French Centers Research Articles

Clinical and radiological results of final fusion in patients who underwent lengthening with magnetically controlled growing rods. About 66 patients with a mean follow-up of 5years.

The aim of this study was to evaluate the effects of definitive arthrodesis on frontal and sagittal spine balance in EOS patients treated with MCGR, as well as the complications associated with this procedure and the outcome at last follow-up. This was a multicentre study in 10 French centres. All patients who underwent posterior spinal arthrodesis after completion of MCGR treatment, regardless of age, etiology of scoliosis between 2011 and 2022, were included. A total of 66 patients who had a final fusion after the lengthening programme were included in the study. The mean follow-up time was 5.5 ± 1.7years (range: 2.1-9). The mean follow-up time after arthrodesis was 24 ± 18months (range: 3-68) and the mean age at arthrodesis was 13.5 ± 1.5years (range: 9.5-17). The main and secondary curves were significantly (p < 0.005 and p = 0.03) improved by arthrodesis (16.4° and 9° respectively) and stabilised at the last follow-up. The T1-T12 and T1-S1 distances increased by 8.4mm and 14mm with spinal fusion, with no significant difference (p = 0.096 and p = 0.068). There was no significant improvement in the rest of the parameters with arthrodesis, nor was there any significant deterioration at last follow-up. After final fusion, there were a total of 24 complications in 18 patients (27.3%) that routinely led to repeat surgery. Final fusion after MCGR provides satisfactory additional correction of the main and secondary curves and a moderate increase in the T1-T12 distance but has no impact on sagittal balance and other radiological parameters. The post-operative complication rate is particularly high in patients at risk of complications. Level 4.

Infarct Core Growth During Interhospital Transfer For Thrombectomy Is Faster At Night.

Preclinical stroke models have recently reported faster infarct growth (IG) when ischemia was induced during daytime. Considering the inverse rest-activity cycles of rodents and humans, faster IG during the nighttime has been hypothesized in humans. We retrospectively evaluated acute ischemic stroke patients with a large vessel occlusion transferred from a primary to 1 of 3 French comprehensive stroke center, with magnetic resonance imaging obtained at both centers before thrombectomy. Interhospital IG rate was calculated as the difference in infarct volumes on the 2 diffusion-weighted imaging, divided by the time elapsed between the 2 magnetic resonance imaging. IG rate was compared between patients transferred during daytime (7:00-22:59) and nighttime (23:00-06:59) in multivariable analysis adjusting for occlusion site, National Institutes of Health Stroke Scale score, infarct topography, and collateral status. Out of the 329 patients screened, 225 patients were included. Interhospital transfer occurred during nighttime in 31 (14%) patients and daytime in 194 (86%). Median interhospital IG was faster when occurring at night (4.3 mL/h; interquartile range, 1.2-9.5) as compared to the day (1.4 mL/h; interquartile range, 0.4-3.5; P<0.001). In multivariable analysis, nighttime transfer remained independently associated with IG rate (P<0.05). Interhospital IG appeared faster in patients transferred at night. This has potential implications for the design of neuroprotection trials and acute stroke workflow.

P-256 Large for gestational age in singletons born following frozen embryo transfer: due to freezing technique or to endometrial preparation protocol? Lessons from the French registry

Abstract Study question Is large for gestational age (LGA) observed in singletons born following frozen embryo transfers (FET) either due to freezing technique or to endometrial preparation protocol? Summary answer Artificial cycles were associated with a higher rate of LGA when compared to ovulatory cycles, whereas no difference was observed between the freezing techniques. What is known already Several studies compared neonatal outcomes after fresh embryo transfer (fresh ET) and FET, and showed that FET was associated with improved neonatal outcomes, including reduced risks of preterm birth, low birth weight and small for gestational age (SGA) when compared to fresh ET. However, these studies also revealed an increased risk of LGA after FET. The underlying pathophysiology remains unclear; parental infertility, laboratory procedures including embryo culture conditions and freezing-thawing processes, as well as endometrial preparation treatments might be at play. Study design, size, duration A multicentric epidemiological data study was performed through a retrospective analysis of the standardized individual clinical records of the French national registry of in vitro fertilisation (IVF) from 2014 to 2018, including deliveries resulting from fresh ET and FET that were prospectively collected in fertility centres. Complementary data were collected from the participating fertility centres including the vitrification media and devices, as well as the endometrial preparation protocols. Participants/materials, setting, methods Data were collected from 35 French fertility centres, leading to the inclusion of a total of 72,789 fresh ET, 10,602 slow-freezing FET and 30,062 vitrification FET cycles. Fetal growth disorders were defined in liveborn singletons according to gestational age and sex-specific weight percentile distribution: SGA and LGA if &amp;lt; 10th and &amp;gt;90th percentile, respectively. Analyses were performed using linear mixed models with the centres as random effect. Main results and the role of chance Among a total of 26,585 liveborn singletons, 16,413 babies were born from fresh ET, 1,644 from slow-freezing FET and 8,528 from vitrification FET. Birthweight was significantly higher in the FET groups compared to the fresh ET group, with no difference between the two freezing techniques. Likewise, LGA rates were higher and SGA rates were lower in the FET groups compared to the fresh ET group (12.0% vs 6.4%, p &amp;lt; 0.001, and 7.8% vs 13.4%, p &amp;lt; 0.001 respectively). In a multivariable analysis, the risk of LGA following FET was not different between stimulated and natural cycles (adjusted odds ratio: 1.06, 95% confidence interval: 0.83-1.35, p = 0.64) but was significantly increased in artificial compared to natural cycles (aOR 1.36 [1.11-1.67], p = 0.003). On the contrary, the risk of LGA was not associated with either the freezing mode (slow-freezing vs vitrification) or the embryo stage (cleaved embryo vs blastocyst). When focusing on vitrification, the risk of LGA was not associated with either the freezing medium used or the embryo stage, and no difference was observed according to the vitrification device. Limitations, reasons for caution Most of the vitrification techniques were performed using the same device, and with two major vitrification media, limiting the interpretability of the comparison of the risk for LGA according to the device or the vitrification media. Wider implications of the findings Our results seem reassuring regarding potential fetal growth disorders following embryo vitrification in comparison to slow-freezing. Even if other factors may be involved, the impact of the endometrial preparation treatments seems to prevail for LGA risk following FET. FET during ovulatory cycles could minimize the risk for fetal growth disorders. Trial registration number N/A

P-238 Non-interventional study comparing the effectiveness and safety of r-hFSH:r-hLH versus r-hFSH in women aged 35-42 years with normal ovarian reserve undergoing GnRH antagonist ART treatment

Abstract Study question Is ovarian stimulation (OS) with r-hFSH:r-hLH more effective than OS with r-hFSH alone in women aged 35-42 with normal ovarian reserve treated with ART? Summary answer Compared to r-hFSH alone, OS with r-hFSH:r-hLH for ART treatment was associated with a significant increase in clinical pregnancy and live birth per initiated cycle. What is known already Meta-analyses and secondary analyses of clinical data provide evidence that OS during ART treatment with r-hFSH:r-hLH is associated with improved reproductive outcomes when compared to r-hFSH alone in various patient groups with: a) advanced maternal age , b) low ovarian reserve or , c) hypo response to OS. Other subgroups of patients might also benefit of the use of r-hFSH:r-hLH during OS for ART treatment. We aimed to determine if, in a real-world setting, OS with r-hFSH:r-hLH is associated with improved clinical benefit when compared to r-hFSH alone in patients aged 35-42 years with normal ovarian reserve. Study design, size, duration A non-interventional study including women aged 35-42 years with normal ovarian reserve biomarkers (menstrual cycle day 2 or 3 FSH&amp;lt;12IU/L or 9&amp;lt;AFC&amp;lt;20 with a 2&amp;lt;diameter&amp;lt;10 mm, or AMH ≥1.2ng/ml) undergoing OS for ART treatment (fresh transfer only; GnRH antagonist protocol) in 12 French centers between 1/1/2008 and 31/12/2016, with a follow-up period up to 31/12/2017. The analysis included two cohorts: a) 4,323 OS cycles with r-hFSH alone, and b) 1,070 OS cycles with r-hFSH:r-hLH. Participants/materials, setting, methods Anonymized data were extracted from the Retrospective Multicenter Statistical database, including 12 French centers. A generalized linear model was used to address lack of randomization. The fixed effect part included age, an ovarian reserve estimator and stimulation; the random effect included age, AMH, AFC, FSH, cause of infertility and number of attempts, center and patient effect. Clusters (matched subsets) were built based on the propensity score by using a two-stage algorithm. Main results and the role of chance We included in our analysis 4,472 women receiving ART treatment after OS with r-hFSH (mean age: 37.8 years; 4,323 cycles) or with r-hFSH:r-hLH (mean age: 38.1 years; 1,070 cycles). In the r-hFSH cohort the mean AMH level was 2.81 ng/ml and mean AFC was 12.0, in the r-hFSH:r-hLH cohort they were 2.14 ng/ml and 10.0, respectively. The mean total r-hFSH dose were 2,275 IU (r-hFSH cohort) and 3,002 IU (r-hFSH:r-hLH cohort). Mean ± SD number of oocytes were 8.1 ± 5.7 (r-hFSH cohort) and 6.1 ± 4.3 (r-hFSH:r-hLH cohort); mean ± SD number of embryos were 4.0 ± 3.4 (r-hFSH cohort) and 3.3 ± 3.2 (r-hFSH:r-hLH cohort). The unadjusted ongoing pregnancy rate reached 17.1% in the r-hFSH cohort and 20.4% in the r-hFSH:r-hLH cohort, whilst the unadjusted live birth rate reached 17.0% and 20.2%, respectively. Unadjusted pregnancy failure rate was 6.6% and 3.7%, respectively. After adjusting for confounders, when compared to OS with r-hFSH, OS with rhFSH:rhLH was associated with a higher clinical pregnancy rate (Risk ratio,RR 1.232; 95% CI 1.058 to 1.436; p-value = 0.007) and a higher live birth rate (RR 1.452; 95% CI 1.227-1.1719, p-value &amp;lt;0.001) per initiated cycle. Limitations, reasons for caution Since this was a real-world data study, no random assignment of stimulation was performed, and some residual confounding is possible due to unmeasured confounders. Live births resulting from further transfers of frozen embryos were not included in the analysis. Wider implications of the findings This study demonstrated that OS with r-hFSH:r-hLH improves live birth rate in women &amp;gt; 35 years old with a normal ovarian reserve, compared to r-hFSH only. Sound RWE studies can be combined with RCTs to guide clinical and payer’s decision making, paving the way to precision medicine. Trial registration number Not applicable

Characteristics and Prognosis of Binocular Diplopia in Patients With Giant Cell Arteritis.

Giant cell arteritis (GCA) is a large vessel vasculitis associated with a risk of permanent ophthalmologic complications. Data about diplopia prognosis in GCA are scarce. This study was designed to better characterize diplopia in newly diagnosed GCA patients. All consecutive patients diagnosed with GCA from January 2015 to April 2021 in a French tertiary ophthalmologic center were retrospectively reviewed. GCA diagnosis relied on a positive temporal artery biopsy or high-definition MRI. Among 111 patients diagnosed with GCA, 30 patients (27%) had diplopia. Characteristics of patients with diplopia were similar to other GCA patients. Diplopia resolved spontaneously in 6 patients (20%). Diplopia was attributed to cranial nerve palsy in 21/24 patients (88%), especially third (46%) and sixth cranial nerve (42%). Ocular ischemic lesions occurred in 11 of the 30 patients with diplopia (37%); 2 patients developed vision loss after initiation of corticosteroids. In the remaining 13 patients, diplopia resolved after treatment onset in 12 patients (92%) with a median delay of 10 days. Patients treated intravenously tended to have a quicker improvement than those treated orally, but with a similar resolution rate of diplopia at 1 month. Two patients had relapse of diplopia at 4 and 6 weeks after an initial treatment course of 24 and 18 months, respectively. Diplopia is a rare feature at GCA diagnosis, but should raise clinician suspicion for GCA when associated with cephalic symptoms and prompt the initiation of corticosteroids to prevent ocular ischemic complications.

Mesures d’hygiène pour les explorations fonctionnelles respiratoires (EFR) après la pandémie de COVID-19 – Résultats d’une enquête nationale auprès de 28 centres hospitaliers en 2023

During the COVID-19 pandemic, airborne transmission of lung disease was a cause for major concern, and scientific societies published strict hygiene guidelines for pulmonary function tests (PFT) and cardiopulmonary exercise testing (CPET). These guidelines led to a major decrease in patient access to PFT and CPET, and their relevance in the 2023 post-pandemic context may be called into question. Under the hypothesis that PFT/CPET expert centers have modified their practices in accordance with the applicable guidelines, a survey was conducted from the 8th through the 23rd of February 2023 in 28 French PFT/CPET hospital departments. An overwhelming majority of the centers (96%) did not limit indications for PFT/CPET, and requested neither a vaccination or recovery certificate (93%) nor a negative diagnostic test (89%). While the use by patients and caregivers of surgical masks and antimicrobial filters was unanimously adopted, only 36% of centers declared that FFP2/N95-filtering face masks were worn. Disinfection of caregivers' hands was carried out by 96%, and a majority of centers reported break time (75%) and disinfection of equipment surfaces (89%) between the testing of two patients. In conclusion: aside from a few modifications, the practices reported by PFT/CPET French expert centers in 2023 were close to those in force prior to the COVID-19 epidemic.

Genetic counselling referral practices for patients with pancreatic adenocarcinoma: A French retrospective multicentre observational cohort study (CAPANCOGEN)

Background/objectivesGenetic counselling (GC) is a key step in the identification of inherited germline mutations. However, the oncogenetic practices are poorly described for pancreatic adenocarcinoma (PA) in Europe. The CAPANCOGEN study aimed to describe the GC referral practices in France and assess the implementation of international guidelines in patients with PA. MethodsInformation about GC referrals with PA was collected in 13 French centres from September 2019 to October 2021. In the 5 largest centres, personal and familial histories of cancers and diseases associated with a higher risk of germline mutations were collected in 460 patients, according to international, American, European and French GC referral guidelines. Univariate and multivariate logistic regression analysis were performed to identify the factors influencing GC referral. ResultsAmong 833 patients, a total of 100 patients (12%) had an indication of GC according to local multidisciplinary tumour board meetings (MTBM). Among these patients, 41% did not undergo GC. The median time between MTBM and GC was 55 days (IQR: 14.5–112). Among 460 patients with collected personal and familial history, 31.5% were not referred to a GC despite an existing indication. In multivariate logistic regression analysis, suspected CDKN2A (p = 0.032) or BRCA mutation (p < 0.001), familial pancreatic cancer history (p < 0.001) and controlled disease with first-line platinum-based chemotherapy (p < 0.001) increased the referral rate. Conversely, older age (p = 0.002) and a locally advanced PA (p = 0.045) decreased the risk of GC referral. ConclusionsGC referral is inadequate despite valuable information in patients’ medical files.

Usefulness of routine early œsophagogram after primary repair of œsophageal atresia: a multicenter study.

Advances in surgical and neonatal care have led to improved survival of patients with œsophageal atresia (OA) over time. Morbidity remains significant, with one-third of patients being affected by a postoperative complication. Several aspects of management are not consensual, such as the use of œsophagogram before starting oral feeding. We conducted a multicenter retrospective study, including all children with OA that underwent a primary anastomosis in the first days of life, between 2012 and 2018 in five French centers, to determine the usefulness of postoperative œsophagogram during the 10 days after early primary repair of OA to diagnose the anastomotic leak and congenital œsophageal stenosis. Among 225 included children, 90 (40%) had a routine œsophagogram and 25 (11%) had an anastomotic leak, clinically diagnosed before the scheduled œsophagogram in 24/25 (96%) children at median postoperative day 4. Ten patients had associated congenital œsophageal stenosis diagnosed on the œsophagogram in only 30% of cases. Early œsophagogram is rarely useful in the diagnosis of an anastomotic leak, which is clinically diagnosed before performing an œsophagogram in the majority of cases. The need for a postoperative œsophagogram should be evaluated on a case-by-case basis. Early œsophagogram is not helpful in the diagnosis of an anastomotic leak in the majority of cases. An anastomotic leak is most often diagnosed clinically before performing an œsophagogram. Early postoperative œsophagogram could be helpful for the diagnosis of congenital œsophageal stenosis. However, dysphagia occurs later and early diagnosis of congenital œsophageal stenosis has no impact on the management and outcome of asymptomatic children. Indication of postoperative œsophagogram has to be evaluated on a case-by-case basis.

Association between radiographic and functional outcome in vertebral osteomyelitis SPONDIMMO, a 6-month prospective multicenter cohort

ObjectivesThis study aimed to describe radiographic and functional evolution over 6 months in a large cohort of VO patients. MethodsWe prospectively recruited patients with VO from 2016 to 2019 in 11 French centers. X-rays were performed at baseline, 3 months, and 6 months to assess progression using structural and static criteria. Functional impairment was evaluated using the Oswestry Disability Index (ODI) at 3 months and 6 months. ResultsTwo hundred and twenty-two patients were included. Mean age was 67.8±14 years, mostly men (67.6%). After 3 months, there was a significant increase in vertebral fusion (16.4% vs 52.7%), destruction of vertebral bodies (10.1% vs 22.8%), and of all the static features (frontal angulation (15.2% vs 24.4%), segmental (34.6% vs 56%) and regional (24.5% vs 41%) kyphosis). From 3 to 6 months, among the different X-ray abnormalities, only the complete fusion progressed significantly (16.6% vs 27.2%). Median ODI showed significant improvement from 3 to 6 months (24, IQR [11.5–38] vs 16, IQR [6–34]). At 6 months, 14.1% of the patients had a severe disability, 2% a major disability. The persistence of vertebral destruction at 6 months was associated with a higher ODI (16, IQR [7.5–30.5] vs 27, IQR [11.5–44.5]). No differences in radiological progression were observed with immobilization using a rigid brace. ConclusionOur study demonstrates structural and static radiographic progression after 3 months. Only the complete fusion progressed over the long-term. Functional impairment was associated with persistence of vertebral destruction.

Heart transplantation as a rescue strategy for patients with refractory electrical storm.

Heart transplantation (HT) can be proposed as a therapeutic strategy for patients with severe refractory electrical storm (ES). Data in the literature are scarce and based on case reports. We aimed at determining the characteristics and survival of patients transplanted for refractory ES. Patients registered on HT waiting list during the following days after ES and eventually transplanted, from 2010 to 2021, were retrospectively included in 11 French centers. The primary endpoint was in-hospital mortality. 45 patients were included (82% men; 55.0 (47.8-59.3) years old; 42.2% and 26.7% non-ischemic dilated or ischemic cardiomyopathies, respectively). Among them, 42 (93.3%) received amiodarone, 29 (64.4%) betablockers; 19 (42.2%) required deep sedation, 22 (48.9%) mechanical circulatory support, and 9 (20.0%) had radiofrequency catheter ablation. Twenty-two patients (62%) were in cardiogenic shock. Inscription on wait list and transplantation occurred 3.0 (1.0-5.0) days and 9.0 (4.0-14.0) days after ES onset, respectively. After transplantation, 20 patients (44.4%) needed immediate hemodynamic support by extracorporeal membrane oxygenation (ECMO). In-hospital mortality rate was 28.9%. Predictors of in-hospital mortality were serum creatinine/urea levels, need for immediate post-operative ECMO support, post-operative complications, and surgical re-interventions. One-year survival was 68.9%. ES is a rare indication of HT but may be lifesaving in those patients presenting intractable arrhythmias despite usual care. Most patients can be safely discharged from hospital, although post-operative mortality remains substantial in this context of emergency transplantation. Larger studies are warranted to precisely determine those patients at higher risk of in-hospital mortality.

#4006 ADDING 6-MONTH PARAMETERS FOR THE PREDICTION OF RENAL PROGNOSIS IN ANCA-ASSOCIATED GLOMERULONEPHRITIS

Abstract Background and Aims Antineutrophil-cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) with kidney involvement (AAV-GN) frequently evolves to end-stage kidney disease (ESKD) despite aggressive immunosuppressive treatment. Several risk scores have been used to assess renal prognosis. We aimed to determine whether kidney function and markers of AAV-GN activity after 6 months could improve the prediction of ESKD. Method This retrospective and observational study included adult patients with AAV-GN recruited from 6 French nephrology centers (including from the Maine-Anjou AAV registry). The primary outcome was kidney survival. Analyses were conducted in the whole population and in a sub-population that did not develop ESKD early in the course of the disease. Results 241 patients were included in the whole cohort, with a median follow-up of 59 months. At diagnosis, Berden classification and Renal Risk Score (RRS) were not found better than kidney function (eGFR) alone, at predicting ESKD (C-index = 0.70, 0.79, 0.82, respectively). At 6 months, 20 patients reached ESKD. In the sub-population of 221 patients, 6 months eGFR outperformed Berden classification and RRS (C-index = 0.88, 0.62, 0.69, respectively) to predict ESKD. RRS performed better when it was updated with the eGFR at 6 months instead of the baseline eGFR. While 6-months proteinuria was associated with ESKD and improved ESKD prediction, hematuria and serological remission did not. Conclusion This work suggests the interest of the reassessment of the renal prognosis 6 months after AAV-GN diagnosis. Kidney function at this time remains the most reliable for predicting renal outcome. To improve the long-term prediction of ESKD, there may be a place for repeated kidney biopsy following induction treatment, in order to obtain a precise evaluation of disease activity, discuss the immunosuppressive treatment strategy and improve prognosis scores.

Does cost minimization of hypofractionated radiation therapy content all health stakeholders?

Does cost minimization of hypofractionated radiation therapy content all health stakeholders?

#6894 KIDNEY TRANSPLANTATION IN PATIENTS WITH AA AMYLOIDOSIS: A FRENCH MULTI-CENTER MATCHED COHORT STUDY IN THE ERA OF BIOTHERAPIES

Abstract Background and Aims Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high allograft recurrence. However, recent advances in biotherapies, especially anti-IL-1 treatments, may have improved patients’ outcome in the transplantation setting. Method We conducted a retrospective multicenter matched cohort study in 26 French centers reporting all patients with AA amyloidosis who received a kidney transplant between 2008 and 2018, and compared them to matched control patients (ratio 1:2 controls) who received a kidney transplant for other causes Results Eighty-six AA amyloidosis transplants and 157 control transplants were included. Median age was 49.4 years (interquartile range 39.7-61.1), and the main cause of amyloidosis was Familial Mediterranean Fever (37 cases, 43%). Sixteen (18.6%) patients received a biotherapy after transplantation. At 5 years, patient survival was 85.5% (95% confidence interval 77.8-94.0) and 86.2% (80.5-92.2) for cases and controls, respectively (p = 0.5). Death censored graft survival was 78.2% (78.2-93.5) and 91.7% (87.0-96.6), respectively (p = 0.05). Histologically proven AA amyloidosis recurrence was found in 5 patients (5.8%). 55.8% of amyloid patients had at least one infection requiring hospitalization and 27.9% an episode of acute graft rejection. In this group, multivariable analysis showed that CRP concentration at time of transplantation was associated with patient survival (HR 1.01, p = 0.01). Conclusion In this recent cohort, patient survival was comparable to controls and recurrence rates were lower than previously reported. Provided the underlying inflammatory disease is well controlled, patients with AA amyloidosis may be transplanted with similar patient and graft outcomes than that of matched controls.

Panitumumab in combination with chemoradiotherapy for the treatment of locally-advanced anal canal carcinoma: Results of the FFCD 0904 phase II trial

Background and purposeStandard treatment of squamous cell carcinoma of the anus (SCCA)is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase II study (EudraCT: 2011–005436-26) assessed the tolerance and complete response (CR) rate at 8 weeks of panitumumab (Pmab) combined with MMC-5FU-based CRT. MethodsPatients with locally advanced tumors without metastases (T2 > 3 cm, T3-T4, or N + whatever T stage) were treated with IMRT up to 65 Gy and concomitant CT according to the doses defined by a previous phase I study (MMC: 10 mg/m2; 5FU: 400 mg/m2; Pmab: 3 mg/kg). The expected CR rate was 80%. ResultsForty-five patients (male: 9, female: 36; median age: 60.1 [41.5–81]) were enrolled in 15 French centers. The most common related grade 3–4 toxicities observed were digestive (51.1%), hematologic (lymphopenia: 73.4%; neutropenia: 11.1%), radiation dermatitis (13.3%), and asthenia (11.1%) with RT interruption in 14 patients. One patient died because of mesenteric ischemia during the CRT, possibly related to treatment. In ITT analysis, the CR rate at 8 weeks after CRT was 66.7% [90%CI: 53.4–78.2]. Median follow-up was 43.6 months [IC 95%: 38.61–47.01]. Overall survival, recurrence-free and colostomy-free survival at 3 years were 80% [95%CI: 65.1–89], 62.2% [IC95%: 46.5–74.6] and 68.8 % [IC95%: 53.1–80.2] respectively. ConclusionPanitumumab in combination with CRT for locally advanced SCCA failed to meet the expected CR rate and exhibited a poor tolerance. Furthermore, late RFS, CFS, and OS did not suggest any outcome improvement to justify further clinical trials.ClinicalTrials.gov identifier: NCT01581840.

Multicenter randomized phase III trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for muscle-invasive bladder cancer (MIBC): Overall survival (OS) data at 5 years in the GETUG/AFU V05 VESPER trial.

LBA4507 Background: The optimal perioperative chemotherapy for patients (pts) with muscle-invasive bladder cancer remains open to discussion. The primary endpoint of the VESPER trial (NCT 018 12369) was previously reported with dd-MVAC improved-3 years PFS over GC schedule. In the neoadjuvant group, a better bladder local control and significant difference on 3y-PFS was observed in the dd-MVAC arm (p=0.025). Patients and Methods: Between February 2013 and February 2018, 500 pts were randomized in 28 French centers and received either 4 cycles of GC every 3 weeks or 6 cycles of dd-MVAC every 2 weeks before surgery (neoadjuvant group) or after surgery (adjuvant group). We report the final analysis of the VESPER phase III trial with the overall survival (OS) data after 5 years of follow-up from randomization. Results: 437 pts (88%) received neoadjuvant chemotherapy, 60% of patients received the planned 6 cycles in the dd-MVAC arm, 84% received 4 cycles in the GC arm, thereafter 91% and 90% of patients underwent surgery, respectively. Final median of follow-up was 5 years and 3 months and 190 deaths were reported within 5 years of follow-up. OS at 5 years was improved in the dd-MVAC arm (64% vs 56%, HR=0.77 (95% CI, 0.58-1.03), p=0.078), as was also disease-specific survival (DSS) (5-year rate: 72% vs 59%, HR=0.63 (95% CI, 0.46-0.86), p=0.004). The main cause of death was bladder cancer progression (83%), other causes included cardio-vascular events (4.2%), toxic deaths (2.1%), second cancers (2.1%), others (4.7%) and undocumented deaths (4.2%). In the neoadjuvant group, OS was significantly superior in the dd-MVAC arm (5-year rate: 66% vs 57%, HR=0.71 (95% CI, 0.52-0.97), p=0.032) as well as DSS (5-year rate: 75% vs 60%, HR=0.56 (95% CI, 0.39-0.80), p=0.001). In the adjuvant group, the results were not conclusive due to the limited sample size (n=56).Conclusions: Dose-dense MVAC provided a better OS at 5 years and improved significantly DSS over GC in the peri-operative setting of MIBC. Clinical trial information: NCT01812369 .

Brain radiotherapy in patients treated for a newly diagnosed primary central nervous system lymphoma: professional practice evaluation in 19 French centers

Introduction The objective of this study was a multicentric evaluation of professional practices, analyzing the irradiation technique itself and its impact on survival and recurrence sites, in primary central nervous system lymphomas (PCNSLs). Methods We retrospectively analyzed the technical and clinical records of 79 PCNSL patients included in the database of the national expert network for oculocerebral lymphoma (‘LOC’) who were treated with brain radiotherapy as first-line treatment for newly diagnosed primary central nervous system lymphoma between 2011 and 2018. Results The number of patients treated with brain radiotherapy gradually decreased over time. The heterogeneity of radiotherapy prescriptions was significant, and 55% of them did not comply with published recommendations in terms of irradiation dose and/or volume. The proportion of complete responders to induction chemotherapy treated with reduced-dose radiotherapy increased over time. Partial brain radiotherapy was associated with significantly lower overall survival in univariate analysis. In partial responders to induction chemotherapy, increasing the total dose to the brain >30 Gy and adding a boost to the WBRT induced a trend toward improved progression-free and overall survival. Five recurrences (13%) occurred exclusively in the eyes, all in patients whose eyes had been excluded from the irradiation target volume and including 2 patients without ocular involvement at diagnosis. Conclusion The visibility of recommendations for prescribing brain radiotherapy for the treatment of newly diagnosed primary central nervous system lymphoma needs to be improved to harmonize practices and improve their quality. We propose an update of the recommendations.

Intravesical injections of botulinum neurotoxin A to treat overactive bladder and/or detrusor overactivity related to multiple sclerosis: 5-Year continuation rate and specific risk factors for discontinuation—A study from the neuro-urology committee of the French Association of Urology

Background: While intravesical injections of botulinum neurotoxin A (BoNT-A) are currently recommended for patients experiencing refractory neurogenic overactive bladder and/or detrusor overactivity (OAB/DO), it is unclear how much this therapy is effective and sustainable in the long-term in patients with multiple sclerosis (MS). Objectives: To assess the mid-term continuation rate of BoNT-A injections to treat neurogenic OAB/DO in MS patients and to investigate MS-specific risk factors for discontinuation. Methods: This retrospective study involved 11 French university hospital centers. All MS patients who received BoNT-A to treat neurogenic OAB/DO between 2008 and 2013 and were subsequently followed up for at least 5 years were eligible. Results: Of the 196 MS patients included, 159 (81.1%) were still under BoNT-A 5 years after the first injection. The combination of the Expanded Disability Status Scale (EDSS < 6 or ⩾ 6) and of the MS type (relapsing–remitting vs progressive) predicted the risk of discontinuation. This risk was 5.5% for patients with no risk factor, whereas patients presenting with one or two risk factors were 3.3 and 5.7 times more likely to discontinue, respectively. Conclusion: BoNT-A is a satisfying mid-term neurogenic OAB/DO therapy for most MS patients. Combining EDSS and MS type could help predict BoNT-A discontinuation.

Heavy metals and diminished ovarian reserve: single-exposure and mixture analyses amongst women consulting in French fertility centres

Research questionDo heavy metals affect the risk of diminished ovarian reserve (DOR) in women of reproductive age? DesignA total of 139 cases and 153 controls were included between 2016 and 2020. The participants were aged between 18 and 40 years and attended consultations for couple infertility in one of four fertility centres in western France. Cases of DOR were defined as women with an antral follicle count less than 7, anti-Müllerian hormone levels 1.1 ng/ml or less, or both. Controls were frequency matched on age groups and centres, and were women with normal ovarian reserve evaluations, no malformations and menstrual cycles between 26 and 35 days. Heavy metals (lead, mercury, cadmium and chromium) were measured in whole blood at inclusion. Single-exposure associations were examined with multivariable logistic regressions adjusted on potential confounders. Mixture effects were investigated with quantile g-computation and Bayesian kernel machine regression (BKMR). ResultsChromium as a continuous exposure was significantly associated with DOR in unadjusted models (OR 2.07, 95% CI 1.04 to 4.13) but the association was no longer significant when confounders were controlled for (adjusted OR 2.75, 95% CI 0.88 to 8.60). Similarly, a statistically significant association was observed for the unadjusted second tercile of cadmium exposure (OR 1.87, 95% CI 1.06 to 3.30); however, this association was no longer statistically significant after adjustment. None of the other associations tested were statistically significant. Quantile g-computation and BKMR both yielded no significant change of risk of DOR for the mixture of metals, with no evidence of interaction. ConclusionsWeak signals that some heavy metals could be associated with DOR were detected. These findings should be replicated in other studies.

REALMA: Subset of patients with Marginal Zone Lymphomas from the French nationwide REALYSA real‐world prospective cohort.

Background: Marginal Zone Lymphomas (MZL) are a heterogeneous group of lymphomas that include three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). Since most of the knowledge comes from clinical trials (with stringent inclusion criteria and limited representativeness), there is a crucial need for real-world evidence in MZL. In 2018 the French REALYSA (Real world dAta in LYmphoma in Adults) study was initiated as a nationwide multicentric prospective cohort of patients newly diagnosed with lymphoma. By Dec 31, 2021, a total of 207 patients with MZL were included in the study. Methods: Patients were recruited in 35 French hematology centers and received routine care. Data were collected from medical records and questionnaires. A first abstraction was performed on Jan 1, 2023, to parse out the available data regarding MZL patients with >1 year of follow-up. Each case was reviewed by medical and pathological experts, and treatments were classified on an intent-to-treat basis. Results: Of the 207 patients with MZL included up to Dec 31, 2021, 111 (53%) presented with EMZL, 47 (23%) with SMZL and 49 (24%) with NMZL. At baseline, median age was of 67 years old (IQR 60,75), 53% of patients were females, 5.5% of patients had a PS of 2–4, 70% were stage III-IV, 19% presented with B-symptoms, 20% had a bulky mass >7 cm and 5.8% had a compressive syndrome. Only 7% of patients reported an auto-immune disease. Diagnosis of MZL was mostly evoked by general practitioners (48%) but patients were finally treated by hematologists (98%). Only 9 patients were referred to an onco-geriatrician. Regarding the initial workup, while at least one imagery was offered in 97% of patients, 18FDG-PET/CT (EMZL 78%, SMZL 62%, NMZL 78%) was performed more frequently than CT-scan at baseline (EMZL 73%, SMZL 62%, NMZL 71%), although 47% patients underwent both procedures. Among the 207 patients, 58 (28%) were not treated. Only 10 patients exclusively received local therapy (radiotherapy n = 6, surgery n = 2, antibiotics n = 2). Regarding systemic therapies, rituximab-chlorambucil was mainly offered in patients with EMZL (40%), while rituximab-monotherapy was preferred in SMZL (60%). For patients with NMZL, physicians mainly offered RCHOP (33%) and rituximab-bendamustine (27%). Only 7 patients with EMZL received the combination of ibrutinib and rituximab. At end of 1st line, 93% of patients had responded to therapy and 75% were in complete response. Among patients assessed with 18FDG-PET/CT, a metabolic complete response was observed in 52/58 (90%) of cases. Conclusion: This is the first analysis describing real-world data of patients with MZL in France. Our cohort features high-quality data both on epidemiological and clinical outcomes. When the total number of patients will increase and data will mature, this dataset will provide insightful information regarding both endpoints and treatment evaluations. Keyword: Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. C. Bommier Research funding: Inserm/AvieSan/ITMO Cancer, LYSA/ELI (Bertrand Coiffier Prize), Philippe Foundation, Institut Servier

Efficacy of tucatinib+trastuzumab+capecitabine (TTC) after trastuzumab-deruxtecan (T-DXd) exposure in Her2-positive metastatic breast cancer: A French multicentre retrospective study.

1014 Background: Recent guidelines have positioned T-DXd as a preferred treatment in the second line setting for HER2+ metastatic breast cancer (MBC). TTC is the preferred treatment in third line, however little is known on the efficacy of this combination after T-DXd exposure. Methods: We conducted a retrospective study in 12 French comprehensive cancer centers. All patients with HER2+ MBC treated with TTC after prior exposure to T-DXd were included. The primary end point was progression-free survival (PFS) in the whole population. Secondary end-points included overall survival (OS), PFS in subgroups and objective response rate. Results: Between 08/2020 and 12/2022, 101 patients were included. Median age was 56.4 y.o. (range 30.8 - 84.8). Median number of prior line of treatment for metastatic disease at TTC start was 4 (2 - 15). 82% and 95% of patients had received previous pertuzumab and T-DM1 respectively. The median duration of previous exposure to T-DXd was 8.9 months (1.4 - 31.4) and 82/101 (81%) patients had progressed under T-DXd while 19 had stopped T-DXd for toxicity or other reasons. TTC regimen was given as a 3rd line or 4th line for metastatic disease in 37/101 (37%) and beyond for the remaining patients. TTC was the immediate subsequent therapy to T-DXd for 86/101 pts (85%). With a median follow-up of 8.5 m (95%CI [7.7; 9.4]), 68/101pts (67%) have stopped TTC for progressive disease. Median PFS was 4.7 m (95%CI [3.8; 5.6]) and median OS not reached (95%CI [10.6; NA]) in the whole population. Patients treated with TTC as the immediate subsequent therapy to T-DXd, had a median PFS of 5.0 m (95%CI [4.0; 6.0]) and a median OS not reached (95%CI [11.9; NA]). Best response to TTC, evaluated by investigators in the 87/101 RECIST evaluable patients, was progressive disease, stable disease, partial response and complete response in 34%, 34%, 30% and 2% of patients respectively. At TTC initiation, 39 (39%) of patients had known brain metastases. Out of the 62 patients without known brain metastases at the initiation of TTC, 2 had brain metastases documented as a site of progression during TTC. Conclusions: In this large retrospective cohort, TTC shows significant efficacy for patients with HER2+ MBC previously exposed to T-DXd. Data and subgroup analyses will be updated for the meeting.