French Centers Research Articles

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.

Longitudinal assessment of cardiac involvement in Erdheim-Chester disease using cardiac magnetic resonance imaging.

7067 Background: Erdheim-Chester disease (ECD) is a rare multi-systemic non-Langerhans cell histiocytosis that affects the heart in nearly half of patients. Atrial infiltration and pericardial effusion are the hallmarks of cardiac involvement and can lead to clinical complications (conduction disorders, coronary artery stenosis, tamponade, constrictive pericarditis). Evolution under treatment is poorly studied. We aimed to investigate the evolution of cardiac involvement in ECD using cardiac magnetic resonance (CMR) imaging. Methods: All ECD patients with a CMR imaging disclosing a cardiac involvement and who underwent at least one follow-up CMR imaging between 2005 and 2020 at a French tertiary center were retrospectively included. First and last CMR imaging were compared. Multivariable analysis was performed to search for independent predictors of cardiac involvement resolution. Variables were included in the model if their P-value was < 0.1 on univariable analysis. Results: Overall, 46 patients were included. Median age at first imaging was 63 years [53-69]. Median delay between the first and the last imaging was 4 years [2-7]. BRAFV600E mutation was present in 43 patients (94%). Patients received a median of 2 [1-3] treatments. All patients (100%) had cardiac involvement at baseline. Right atrio-ventricular sulcus (RAVS) was infiltrated in 38 patients (83%) and was the main cardiac feature.Overall, complete regression was observed in 6 patients (13%), partial regression in 26 patients (56%), stable imaging in 12 patients (26%), and worsening in 2 patients (5%). In patients with RAVS infiltration, complete regression was observed in 5 patients (16%) and partial regression was seen 22 patients (58%) regression. On univariable analysis, patients with regression of their infiltration had a lower rate of death (16% versus 64%, P= 0.002), a higher rate of atrial infiltration late gadolinium enhancement (LGE) (97% versus 71%, P= 0.01), a higher rate of hydronephrosis (50% versus 14%, P= 0.03) and a lower rate of interferon prescription (69% versus 100%, P= 0.02). A similar rate of vemurafenib use was observed in both groups (69% versus 54%, P= 0.3). On multivariable analysis, death remained significantly associated with follow-up imaging status (ß = -2.3 P= 0.01), while atrial infiltration LGE (ß = 2.7, P= 0.06), hydronephrosis (ß = 1.6, P= 0.1) and treatment with interferon (ß = -16, P= 1) were no longer significantly associated with imaging status. Conclusions: Partial or complete resolution of cardiac involvement was observed in 69% of patients with ECD and was significantly associated with a lower rate of death on multivariable analysis.

Web-based patient-reported outcome measures (PROMs) in elderly cancer patients: A French multicentric prospective feasibility trial (the FASTOCH study).

12011 Background: Web-based PROMs in cancer care improve overall survival and quality of life. There is, nonetheless, no data available on this type of follow-up in the elderly population. Methods: From February 2021 to April 2022, 75 or more years-old patients ongoing any active anti-cancer treatment (such as chemotherapy, targeted therapy, hormonotherapy, immune therapy) were included, in six French cancer centers. Feasibility of the web-based PROMs was assessed as the part of the population included that could use the Ana-Health’s web-based application “ANA” to monitor their symptoms, the others being considered as in “primary failure” due to technological barriers or refusal to participate. Among the patients that agreed to participate, we then defined as “active” those who filled at least one form during the three months follow up. We also searched for factors restraining elderly patients to use “ANA” and evaluated their satisfaction. Results: Overall, 473 patients were included in the study. There were 288 patients in “primary failure” (233 without Internet access, 17 not comfortable enough to use web-based PROMs, 38 refusals to participate). Among the 185 patients “willing to participate”, there were 122 “active” patients and 63 “inactive” ones, leading to a 26% feasibility in intention-to-test and a 66% feasibility in per protocol analysis. Patients “willing to participate” were from higher socio-professional category (p = 0.002) and had a significantly higher G8 score (13.5 versus 12, p < 0.001), particularly when considering the autonomy (p = 0.028), cognitive assessment (p = 0.003) and general condition (p < 0.001) items. In the multivariate analysis, the socio-professional category and the general condition were still significantly different (p = 0.009 and 0.002 respectively). The only factor that remained significantly different between the “active” and “inactive” populations was the better general condition in the “active” group (p < 0.001). The “inactive” patients prematurely ended their participation because they lost interest in the web-based follow up significantly more than the “active” group (28 “inactive” patients, i.e. 44%, vs 5 “active” patients, i.e. 4%, p < 0.001). Similarly, the “active” patients were significantly more satisfied with “ANA” than the “inactive” (71% vs 29%, p < 0.001). Conclusions: Our study shows that, in the elderly population treated for a cancer, a web-based application to measure PROs is feasible, however socio-professional category, general condition and above all technological barriers are of some concern.

Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial.

Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients. In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2. Eligible patients were randomly assigned (1:1 ratio) to receive an intermediate weight-adjusted prophylactic dose or a fixed-dose of subcutaneous low-molecular-weight heparin during the hospital stay. The primary outcome corresponded to symptomatic deep-vein thrombosis (fatal) pulmonary embolism during hospitalization (COVI-DOSE ClinicalTrials.gov number: NCT04373707). Between May 2020, and April 2021, 1000 patients underwent randomisation in medical wards (noncritically ill) (80.1%) and intensive care units (critically ill) (19.9%); 502 patients were assigned to receive a weight-adjusted intermediate dose, and 498 received fixed-dose thromboprophylaxis. Symptomatic venous thromboembolism occurred in 6 of 502 patients (1.2%) in the weight-adjusted dose group and in 10 of 498 patients (2.1%) in the fixed-dose group (subdistribution hazard ratio, 0.59; 95% CI, 0.22-1.63; P=0.31). There was a twofold increased risk of major or clinically relevant nonmajor bleeding: 5.9% in the weight-adjusted dose group and 3.1% in the fixed-dose group (P=0.034). In the COVI-DOSE trial, the observed rate of thromboembolic events was lower than expected in patients hospitalized for COVID-19 infection, and the study was unable to show a significant difference in the risk of venous thromboembolism between the two low-molecular-weight-heparin regimens. French Ministry of Health, CAPNET, Grand-Est Region, Grand-Nancy Métropole.

Early palliative care for patients with metastatic upper gastrointestinal cancers: A survival analysis of the EPIC randomized trial.

12102 Background: In 2010, Temel et al. reported that early palliative care (PC) (EPC) led to significant improvements in quality of life and, surprisingly, on overall survival (OS) over standard oncologic care (SOC) for patients (pts) with metastatic lung cancer. The American Society of Clinical Oncology then recommended “combined standard oncology care and PC earlier in the course of the illness for any patient with metastatic cancer”. The median OS of unselected pts with metastatic upper gastrointestinal cancers (mUGIC) does not exceed 11 m. Whether EPC benefits also apply to pts with mUGIC was unknown. Methods: EPIC (NCT02853474) is a randomized 1:1, open-label, multicenter, phase 3 trial aiming to evaluate the OS benefit of EPC compared to SOC in pts with mUGIC (esophageal, HER2 negative esogastric junctional and gastric, pancreatic, and biliary tract cancers), with ECOG PS ≤ 2, to be treated by first-line chemotherapy (CT). EPC included 5 PC visits scheduled every month, starting within 3 weeks of randomization. Pts allocated to SOC could access to PC visits upon request in case of worsening of health status. The primary endpoint was OS. Other endpoints included quality of life, and depression and anxiety assessment. A total of 381 deaths was required (1 year OS 40% vs. 50.3%, HR = 0.75, 2-sided alpha 5%, 80% power). Randomization was balanced on center, ECOG-PS and tumor site. Results: 473 pts were randomized from 10/2016 to 12/2021 in 19 French centers. Modified intention-to-treat population was 470. Median age = 67.5 (range, 24-90); 273 males; tumor site: esophagus 39, esogastric 48, pancreas 297, biliary tract 86; ECOG PS 0/1/2: 104/278/88. 74/233 pts (32%) in EPC arm had less than the planned EPC visits (major deviation): 3 related to treatment, 17 due to pt decision, 45 due to the clinical team decision, 2 other reasons, 7 unknown. 57/237 pts in the SOC arm got at least 1 PC visit, including 3 major deviation (performed < 6 months of treatment and set for a reason other than worsening of the health condition). Median follow-up was 46 m, and 35/470 pts were still alive. We did not observe any OS difference between arms (EPC, median OS: 7.0 m [95%CI: 6.1-8.8 m] and 1-year OS: 33%; SOC, median OS: 8.6 m [6.8-9.8 m] and 1-year OS: 32%; stratified HR = 1.04 [0.86-1.26], p = 0.68). Results were similar on the per-protocol dataset (excluding major violations). Results were homogeneous across the different tumor locations, and ECOG-PS groups. Conclusions: OS was lower than expected in both arms, which may reflect the difference between pharma-sponsored and academic trials with less stringent exclusion criteria. Also, only 68% of the pts got the planned number of PC visits in the experimental arm. EPC was not found to prolong OS over SOC in pts with mUGIC in this EPIC trial. Clinical trial information: NCT02853474 .

Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer

Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers. To assess whether adaptive radiotherapy (ART) improves salivary function compared with IMRT in patients with head and neck cancer. This phase 3 randomized clinical trial was conducted in 11 French centers. Patients aged 18 to 75 years with stage III-IVB squamous cell oropharyngeal cancer treated with chemoradiotherapy were enrolled between July 5, 2013, and October 1, 2018. Data were analyzed from November 2021 to May 2022. The patients were randomly assigned (1:1) to receive standard IMRT (without replanning) or ART (systematic weekly replanning). The primary end point was the frequency of xerostomia, measured by stimulating salivary flow with paraffin. Secondary end points included salivary gland excretory function measured using technetium-99m pertechnetate scintigraphy, patient-reported outcomes (Eisbruch xerostomia-specific questionnaire and the MD Anderson Symptom Inventory for Head and Neck Cancer questionnaire), early and late toxic effects, disease control, and overall and cancer-specific survival. A total of 132 patients were randomized, and after 1 exclusion in the ART arm, 131 were analyzed: 66 in the ART arm (mean [SD] age at inclusion, 60 [8] years; 57 [86.4%] male) and 65 in the standard IMRT arm (mean [SD] age at inclusion, 60 [8] years; 57 [87.7%] male). The median follow-up was 26.4 months (IQR, 1.2-31.3 months). The mean (SD) salivary flow (paraffin) at 12 months was 630 (450) mg/min in the ART arm and 584 (464) mg/min in the standard arm (P = .64). The mean (SD) excretory function of the parotid gland at 12 months, measured by scintigraphy, improved in the ART arm (48% [17%]) compared with the standard arm (41% [17%]) (P = .02). The 2-year-overall survival was 76.9% (95% CI, 64.7%-85.4%) in both arms. This randomized clinical trial did not demonstrate a benefit of ART in decreasing xerostomia compared with standard IMRT. No significant differences were found in secondary end points except for parotid gland excretory function, as assessed by scintigraphy, or in survival rates. ClinicalTrials.gov Identifier: NCT01874587.

Impact of renal impairment on dihydropyrimidine dehydrogenase (DPD) phenotyping

The chemotherapeutic agent 5-fluorouracil (5-FU) is catabolized by dihydropyrimidine dehydrogenase (DPD), the deficiency of which may lead to severe toxicity or death. Since 2019, DPD deficiency testing, based on uracilemia, is mandatory in France and recommended in Europe before initiating fluoropyrimidine-based regimens. However, it has been recently shown that renal impairment may impact uracil concentration and thus DPD phenotyping. The impact of renal function on uracilemia and DPD phenotype was studied on 3039 samples obtained from three French centers. We also explored the influence of dialysis and measured glomerular filtration rate (mGFR) on both parameters. Finally, using patients as their own controls, we assessed as to what extent modifications in renal function impacted uracilemia and DPD phenotyping. We observed that uracilemia and DPD-deficient phenotypes increased concomitantly to the severity of renal impairment based on the estimated GFR, independently and more critically than hepatic function. This observation was confirmed with the mGFR. The risk of being classified 'DPD deficient' based on uracilemia was statistically higher in patients with renal impairment or dialyzed if uracilemia was measured before dialysis but not after. Indeed, the rate of DPD deficiency decreased from 86.4% before dialysis to 13.7% after. Moreover, for patients with transient renal impairment, the rate of DPD deficiency dropped dramatically from 83.3% to 16.7% when patients restored their renal function, especially in patients with an uracilemia close to 16 ng/ml. DPD deficiency testing using uracilemia could be misleading in patients with renal impairment. When possible, uracilemia should be reassessed in case of transient renal impairment. For patients under dialysis, testing of DPD deficiency should be carried out on samples taken after dialysis. Hence, 5-FU therapeutic drug monitoring would be particularly helpful to guide dose adjustments in patients with elevated uracil and renal impairment.

0956 Evaluation of a novel automated oxygen desaturation analysis

Abstract Introduction The oxygen desaturation index (ODI) quantifies the number of desaturations per hour of sleep and is a valuable parameter in diagnosing sleep-related breathing disorders. While oximetry alone is insufficient for an accurate diagnosis, it provides meaningful insights for Obstructive Sleep Apnea (OSA) and the ODI has been shown to correlate with the Apnea-Hypopnea Index (AHI). The close relationship between the ODI and other parameters is especially interesting for home-based sleep studies and/or screening, which typically use a limited set of sensors (but almost always include oximetry) and are becoming increasingly more prevalent. An accurate and automated tool for oximetry analysis will thus be paramount for the sleep clinician. Methods The current study aims to evaluate a novel automated solution for oxygen desaturation scoring, provided by Somnilog. We selected 20 overnight recordings, a mix of hospital- and home-based recordings from a dataset from the Antwerp University hospital and an internal database collected from several French sleep centers. The analyzed population (10 females, age 53.0±16.7 years old, BMI of 28.8±4.8 kg/m²) had a variety of diagnoses, including non-apneic snoring and central and obstructive sleep apnea. Each recording was also scored for oxygen desaturations by a sleep expert, using the AASM guidelines and a 3% drop criterion. Results The automated solution accurately detected desaturation events with a precision and recall of 0.97 and 0.96, respectively. The reported ODI had an intraclass correlation (ICC) of 0.99 with the index found by the expert. The difference in the number of events reported by the automated solution and the expert was not significant between the lab- and home-recorded patients (p=0.23). We furthermore validated the novel solution with another well-used commercial package and obtained similar performance metrics: precision and recall of 0.96 and ICC of 0.99. Conclusion The current study demonstrates the validity of the novel commercial package for oxygen desaturation scoring. The automated tool achieved near-perfect agreement with the sleep experts, and a similar performance to another existing solution in the market. The tool is robust for home-based recordings which are typically more artifact-prone, thereby supporting the increasing demand for out-of-centre overnight studies. Support (if any) n/a

Institutionalised autonomisation of language learning in a French language centre

Abstract The UFR Lansad (Language centre teaching languages to specialists of other disciplines) was created in 2014 at the University of Lorraine. The process leading to its creation was led by a small number of teachers and researchers, from the pre-existing teams of the previous Lorraine universities (Molle et al. 2019). It is the result of didactic reflection and expertise, which convinced the University board to set up a structure dedicated to foreign language teaching. After several evolutions, the newly-created structure positioned itself as a policy maker in language teaching. Finally, the university board asked the UFR to set up a language training model that could be implemented throughout the institution. This training model involves blended-learning systems that emphasise the concepts of self-directed learning and autonomy and gives a central role to the EDOlang platform and the self-access centres since “part of the research and practice on learner autonomy is situated in self-access language learning settings” (Chateau and Tassinari 2021: 53). After a brief history of the creation of the UFR, the article focuses on this model, inspired by research carried out within the CRAPEL team (Guèly et al. 2021; Holec 2000). It also describes how the model is the result of the dissemination of innovative training courses implemented through action research over the last ten years (Chateau and Zumbihl 2010, 2012; Chateau and Bailly 2021). Furthermore, the paper explains how the institutional recognition of the training framework illustrates the need to promote a strong link between research and training.

Brief Report: Severe Sotorasib-Related Hepatotoxicity and Non-Liver Adverse Events Associated With Sequential Anti–Programmed Cell Death (Ligand)1 and Sotorasib Therapy in KRASG12C-Mutant Lung Cancer

IntroductionSequential anti–programmed cell death protein 1 (PD-1) or anti–programmed death-ligand 1 (PD-L1) followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in NSCLC. KRASG12C inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used in sequence or in combination with anti–PD-(L)1. This study was designed to address whether sequential anti–PD-(L)1 and sotorasib therapy increases the risk of hepatotoxicity and other AEs. MethodsThis is a multicenter, retrospective study of consecutive advanced KRASG12C-mutant NSCLC treated with sotorasib outside clinical trials in 16 French medical centers. Patient records were reviewed to identify sotorasib-related AEs (National Cancer Institute Common Classification Criteria for Adverse Events—Version 5.0). Grade 3 and higher AE was considered as severe. Sequence group was defined as patients who received an anti–PD-(L)1 as last line of treatment before sotorasib initiation and control group as patients who did not receive an anti–PD-(L)1 as last line of treatment before sotorasib initiation. ResultsWe identified 102 patients who received sotorasib, including 48 (47%) in the sequence group and 54 (53%) in the control group. Patients in the control group received an anti–PD-(L)1 followed by at least one treatment regimen before sotorasib in 87% of the cases or did not receive an anti–PD-(L)1 at any time before sotorasib in 13% of the cases. Severe sotorasib-related AEs were significantly more frequent in the sequence group compared with those in the control group (50% versus 13%, p < 0.001). Severe sotorasib-related AEs occurred in 24 patients (24 of 48, 50%) in the sequence group, and among them 16 (67%) experienced a severe sotorasib-related hepatotoxicity. Severe sotorasib-related hepatotoxicity was threefold more frequent in the sequence group compared with that in the control group (33% versus 11%, p = 0.006). No fatal sotorasib-related hepatotoxicity was reported. Non-liver severe sotorasib-related AEs were significantly more frequent in the sequence group (27% versus 4%, p < 0.001). Severe sotorasib-related AEs typically occurred in patients who received last anti–PD-(L)1 infusion within 30 days before sotorasib initiation. ConclusionsSequential anti–PD-(L)1 and sotorasib therapy are associated with a significantly increased risk of severe sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding starting sotorasib within 30 days from the last anti–PD-(L)1 infusion.

A-140 MANAGEMENT OF NON-METASTATIC DUODENAL NEUROENDOCRINE TUMOURS

Abstract Background The management of duodenal neuroendocrine tumours (NET) between 1 and 2 cm is not codified. Currently, depending on the centre, endoscopic (ER) or surgical (SR) resection is offered. The main objective of our study was to describe the management of non-metastatic duodenal NETs in France. Methods A study was conducted on 153 patients with non-metastatic duodenal NET diagnosed between 2000 and 2019 in 14 French centres by the GTE group (Endocrine Tumors Group). Results 58 (37.9%) patients treated with ER and 95 (62.1%) patients treated with SR were found. Surgery allowed significantly more complete resection than endoscopy (p &amp;lt; 0.001). ER margins were significantly less well-defined than SR margins (p &amp;lt; 0.001). Among the 51 patients with positive lymph node dissection, tumour size was ≤ 1 cm in 25 cases, between 1 and 2 cm in 14 cases and ≥ 2 cm in 12 patients. No difference in survival was demonstrated regardless of type of treatment. Surgical complications were more numerous than endoscopic complications (p = 0.001). Regardless of the type of incomplete resection, there was no significant difference between the two groups according to the criteria of location, size, grade, or adenopathy. In the subgroup analysis of duodenal NETs between 11 and 19 mm, the tumour stages were equivalent in pre-procedure between the two groups. In contrast, there was a difference in post-procedure after anatomopathological analysis (p = 0.001). Conclusion Based on the study results, the type of endoscopic or surgical resection of duodenal NETs has no impact on the long-term results. Lymph node invasion is independent of tumour size.

Efficacy, Safety, and Reoperation-free Survival of Artificial Urinary Sphincter in Non-neurological Male Patients over 75 Years of Age

BackgroundArtificial urinary sphincter (AUS) is a gold standard treatment in male stress urinary incontinence but remains poorly used in elderly patients. ObjectiveTo assess the efficacy, safety, and reoperation-free survival of AUS implantation in male patients over 75 yr of age. Design, setting, and participantsWe retrospectively reviewed the charts of all 1233 non-neurological male AUS implantations between 2005 and 2020 at 13 French centers. We compared 330 patients ≥75 yr old (GROUP75+) with 903 patients <75 yr old (GROUP75–) at the time of AUS implantation. Outcome measurements and statistical analysisOur primary endpoint was social continence at 3 mo defined as the use of one or fewer pad daily. We used Kaplan-Meier analyses to assess reoperation-free survival. We sought factors of erosion using logistic regression. Results and limitationsEarly postoperative continence was comparable in both groups (74.4% vs 80.1%, p = 0.114). We observed a higher rate of postoperative complications in GROUP75+ (18.8% vs 12.6%, p = 0.014), but the complications were more frequently of low grade in GROUP75+ (p = 0.025). The overall reoperation-free survival was similar (p = 0.076) after a median follow-up of 2 yr. However, patients in GROUP75+ had poorer explantation-free survival (p < 0.0001). A history of radiotherapy was a predictive factor of erosion (odds ratio [OR] = 5.31, p < 0.01), but age was not (OR = 1.08, p = 0.87). Unfortunately, our dataset did not include a systematic geriatric evaluation. ConclusionsAUS in elderly patients appears to be an effective option to treat stress urinary incontinence. However, we observed more postoperative complications and explantations, although age was not associated with the onset of erosion. A prospective study is required to determine whether a geriatric evaluation would be an effective strategy to select patients before surgery. Patient summaryIn this study, we looked at outcomes of artificial urinary sphincter in elderly men in a large population. We found satisfying efficacy but slightly more postoperative complications and device infections.

Congenital ventricular outflow tract obstructions in Boxer dogs: Results of a 17-year cardiovascular breed screening program in France (3126 dogs).

Ventricular outflow tract obstructions including aortic (AS) and pulmonic stenosis (PS) are the most common canine congenital heart diseases, with Boxer dogs being predominantly affected. This has led to the French Boxer club adopting a mandatory national control program against AS and PS. The objective of this retrospective study was to analyze the results of 17 years of this cardiovascular breed screening program (2005-2021). The records of untreated and non-anesthetized adult Boxer dogs screened between 2005 and 2021 were retrospectively reviewed. All dogs underwent physical examination and standard transthoracic echocardiography with concomitant ECG tracing. All examinations were reviewed by one single board-certified specialist in cardiology. Out of the 3126 dogs screened during the study period, 3001 dogs (female:male sex ratio = 2.2, median age [IQR] = 1.6 years [1.2-2.1]) were recruited for data analysis. A total of 218 operators were involved in the screening program. For most Boxer dogs (i.e., 93.8% for AS and 94.5% for PS), a single examination was required to obtain a definitive cardiac status, although most operators were non-specialist general practitioners. A left basilar systolic heart murmur was detected in all dogs with AS and PS, but also in 7.4% dogs free of heart diseases. A significantly higher proportion of the latter was detected when operators were board-certified specialists (P<0.001). Lastly, when comparing the start and the end of the breeding program, among dogs diagnosed with AS and PS (n = 364) in a French referral cardiology center, Boxer went from the 1st affected breed by AS to the 3rd, and from the 3rd affected breed by PS to the 6th. This 17-year screening program has experienced a strong involvement of veterinarians, breeders, and owners throughout France. This may have contributed to reduce AS and PS prevalence in Boxer dogs at the studied referral cardiology center.

Multicenter External Validation of the Deep Pelvic Endometriosis Index Magnetic Resonance Imaging Score

Preoperative mapping of deep pelvic endometriosis (DPE) is crucial as surgery can be complex and the quality of preoperative information is key. To evaluate the Deep Pelvic Endometriosis Index (dPEI) magnetic resonance imaging (MRI) score in a multicenter cohort. In this cohort study, the surgical databases of 7 French referral centers were retrospectively queried for women who underwent surgery and preoperative MRI for DPE between January 1, 2019, and December 31, 2020. Data were analyzed in October 2022. Magnetic resonance imaging scans were reviewed using a dedicated lexicon and classified according to the dPEI score. Operating time, hospital stay, Clavien-Dindo-graded postoperative complications, and presence of de novo voiding dysfunction. The final cohort consisted of 605 women (mean age, 33.3; 95% CI, 32.7-33.8 years). A mild dPEI score was reported in 61.2% (370) of the women, moderate in 25.8% (156), and severe in 13.1% (79). Central endometriosis was described in 93.2% (564) of the women and lateral endometriosis in 31.2% (189). Lateral endometriosis was more frequent in severe (98.7%) vs moderate (48.7%) disease and in moderate vs mild (6.7%) disease according to the dPEI (P < .001). Median operating time (211 minutes) and hospital stay (6 days) were longer in severe DPE than in moderate DPE (operating time, 150 minutes; hospital stay 4 days; P < .001), and in moderate than in mild DPE (operating time; 110 minutes; hospital stay, 3 days; P < .001). Patients with severe disease were 3.6 times more likely to experience severe complications than patients with mild or moderate disease (odds ratio [OR], 3.6; 95% CI, 1.4-8.9; P = .004). They were also more likely to experience postoperative voiding dysfunction (OR, 3.5; 95% CI, 1.6-7.6; P = .001). Interobserver agreement between senior and junior readers was good (κ = 0.76; 95% CI, 0.65-0.86). The findings of this study suggest the ability of the dPEI to predict operating time, hospital stay, postoperative complications, and de novo postoperative voiding dysfunction in a multicenter cohort. The dPEI may help clinicians to better anticipate the extent of DPE and improve clinical management and patient counseling.

Impact of newly diagnosed prostate cancer at time of evaluation for renal transplantation.

Systematic screening for prostate cancer is widely recommended in candidates for renal transplant at the time of listing. There are concerns that overdiagnosis of low-risk prostate cancer may result in reducing access to transplant without demonstrated oncological benefits. The objective of the study was to assess the outcome of newly diagnosed prostate cancer in candidates for transplant at the time of listing, and its impact on transplant access and transplant outcomes according to treatment options. This retrospective study was conducted over 10 years in 12 French transplant centers. Patients included were candidates for renal transplant at the time of prostate cancer diagnosis. Demographical and clinical data regarding renal disease, prostate cancer, and transplant surgery were collected. The primary outcome of the study was the interval between prostate cancer diagnosis and active listing according to treatment options. Overall median time from prostate cancer diagnosis to active listing was 25.0 months [16.4-40.2], with statistically significant differences in median time between the radiotherapy and the active surveillance groups (p=.03). Prostate cancer treatment modalities had limited impact on access and outcome of renal transplantation. Active surveillance in low-risk patients does not seem to compromise access to renal transplantation, nor does it impact oncological outcomes.

Risk Factors of Progression in Low-tumor Burden Follicular Lymphoma Initially Managed by Watch and Wait in the Era of PET and Rituximab

Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diagnosis. Time to lymphoma treatment (TLT) initiation can however be very heterogeneous and risk factors of progression are poorly studied. Our study evaluated 201 pts with grade 1-3a low-tumor burden FL diagnosed in four French centers between 2010 and 2020 and managed by a watch and wait strategy in real-life settings. After a median follow-up of 4.8 years, the median TLT was 4.2 years (95% confidence interval, 3.1-5.5). On multivariate analysis, elevated lactate dehydrogenase (hazard ratio [HR] = 2.2; P = 0.02), more than 4 nodal areas involved (HR = 1.7; P = 0.02) and more than 1 extranodal involvement (HR = 2.7; P = 0.01) were identified as independent predictors of TLT. The median TLT was 5.8 years for pts with no risk factor, 2.4 years for 1 risk factor, and 1.3 years for >1 risk factors (P < 0.01). In a subanalysis of 75 pts staged with positron emission tomography-computed tomography (PET-CT), total metabolic tumor volume (TMTV) ≥14 cm3 and standardized Dmax (reflecting tumor dissemination) >0.32 m-1 were also associated with shorter TLT (HR = 3.4; P = 0.004 and HR = 2.4; P = 0.007, respectively). In multivariate models combining PET-CT parameters and clinical variables, TMTV remained independent predictor of shorter TLT. These simple parameters could help to identify FL patients initially observed at higher risk of early progression. The role of PET-CT (extranodal sites and PET metrics) in low-burden FL appears promising and warrants further assessment in large cohorts.

Impact of Initial Management on Disease Evolution in Vogt–Koyanagi–Harada Syndrome: A Retrospective Cohort of 50 Patients

ABSTRACT Purpose The study aims to determine the impact of initial management in Vogt–Koyanagi–Harada syndrome (VKHS). Methods Patients diagnosed with a VKHS between January 2001 and December 2020 in two French tertiary centers were included in a retrospective study. Results Fifty patients were included with a median duration of follow-up of 29.8 months. All patients received oral prednisone after methylprednisolone in all but four of them. Five patients received at least one associated immunosuppressive therapy (IST) within the first 6 months and 26 patients received IST during the entire follow-up period. Twenty-eight patients presented at least one relapse at a median of 5.4 months from diagnosis. Multivariate analyses demonstrated a significant association between relapse and delayed treatment (>26 days) (HR = 3.69, CI95% 1.30–10.47, p = .01), whereas no association was observed between relapse and the number of corticosteroid pulses at initial management. Conclusion An early corticosteroid treatment within the first 26 days of symptoms decreased the relapse rate.

Cardiogenic shock in adults with congenital heart disease: Insights from the FRENSHOCK registry

Data on cardiogenic shock (CS) in adults with congenital heart disease (ACHD) are scarce. We sought to describe CS in ACHD in a nationwide CS registry. From the multicentric FRENSHOCK registry (n = 772 CS from 49 French centers between April and October 2016), ACHD CS were compared with non-ACHD ones. The primary outcome was defined by all-cause mortality, chronic ventricular assist device (VAD) or heart transplantation at 1-year. Out of the 772 patients, 7 (1%) were ACHD. ACHD patients were younger (54 vs. 66 years old), with less cardiovascular risk factors, such as hypertension (14.2 vs. 47.5%) and diabetes (14.3 vs. 36.1%), and no ischemic cardiopathy (0 vs. 61.5%). Right heart catheterization (57.1 vs. 15.4%), pacemaker (28.6 vs. 4.6%) and ICD (28.6 vs. 4.8%) were more frequently indicated in the ACHD CS management compared to non-ACHD CS, whereas temporary MCS (0 vs. 7.2%) and invasive mechanical ventilation (14.3 vs. 38.1%) were less likely used in ACHD. At 1-year, primary outcome occurred in 85.7% ACHD and 52.2% non-ACHD (P = 0.127) (Fig. 1). Although 1-year mortality was similar (45.4 vs. 42.9% respectively for ACHD and non-ACHD patients, P = 1), VAD (14.3 vs. 5.4%, P = 0.325), and heart transplantation (28.6 vs. 5.2%, P = 0.05) seemed more frequent in ACHD group. CS in ACHD is rare accounting for only 1% of an unselected CS population. Despite a younger age and less comorbidities its prognosis remains severe and similar to others patients.

MP-453092-9 PROGNOSTIC SIGNIFICANCE OF SUSTAINED VENTRICULAR ARRHYTHMIAS OCCURRING UNDER WEARABLE CARDIOVERTER DEFIBRILLATOR PROTECTION IN POST-INFARCT PATIENTS WITH A LEFT VENTRICULAR DYSFUNCTION

Although the first few months after acute myocardial infarction (MI) are associated with an increased risk of SCD, in particular when LVEF is ≤0.35, prophylactic ICDs are not recommended until LVEF has been reassessed after a period of 40 to 90 days following an acute MI. During this ‘waiting period’, wearable cardioverter defibrillators (WCD) may be used in patients considered at high-risk of SCD, but the prognostic significance of sustained VT/VF occurring under WCD protection is unknown. We sought to evaluate whether the occurrence of VT/VF, successfully treated by a WCD in the early post-MI phase, is associated with a poorer outcome with regard to death or VT/VF recurrences at one year. We recruited a series of patients with an acute MI and a resulting LVEF≤0.35 (evaluated 2-5 days after admission) who were prescribed a WCD upon hospital discharge (for a maximal expected duration of 3 months) and who were subsequently implanted with an ICD either because sustained VT/VF occurred while on WCD (Group A) or because LVEF remained ≤0.35 after the post-MI ‘waiting period’ (Group B). Informed consent was mandatory to participate in the study. Adjudication of arrhythmic events was based on the analysis of ICD/WCD recordings. Based on previous publications, eleven relevant clinical parameters (associated with a higher risk of SCD after MI) were assessed for statistical analysis in addition to the occurrence of VT/VF while on WCD. The study population consisted of 1032 consecutive patients (Group A: n=72, Group B: n=960) from 41 French centers. The median follow-up after ICD implantation was 2.6 years [interquartile range=1.5-3.9]. The clinical characteristics of the patients are shown in Table 1. At one year: 1) VT/VF requiring ICD treatment occurred in 22.2% vs 3.5% (p<0.0001) respectively in Group A and Group B patients and 2) death from any cause occurred in 11.1% vs 3.4% (p=0.001) respectively in Group A and Group B patients (Figure 1). Occurrence of VT/VF while on WCD was independently associated with the occurrence of VT/VF and all-cause death after ICD implantation. Our study suggests that the occurrence of VT/VF, while on WCD in the early post-MI period after an acute MI, is an independent marker of a poorer one-year prognosis in patients with a LVEF≤0.35. Further studies are needed to assess which therapeutic strategies might improve the short-term prognosis in these patients.Tabled 1Table 1: Patient characteristicsVariablesGroup A (n = 72)Group B (n = 960)p-valueGender (male, %)88.9%82.9 %0.25Age at ICD implantation (years, mean ± SD)61.5 ± 9.060.7 ± 10.50.52Current smoker (%)50.7 %47.9 %0.90Diabetes mellitus (%)30.6 %23.2 %0.20History of hypertension (%)47.9 %41.7 %0.32History of atrial fibrillation (%)8.3 %4.8 %0.17History of previous myocardial infarction (%)16.7 %18.8 %0.75Early (<24 hours) coronary revascularization for the index myocardial infarction (%)51.4 %66.3 %0.014Average heart rate during WCD (bpm, mean ± SD)73.2 ± 12.568.3 ± 9.6<0.0001NYHA III/IV class at ICD implantation (%)39.6%19.1%0.001Serum creatinine at ICD implantation [mg/L, median (Q1 - Q3)]10.8 (9.2 - 13.1)10.7 (8.9 - 13.2)0.42LVEF at ICD implantation (%, mean ± SD)29.1 ± 6.629.3 ± 6.20.78 Open table in a new tab