BACKGROUND:Hypofractionated radiotherapy is standard for whole-breast radiotherapy, but 50 Gy in 25 fractions (5-week radiotherapy) is still standard in many countries when nodal radiotherapy is needed for morbidity concerns. The UNICANCER HypoG-01 trial aimed to assess morbidity and efficacy of hypofractionated locoregional radiotherapy delivering 40 Gy in 15 fractions (3-week radiotherapy) versus 5-week radiotherapy. METHODS:This non-inferiority, open-label, multicentre, randomised phase 3 trial, conducted in 29 centres in France, included female patients 18 years and older, with invasive breast carcinoma requiring nodal irradiation after complete microscopic resection of the primary tumour. Patients were randomly allocated in a 1:1 ratio to either 3-week radiotherapy (experimental group) or 5-week radiotherapy (control group) to the regional nodes and thoracic wall or breast. The primary endpoint was ipsilateral arm lymphoedema, defined as a 10% or greater increase in arm circumference at 15 cm proximal, 10 cm distal, or both, to the ipsilateral olecranon relative to baseline and contralateral arm, with a non-inferiority margin on the hazard ratio (HR) of 1·545. This trial was registered at ClinicalTrials.gov (NCT03127995) and is closed to recruitment. FINDINGS:Between Sept 26, 2016, and March 27, 2020, 1265 patients were enrolled, and 1221 were included in per-protocol analysis (median follow-up 4·8 years [IQR 4·01-5·02]), 614 assigned to 3-week radiotherapy and 607 to 5-week radiotherapy. The median age was 58 years (IQR 49-68). Arm lymphoedema occurred in 275 (25%) patients (143 with 3-week radiotherapy and 132 with 5-week radiotherapy). 3-week radiotherapy was non-inferior to 5-week radiotherapy regarding arm lymphoedema risk (HR 1·02 [95% CI 0·79-1·31] pnon-inferiority<0·001), with a 3-year cumulative incidence of 23·4% (95% CI 19·7-27·6) and 22·2% (95% CI 19·5-26·3), respectively. Safety profiles were similar between groups; grade 3 or worse adverse events frequencies were 8% and 13%, respectively. Following French regulation, data on race and ethnicity were not collected. INTERPRETATION:3-week radiotherapy (40 Gy in 15 fractions) was found to be non-inferior to 5-week radiotherapy (50 Gy in 25 fractions) for arm lymphoedema risk and was comparably safe regarding other late normal tissue effects for patients prescribed locoregional radiotherapy for early-breast cancer. FUNDING:French National Cancer Institute.

Reirradiation (reRT) has become an essential therapeutic option for selected patients with locoregional recurrences, when surgery or systemic therapies alone provide limited benefit. Initially restricted to palliative intent, reRT is now increasingly delivered with curative aims, supported by major advances in imaging and radiation techniques such as IMRT, stereotactic body radiotherapy (SBRT), brachytherapy, and image-guided proton therapy. Although few randomized trials exist, they have provided meaningful insights across tumor sites: in glioblastoma, combining reRT with bevacizumab improves progression-free survival without an overall survival benefit; in postoperative head and neck cancers, reRT improves locoregional control but not survival; and in nasopharyngeal carcinoma, hyperfractionation reduces late toxicity and improves 3-year survival. Median survival varies by site, ranging from approximately 8 months in glioblastoma to over 16 months in favorable head and neck subgroups, reaching 2-year survival rates up to 60% in selected peripheral lung or prostate recurrences, and several years in breast cancer. Patient selection remains pivotal, based on performance status, interval since prior irradiation, organ function, and tumor volume. Future perspectives rely on technological innovations - including FLASH radiotherapy, minibeams, hadron therapy, nanoparticles, and artificial intelligence - alongside international standardization efforts (ESTRO, ReCOG, FReTREAT) and the development of robust dose-summation platforms. Together, these advances aim to expand indications while improving treatment safety and harmonization.

Purpose:Understanding how hormonal treatment affects prostate volume is essential for optimizing external beam radiotherapy (EBRT) planning in localized prostate cancer. The study aimed to characterize the kinetics of prostate volume reduction during hormonal therapy and assess its implications for EBRT delivery and planning strategies. Methods and materials:A systematic review following PRISMA guidelines was conducted. Clinical studies assessing prostate volume changes under hormonal therapy in non-metastatic prostate cancer patients were included. Imaging modalities (MRI, CT, TRUS) were used to track prostate volume over treatment durations of up to 25 months. The review excluded preclinical studies and salvage therapy cases. Data were synthesized descriptively due to heterogeneity in regimens and methodologies. Results:Across 35 studies, prostate volume followed a logarithmic decay under hormonal treatment, with the most significant reductions occurring in the first three months (up to 35%). The extent of volume reduction during EBRT varied by EBRT initiation timing and fractionation scheme, with greater changes observed in normofractionated regimens. A weak correlation was found between initial prostate volume and reduction rate. Limitations included heterogeneity in imaging protocols and lack of formal bias assessment. Conclusions:Prostate volume reduction is most pronounced early in hormonal treatment, emphasizing the need to synchronize imaging and EBRT planning. For high-precision techniques (e.g., SBRT or DIL boosting), accounting for volume kinetics is critical. Clinical practice should evolve toward integrating prostate volume reduction timelines into EBRT workflows.

BACKGROUND:The management of oligorecurrent pelvic lymph nodes in patients with prostate cancer is debated. Intermittent androgen-deprivation therapy (ADT; IADT) is often proposed. Elective pelvis irradiation (ENRT) may prolong tumor control and decrease subsequent spread. OBJECTIVE:To assess the efficacy of a combination of 6 mo of IADT with or without ENRT to treat patients with oligorecurrent pelvic and para-aortic lymph nodes of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS:The OLIGOPELVIS 2-GETUG P12 trial is a multicenter randomized phase 3 trial, randomizing patients with 1-5 oligorecurrent pelvic and/or para-aortic lymph nodes of prostate cancer between arm A (IADT alone for 6 mo) versus arm B (salvage pelvic image-guided intensity-modulated radiotherapy [IG-IMRT], 54 Gy, 30 fractions to the pelvis and 66 Gy, 30 fractions to the lymph nodes) combined with IADT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The primary outcome is progression-free survival, defined as the time from randomization until a biochemical-clinical failure is detected or death from any cause. In total, 256 patients will be included. RESULTS AND LIMITATIONS:In this population of patients requiring ADT, ENRT may demonstrate antitumoral efficacy while achieving acceptable toxicity and maintaining quality of life. Limitations are mainly inherent to the open-label design of this study. CONCLUSIONS:This phase 3 study will explore the role of salvage pelvic IG-IMRT combined with IADT in patients with oligorecurrent pelvic lymph nodes of prostate cancer in prolonging the first failure-free interval between the first and the second IADT courses. PATIENT SUMMARY:The OLIGOPELVIS 2-GETUG P12 clinical trial assesses short-term (6 mo) androgen-deprivation therapy in association with external beam radiation therapy in men with prostate cancer relapsing to pelvic and para-aortic lymph nodes of prostate cancer. The trial investigates whether radiotherapy targeting pelvic and para-aortic lymph nodes can improve the biological response while maintaining a favorable tolerability profile. TRIAL REGISTRATION:NCT03630666, RCB 2018-A00551-54, date of registration: 2018-12-04.

In this article, we report a case of perineal recurrence of prostate cancer occurring 9 years after postoperative radiotherapy following radical prostatectomy for localized prostate cancer. We describe the use of stereotactic body radiotherapy as a potential ablative treatment. Pelvic magnetic resonance imaging identified an 8-mm lesion located below the penile root on the left side, which was distinct from the prostatectomy site. Recurrence was proven by biopsy. Stereotactic body radiotherapy delivered 36Gy in six fractions every other day. The patient showed no recurrence or toxicity by 55 months of follow-up. To the best of our knowledge, this is the first reported case of perineal recurrence successfully treated using stereotactic body radiotherapy.

The rapid emergence of 3D CT foundation models has opened new avenues for predictive modeling from CT imaging, offering a compelling alternative to traditional radiomics which is known to suffer from reproducibility issues and sensitivity to acquisition protocol variations. Yet, as these models grow in availability, a critical need arises to evaluate how well their learned representations generalize across diverse clinical settings and whether adaptation to specific downstream tasks is necessary to unlock their full potential. To address these questions, we benchmarked several 3D CT foundation models for predicting recurrence-free survival in head and neck cancer across two public datasets totaling 3,644 patients, evaluating various adaptation strategies and modality fusion mechanisms. Our findings reveal persistent difficulty in identifying features that generalize consistently across different imaging distributions, as evidenced by significant performance drops on external validation cohorts. Ultimately, the integration of imaging features with clinical data remains the most accurate approach for prognostic prediction, though achieving universal generalization across varied clinical contexts continues to represent a substantial challenge for the current generation of models.

Stereotactic radiotherapy (SRT), including stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hfSRT), plays a key role in the management of brain metastases (BM). As advances in systemic therapies prolong survival, local recurrence of BM has become more frequent, prompting interest in salvage reirradiation strategies. This systematic review aimed to evaluate the efficacy and safety of a second course of stereotactic radiotherapy (SRT2) for in-field recurrent brain metastases. Data on local control, overall survival, and radionecrosis were extracted and pooled using random-effects models. Eleven retrospective studies published between 2020 and 2025 were included, comprising 914 patients and 2,352 brain metastases, with 389 lesions treated with salvage SRS2/SRT2. Patients who had received prior whole-brain radiotherapy were excluded. The pooled 1-year local failure rate was 24

This systematic literature review explores the potential clinical benefits of magnetic resonance imaging-guided linear accelerator for radiotherapy of prostate cancer, across multiple indications: primary treatment, salvage therapy following radical prostatectomy, reirradiation, and focal boosting of the dominant intraprostatic lesion. Technical considerations related to magnetic resonance imaging-guided radiotherapy are also addressed. Most of the available studies are single-centre or prospective non-randomized trials, with notable methodological heterogeneity regarding irradiation protocols and outcome measures. To date, the MIRAGE trial remains the only published phase III randomized study comparing magnetic resonance imaging-guided radiotherapy to standard stereotactic body radiotherapy. Significant reduction in both acute and late urinary and gastrointestinal toxicity has been demonstrated, attributed to the enhanced precision of imaging-guidance and the reduction in planning target volume margins. However, long-term oncological efficacy remains to be established. Further phase III trials and health economic evaluations are clearly needed to establish the clinical value of this technology. As of today, the implementation of magnetic resonance imaging-guided linear accelerators in routine clinical practice remains limited by technical, organizational, and financial challenges, with accessibility restricted to a limited number of centres and reimbursement strategies yet to be adequately defined.

La ré-irradiation est devenue une option thérapeutique incontournable pour certains patients atteints de récidives locorégionales, lorsque la chirurgie ou les traitements systémiques seuls offrent un bénéfice parfois insuffisant. Initialement cantonnée à des indications palliatives, la ré-irradiation est désormais envisagée à visée curative grâce aux progrès de l’imagerie et des techniques modernes, telles que l’IMRT, la radiothérapie stéréotaxique (SBRT), la curiethérapie et la protonthérapie guidée par l’image. Les essais randomisés disponibles, bien que rares, ont apporté des données importantes selon les localisations : dans le glioblastome, l’association de ré-irradiation et bévacizumab prolonge la survie sans progression sans impact sur la survie globale ; dans les cancers ORL opérés, la ré-irradiation postopératoire améliore le contrôle locorégional sans bénéfice en survie globale ; dans le nasopharynx, l’hyperfractionnement réduit la toxicité tardive et améliore la survie à trois ans. Selon les sites, les survies médianes varient d’environ huit mois pour les glioblastomes à plus de seize mois dans les sous-groupes ORL favorables, et atteignent jusqu’à 60 % de survie à deux ans pour certaines récidives pulmonaires ou prostatiques sélectionnées, voire plusieurs années pour les cancers du sein. La sélection des patients demeure un enjeu majeur, fondée sur l’état général, l’intervalle depuis la première irradiation, la fonction d’organe et le volume tumoral. Les perspectives reposent sur les innovations technologiques (FLASH, minifaisceaux, hadronthérapie, nanoparticules, intelligence artificielle), la standardisation internationale (ESTRO, ReCOG, FReTREAT) et le développement d’outils fiables de cumul de dose, visant à élargir les indications tout en renforçant la sécurité des traitements.

BACKGROUND AND OBJECTIVE:Muscle-invasive bladder cancer (MIBC) may present de novo (primary MIBC [pMIBC]) or progress from non-muscle-invasive disease (secondary MIBC [sMIBC]). While sMIBC has been associated with adverse outcomes after radical cystectomy, its prognostic impact in patients undergoing trimodal therapy (TMT) is unclear. We aimed to compare the outcomes between pMIBC and sMIBC in a multicenter cohort treated with bladder-preserving TMT. METHODS:We conducted a retrospective study including patients with MIBC treated with curative-intent TMT. Eligible patients had stage ≥T2 disease and completed TMT without discontinuation. Patients were classified as those having pMIBC (≥T2 at diagnosis) or sMIBC (progression after prior non-muscle-invasive bladder cancer [NMIBC]). The primary endpoint was recurrence-free survival; the secondary endpoints were metastasis-free survival, cancer-specific survival (CSS), overall survival, and treatment-related toxicity. Survival was assessed using Kaplan-Meier methods and multivariable Cox regression. KEY FINDINGS AND LIMITATIONS:Among 294 patients (234 with pMIBC and 60 with sMIBC), the median age was 77 yr. The median follow-up was 34 mo for pMIBC and 24 mo for sMIBC. The 3-yr CSS rate was 78% for pMIBC and 79% for sMIBC. After adjustment for clinical covariates, sMIBC was not associated with an increased risk of recurrence (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.85-2.13) and cancer-specific death (HR 0.88, 95% CI 0.44-1.76). Toxicities were mostly of grade 1-2; grade ≥3 events were rare. Limitations include the retrospective design, a smaller sMIBC subgroup, and a relatively short follow-up. CONCLUSIONS AND CLINICAL IMPLICATIONS:Outcomes after TMT were broadly similar between pMIBC and sMIBC, although overall survival was lower in patients with secondary disease. A prior NMIBC history should therefore not preclude consideration of bladder-preserving therapy in appropriately selected patients.

Background and purpose Magnetic resonance–guided radiotherapy provides real-time soft-tissue–based targeting during dose delivery. Beyond image guidance, magnetic resonance linear accelerator (MR-Linac) systems offer new opportunities for developing magnetic resonance imaging (MRI)-derived radiomics biomarkers. However, the reproducibility of these biomarkers in a low-field MR-Linac environment remains unclear. Materials and methods This study evaluated the repeatability and reproducibility of MRI-derived radiomic features acquired on a 0.35 T MR-Linac using a tissue-mimicking phantom containing multiple tissue-equivalent materials. Fifty balanced steady-state free precession acquisitions were performed over 10 sessions, enabling both intra- and inter-session analyses. Forty-eight preprocessing pipelines combining normalization, discretization, and bias-field correction were assessed using the coefficient of variation and intraclass correlation coefficient for 68 radiomic features across 12 defined regions of interest. Results The combination of N4 bias correction and z-score normalization yielded the highest overall stability, with several first-order (e.g. Entropy, Mean) and texture-based (e.g. glcm_DifferenceEntropy and glrlm_ShortRunEmphasis) features showing a coefficient of variation <5% and/or an intraclass correlation coefficient (2,1) > 0.85 across phantom materials. Stability varied with phantom composition, with higher reproducibility in homogeneous PVP-40 and water inserts compared to fat or fibroglandular compartments. Comparison with previous 0.35 T MR-Linac studies identified a consistent subset of robust features, supporting their potential as standardized MRI-derived radiomic biomarkers. Conclusions These findings demonstrated the critical role of preprocessing and tissue composition in feature reproducibility and highlighted the importance of tissue-mimicking phantoms for validating MR-Linac-based quantitative imaging pipelines.

PURPOSE:/objective: Limited pelvic/para-aortic nodal relapse of prostate cancer after radical local treatment remains a major challenge for locoregional salvage strategies. Salvage Elective Nodes radiotherapy (ENRT) is an appealing option, but concerns persist regarding its toxicity. This study evaluates the 18-months toxicity profile of salvage ENRT combined with intermittent androgen deprivation therapy (iADT) in patients with pelvic and para-aortic oligometastatic disease, compared with iADT alone. MATERIAL:/Methods: OLIGOPELVIS-2/GETUG P12 was a prospective, multicenter, randomized phase III trial. Patients were randomized 1:1 to arm A (6-months iADT alone) or arm B (6-months iADT + ENRT: 54 Gy/1.8 Gy per fraction to the pelvic lymph nodes and 66 Gy/2.2 Gy per fraction to pathological nodes). ENRT started after three months of iADT. After analyzing relapse patterns in the OLIGOPELVIS GETUG P07 study, a December 22, 2021 amendment permitted the inclusion of para-aortic lymph nodes and extended irradiation fields up to the renal arteries. Toxicity was defined using NCI-CTCAE v4.0. RESULTS:A total of 256 patients were enrolled across 17 French centers between 12/2018 and 05/2023. The safety population included 127 patients in arm A and 121 in arm B. Eight patients in arm B were excluded as they did not ultimately receive radiotherapy. Prior prostate or prostatic bed irradiation was reported in 57% and 55% of patients, respectively. In arm B, 39 patients also received para-aortic irradiation. At 6 months, grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 2.4% vs 9.9% (p = 0.02) and 0% vs 19.8% (p < 0.001) of patients in arms A and B, respectively. At 18 months, grade ≥ 2 GU toxicity was 4.1% vs 10.7%, (p = 0.04) in arms A and B, respectively, while no difference in GI toxicity was observed. Prior prostate or prostatic bed irradiation did not increase toxicity at any time point. Among patients receiving para-aortic irradiation, compared to those without : grade ≥ 2 toxicity was similar at 6 months (GU: 12.8% vs 8.5%, p = 0.8; GI: 20.5% vs 19.5%, p = 0.9), or at 18 months (GU: 10.3% vs 11%, p = 1.0; GI: 0% vs 6.1%, p = 0.17), though 6 months upper grade ≥ 1 GI disorders were more frequent (25.6% vs 9.8%, p = 0.02). CONCLUSIONS:Eighteen-month toxicity of salvage ENRT with a simultaneous boost to the pathological lymph nodes, associated with 6-months iADT was acceptable, even among patients with prior prostate irradiation or additional para-aortic irradiation (NCT03630666- RCB 2018-A00551-54; FundingPHRC-K 16-129).

PURPOSE:The CYGNUS study aims to assess both toxicity and efficacy of stereotactic body radiation therapy performed as salvage approach for pelvic nodal metachronous oligorecurrent (PNMOR) hormone-sensitive prostate cancer, in previously irradiated territory. METHODS AND MATERIALS:Inclusion criteria were histologically history of proven prostate cancer, locally treated with a radical intent and a biochemical relapse as defined by the European Association of Urology guidelines. All patients had a radiological suspicion of PNMOR, defined as a recurrence occurring in pelvic nodal areas with up to 5 suspect lymph nodes. Reirradiation was defined according to the European Society for Radiotherapy and Oncology-European Organisation for Research and Treatment of Cancer (ESTRO-EORTC) consensus on reirradiation as an irradiation with a geometric overlap with a previous course of radiation therapy. RESULTS:A total of 155 reirradiation among 150 patients relapsing on 192 nodal sites were retrospectively included, from 13 French centers. The majority of patients (80.7%) received radical prostatectomy as primary treatment. After a median follow-up of 30.5 months, late grade 2 and grade 3 gastrointestinal and genitourinary toxicity occurred in 1.9%, 0%, and 7.1%, and 2.6% of the cases, respectively. The 2-year radiological progression-free survival reached respectively 44.6% (95% CI, 36.2%-55%). The 2-year androgen deprivation therapy-free survival (ADT-FS) reached 52.6% (95% CI, 42%-65.9%). Previous ADT prescription was predictive in multivariable analysis of both radiological progression-free survival (hazard ratio, 2.02; 95% CI, 1.25-3.26; P = .004) and ADT-FS (hazard ratio, 2.49; 95% CI, 1.28-4.72; P = .006). A prostate-specific antigen doubling time <5 months correlated with a shorter ADT-FS (area under the curve, 0.629; P = .014). CONCLUSIONS:The CYGNUS retrospective study suggests that reirradiation with stereotactic body radiation therapy for PNMOR is associated with a low rate of toxicity. However, further data with plan summation and longer follow-up are needed to confirm these findings.

There is considerable uncertainty regarding the optimum approaches to target volume and organ at risk (OAR) delineation and tolerances to reirradiation for locally recurrent prostate cancer. To address these uncertainties, we undertook a literature review of treatment planning approaches of stereotactic body radiotherapy (SBRT) or brachytherapy reirradiation in published and ongoing prospective studies. Twenty published and 11 ongoing studies were identified. No phase 3 clinical trials were identified. Both focal and whole gland with/without simultaneous integrated boost approaches to target volume delineation were used. SBRT dose-fractionation schedules ranged from 25 to 42.5Gy in 5 fractions and 36-38Gy in 6 fractions with varying approaches to target objectives. Brachytherapy studies utilised both low dose rate and high dose rate approaches and employed a range of dose-fractionation schedules. Approaches to OAR delineation and constraints were heterogenous. No published and only 1 ongoing study utilises cumulative OAR constraints. Acceptable rates of genitourinary and gastrointestinal toxicities were observed in the majority of studies although some studies reported relatively high rates of severe toxicity events. The relatively short follow-up of some published series may underestimate the incidence of late toxicities. There remains uncertainty regarding optimum dose-fractionation schedules, target volumes and OAR constraints and how these influence toxicity. Prostate reirradiation using SBRT or brachytherapy can be used for treatment of locally recurrent prostate cancer. Treatment is recommended within prospective studies or registries with robust target definition, treatment delivery and comprehensive assessment of toxicity so that evidence to optimise treatment can be generated.

BACKGROUND:Extensive disease small cell lung cancer (ED-SCLC) accounts for more than 70% of new diagnoses of SCLC with a 5-year survival of 12%. A limited percentage of ED-SCLC achieved a long term survival but their clinical and biological characteristics are largely unknown. Here we reported baseline clinical characteristics and treatment sequences of a large cohort of Long Survivors ED-SCLC compared to patients with poor outcomes. METHODS:The Epidemio-Strategy and Medical Economics (ESME) lung cancer data platform is a multicenter real-life database using a retrospective data collection process. We selected ED-SCLC patients diagnosed between 2014 and 2021. Long Survivors were defined as having an overall survival (OS) ≥ 24 months. Statistical comparisons were performed by Pearson's Chi-square, and logistic regression. RESULTS:We identified 3150 ED-SCLC and 489 long survivors representing 13 % of the study population. mOS was 36 months (95 %CI 34 to 39) in Long Survivors and 9 months (95 %CI 8.9 to 9.4) in other patients. Compared to Short Survivors, Long Survivors were enriched in women, patients younger than 65 years-old, ECOG PS 0-1 at diagnosis less than 3 metastatic sites and never or former smokers. The C-statistic of the multiparametric model based on patient's clinical characteristics was estimated at 0.70, with a 95 % CI (0.68, 0.73). Among those patients receiving a platinum-based chemotherapy with or without immunotherapy in first-line, a prolonged survival benefit from the chemo-immunotherapy strategy was found exclusively within the Long Survivors group even thus not statistically significant (p = 0.058). CONCLUSION:Long Survivors represents a small proportion of ED-SCLC characterized by a less extensive disease and better general conditions at diagnosis. This group of patients is most likely to benefit from immunotherapy in first line setting. Biological characteristics of these patients should be investigated in order to inform clinical research for new therapeutic strategies.