better acute bowel and urinary quality of life. However, the impact on long-term cancer outcomes is unclear. METHODS:Men with favourable-risk localised prostate cancer in the PATRIOT trial were randomised to five-fraction prostate SABR every other day (EOD; n = 77) or once weekly (QW; n = 75).The cancer outcomes evaluated in this post hoc analyses were biochemical failure (BF), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). KEY FINDINGS AND LIMITATIONS:Median follow-up was 91 mo. The 8-yr cumulative incidence rates for BF were 5.5% in the EOD arm versus 9.6% the QW arm (p = 0.2). The 8-yr probability rates were 100% versus 95.9% for MFS (p = 0.08), 100% versus 97.2% for PCSS (p = 0.2), and 96.0% versus 85.4% for OS (p = 0.3) for the EOD versus QW arms, respectively. The study is limited by the small sample size (powered to detect significant differences in acute bowel quality of life). CONCLUSIONS:This study suggests no significant differences in long-term cancer outcomes between EOD and QW schedules for five-fraction prostate SABR. This trial is registered on ClinicalTrials.gov as NCT01423474.

The standard treatment for patients with locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiation. However, clinical responses are heterogeneous and generally not known until after the completion of therapy. Multiple studies have investigated imaging predictors (radiomics) for different cancer histologies, but little exists for NSCLC. The objective of this study was to develop a multivariate CT-based radiomics model to a priori predict responses to definitive chemoradiation in patients with lung adenocarcinoma. Methods: Patients diagnosed with locally advanced unresectable lung adenocarcinoma who had undergone chemoradiotherapy followed by at least one dose of maintenance durvalumab were included. The PyRadiomics Python library was used to determine statistical, morphological, and textural features from normalized patient pre-treatment CT images and their wavelet-filtered versions. A nested leave-one-out cross-validation was used for model building and evaluation. Results: Fifty-seven patients formed the study cohort. The clinical stage was IIIA-C in 98% of patients. All but one received 6000–6600 cGy of radiation in 30–33 fractions. All received concurrent platinum-based chemotherapy. Based on RECIST 1.1, 20 (35%) patients were classified as responders (R) to chemoradiation and 37 (65%) patients as non-responders (NR). A three-feature model based on a KNN k = 1 machine learning classifier was found to have the best performance, achieving a recall, specificity, accuracy, balanced accuracy, precision, negative predictive value, F1-score, and area under the curve of 84%, 70%, 80%, 77%, 84%, 70%, 84%, and 0.77, respectively. Conclusions: Our results suggest that a CT-based radiomics model may be able to predict chemoradiation response for lung adenocarcinoma patients with estimated accuracies of 77–84%.

Background and objective: Recent randomized controlled trials have demonstrated the efficacy of five-fraction stereotactic body radiotherapy (5F-SBRT) for prostate cancer (PC), but there is no comparative evidence for fewer fractions. We compare outcomes of prostate two-fraction SBRT (2F-SBRT) and 5F-SBRT using prospective data for patients with intermediate-risk (IR) PC. Methods: This meta-analysis of individual patient data evaluated IR-PC from four prospective trials of prostate SBRT (two trials each of 2F-and 5F-SBRT). The primary endpoint was the cumulative incidence of biochemical failure (BCF). Secondary endpoints included the cumulative incidence of distant metastases (DM) and patient-reported quality of life (QoL). Key findings and limitations: Of the 199 patients meeting the eligibility criteria, 143 (72%) were in the 5F-SBRT group and 56 (28%) were in the 2F-SBRT group. Median follow-up was 9.4 years. There was no significant difference in BCF with a 5-year cumulative incidence of 3.6% (95% CI 0-8.6%) in the 2F-SBRT group and 6.0% (95% CI 1.8-10.2%) in the 5F-SBRT group (p = 0.73). There was no significant difference in DM incidence. We found no differences in acute and late urinary or bowel QoL. Limitations include the non-randomized comparison. Conclusions and clinical implications: We report the first prospective comparison of prostate 2F-SBRT and 5F-SBRT. We found no significant difference in efficacy, or in urinary or bowel QoL. This meta-analysis further encourages the potential of 2F-SBRT to be a standard-of-care option for IR PC. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Background Patients with interstitial lung disease (ILD) who develop lung cancer represent a unique challenge, as they are at higher risk for serious toxicity from local and systemic therapies. The aim of this study is to provide an up-to-date analysis on toxicities and outcomes associated with definitive radiation therapy (RT) in patients with ILD and early-stage non-small cell lung cancer (ES-NSCLC). Methods and Materials We performed a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed (MEDLINE), EMBASE, and Cochrane Library databases were searched from inception until June 2024, for studies including patients with ILD who underwent definitive RT alone for ES-NSCLC. Data including treatment-related mortality, toxicity, local control, and overall survival were collected and analyzed. Results Of 3545 records reviewed, 24 studies were identified for full data abstraction, contributing a total of 705 patients. A specific ILD subtype was not reported for 71% (n = 502) of patients. ILD severity was not reported for 62% (n = 440) of patients. Risk of treatment-related mortality was 7.9%, with severe treatment-related respiratory toxicity 15.7%. A higher volume of lung receiving ≥5 Gy (V5) was significantly correlated with mortality. The estimated local control at 3 year was 76% and median overall survival was 2.5 years. Conclusions The relative merits of RT for the treatment of ES-NSCLC in patients with ILD should be considered in the context of the rates of treatment-related mortality and toxicity. Future studies would benefit from consistent reporting of ILD characteristics, which may help in risk stratification in this challenging clinical scenario.

Introduction In oligometastatic disease, stereotactic body radiotherapy is being increasingly used in many different histologies to delay progression. However, by virtue of pancreato-biliary cancers not being as common and more aggressive natural history, data on its usage in pancreato-biliary cancers have been limited. Herein, our study aims to evaluate the outcomes of extracranial SBRT for oligometastatic pancreato-biliary cancers. Methods A retrospective review was conducted on patients with oligometastatic pancreato-biliary cancer treated with extracranial SBRT between 2014 and 2023 at our institution. The analysis examined cumulative incidence of local failure (LF), progression-free survival (PFS), cumulative incidence of start or change systemic therapy (SCST), overall survival (OS) and Radiation Therapy Oncology Group (RTOG)-graded treatment-related toxicities. Kaplan-Meier methodology and Cox proportional hazard models were used for survival analysis. Results Among the 62 patients (115 lesions) identified, the median follow-up was 13.4 months. By primary location, 71% had pancreas, 15% had cholangiocarcinoma and 15% ampullary cancer. Synchronous and metachronous oligometastatic disease was 37% and 63%, respectively. 87% of patients had 1-2 lesions treated with SBRT. At 12-months, LF, PFS, SCST and OS was 21.5%, 28.0%, 33.6% and 61.7%, respectively. On multivariable analysis (MVA), the only predictor of worse PFS was higher PTV volume. No grade 3-5 toxicities were reported. Conclusion Similar to other cancers, SBRT appears to be a promising option for those with oligometastatic pancreato-biliary cancer. More research in how to optimize integration of SBRT in a multidisciplinary setting for this challenging disease would be of benefit.

ObjectiveConcerns regarding offering radiotherapy to patients with systemic sclerosis (SSc) stem from the potential worsening of SSc manifestations and radiotherapy toxicity. We conducted a systematic review to evaluate the effects of radiotherapy on SSc outcomes and radiotherapy-related toxicity.MethodsMEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were searched for SSc and radiotherapy. Inclusion criteria were SSc diagnosis, subsequent cancer development, and radiotherapy exposure. Outcomes were SSc manifestations (cutaneous thickening, pulmonary fibrosis, and SSc flare) and radiotherapy toxicity (acute and late) using Common Terminology Criteria for Adverse Events for grading. Grade 1 and 2 toxicities were categorized as nonsevere and grade 3 to 5 toxicities as severe.ResultsOf 121 patients with SSc undergoing radiotherapy (mean age 56.4 years, 83.3% female, median radiotherapy dose 50 Gy), most did not show worsened SSc skin thickening (74.5%) or pulmonary complications (74%) post radiotherapy. In retrospective studies, the average rates of acute adverse effects were 57.3% for nonsevere and 25.8% for severe, whereas the rates of late adverse effects were 32.4% for nonsevere and 24% for severe.ConclusionAlthough most patients with SSc do not exhibit significant worsening of SSc manifestations post radiotherapy, there is a variable risk of acute and late toxicity. These findings suggest that although radiotherapy may be a viable option for patients with cancer with SSc, it requires caution.