Evolving Practices in Immune-Related Adverse Event Management: Insights From the IMMUCARE Multidisciplinary Board.

PURPOSE: The management of immune-related adverse events (irAEs) requires multidisciplinary boards to handle complex cases. This study aimed to examine the evolving practices of the IMMUCARE board and to evaluate its impact on clinical practices. MATERIALS AND METHODS: The IMMUCARE board gathers oncologists and organ specialists from the Cancerology Institute of the Lyon University Hospital since 2018. We conducted a retrospective analysis of its activity (participants' specialty, referred cases, and recommendations) from 2018 to 2021, coupled with a survey among the physicians who participated. RESULTS: Across 68 board meetings, 245 cases from 195 patients were discussed. Each board had a median of six participants (IQR, 5-8). Participation rates varied across specialties and also over time (participation of nephrologists and rheumatologists significantly increased over time, whereas it decreased for endocrinologists). Most of the referred patients (89%) were treated at our center. Only 4% of referrals concerned eligibility for immune checkpoint inhibitor (ICI), whereas the majority pertained to irAEs. The board recommended ICI interruption for 56% and steroids for 41% of them. Immunosuppressants were recommended in 17% of cases, with a notable increase over time. ICI reintroduction was debated in 50% of cases, and the board identified a definitive contraindication in 26% of them. The survey of 49 of 98 physicians showed that the board significantly affected immunosuppressant introduction and ICI rechallenge decisions. The board's educational and collaborative benefits were highlighted, but time constraints posed challenges. CONCLUSION: Our 4-year analysis of irAE management practices reveals changing patterns in the distribution of cases presented and in specialists' involvement. Dedicated multidisciplinary boards remain essential, particularly for intricate cases. Expanding access to these boards is crucial to ensure comprehensive care for all patients.

Implementing Indicators and Trajectories of Return to Work After Breast Cancer Diagnosis: A Mixed-Methods Study Using the French National Healthcare Insurance Database and Stakeholder Consultation.

PURPOSE: Return to work (RTW) is important for quality of life after breast cancer but its analysis at the population-level remains limited in France. This study aimed to implement Electronic Healthcare Data (EHD)-based indicators and trajectories to measure RTW after breast cancer diagnosis, and to examine stakeholders' perspectives regarding these indicators. METHODS: We followed a mixed-methods approach that consisted of (i) implementing RTW indicators and identifying clusters of trajectories using state sequence analysis with data from a representative sample of the French National Health Data System and (ii) exploring, through qualitative focus group and interviews, stakeholders' perceptions on the interpretation, limitations, and utility of these indicators. RESULTS: We extracted data from 317 women aged 25-55 years with a first diagnosis of early-stage breast cancer. The median number of sickness absence periods was 2 for a total of 434 days during the 3-year follow-up, and the median time to sustainable RTW was 240 days. Three clusters of RTW trajectories were identified: "early RTW" (49.5% of the population), "RTW after partial resumption" (37.5%) and "continuous compensation" (12.9%). Feedback from stakeholders highlighted the multi-factorial nature of RTW and underscored the added value of EHD for studying RTW, despite certain limitations. CONCLUSIONS: We demonstrated the feasibility of calculating RTW indicators and identifying trajectories using the French National Health Data System. These indicators can serve as outcome measures in RTW promotion and provide a basis for designing targeted interventions for breast cancer survivors.

[Last year of residency for oncologists: Overview and perspectives]. / Premiers docteurs juniors d'oncologie médicale : état des lieux et perspectives.

CONTEXT: The reform of the third cycle of medical studies in France has introduced of the "Junior Doctor" status during the concluding year of residency. We wish to evaluate its implementation for the first promotion of medical oncology residents during 2021-2022 in correlation with the published guidelines. METHOD: AERIO conducted a cross-sectional study among French medical oncology residents. The survey was released via social networks and emails. RESULTS: Twenty-eight of 47 residents responded. The typical week involved one to two half-days of consultation, one dedicated to clinical research, one multidisciplinary team meetings, with the rest of time being occupied by day care (mostly) and hospitalization. Teaching and quality management activities were infrequent (monthly or less). The Junior Doctors rated their overall satisfaction at 8/10. A large majority (92.5 %) felt equipped to handle most of the situations they encountered. Almost all residents (92.9 %) had negotiated with their placement supervisor prior to the selection procedure. In one third of the cases (35.7 %), the principle of mismatch between the number of residents and the number of training sites was not respected. Only 42.9 % received training in scientific writing and 82.2 % of the residents agreed on the relevance of the post-internship training modules developed in other specialties. CONCLUSIONS: Junior doctors in medical oncology express overall satisfaction with this reform, which aligns with the recommendations. Nevertheless, certain concerns, such as selection procedure and inadequacy, along with areas requiring improvement, such as post-internship training and scientific writing, are clearly established.

Analysis of the benefit of salvage chemotherapy after progression on nivolumab in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Checkpoint inhibitor (CI) therapies have shown benefit in the treatment of locally recurrent or metastatic head and neck squamous cell carcinoma (R L/M HNSCC). Previous studies have suggested a superior benefit of salvage chemotherapy (SCT) in R/M HNSCC after progression on CI. We aimed to describe the benefit of SCT after progression on nivolumab. PATIENTS AND METHODS: Patients were eligible if they received at least one injection of SCT in the treatment of R/M HNSCC after progression on nivolumab between 2017 and 2022. The present work was a retrospective and monocenter study. Primary endpoint was the objective response rate (ORR) on first regimen of salvage chemotherapy (SCT1). Secondary endpoints were disease-control rate (DCR), ORR on second course of SCT (ORR2), progression-free survival (PFS) on SCT1 and SCT2 (PFS2) and overall survival (OS). RESULTS: Eighty-three patients received an SCT. The ORR on STC1 was 32%. Median progression-free survival (PFS) was 2.20 months (CI 95% 2.06-3.71). Median OS was 5.55 months (CI 95% 4.82-10.20). The ORR to the first line of treatment in the relapse setting was an independent prognostic factor for SCT1 PFS and OS. CONCLUSION: In R/M HNSCC, SCT following nivolumab is associated with ORRs of 32%. These results are consistent with other publications that suggest a superior benefit of SCT after CI treatment, independent of the tumor outcome on previous immunotherapy.

Clinical results of the EVESOR trial, a multiparameter phase I trial of everolimus and sorafenib combination in solid tumors.

PURPOSE: Everolimus (EVE) and sorafenib (SOR) combination was associated with synergistic activity in preclinical models. However, previous clinical studies were hampered by cumulative toxicities when both were given continuously. The academic EVESOR trial (NCT01932177) was designed to assess alternative doses and intermittent dosing schedules of EVE and SOR combination therapy to improve the benefit-risk ratio for patients with solid tumors. METHODS: EVESOR is a multiparameter dose-escalation phase I trial investigating different doses and dosing schedules, with the final objective of generating data for modeling and simulation. Patients were allocated into continuous (A and B) or intermittent (C and D) schedules to determine the recommended phase II dose (RP2D). The clinical outcomes are presented here. RESULTS: Forty-three patients were included from 2013 to 2019. Most of them had gynecological (25.6%), cholangiocarcinomas (23.2%), colorectal (14.0%), and breast cancers (11.6%). Dose-escalation up to EVE 10 mg QD and SOR 400 mg BID was possible on intermittent schedules. Five dose-limiting toxicities were observed, and dose reductions were required in 39.5% patients, stabilizing at EVE 5 mg and SOR 200 mg BID for 58.1% of them. The overall response rate was 6.3%, and disease control rate was 75.0%. The median progression-free survival (PFS) was 3.6 months. The longest median PFS were observed in cholangiocarcinomas (9.9 months), and gynecological adenocarcinomas (9.2 months). CONCLUSION: Intermittent arms were associated with improved efficacy/toxicity profiles; and EVE 5 mg QD and SOR 200 mg BID was defined a clinically feasible dose. Strong signs of efficacy were found in cholangiocarcinomas and gynecologic carcinomas. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01932177.

Hyperprogressive Disease After Combined Anti-PD-L1 and Anti-CTLA-4 Immunotherapy for MSI-H/dMMR Gastric Cancer: A Case Report.

Immune checkpoint inhibitors (ICI) have been developed in gastric adenocarcinomas and approved in first-line metastatic setting (in combination with chemotherapy) as well as in pretreated patients. Microsatellite instability-high (MSI-H) tumors are predicted to derive high benefit from ICI but data in gastric locations are limited. Here, we describe the case of a 68-year old patient with stage IV MSI-H gastric adenocarcinoma, referred to our center to receive immunotherapy after failure of standard of care (surgery with perioperative platin-based chemotherapy and paclitaxel plus ramucirumab at disease progression). The patient received one injection of durvalumab and tremelimumab and was hospitalized eighteen days after because of occlusive syndrome. The CT scan showed hyperprogression of the lymph nodes and hepatic lesions, compressing the gastric stump. He died few days later. Molecular analyses did not explain this outcome. To our knowledge, this is one of the first reported cases of hyperprogressive disease after combined ICI for a patient with MSI-H tumor. We review the potential causes and discuss the emerging literature regarding predictive factors of hyperprogression in the particular subset of MSI-H patients. If some data were available in retrospective studies, validation of strong predictive factors is needed to avoid such dramatic evolutions.

Using Breast Cancer Gene Expression Signatures in Clinical Practice: Unsolved Issues, Ongoing Trials and Future Perspectives.

The development of gene expression signatures since the early 2000's has offered standardized assays to evaluate the prognosis of early breast cancer. Five signatures are currently commercially available and recommended by several international guidelines to individualize adjuvant chemotherapy decisions in hormone receptors-positive/HER2-negative early breast cancer. However, many questions remain unanswered about their predictive ability, reproducibility and external validity in specific populations. They also represent a new hope to tailor (neo)adjuvant systemic treatment, adjuvant radiation therapy, hormone therapy duration and to identify a subset of patients who might benefit from CDK4/6 inhibitor adjuvant treatment. This review will highlight these particular issues, address the remaining questions and discuss the ongoing and future trials.

Virtual reality distraction during uterovaginal brachytherapy applicators' removal: A pilot comparative study.

PURPOSE: To assess the relevance of virtual reality distraction (VR) during uterovaginal brachytherapy applicators' removal, as an alternative to nitrous oxide (N2O) conscious sedation, to decrease anxiety and pain perception. METHODS AND MATERIALS: We prospectively evaluated 35 patients treated with cervical brachytherapy for locally or locally advanced cervical cancer. Brachytherapy applicators were removed in the patient's room at the end of the treatment. Patients were assigned to N2O conscious sedation (reference group) or VR (experimental group). Anxiety and pain were evaluated with the STAI-E score and with Visual Analogical Scales (VAS). RESULTS: Fourteen patients were treated with VR and 21 with N2O. STAI-E baselines scores were 35 in the VR group and 38 in the reference group and declined to 30 and 28, respectively after procedure. The mean VAS-anxiety was 2.9 before and 2.7 at the peak in the VR group versus 4.1 and 1.6, respectively in the reference group. The mean VAS-pain was 1.0 before, 3.1 at the peak and 0.4 after the procedure in the experimental group, versus 1.8, 2.0, and 0.6 respectively in the N2O group. Four patients in the VR group experienced mild nausea/vomiting or dizziness during the procedure. The preparation duration was higher in the VR group, with a similar duration for the removal itself. CONCLUSIONS: Replacing a medical gas by a virtual reality device was feasible and led to acceptable levels of pain and anxiety. Prospective randomized trials are needed to confirm efficacy and to determine which patients could benefit the most from this approach.

Actionable molecular alterations in advanced gynaecologic malignancies: updated results from the ProfiLER programme.

OBJECTIVES: The objectives of this study were to identify actionable genomic alterations in the gynaecological subpopulation of the ProfiLER programme and to report clinical efficacy of recommended targeted treatment (RTT). METHODS: The ProfiLER programme (NCT01774409) is a multicentric prospective trial aiming to implement molecular profiling in patients with advanced refractory cancers. In this programme, tumour DNA is analysed by targeted next-generation sequencing (69 genes) and by whole genome array comparative genomic hybridisation. Clinical cases and genomic profiles are presented in a dedicated molecular tumour board to guide treatment strategies. We report here an analysis of patients with gynaecological cancers included in this trial. RESULTS: From February 2013 to February 2017, 309 patients with gynaecologic cancer were included; 279 (90%) had sufficient quality, and 131 patients (42.4%) had at least one actionable genomic alteration in cancer cells. Four alterations were shared by at least 3% of the patients: 27 (9.7%) PIK3CA mutations, 15 (5.4%) KRAS mutations, 11 (3.9%) ERBB2 amplifications and 9 (3.2%) CDKN2A deletions. Forty-one treatments were initiated among 39 patients (12.6% of the screened population): 8 (20%) had a partial response, and other 10 (24%) had a stable disease. The median progression-free survival was 2.7 months. The median overall survival was 15.6 months for patients who received a RTT. CONCLUSION: Molecular profiling identified actionable alterations in 42.4% of patients with advanced refractory gynaecologic cancer, but only 12.6% were treated with a RTT. Among them, 46% derived clinical benefit (5.8% of the screened population).