Gustave Roussy is the first leader cancer-research hospital in Europe and ranked among the top 5 best specialized hospitals in the world . It is a centre for high quality patient care, research and teaching. It is highly-known for the treatment of (among others): skin cancers like melanoma, breast cancer, and lung cancer. It provides access to care with many expert doctors who have historically revolutionized the treatment of cancer and contributed to the surge of new molecules in the treatment of cancers and tumors. It is located in the Parisian area. It is named after Gustave Roussy, a Swiss-French neuropathologist.In April 2019, three new interventional radiology rooms were inaugurated, making it the largest platform of this type in Europe, entirely dedicated to oncology. Interventional radiology is a so-called "minimally invasive" diagnostic and treatment technique, which uses images to guide access to deep-lying organs, without having to "open up" patients. Gustave Roussy carries out more than 4,000 operations of this type each year.
BACKGROUND:PORTEC-4a investigated molecular risk profile-based individualised adjuvant treatment for women with high-intermediate risk endometrial cancer, aiming to reduce both overtreatment and undertreatment while optimising locoregional control. METHODS:PORTEC-4a was a randomised, open-label, phase 3, multicentre, non-inferiority trial, conducted across eight European countries. Women (aged ≥18 years and with a WHO performance score of 0-2) with early stage high-intermediate risk endometrial cancer were eligible. Patients were randomly assigned post-surgery in a 2:1 ratio to either adjuvant treatment according to their molecular integrated risk profile or to standard vaginal brachytherapy. Allocation used a biased-coin minimisation with stratification for participating centre, grade, and lymphadenectomy. Adjuvant treatment in the molecular-profile group in case of favourable profile (POLE-mutated or no specific molecular profile [NSMP]-CTNNB1 wildtype) was observation, for intermediate profile (mismatch repair deficient or NSMP-CTNNB1 mutated) was brachytherapy (21 Gy in three fractions of 7 Gy given at 5 to 7 day intervals), and for unfavourable profile (p53 abnormal or substantial lymphovascular space invasion or L1 cell adhesion molecule overexpression) was pelvic radiotherapy (45·0-48·6 Gy in 1·8-2·0 Gy fractions, 5 days per week). The primary endpoint was overall 5-year cumulative incidence of vaginal recurrence as first event. Kaplan-Meier, Cox model, and cumulative incidence with competing risks were used for final analysis in the intention-to-treat population. Patient advocates were involved during grant application and trial conduct. The trial is registered with the Netherlands Trial Registry (NTR5841), the ISRCTN registry (ISRCTN11659025), and ClinicalTrials.gov (NCT03469674), and follow-up is ongoing. FINDINGS:Between June 1, 2016, and Dec 24, 2021, 569 patients were enrolled in PORTEC-4a. After the addition of 23 favourable patients out of PORTEC-4, the final combined PORTEC-4a cohort consisted of 564 eligible and evaluable patients (367 in the molecular profile group and 197 in the standard group). All patients were female, the median age was 69·0 years (IQR 63·0-73·5), and data on race and ethnicity were not collected. Median follow-up was 58·1 months (IQR 40·7-63·6). In the molecular profile group 168 (46%) patients had a favourable profile, 148 (40%) had an intermediate profile, and 51 (14%) had an unfavourable profile. The 5-year cumulative incidence of vaginal recurrence was 4·5% (95% CI 2·23-6·76) in the molecular profile group and 1·6% (0·00-3·32) in the standard group (HR 2·71 [95% CI 0·79-9·34]). The upper-bound of the one-sided confidence interval of the difference (5·3%) was below the predefined-equivalence margin of 7·0% (pnon-inferiority=0·005). The second primary analysis in patients with a favourable molecular profile showed 5-year vaginal recurrence of 4·1% (95% CI 0·81-7·37) in the molecular profile group versus 0·9% (0·00-2·78) in the standard group (HR 3·97 [95% CI 0·48-32·95]). Adverse events were mainly grades 1-2, with grade 3 or above related genitourinary toxicities in four (1%) of 367 versus four (2%) of 197, without substantial differences between groups. Five serious adverse events occurred, of which one was possibly related to treatment (vaginal scar dehiscence). No treatment-related deaths occurred. INTERPRETATION:Individualised adjuvant treatment by molecular integrated risk profile is safe and effective for patients with high-intermediate risk endometrial cancer; it spared 46% of patients with a favourable profile from adjuvant treatment, and reduces both overtreatment and undertreatment. FUNDING:KWF Dutch Cancer Society.
BACKGROUND:Dual anti-human epidermal growth factor receptor 2 (HER2) therapy plus chemotherapy followed by maintenance treatment with HER2-targeted and endocrine therapies is standard first-line treatment for hormone-receptor-positive, HER2-positive metastatic breast cancer. On the basis of preclinical and clinical data, the addition of palbociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) may overcome resistance to both endocrine and HER2-directed therapies. METHODS:In this phase 3, open-label, randomized trial, we enrolled patients with hormone-receptor-positive, HER2-positive metastatic breast cancer who did not have disease progression after four to eight cycles of chemotherapy plus HER2-targeted therapy. Patients were randomly assigned in a 1:1 ratio to receive maintenance HER2-targeted and endocrine therapies with or without palbociclib. The primary end point was investigator-assessed progression-free survival. Secondary end points included the objective response, clinical benefit, safety, and overall survival. RESULTS:A total of 518 patients underwent randomization: 261 were assigned to receive palbociclib and 257 to receive standard therapy. At a median follow-up of 53.5 months, patients in the palbociclib group had significantly longer progression-free survival than those in the standard-therapy group (median duration, 44.3 months vs. 29.1 months; hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; two-sided P = 0.02). Grade 3 and 4 adverse events, predominantly from neutropenia, occurred in 79.7% and 10.0% of the patients, respectively, in the palbociclib group, as compared with 30.6% and 3.6% of the patients, respectively, in the standard-therapy group. CONCLUSIONS:The addition of palbociclib to maintenance anti-HER2 and endocrine therapies led to a significant improvement in progression-free survival over standard therapy, with increased toxic effects, mainly neutropenia. (Funded by Pfizer and others; PATINA ClinicalTrials.gov number, NCT02947685.).
ABSTRACT:Large B-cell lymphoma (LBCL) patients failing anti-CD19 chimeric antigen receptor (CAR) T-cell therapy exhibit poor prognosis. Most progressions/relapses occur within 3 months from infusion whereas only a few events occur thereafter (late failure, [LF]). We analyze features, treatments, and outcomes of patients with LF from DESCAR-T, a nationwide registry collecting real-life data for patients treated with approved CAR T-cell therapy in France. Between July 2018 and March 2024, 298 (39.9%) LBCL LF patients (median age, 62 years [range, 18-79]; male, 61.7%) were collected from DESCAR-T. Most patients had diffuse LBCL (n = 205 [68.8%]), advanced stage disease (84.6%), and age-adjusted International Prognostic Index of 2 to 3 (59.3%) at CAR T-cell eligibility. After failure, 76.5% of patients received a systemic therapy and overall response rate was 22.6% (complete response, 18%). At a median follow-up since first LF event of 13.8 months (95% confidence interval [CI], 12.1-15.4), the median overall survival and progression-free survival 2 (PFS-2) were 4.4 (95% CI, 3.8-5.8) and 13.2 (95% CI, 9.6-18) months, respectively. Compared with chemotherapy (hazard ratio [HR], 0.350; 95% CI, 0.193-0.633) and with pooled other treatment groups (HR, 0.483; 95% CI, 0.290-0.805), salvage treatment with bispecific antibodies (bsAb) after CAR T-cell failure showed better PFS-2. Radiotherapy obtained prolonged responses in some patients with 12-month PFS-2 of 41.5% (95% CI, 22.5-59.5). This work is, to our knowledge, the first study describing LBCL patients with LF after CAR T-cells. bsAb seem to be more effective compared with other strategies in the LF setting and this should be considered in the design of new clinical trials.
This is a summary of a research article reporting the findings of the HER2CLIMB-05 trial (NCT05132582), a randomized, double-blind, placebo-controlled, international, phase III trial. The HER2CLIMB-05 trial was conducted to compare the efficacy and safety of adding tucatinib versus placebo to first-line maintenance therapy (trastuzumab and pertuzumab) following induction chemotherapy, in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. The key finding of the HER2CLIMB-05 trial was that progression-free survival was significantly improved in the tucatinib arm over the control arm (24.9 vs 16.3 months). The safety profile of tucatinib plus maintenance therapy was consistent with the known toxicities of each individual drug. The HER2CLIMB-05 regimen, with its high efficacy and manageable toxicity, represents a valuable option for first-line maintenance therapy in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.
Radiotherapy alone or in association with systemic treatment plays a major role in the treatment of head and neck tumours, either as a primary treatment or as a postoperative modality. The management of these tumours is multidisciplinary, requiring particular care at every treatment step. We present the 2025 update of the recommendations of the Société française de radiothérapie oncologique (the French society for radiation oncology) on the radiotherapy of head and neck tumours from the imaging work-up needed for optimal selection of treatment volume, to optimization of the dose distribution and delivery.
