Centre Antoine Lacassagne

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.

Semiconductors form the basis of high-performance optoelectronic devices, enabling efficient light emission and detection. While crystalline perfection is generally sought to optimize device performance, specific lattice defects can endow materials with unexpected and useful functionalities. Here, we show that engineered defect states in gallium nitride (GaN) diodes markedly enhance their response to high-energy protons. Through a combination of device simulations and experimental measurements, we demonstrate that forward biasing the diode just below its turn-on voltage activates a defect-mediated photoconductive regime. This operating mode induces substantial carrier trapping and photoconductive gain while simultaneously suppressing the dark current-a behaviour in stark contrast to conventional photoconductors. The exploitation of this previously underexplored detection mechanism yields a three-orders-of-magnitude enhancement in sensitivity over standard photovoltaic operation, enabling reliable quantification of proton fluxes down to a few particles per second. This novel mode of operation is not limited to protons but also extends to X-rays and other high-energy particles, and may be generalized to a broader class of semiconductors exhibiting high levels of doping compensation. These findings open new avenues for very low-flux particle detection across diverse application spaces, including medical, astronomy, and industrial imaging.

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.

Onychocytic matricoma (OCM) is an acquired benign onychogenic tumor producing a localized thickening of the nail plate that usually presents as longitudinal pachymelanonychia. However, longitudinal pachyleukonychia as the presenting sign of OCM is increasingly recognized in clinical practice. To our knowledge, polydactylous OCM has not previously been reported in the literature. This study aims to describe a new nail genodermatosis presenting as polydactylous longitudinal leukonychia with histology typical of OCM. Four cases were identified. The previously unreported familial nail abnormality occurred in at least 2 first-degree relatives. Longitudinal white bands located exclusively on the fingernails were the only characteristic of this disease. The longitudinal bands varied in number from 2 to 4 per nail. Nail changes may appear during childhood, but most cases were observed between the ages of 20 and 50 years. The multiple longitudinal bands corresponded histologically to multiple OCM. Three cases in this series had no relevant personal of family history of neoplasm, but only 2 generations were analyzed. In 1 family, polydactylous OCM was associated with a family history of melanoma and renal cell carcinoma. The genomic profile of this single family allowed a diagnosis of OCM associated with BRCA1-associated protein ( BAP1 ) tumor predisposition syndrome (TPDS). Our results are limited by incomplete follow-up and the small size of this retrospective case series. As such tumors are rare, additional cases need to be collected to clarify the role of onychocytic hamartoma as an early indicator of BAP1 TPDS.