Anger E, Supiot S, Josset Q
… +21 more, Pasquier D, Vaugier L, Riet FG, Pointreau Y, Ruffier A, Loos G, Terlizzi M, Blanchard P, Martin E, Sargos P, Guerni M, Schick U, Bera G, Roman J, Latorzeff I, Créhange G, Castelli J, Barateau A, De Crevoisier R, Nicosia L, Le Guévelou J
Int J Radiat Oncol Biol Phys
· 2026 Mar · PMID 41864432
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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 can...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.
Gulstene S, Chuk E, Conway J
… +9 more, Hanuschak J, Han K, Milosevic M, Lukovic J, Ferguson SE, Salman A, Santiago AT, Rink A, Croke JM
Int J Radiat Oncol Biol Phys
· 2026 Mar · PMID 41862031
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PURPOSE: Definitive radiation therapy for cervical cancer results in significant vaginal and sexual toxicity. Prior work has investigated dosimetric predictors of vaginal toxicity; however, sexual health outcomes are lac...PURPOSE: Definitive radiation therapy for cervical cancer results in significant vaginal and sexual toxicity. Prior work has investigated dosimetric predictors of vaginal toxicity; however, sexual health outcomes are lacking. METHODS AND MATERIALS: Patients with stage IB to IVA cervical cancer treated with definitive chemoradiation and magnetic resonance-guided brachytherapy were enrolled in a prospective, cross-sectional study. Sexual toxicity was assessed using 2 validated patient-reported outcome measures: Female Sexual Function Index and Female Sexual Distress Scale-Revised. Clinical and treatment data were collected by chart review. Vaginal dosimetry was abstracted from individual treatment plans, including: vaginal D (minimum dose to hottest 2 cm of vagina), International Commission on Radiation Units and Measurements rectovaginal point (point dose 5 mm posterior to the applicator at the top of vagina), lateral point (point dose 5 mm lateral to the applicator at the top of vagina), point dose at posterior-inferior border of the symphysis (PIBS), and PIBS ± 2 cm (point dose ± 2 cm to PIBS). Vaginal Total Reference Air Kerma assessed dose loading within the vagina. Descriptive statistics summarized the data. Correlations were evaluated using logistic and linear regression analyses. RESULTS: Between August 2018 and April 2022, 73 patients were eligible. Median age was 49 (range, 25-81), median stage was IIB, 58% had vaginal involvement at diagnosis, and 33% had vaginal involvement at brachytherapy. Patients completed patient-reported outcome measures at a median of 19 months (range, 3-63) post treatment. Criteria for sexual dysfunction and distress were met in 73% (Female Sexual Function Index ≤ 26) and 55% (Female Sexual Distress Scale-Revised ≥ 11) of participants, respectively. Cumulative International Commission on Radiation Units and Measurements rectovaginal point dose >65 Gy (odds ratio, 5.04; 95% CI, 1.18-27.99; P = .040) and Vaginal Total Reference Air Kerma (odds ratio, 1.71; 95% CI, 1.04-3.04; P = .045) were associated with increased sexual distress on multivariable analysis. CONCLUSIONS: Sexual health following radiation therapy for cervical cancer is a multifactorial issue. This analysis identifies a novel association between brachytherapy dosimetry and sexual toxicity. Further attention to and evaluation of vaginal doses could improve our understanding of sexual health outcomes.
Vetrugno I, Telarovic I, Sanchez-Fernandez A
… +4 more, Reichl S, Torelli N, Unkelbach J, Pruschy M
Int J Radiat Oncol Biol Phys
· 2026 Mar · PMID 41862030
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PURPOSE: Radiation therapy exerts direct cytotoxic effects on cancer cells, but also induces immunogenic responses in the tumor microenvironment (TME), eliciting both immune-stimulatory and immune-suppressive dynamics. T...PURPOSE: Radiation therapy exerts direct cytotoxic effects on cancer cells, but also induces immunogenic responses in the tumor microenvironment (TME), eliciting both immune-stimulatory and immune-suppressive dynamics. These effects are influenced by fraction size, fractionation regimen, and timing of radiation therapy-immunotherapy co-administration. In this study, 2 opposing 2-fraction regimens were investigated, in which the same cumulative physical dose was applied to the tumor, but low- and high-dose fractions were administered in opposite order. METHODS AND MATERIALS: Using 2 murine tumor models (MC38 and B16F10-Luc) implanted heterotopically, we investigated how dose sequencing affects the immune dynamics interplay in the TME and characterized the TME in response to low (6 Gy) and high (12 Gy) single doses of ionizing radiation and to 2 opposing fractionation regimens (6 + 12 Gy vs 12 + 6 Gy). Furthermore, we assessed the effect of the different radiation therapy regimens on tumor growth and survival and strategically combined the 2-fraction regimens with an immune checkpoint blockade. RESULTS: We demonstrated that the 2 opposing fractionation regimens generated distinct TMEs, depending on the sequence of low- and high-dose fractions. Although the 12 + 6-Gy regimen resulted in a TME enriched with CD8+ T cells with increased effector function, tumors treated with the 6 + 12-Gy regimen exhibited an enhanced proportion of suppressive CD4+ FOXP3+ regulatory T cells, thereby shaping ionizing radiation-induced antitumor immunity. By combining an immune checkpoint blockade with radiation therapy, we effectively counteracted the immune-suppressive effect, predominantly associated with the 6 + 12-Gy regimen. We demonstrated superior tumor control and a strengthened immunologic memory in response to this combinatorial approach and corroborated these findings in a secondary tumor model. CONCLUSIONS: The sequence of low and high radiation doses impacts the immunologic response and must be carefully considered for the delivery of heterogeneous fractionation schemes, particularly when combined with immunotherapy.
Chang JS, Kim MH, Lee BM
… +2 more, Sohn J, Kim GM
Int J Radiat Oncol Biol Phys
· 2026 Mar · PMID 41862029
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PURPOSE: To analyze patterns of progression after first-line systemic therapy in metastatic breast cancer (MBC) patients who did not undergo metastasis-directed therapy (MDT), and to explore whether baseline circulating...PURPOSE: To analyze patterns of progression after first-line systemic therapy in metastatic breast cancer (MBC) patients who did not undergo metastasis-directed therapy (MDT), and to explore whether baseline circulating tumor DNA (ctDNA) copy number aberration burden is associated with progression to widespread metastases. METHODS AND MATERIALS: We reanalyzed a prospective cohort of 207 patients with de novo or recurrent MBC enrolled between 2017 and 2021. Serial imaging studies were retrospectively reviewed to enumerate metastatic lesions and classify progression as involving preexisting lesions (L), new lesions (D), or both (L + D). Lesion-burden was categorized as 1-5, 6-10, or >10 lesions. Baseline plasma samples were analyzed using low-pass whole-genome sequencing to quantify genome-wide copy number aberration burden, expressed as the I-score. RESULTS: Among 207 patients, baseline lesion counts were 1-5 in 29.5%, 6-10 in 17.9%, and >10 in 52.7%. With a median follow-up of 47.4 months, 5-year overall survival was 75.4% for 1-5 lesions, 65.9% for 6-10 lesions, and 44.9% for >10 lesions, demonstrating a stepwise gradient by baseline lesion count. Patterns-of-failure were L in 39.3%, D in 27.1%, and L + D in 33.6%, indicating that new lesions accounted for 60.7% of first progression events. Across subsequent therapy lines, progression increasingly manifested as >5 lesions and D-only events. Higher baseline I-score correlated with lesion-burden (ρ = 0.35, P < .001) and independently predicted widespread progression (>10 lesions; hazard ratio, 3.21; 95% CI, 2.01-5.13), along with younger age, triple-negative breast cancer, and higher baseline lesion count. CONCLUSIONS: MBC frequently evolves toward widespread dissemination, with new-lesion failures predominating. These patterns provide context for prior MDT trial results and highlight the limitations of lesion count alone. Elevated ctDNA copy number burden independently predicted widespread progression, supporting further study of ctDNA profiling to identify patients at high risk of rapid dissemination, in whom MDT is unlikely to provide benefit.