Centre Georges François Leclerc

The aim of this study was to assess return to work (RTW) after breast cancer (BC) by baseline employment status. Using data from the CANTO cohort (NCT01993498), we examined RTW among women below age 57 at BC diagnosis 2 and 4 years after BC diagnosis. We also assessed continuous work between years 2 and 4 post-diagnosis. Poisson regression models investigated associations between baseline employment (self-employed vs. employees) and RTW outcomes, adjusting for clinical, sociodemographic, and work-related factors and quality of life. We used education (above high school; high school or lower) as a proxy to further distinguish between white collar self-employees vs. blue collar self-employees (vs. employees). About 8% of women were self-employed at diagnosis. RTW was slightly higher among the self-employed compared to employees 2 years (N = 3178; PR = 1.04, 95%CI 0.98–1.10) and 4 years after diagnosis (N = 2329; PR = 1.05, 0.99–1.12). This effect was limited to white collar self-employed women. Among those who returned to work 2 years after diagnosis (N = 1683), self-employed women showed a 1.15 (1.01–1.31) higher prevalence of continuous work until year 4 post-diagnosis than employees. Self-employed women do not strongly differ from employees when assessing RTW at specific time points, however once returned to work, they experience fewer work interruptions than employees. This was observed in adjusted models, showing the intrinsic importance of job status in the RTW process. These findings highlight the importance of viewing RTW as an ongoing process, in order to provide appropriate and sustained support.

Trimodal therapy (TMT) is a viable option for muscle-invasive bladder cancer (MIBC), but the optimal chemotherapy regimen remains unclear. This phase II randomized trial (NCT01495676) compared cisplatin (CDDP) with twice-weekly gemcitabine (GEM) and radiation therapy (RT) with CDDP plus RT. Patients with pT2-pT3N0M0 MIBC, after macroscopically complete transurethral resection (TURBT), received RT (63Gy to the bladder, 45Gy to the pelvis, 1,8 Gy/ fraction) with chemotherapy (CDDP 20mg/m2/day for 4days every 21days alone or plus GEM 25mg/m2 twice weekly). The primary endpoint was 2-year disease-free survival (DFS); secondary endpoints included overall survival (OS) and toxicities. A 1:2 randomization was planned to include 36 patients in the control arm and 73 patients in the experimental arm. Sixty-nine patients were included: 24 in the RT/CDDP arm and 45 in the RT/CDDP/GEM arm. The median follow-up was 63months. Two-year DFS was similar between groups (58.3% CI95% [36.6-77.9] vs. 60.0% CI95% [44.3-74.3]), with median DFS of 29.8 (RT/CDDP) vs. 37.4 (RT/CDDP/GEM) months. OS at 24 and 60months was 91.3% [IC 95% 69.5-97.8] and 66.8% [IC 95% 39.6-83.9] (RT/CDDP) vs. 66.7% % [IC 95% 50.2 - 78.8] and 53.7% [IC 95% 37.2 - 67.6] (RT/CDDP/GEM). Toxicity profiles were comparable except for increased cytopenias in the GEM arm. Adding GEM to CDDP did not improve 2-year DFS in MIBC patients treated with TMT. Results should be interpreted cautiously due to early study termination and insufficient accrual.

Salvage brachytherapy (BT) after definitive irradiation for prostate cancer is gaining increasing interest, although many areas of uncertainty remain. We established a large national retrospective cohort including all patients treated with salvage prostate BT for isolated prostatic local relapse after definitive radiotherapy between 2006 and 2022 in seven French expert centers. A total of 266 patients were included. At initial diagnosis, 42% of patients presented with high-risk disease. Primary irradiation consisted of external beam radiotherapy (EBRT) in 78% of cases, most commonly delivered with a 3D conformal technique (51%), with a median dose of 74Gy. Median PSA at relapse was 3.7ng/mL. Salvage BT was performed using low-dose-rate (LDR) permanent iodine seed implantation in 63% of patients and high-dose-rate (HDR) brachytherapy in 37%. Seventy percent of patients were treated with whole-gland irradiation, while the remainder received a focal approach. In 34.5% of cases, androgen deprivation therapy (ADT) was combined with salvage BT. After a median follow-up of 60.1months, 135 (50.7%) of patients experienced biochemical relapse. Median biochemical progression-free survival (bPFS) was 40.0months. On multivariate analysis, initial risk group (high-risk: HR=1.64, 95% CI [1.13-2.37], p=0.008), BT technique (HDR: HR=2.14, 95% CI [1.41-3.26], p=0.0004), and treated volume (focal vs. whole-gland: HR=2.14, 95% CI [1.23-3.73], p=0.007) were significantly associated with bPFS. Late grade 3 gastrointestinal and genitourinary toxicities occurred in 3% and 14% of patients, respectively. Salvage BT provides encouraging disease control with an acceptable toxicity profile. Careful patient selection remains essential.

To evaluate the surgical management and oncologic outcomes of patients with FIGO stage IV ovarian cancer, using data from the French national ESME cohort. This retrospective multicenter study included patients diagnosed with FIGO stage IV ovarian cancer between January 2011 and December 2016, treated in 18 French Comprehensive Cancer Centers participating in the ESME-OVR program. Clinical characteristics, treatment strategies, metastatic site patterns, and survival outcomes (overall survival [OS], progression-free survival [PFS]) were analyzed and compared between FIGO IVA and IVB stages. A total of 159 patients were identified, of whom 107 (67.3 ​%) had FIGO stage IVB disease. Regardless of metastatic stage, surgical strategies and were comparable. Complete debulking surgery was achieved in 75 ​% of cases. Most of FIGO stage IVB patients (88.8 ​%) presented a single metastatic site including extra-abdominal lymph nodes (50.5 ​%), liver (20.6 ​%), and lungs (10.3 ​%); 15.9 ​% of patient with distant metastases underwent local treatment and predominantly targeted nodal disease. Complete debulking surgery was significantly associated with improved OS and PFS (p ​= ​0.002 and p ​< ​0.001, respectively), while local treatment of metastases did not provide survival benefit. The number of metastatic sites did not significantly influence prognosis. Complete debulking surgery is the critical factor from a progronostic point of view, whether in FIGO stage IVA or IVB. Feasibility of local treatment for distant metastases is observed, its impact on oncologic outcomes remains unclear and we need further prospective investigation. Surgical strategies should be integrated into a personalized approach to optimize management in advanced-stage disease.

Optimizing radioenhancerdesign for cancer therapy has been limitedby inconsistent metal comparisons and unclear nanoscale mechanisms.High-Z nanoparticles are expected to enhance radiation effects throughincreased photoelectric absorption and secondary electron production,with the common assumption that radioenhancement efficacy increasesuniformly with atomic number. However, this linear relationship maybe oversimplified. Here, we introduce a versatile, supramolecularpeptide platform enabling direct and standardized comparison of gadolinium(Gd), bismuth (Bi), and hafnium (Hf) as radioenhancers within a single,biologically targeted framework. This system is based on autoassembledpeptide heterodimers (E3-K3) incorporating a flexible chelator (DOTAGA)and variable heavy-chain antibody (VHH) domains, ensuring uniformcellular uptake and precise tumor targeting. Systematic invitro and in vivo analyses across HER2+breast cancer and disseminated multiple myeloma models demonstratethat radioenhancement efficacy correlates with atomic number but notin a simple linear fashion, with physicochemical properties of eachmetal determining biological outcomes such as DNA damage induction,reactive oxygen species generation, and clonogenic survival reduction.Specifically, Gd- and Bi-loaded formulations significantly enhancedtumor control under external beam radiotherapy, with Bi exhibitingsuperior efficacy, while Gd-based constructs facilitated MRI-guidedradioligand therapy. Our study elucidates fundamental physical mechanismsgoverning metal-dependent radioenhancement at the nanoscale but alsoestablishes a broadly applicable theranostic approach with significanttranslational implications for personalized radiation oncology.