Purpose: Circulating nucleosomes (DNA wound around histone proteins) are emerging cancer biomarkers. We investigated their association with clinical outcomes in advanced ovarian cancer. Patients and methods: Circulating levels and longitudinal kinetics of two nucleosomes (H3K27Me3 and H3K36Me3, log-scale) were assessed at baseline, during neoadjuvant chemotherapy after interval cytoreductive surgery, and at progression in patients with advanced ovarian cancer patients from the randomized phase II CHIVA trial. Nucleosomes were measured with Nu.Q® immunoassays,compared to those from 201 healthy subjects, and analyzed in relation to surgical outcomes, progression-free survival, with respect to the modeled CA–25 ELIMination rate constant K (KELIM) along with established clinical covariates. Results: H3K27Me3 and H3K36me3 nucleosome concentrations were available for 148/188 patients. Both nucleosomes were significantly higher in ovarian cancer patients compared with healthy controls and showed correlated baseline levels. Lower baseline H3K36Me3 was independently associated with complete interval cytoreduction surgery and progression-free survival, complementary to CA–25 KELIM. Longitudinal changes in nucleosome levels showed a decrease during neoadjuvant chemotherapy, but were not associated with radiological response, completeness of interval cytoreductive surgery or progression-free survival. Conclusion: Baseline H3K36Me3 and H3K27Me3 levels may represent non-invasive biomarkers in advanced ovarian cancer and warrant further evaluation for their potential clinical utility.
BACKGROUND:For patients with high-risk prostate cancer, the role of dose-escalated radiotherapy in combination with long-term androgen deprivation treatment (ADT) is controversial, without any demonstrated benefit on cancer-specific or overall survival. We aimed to evaluate the effect of a 10 Gy dose increase, from 70 Gy to 80 Gy, on progression-free survival in men with high-risk prostate cancer. METHODS:In this multicentre, open-label, randomised, phase 3 trial, we enrolled patients with high-risk prostate cancer, defined as prostate-specific antigen of 20 ng/mL or more, Gleason score of at least 8, or clinical stage T3-T4, from 25 centres in France. Participants were randomly assigned (1:1) by minimisation, stratified by centre and previous pelvic lymph node dissection, to receive prostate-targeted dose-escalated external beam radiotherapy (80 Gy; 2 Gy per fraction for 8 weeks) or standard-dose external beam radiotherapy (70 Gy; 2 Gy per fraction for 7 weeks), combined with long-term ADT. Neither the participants nor the investigators were masked to the allocated treatment. The primary endpoint was 5-year progression-free survival defined as the time from randomisation to first biochemical (defined as prostate-specific antigen >nadir plus 2 ng/mL) or clinical (ie, local, regional, or metastatic) disease progression, analysed in the intention-to-treat population, with 197 events required. 5-year progression-free survival was the prespecified endpoint, and 10-year progression-free survival was additionally reported (post hoc) in view of the low number of events at 5 years. The trial is registered at ClinicalTrials.gov, NCT00967863, and is complete. FINDINGS:Between April 6, 2009, and Jan 24, 2013, 505 patients with high-risk prostate cancer were enrolled; 250 were assigned to receive dose-escalated radiotherapy (80 Gy) and 255 to receive standard dose radiotherapy (70 Gy). All participants were male and ethnicity data were not collected. At a median follow-up of 9·5 years (IQR 8·5-10·3), 5-year progression-free survival was 91·4% (95% CI 87·0-94·4) in the dose-escalation group versus 88·1% (83·2-91·6) in the control group, and 10-year progression-free survival was 83·6% (77·8-88·0) versus 72·2% (65·3-78·0; stratified HR 0·56, 95% CI 0·40-0·78, p<0·0001). Grade 3 or worse adverse events assessed at 6 months (acute toxicity) were observed in 60 (24%) of patients in the dose-escalation group and 62 (25%) in the control group. The most frequent grade 3 or worse adverse events were sexual disorders (28 [11%] in the dose-escalation group vs 20 [8%] in the control group) and bladder or urethra disorders (12 [5%] vs 19 [8%]). Adverse events assessed at 5 years (late toxicity) occurred in 118 (70%) of 168 in the dose-escalation group and 122 (73%) of 168 in the control group; grade 3 or worse late toxicities occurred in 19 (8%) participants in the dose-escalated radiotherapy group versus 17 (7%) participants in the control group. The most common late grade 3 adverse event was bladder or urethra disorders (seven [4%] vs three [2%], respectively). Serious adverse events occurred in nine (4%) patients in the dose escalation group and nine (4%) in the control group; none were considered to be treatment related. There were no treatment-related deaths. INTERPRETATION:For patients with high-risk prostate cancer, radiotherapy at a total dose of 80 Gy, in combination with long-term ADT, improved progression-free survival and could be a potential option in this situation. However, given the low number of events, further research is needed to consolidate and confirm the benefit in dose-escalation in prostate cancer-specific survival and overall survival. FUNDING:French National Cancer Institute and AstraZeneca.
Purpose This study investigates gendered trajectories of spousal grief following cancer within palliative care contexts, including continuous deep sedation until death (CDSUD). It examines (1) how men and women narrate and experience bereavement, and (2) how their emotional, relational, and cognitive processes evolve over 18 months. Methods This longitudinal qualitative study is part of the AfterSedatio project. Twenty-two bereaved spouses (12 men, 10 women) were interviewed at 3 (T0), 6 (T1), and 12 months (T2) after the loss of their partner. Interviews were analyzed using ALCESTE lexical analysis, complemented by reflexive thematic analysis, following Braun & Clarke’s framework. Results Gendered patterns emerged across time. At T0, women provided vivid, emotionally embodied accounts of bodily decline, emergency care, and CDSUD decision-making. In contrast, men offered more structured, pragmatic narratives focused on logistics, clinical details, and prior family losses. At T1, women reported heightened emotional vulnerability and intrusive end-of-life memories; men highlighted routine disruption and relational absence. By T2, women approached future planning cautiously, maintaining strong emotional bonds, while men re-engaged in social life and personal projects. Across genders, the quality of palliative communication and clarity about sedation practices shaped grief integration. Women showed markedly higher financial vulnerability after bereavement. Conclusion Gender shapes—but does not rigidly determine—grief trajectories after cancer-related spousal loss. Emotional, relational, and pragmatic registers evolve, underscoring the need for individualized, gender-sensitive bereavement support. End-of-life communication, particularly around sedation, plays a critical role in later grief adjustment.
PURPOSE:Platinum-based chemotherapy and surgery are pivotal in managing ovarian cancer (OC), yet prognosis remains poor, and early biomarkers for platinum resistance are needed. The neoadjuvant setting provides an opportunity to evaluate tumor responsiveness to platinum chemotherapy in vivo. This study evaluated whether early measures of platinum response combined with molecular alterations could predict surgical outcomes and survival in patients with OC treated with neoadjuvant chemotherapy (NACT). METHODS:The CHIVA study enrolled stage III/IV OC patients eligible for three cycles NACT with or without nintedanib, followed by interval debulking surgery. Archival samples underwent extensive sequencing to detect clinically relevant variants and copy number alterations and calculate genomic instability (GIS). Early chemotherapy response measures-cancer antigen 125 kinetics by KELIM, major pathologic response, GIS status, tumor infiltrating lymphocytes (TILs) abundance, and genomic alterations-were correlated with surgery completeness and survival. RESULTS:Among 127 patients, the overall response rate was 44%, and the complete cytoreduction (CC0) rate was 54.8%. Homologous recombination deficiency (HRD) was identified in 56% of patients and was associated with better survival. The median progression-free survival was 21.4, 20.5, and 14.4 months in the BRCAmut, BRCAwt/GIS-high, and BRCAwt/GIS-low subgroups, respectively (P = .001). Unfavorable KELIM predicted lower objective response rate, CC0, and shorter survival, while low intraepithelial TILs (ieTILs) correlated with poor outcomes. Multivariate analysis confirmed KELIM, HRD status, and ieTILs as independent biomarkers. CCNE1 amplifications, observed in 20% of patients, were associated with moderate chemotherapy sensitivity. CONCLUSION:HRD status, KELIM, and TILs are key independent biomarkers in advanced OC. CCNE1 amplifications, although typically associated with platinum resistance, were linked to moderate chemotherapy sensitivity, defining an intermediate prognostic subgroup.
Ocrelizumab is an anti-CD20 monoclonal antibody that is highly effective in multiple sclerosis (MS) but is associated with an increased risk of opportunistic infections that may be difficult to diagnose. We report three MS patients treated with ocrelizumab who developed severe meningoradiculitis. Routine investigations failed to identify any pathogen, whereas metatranscriptomic analysis of cerebrospinal fluid (CSF) detected Borrelia miyamotoi RNA. All patients improved after appropriate antibiotic therapy. B. miyamotoi should be considered in anti-CD20-treated MS patients presenting with meningoradiculitis, and CSF metatranscriptomics should be used to investigate undiagnosed central or peripheral nervous system infections, particularly in immunocompromised individuals. Ocrelizumab is a highly effective treatment widely used in MS but has been associated with an increased risk of infection. We report three cases of B. miyamotoi infections in patients receiving ocrelizumab in which routine laboratory tests failed to detect the pathogen.
