Accurate CT-MRI registration is critical for stereotactic radiosurgery (SRS) of brain metastases (BM), but even expert manual fusion shows variability. Without a true ground truth, algorithm validation requires a clinically meaningful benchmark. This study aimed to define a probabilistic gold standard (GS) for rigid registration and to establish acceptance thresholds for automatic algorithms. Twenty CT-MRI pairs (39 BM) were registered twice by six operators (n = 240). Variability was assessed by bootstrap resampling to estimate 99% confidence intervals (CIs) for rotational and translational mean absolute error (MAE), BM barycenter shift, DICE, and HD. For each case, the GS was defined as the median translational and rotational components across experts. Deviations from the GS were bootstrapped to derive expert-to-GS variability, used as acceptance range. Three mutual-information (MI)-based methods were tested: standard MI, skull-box MI, and contour-based (CB) MI (manual or AI-generated contours). Less-experienced operators were also evaluated. Experts showed low but non-negligible variability (99% CI: 0.31° rotation, 0.34 mm translation; max: 0.92°, 1.19 mm; median barycenter shift: 0.7 mm, range 0.0-2.8 mm). Only the CB algorithm achieved median values within expert acceptance for all metrics except HD, with no significant differences between manual and AI-generated contours (P > 0.05). Less-experts showed larger deviations, markedly reduced when starting from CB-aligned datasets. Quantifying multi-expert variability enables a probabilistic GS and clinically relevant thresholds for CT-MRI registration. This benchmark reflects human performance and provides a framework for algorithm validation. An AI-driven CB algorithm demonstrated high reliability, reduced operator dependence, and may streamline SRS workflows.

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.

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.