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.

BACKGROUND:Lymphomas involving ocular structures are well documented, particularly in the conjunctiva, vitreoretina, and choroid. In contrast, no primary lymphoma of the cornea has previously been reported in humans, whereas it has only been described in animals, essentially in rare, small series in horses. This study aimed to determine whether corneal lymphoma exists in humans and to describe its epidemiologic and clinical characteristics. METHODS:A retrospective, population-based analysis was conducted using the SEER 17 registries (November 2024 submission). All lymphoma cases coded as C69.1 (cornea) between 2000 and 2022 were included. Demographic, pathological, treatment, and survival data were extracted using SEER*Stat version 9.0.42.0. Incidence rates were age-adjusted to the 2000 U.S. standard population. Survival was calculated from diagnosis to death or last follow-up. RESULTS:Five cases of corneal lymphoma were identified, all strictly localized to the cornea, corresponding to an incidence of 0.0028 cases per million persons per year. The mean age at diagnosis was 75 years, with a 4:1 male predominance. Histologic subtype was available in 3 cases, all of which were mucosa-associated lymphoid tissue (MALT) lymphomas. All patients underwent local surgical management, and radiotherapy was administered in unilateral cases. No systemic therapy was reported. Median follow-up was 99 months. Two deaths occurred (1 unrelated to lymphoma and 1 lymphoma-related) while 3 patients remained alive, including 2 long-term survivors with follow-up exceeding 14 years. CONCLUSION:Corneal lymphoma does occur in humans, is exceptionally rare, and appears to share the favorable prognosis of other ocular MALT lymphomas. Radiotherapy may provide durable control in localized disease. These findings represent the first evidence of this entity and support heightened diagnostic awareness in ocular oncology.

Breast cryoablation has emerged as a minimally invasive alternative to lumpectomy for selected patients with small, biologically favorable breast cancers. Its appeal lies in the combination of focal tumor destruction, outpatient treatment under local anesthesia, low procedural burden, and potentially improved cosmetic and functional outcomes. However, cryoablation should not be viewed as a simple technical substitute for surgery: its oncologic credibility depends on appropriate tumor selection, accurate imaging-based staging, adequate ablative margins, and coherent integration with adjuvant therapy and follow-up. This review summarizes the current evidence on breast cryoablation, focusing on biological rationale, validation studies with surgical confirmation, prospective non-excision cohorts, practical indications, and post-ablation imaging surveillance. Surgical-validation studies show that cryoablation can achieve high rates of complete tumor destruction, but mainly in a narrow subgroup of small, ultrasound-visible, hormone receptor-positive, HER2-negative invasive ductal carcinomas, particularly those measuring 15-20 mm or less. These studies also show that failure often reflects occult multifocality or underestimation of microscopic disease extent rather than failure to destroy the index lesion itself. Prospective non-excision studies, particularly ICE3 and FROST, have moved the field beyond feasibility alone. In highly selected older women with low-risk tumors, ICE3 reported a low 5-year ipsilateral breast tumor recurrence rate of 4.3%, while FROST showed similarly encouraging local control, with a 5-year ipsilateral breast tumor recurrence rate of 3.6%, and underscored the importance of structured post-ablation verification. These results also reflect technical progress, as single-probe liquid nitrogen platforms have simplified and standardized treatment delivery compared with earlier multi-probe approaches. Current evidence therefore supports cryoablation only within a narrow clinical setting. Broader adoption will require standardized patient selection, harmonised adjuvant strategies, robust imaging follow-up, and comparative trials against surgery or endocrine therapy-based approaches.

BACKGROUND:Consolidation radiotherapy following chemotherapy represents the standard of care for stage I-II classical Hodgkin lymphoma, yet treatment adherence varies in clinical practice. No previous study has systematically examined the patient characteristics associated with radiotherapy refusal or its impact on survival outcomes. We aimed to identify determinants of consolidation radiotherapy refusal and evaluate its consequences on cause-specific (CSS) and overall survival (OS). METHODS:We conducted a retrospective cohort study using the SEER database (2024 submission, 17 registries) analyzing patients diagnosed with stage I-II Hodgkin lymphoma between 2000 and 2022 who received chemotherapy with indicated consolidation radiotherapy. Patients were categorized based on radiotherapy receipt versus refusal. Chi-square tests compared patient characteristics between groups. Kaplan-Meier methods assessed survival outcomes, and Cox proportional hazards models identified prognostic factors among radiotherapy recipients. RESULTS:Among 9150 patients, 141 (1.5%) refused consolidation radiotherapy despite medical indication. Radiotherapy refusal was significantly associated with non-white ethnicity (35.5% vs. 29.9%, p < 0.01) and residence in large metropolitan areas (> 1 million population; 68.8% vs. 59.0%, p < 0.01), with a trend toward higher refusal among women (56.7% vs. 49.0%, p = 0.08). Radiotherapy refusal was significantly associated with inferior survival outcomes: 10-year OS was 83.3% versus 90.0% (p = 0.0014) and 10-year CSS was 90.4% versus 95.0% (p = 0.029) for refusers versus recipients, respectively. Among radiotherapy recipients, multivariable analysis revealed significant socioeconomic disparities, with living with a partner (HR = 0.630, p < 0.001) and higher household income (HR = 0.750, p < 0.001) as protective factors for CSS. CONCLUSION:Non-white ethnicity and residence in a large metropolitan area are risk factors for consolidation radiotherapy refusal in stage I-II Hodgkin lymphoma, with significant adverse associations with survival outcomes. Substantial socioeconomic disparities exist in outcomes among treated patients. These findings highlight the need for targeted educational interventions and culturally sensitive counseling to ensure equitable access to optimal care in this highly curable disease.

PURPOSE:Primary cutaneous T-cell lymphomas are a heterogeneous group of T-cell neoplastic entities associated with significant morbidity and high radiosensitivity. Although research on reduced-dose radiation treatment for mycosis fungoides and Sézary syndrome has significantly increased over the past 2 decades, randomized data are lacking. We aim to summarize the available evidence and analyze the safety and efficacy of reduced-dose total skin electron beam therapy (TSEBT). METHODS AND MATERIALS:A literature search for evidence was conducted, selecting studies with reduced-dose TSEBT in mycosis fungoides and Sézary syndrome that met the inclusion criteria. The studies were critically appraised, and the results were synthesized and interpreted. RESULTS:The analyzed data comprised 11 prospective studies and 11 retrospective studies, with a total of 883 patients. The meta-analysis revealed a pooled overall response rate of 91% (95% CI, 88-93) and complete response rate of 26% (95% CI, 21-31) to reduced-dose TSEBT. The most common toxicities reported were grade 1 and 2 skin reactions. Documented in 7 studies, the time to response ranged from 4 to 8 weeks. Seven studies evaluated the impact of reduced-dose TSEBT on quality of life, and all reported significant improvements in 1 or more subdomains. Fourteen studies indicated that 337 patients (38%) received consolidation/subsequent therapy after TSEBT to maintain remission. Compared with TSEBT monotherapy, the addition of consolidation/subsequent treatments to sustain the response was associated with a progression-free survival or other clinical advantage in 4 of 5 trials. CONCLUSIONS:Reduced-dose TSEBT quickly achieves high overall response rate and improves quality of life with minimal risk of severe adverse events. Knowledge gaps remain on how to optimally prolong these benefits. Investigating maintenance therapy is needed to ensure sustained remission.

PURPOSE:Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a rare but indolent B-cell lymphoma, most often presenting as localized disease. Radiotherapy is a curative option, but its proximity to the heart raises concerns about long-term cardiac toxicity, which remains poorly documented. The purpose of this work was to evaluate the potential risk of cardiac toxicity following radiotherapy in patients with pulmonary MALT lymphoma. PATIENTS AND METHODS:This retrospective, population-based study used Surveillance, Epidemiology, and End Results (SEER) data (17 registries, 2000-2022; November 2024 submission). We identified patients with primary pulmonary MALT lymphoma treated with radiation. Demographic and clinical characteristics, including age, sex, Ann Arbor stage, tumour laterality, lobe involvement, and treatment modality, were collected. Outcomes included overall survival, cancer-specific survival, cardiac-specific survival, and non-cancer/non-cardiac-specific survival. Survival estimates were generated using Kaplan-Meier methods; univariate and multivariate Cox models assessed factors associated with cardiac-specific mortality. RESULTS:Among 248 patients, the median age was 70 years; 54.0 % were women and 81.9 % Caucasian. Most had early-stage disease (90.3 %) and right-sided tumours (57.3 %). Radiotherapy alone was used in 86.7 %. With a median follow-up of 59 months, median overall survival was 120 months. At 20 years, overall survival rate was 28.9 %, cancer-specific survival rate 85.5 %, and cardiac-specific survival rate 85.0 %. In competing risk multivariate analysis, age greater than 70 years (hazard ratio [HR]: 10.51; 95 % confidence interval [CI]: 1.11-99.8; p=0.040) and stage III-IV (HR: 6.52; 95 % CI: 1.17-36.4; p=0.032) were independently associated with cardiac-specific mortality. CONCLUSION:Radiotherapy for pulmonary MALT lymphoma is associated with excellent long-term outcomes and low cardiac-specific mortality. Tumour location within the lung does not influence cardiac risk, supporting the absence of significant radiation-induced cardiotoxicity.

PURPOSE:Radiation-induced sarcomas are a rare but serious long-term complication of radiotherapy. While radiotherapy is an effective treatment for low-grade non-Hodgkin lymphomas, the incidence and characteristics of radiation-induced sarcomas in this setting have not been previously described. The purpose of this study was to analyse the incidence and outcomes of radiation-induced sarcomas following radiotherapy for low-grade non-Hodgkin lymphomas. PATIENTS AND METHODS:We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database (17 registries, 2024 submission) to identify patients diagnosed with follicular or marginal zone lymphoma between 2000 and 2022 who received radiotherapy. Cases of subsequently histologically-confirmed sarcoma were screened and classified as confirmed or possible radiation-induced sarcomas based on anatomical localization and a minimum latency of 3 years. Clinical characteristics, treatments, latency intervals, and survival outcomes were analysed. RESULTS:Among 18,293 patients with low-grade non-Hodgkin lymphomas treated with radiation, 19 developed sarcomas (0.10 %). Ten cases were excluded (eight due to anatomical mismatch, two due to insufficient latency). Of the nine remaining cases, six met criteria for confirmed radiation-induced sarcomas. The median age at lymphoma diagnosis was at least 70years, and the median latency to radiation-induced sarcoma was 12years (range: 3-20years). All sarcomas were localized and treated surgically; three patients also received radiotherapy. After a median follow-up of 78months, the 5-year overall survival rate was estimated at 83.3 % (95 % confidence interval: 43.6 %-97.0 %). One patient died from lymphoma progression. CONCLUSION:Radiation-induced sarcomas following radiotherapy for low-grade non-Hodgkin lymphomas is extremely rare, with favourable outcomes when it occurs. These results provide reassuring data supporting the long-term safety of modern radiotherapy for low-grade non-Hodgkin lymphomas and underscore the importance of continued surveillance and treatment planning in patients with prolonged life expectancy.

Introduction: Adjuvant radiotherapy improves locoregional control after breast cancer surgery, but dose prescription remains based mainly on clinicopathological risk rather than individual tumor radiosensitivity. The radiation sensitivity index (RSI) and genomic-adjusted radiation dose (GARD) provide a framework for biologically guided radiotherapy personalization. In the neoadjuvant setting, however, radiosensitivity measured on the diagnostic biopsy may not reflect the residual disease ultimately targeted by adjuvant radiotherapy.Materials and Methods: We analyzed matched pre-treatment and post-treatment RNA sequencing data from two public cohorts of hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer treated with neoadjuvant chemotherapy. The discovery cohort included 16 matched pairs from GSE191127, and the validation cohort included 14 matched HR+/HER2- pairs from GSE309004. RSI was computed using a ten-gene rank-based model. ΔRSI was defined as RSI_post - RSI_pre. Immune fractions were inferred using quanTIseq, and GARD was calculated for START-B, RTOG 1005, and FAST-Forward adjuvant radiotherapy schedules.Results: In the discovery cohort, mean RSI increased from 0.602 to 0.677 after neoadjuvant chemotherapy, with 12 of 16 patients (75%) showing a post-treatment increase. In the validation cohort, mean RSI increased from 0.489 to 0.593 (Wilcoxon p = 0.014), with 11 of 14 patients (78.6%) showing an increase. In the pooled cohort, mean ΔRSI was +0.089, and 23 of 30 patients (76.7%) showed increased RSI after chemotherapy (Wilcoxon p = 0.005). Higher pre-treatment M2 macrophage fraction correlated with larger ΔRSI. RSI changes translated into heterogeneous GARD modifications across fractionation schedules.Conclusion: Neoadjuvant chemotherapy is associated with a reproducible increase in RSI in HR+/HER2- breast cancer, suggesting that residual tumors may become more radioresistant at the genomic level after systemic therapy. Post-neoadjuvant RSI warrants prospective evaluation for individualized adjuvant radiotherapy strategies.

Introduction: Primary ovarian lymphoma represents a rare clinical entity accounting for 0.5% of non-Hodgkin lymphomas and 1.5% of ovarian neoplasms. Current literature is limited to small case series, with poorly defined prognostic factors and optimal treatment strategies. Methods: This retrospective cohort study utilized the SEER database (2000-2020) to identify patients with ovarian lymphoma. Patients were categorized as localized primary ovarian lymphoma (L-POL, stage I) or lymphoma involving the ovary (LIO, stages II-IV, or unknown). Cox proportional hazards regression identified independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Results: A total of 221 patients were identified, representing the largest ovarian lymphoma cohort ever reported. The cohort included 75 L-POL (33.9%) and 146 LIO (66.1%) patients. Median age was 49 years. Diffuse large B-cell lymphoma was the most common histology (62.0%). L-POL patients demonstrated higher proportions of Black patients (13.3% vs. 4.1%, p = 0.022), follicular lymphoma (22.7% vs. 12.3%), and unilateral disease (89.3% vs. 61.6%). At median follow-up of 80 months, 5-year and 10-year CSS rates were 77.7% and 75.3% overall, and 87.4% and 85.5% for L-POL patients. In multivariate analysis, age (HR 1.035, p < 0.001), L-POL (grade I) classification (HR 0.435, p = 0.023), and high-grade histology (HR 4.898, p = 0.009) were independent prognostic factors for CSS. Surgery, radiotherapy, and chemotherapy showed no survival benefit in multivariate analysis. Surgery was performed in 86.9% of patients, with 9.9% undergoing inappropriate debulking procedures. Conclusions: L-POL represents a distinct clinical presentation with excellent long-term prognosis. Age, L-POL classification, and histological grade are independent prognostic factors. The high rate of inappropriate surgical procedures, ranging from hysterectomy and debulking to pelvic exenteration, underscores the critical need for improved preoperative recognition. Optimal management should emphasize limited surgical intervention for diagnosis and fertility preservation, followed by systemic chemotherapy tailored to lymphoma subtype and stage.

Bridging radiotherapy has emerged as a valuable strategy to ensure optimal conditions for chimeric antigen receptor T-cell (CAR-T) therapy in relapsed or refractory hematologic malignancies. By controlling disease burden and maintaining clinical stability in the interval between leukapheresis and CAR-T infusion, it helps counteract the risk of tumor progression that can diminish treatment efficacy. Evidence from diffuse large B-cell lymphoma (DLBCL) and other lymphomas supports the use of hypofractionated radiotherapy to achieve rapid local control with minimal delays, while preliminary data in multiple myeloma expand its applicability. Radiotherapy's immunomodulatory effects, including enhanced antigen presentation and inflammation, may bolster CAR-T cell activity, though careful consideration is required to avoid potential immunosuppressive consequences. The optimal integration of bridging radiotherapy encompasses timing after leukapheresis, rapid planning and delivery, judicious choice of fractionation, and close coordination between hematology and radiotherapy teams. Tailoring dose and technique further refines the therapeutic window, minimizing toxicity while maintaining efficacy. These evidence-based practice propositions provide a comprehensive framework for implementing bridging radiotherapy. By outlining indications, workflow, fractionation schemes, and technical approaches, these guidelines facilitate the seamless incorporation of radiotherapy into CAR-T therapy protocols, ultimately aiming to improve patient outcomes through enhanced disease control and synergistic antitumor immunity.

Personalizing radiotherapy dose in breast cancer remains a major unmet need, as current treatment paradigms rely on uniform prescriptions that overlook interpatient variability in intrinsic radiosensitivity. Over the past decade, transcriptome-based biomarkers such as the Radiosensitivity Index (RSI) and its radiobiological extension, the Genomic-Adjusted Radiation Dose (GARD), have emerged as promising tools capable of quantifying this biological heterogeneity and linking it to expected therapeutic effectiveness. Retrospective clinical studies across diverse breast cancer cohorts have consistently demonstrated that RSI and GARD correlate with locoregional control, identify radioresistant subgroups that may benefit from dose escalation, and reveal radiosensitive tumors for which de-escalation may be safely explored. These findings challenge the assumption that radiation response is uniform within histological or molecular subtypes and highlight the opportunity for biologically tailored dosing. Yet despite early evidence, translation into clinical practice remains limited. Key barriers include the absence of prospective validation, heterogeneous analytic pipelines for RNA sequencing and RSI computation, uncertainty regarding optimal biomarker timing in the neoadjuvant era, and sensitivity of bulk transcriptomic assays to spatial and microenvironmental heterogeneity. Addressing these challenges will require standardization, consensus on clinically meaningful GARD thresholds, and coordinated international efforts to define methodological and regulatory pathways. Emerging approaches in radiomics, digital pathology, and multimodal artificial intelligence may further refine radiosensitivity assessment and reduce reliance on invasive sampling. As the field progresses, genomic personalization of radiotherapy has the potential to transform breast cancer management by replacing one-size-fits-all prescriptions with biologically informed dose adaptation aimed at maximizing tumor control while minimizing toxicity.

Abstract We evaluated outcomes by management type for patients with stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in the Global NLPHL One Working Group retrospective database of 2243 patients with stages I to IV disease diagnosed from 1992 to 2021 at 38 international institutions. A total of 779 patients had stage IA disease with median age of 35 years (range, 3-89) and median follow-up of 6.1 years. The 6-year progression-free survival (PFS) and overall survival were 86.3% and 97.7%, respectively. Outcomes were analyzed for the 2 groups: complete resection and unresected disease. Patients with a complete resection and observation alone (n = 99) had a 6-year PFS of 65.5% vs 90.5% for those who received radiotherapy (RT) (n = 53). Patients with unresected disease (n = 627; 80.5%) had a 6-year PFS of 62.0% for rituximab alone (n = 31), 89.6% for RT alone (n = 325), 76.8% for ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) alone (n = 40), and 94.3% for ABVD plus RT (n = 130). A total of 127 patients relapsed (16.3%), of which 25 (19.7%) had transformation. Our analysis suggests the following: (1) RT improves the PFS in patients with completely resected disease; (2) rituximab or ABVD alone does not appear to achieve a durable response; and (3) chemotherapy was not observed to add additional PFS benefit when used in combination with RT. Thus, for stage IA NLPHL, RT alone is likely sufficient for definitive treatment.

Radiotherapy and systemic therapies have revolutionised cancer treatments and improved survival, with generally acceptable toxicity. Modern radiotherapy techniques offer precision in targeting tumours, while minimising harm to the surrounding tissues. Novel systemic therapies represent opportunities for combining innovative treatments with radiotherapy. New agents are increasingly more tumour-specific than chemotherapy, and new rational combinations with radiotherapy are emerging, allowing for a more personalised approach. The European Society for Radiotherapy and Oncology (ESTRO) has formed a focus group to explore the integration of innovative agents with radiotherapy. This Policy Review highlights the potential of combining radiotherapy with novel drugs, while addressing current evidence gaps and unmet needs in cancer care. The group emphasises a collaborative approach involving multiple stakeholders to drive sustainable improvements in oncological therapies, suggesting careful selection of combinations based on robust preclinical data. Key insights and proactive strategies can shape future clinical practices, particularly with the early introduction of radiotherapy in the development of novel agents.

Background and purpose Total skin electron beam therapy (TSEBT) is an established radiation treatment modality for the management of cutaneous T-cell lymphoma (CTCL). In recent years, there has been an increasing interest in dose de-escalation strategies aimed at lowering treatment-induced side effects whilst maintaining efficacy. This evolution in clinical practice has highlighted the need for consistent technical standards to ensure treatment quality and comparability across medical institutions. A unified set of recommendations for TSEBT in the modern era was sought by the European Society for Radiotherapy and Oncology (ESTRO) Guidelines Sub-Group on Physics, including physical requirements, with the aim of harmonizing clinical practice, promoting homogeneity for clinical trials, and facilitating wider adoption of the technique. Material and methods The ESTRO Guidelines Committee developed these recommendations using a Delphi consensus methodology. An expert panel consisting of radiation oncologists and medical physicists with specific expertise in the radiation treatment of primary cutaneous lymphoma was convened. Panel members completed a 14-question survey focusing on key technical aspects of TSEBT. Results Consensus was achieved on the principal physical and technical components of TSEBT delivery, including prescribed dose levels, field dimensions, treatment techniques, and QA requirements. Areas of agreement reflect current best practices and address sources of variability that may impact treatment reproducibility. Conclusions ESTRO recommendations provide a standardised framework for the delivery of TSEBT in the management of CTCL, supporting safe implementation and consistency across medical institutions in the context of reduced-dose treatment approaches.