Hôpital Lyon Sud

CHRONOS is a multicenter, retrospective, cohort study involving acute graft-versus-host disease (aGvHD) adult patients with gastrointestinal (GI) symptoms, steroid- and ruxolitinib refractory, who initiated third-line therapy between 30 May 2019 and 30 September 2024. Primary endpoints were all-organ overall response rate (ORR) and GI-specific ORR (GI-ORR) around 28 days after treatment initiation. Secondary endpoints included duration of response, real-world progression-free survival (rwPFS) of underlying malignancy, and overall survival (OS). Fifty-nine patients from 16 sites in Europe were included. On Day 28, ORR was 36% (95% CI: 24-49%), GI-ORR was 37% (95% CI: 25-51%); 29% (95% CI: 11-49%) of responders lost response within 30 days, and 52% (95% CI: 29-72%) within 90 days. Median rwPFS and median OS were both 86 days (95% CI: 54-128 days). Median OS was higher in responders than in non-responders (186 versus 45 days). Over the 12-month follow-up period, 41 patients died, mainly due to aGvHD progression (n = 25), and infectious complications (n = 9). Within 3 months, Grade ≥ 2 infectious events occurred in 51% of patients; Grade 3-4 thrombocytopenia and neutropenia in 64% and 32%, respectively. These findings demonstrate limited effectiveness of third-line therapy in this cohort of steroid- and ruxolitinib-refractory aGvHD patients with GI symptoms.

Oxaliplatin (Ox) is one of the recommended agents in Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) that benefitted of several phase I trials. Based on these data, the dose of 120mg/m2 was suggested by an expert consensus for fit patients with peritoneal metastases (PM) of gastrointestinal cancers. The aim of the current study is to determine the real-life feasibility and safety profile of this regimen. This retrospective study included all patients treated with PIPAC-Ox 120mg/m2 in six referral centers specialized in PM. The patients were assessed for all potential toxicities associated to high dose oxaliplatin. Adverse events were expressed with the use of CTCAE for medical complications and Clavien-Dindo for surgical complications. Logistic regression and multivariate analysis were performed. 259 PIPAC procedures were performed in 91 patients (53 male) diagnosed with unresectable PM of various origins; most patients (n=62) having colorectal PM. Concomitant IV 5FU was performed in 70 patients. All patients underwent the first PIPAC-Ox 120mg/m2, and 44 patients (48.3%) had ≥3 PIPAC. Abdominal pain was the most frequent grade III toxicity at the first PIPAC-Ox (n=34) while 30 patients routinely received continuous IV opioids. Nausea-vomiting and ascites infection were the others grade III toxicity observed at PIPAC 1, one in each case respectively. After PIPAC 3, RECIST partial/stable response in 68.2%; PRGS 1-2 in 77.3% and negative cytology in 50% of patients. High-dose PIPAC-Ox is feasible and safe. Local and histological response are well identified. However abdominal pain remains a main concern and continuous IV protocols should be considered routinely.

Chronological age is an imperfect proxy for risk assessment in geriatric oncology. There is an urgent need for an objective, easily measurable biological aging signature to refine patient stratification and personalize therapeutic decisions. We analyzed a panel of seven aging-related biomarkers (including markers of inflammation, anabolic reserve, and telomere status) in 244 nonmetastatic breast cancer patients from two age groups ("Old", ≥70 years, N = 162; "Young", ≤60 years, N = 82). We used Latent Class Analysis (LCA) to integrate these markers and identify distinct biological risk profiles. These profiles were then evaluated for their association with Overall Survival (OS) and Cancer-Specific Death (CSD) via Competing Risk Analysis. LCA identified two patient profiles. The Unfavorable Biologic Profile (56.1% of the cohort) was defined by a triad of high MCP-1, high Chitinase activity, and low IGF-1. This profile was strongly associated with poorer OS (Age-adjusted HR=1.82, p = 0.018). Crucially, 15% of chronologically "Young" patients were assigned to this high-risk profile, while 23% of "Old" patients were assigned to the Favorable Profile. Furthermore, the Unfavorable Profile was more strongly and specifically associated with CSD (Subdistribution HR: 2.05, p = 0.012) than with Non-Cancer Death. Our results delineate an unfavorable, trans-chronological biological profile that identifies patients with low host reserve, largely driven by inflammaging and catabolism. This integrated signature provides a robust, objective screening tool to identify biologically frail patients, validating the need for Comprehensive Geriatric Assessment (CGA) and biomarker-guided therapeutic de-escalation (e.g., avoiding adjuvant chemotherapy) to improve individualized outcomes in oncology. BS32220096117.

Vedolizumab has become the preferred first-line advanced therapy in ulcerative colitis (UC). However, the optimal second-line treatment following vedolizumab failure remains unclear. We aimed to evaluate the effectiveness and safety of second-line therapies after first-line vedolizumab. We conducted a multicenter retrospective study including UC patients from 31 centers who received infliximab (IFX), subcutaneous (SC) anti-TNFs, or ustekinumab after vedolizumab failure. The primary endpoint was steroid-free clinical remission (SFCR) at week 14. Predictors of remission were identified using multivariate logistic regression. Among 196 patients, 99 received IFX, 27 anti-TNF SC, and 70 ustekinumab. At week 14, SFCR was achieved in 78 patients (39.8%): 38 (38.4%) with IFX, 8 (29.6%) with anti-TNF SC, and 32 (45.7%) with ustekinumab, with no significant difference between groups (p=0.32). Median treatment persistence ranged from 8 to 9.2months. Baseline corticosteroid use was associated with lower odds of SFCR (OR=0.37, 95% CI [0.18-0.73]). Adverse events occurred in 15.8% of patients, including 12.2% serious events. Overall adverse events were less frequent with ustekinumab than with IFX (10.0% vs. 24.2%, p=0.02), while serious events were comparable (5.7% vs. 16.1%, p=0.08). Discontinuation due to adverse events was more frequent with IFX (12.1%) and anti-TNF SC (14.8%) than with ustekinumab (2.9%, p=0.045 and 0.049). In UC patients failing vedolizumab, second-line IFX, anti-TNF SC, and ustekinumab showed similar effectiveness and persistence. Infliximab remains a robust option for rapid control in high inflammatory burden, whereas ustekinumab may be preferred for its superior safety profile in high-risk patients.