We aimed to evaluate whether progression-directed radiation therapy (PDRT) can prolong the initiation of a subsequent systemic therapy regimen in a cohort of patients with oligoprogressive NSCLC. A retrospective analysis was conducted on NSCLC patients who underwent PDRT for extracranial oligoprogressive NSCLC, defined as limited (up to five) progressing lesions following initial complete, partial, or stable response to systemic therapy according to REC1ST 1.1 and/or PERCIST 1.0 criteria. Cox proportional hazard regressions were performed to identify factors influencing time to next treatment (TTNT), which was considered the primary endpoint. Forty patients were analyzed. First, second, and ≥3 lines of systemic therapy were administered in 22 (58.2%), 14 (27.2%), and 4 (14.6%) cases, respectively. The median total dose was 36 Gy (range: 12–60) in five fractions (1–10), with a median biological effective dose for tumor control (BED10) of 52 Gy (26.4–151.2). After a median follow-up of 11 months (2–50), PDRT delayed further systemic therapy in 32 (80.0%) treatments. Median TTNT was not reached at 8 months (1–47) with a one-year Kaplan–Meier estimate of 81.4% (95% CI: 75.0% to 87.8%). No >grade 3 adverse event was observed. On multivariate analysis, patients with ≥3 lines of systemic therapy and/or with larger CTV volumes did not benefit from PDRT. Despite the use of sub-ablative doses, our findings show that PDRT represents an effective, safe, and viable option for oligoprogressive NSCLC. Patients irradiated early during their systemic treatment course, with a low volume of disease and nonmetastatic oligoprogression, could derive substantial benefits from PDRT.

Radiation therapy offers well-established benefits in enhancing loco-regional control, distant disease control, and breast-cancer-specific survival. However, it is not without its challenges, particularly in breast cancer patients, where advances in systemic therapies and other treatment modalities have significantly improved survival outcomes. As radiation oncologists, our responsibility is to deliver the most effective treatments while minimizing toxicity for each patient. This scoping review aims to retrieve and assess the literature on factors associated with increased radiation-induced late breast toxicity. Specifically, we seek to identify both non-modifiable variables and those that can be influenced by the choices made by radiation oncologists. This review highlights which clinical decisions could directly impact late breast toxicity following adjuvant radiation therapy after breast-conserving surgery.

Introduction: To assess the efficacy of progression-directed radiation therapy (PDRT) in patients with oligoprogressive non-small cell lung cancer (NSCLC), with particular focus on disease progression and changes in systemic therapy. Materials and methods: From January 2020 to October 2025, a retrospective single-center analysis was conducted at our Institution, including NSCLC patients treated with PDRT for oligoprogressive disease. Oligoprogression was defined as progression involving fewer than five extracranial lesions or a total intracranial disease volume of ≤14 cc, following an initial response to systemic treatment. The primary endpoint was event-free survival (EFS), defined as the occurrence of any of the following: change in systemic therapy, progression within 6 months, or development of >3 progressive lesions. Multivariate Cox regression models were applied to identify predictors of oncological outcomes. Results: Eighty-seven patients were included, with a median age of 68 years (range: 43–87) and a median follow-up of 14 months. Adenocarcinoma was the predominant histology (75 cases, 86.2%), followed by squamous cell carcinoma (12 cases, 13.8%). PDRT was administered after first-line systemic therapy in 61 patients (70.1%). At the last assessment, 12 (13.8%) patients achieved a complete response, 29 (33.3%) a partial response, and 46 (52.9%) stable disease. The median time to event, death or last follow-up was 5 months (range: 1–48), with a one-year actuarial EFS rate of 52.1% (95% CI: 46.4–57.8%). Median time to next treatment (TTNT) was 8 months (range: 1–68), while median progression-free survival was 5 months (range: 1–39). On multivariate analysis, both PDRT directed at the primary tumor (HR = 0.28, 95% CI: 0.12–0.66; p < 0.01) and achieving a complete response prior to oligoprogression (HR = 0.31, 95% CI: 0.10–0.95; p = 0.04) were significantly associated with improved EFS. Conversely, chemotherapy use (HR = 2.33, 95% CI: 1.21–4.48; p = 0.02) and larger CTV volumes (HR = 1.01, 95% CI: 1.0004–1.0111; p = 0.03) were associated with worse outcomes. Conclusions: PDRT achieved a median EFS of 5 months and extended the median time to next systemic therapy to 8 months. These findings suggest that PDRT may represent an effective approach to maintaining disease control and postponing systemic treatment in oligoprogressive NSCLC. Larger, prospective studies with extended follow-up are warranted to confirm these results.

To investigate the association between radiation dose to pelvic functional substructures and the incidence of urinary and sexual side-effects following single-dose ablative radiotherapy (SDRT) for localized prostate cancer. A post hoc analysis was conducted on the 30 patients from the prospective ABRUPT trial (NCT04831983). Functional substructures, including the bladder trigone, urogenital diaphragm, neurovascular bundles (NVB), penile bulb (PB), internal pudendal arteries (IPA), and crura, were contoured by an experienced radiation oncologist. Maximum and mean doses were extracted from planning dose-volume histograms. Adverse events (AEs) were assessed using CTCAE and patient-reported outcomes (PRO). Logistic regression, Wilcoxon-Mann-Whitney, and ROC analyses were used to explore dose-toxicity associations and predictive thresholds, with cross-validation for robustness. Late urinary dysfunction correlated with bladder trigone D1cc ≥ 20.3 Gy (cross-validated AUC = 0.80; PPV = 64.3%; NPV = 75.0%), consistent across physician- and patient-reported endpoints. Larger bladder volumes (>166.8 cc) were also associated with urinary PRO deterioration (p = 0.030). Among 22 patients (76% of 29) who recovered testosterone (median = 10 months post ADT completion), erectile dysfunction showed a suggestive association with NVB D0.035 cc ≥ 23.6 Gy (apparent AUC = 0.98), although based on a limited number of events. Trends toward higher IPA and crura doses were observed in patients with sexual dysfunction, while no relationship was observed for PB dose. This exploratory analysis highlights the bladder trigone as potential predictor of urinary morbidity in SDRT. Incorporating substructure-sparing into treatment planning could improve functional preservation and reduce late toxicity, pending prospective validation in larger trials.

Background/Objectives: We aimed to prospectively evaluate the safety, patient-reported quality of life (QoL), and early oncological outcomes of a three-fraction SBRT regimen with real-time transperineal ultrasound guidance in localized prostate cancer. Methods: This prospective single-centre study enrolled patients with localized prostate cancer of all risk groups treated with SBRT (30 Gy in three fractions) between November 2023 and October 2025. Treatment was delivered using VMAT with CBCT-based setup verification and continuous real-time transperineal ultrasound for intrafraction motion monitoring. The primary endpoint was the incidence of acute and late grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) according to CTCAE v5.0. Secondary endpoints included patient-reported QoL (IPSS, EPIC-CP, IIEF-5), biochemical recurrence-free survival (BRFS), PSA kinetics, and factors associated with treatment-related AEs. Results: Seventy-two patients (median age, 78 years; range, 56–87) were enrolled, with a median follow-up of 16 months (range, 6–27). Acute grade ≥ 2 GU and GI AEs occurred in 34.7% and 8.3% of patients, respectively; late grade ≥ 2 GU and GI AEs occurred in 13.9% and 4.2%. One acute and one late grade 3 GU event were observed, with no grade 4–5 AEs. Although several QoL scores changed significantly over time, none exceeded the threshold for clinically meaningful deterioration. Higher baseline IPSS was associated with acute grade ≥ 2 GU AEs (aOR = 1.12, 95% CI: 1.00–1.26; p = 0.045). Median PSA declined from 7.90 to 0.44 ng/mL, and estimated BRFS was 98.2% at 12 months and 96.1% at 24 months. Conclusions: Three-fraction SBRT with real-time transperineal ultrasound guidance was feasible, with severe urinary and bowel AEs remaining uncommon, and associated with preserved clinically meaningful QoL, and encouraging preliminary biochemical control in patients with localized prostate cancer across all risk groups. This regimen may represent a practical intermediate strategy between conventional five-fraction SBRT and ultra-short fractionation, warranting longer follow-up and comparative prospective evaluation.