Clinical spectrum and evolution of immune-checkpoint inhibitors toxicities over a decade-a worldwide perspective.

Background: Immune-checkpoint inhibitors (ICI) have revolutionized cancer treatment by harnessing the immune system but ICI can induce life-threatening immune-related adverse events (irAE) affecting every organ. Methods: We extracted irAE from VigiBase, the international pharmacovigilance database, first reported in 2008 until 01/2023 to characterize irAE reporting trends, clinical features, risk factors and outcomes. Findings: We distinguished 25 types of irAE (n = 50,347cases, single irAE/case in 84.9%). Cases mainly involved anti-PD1 (programmed-death-1) monotherapy (62.4%) in male (61.7%) aged 64.3 ± 12.6 years. After 2020 vs. prior to 2016, proportion of anti-CTLA4 (Cytotoxic-T-Lymphocyte-Antigen-4) monotherapy prescription almost vanished (1.6% vs. 47%, respectively) contrasting with increased use of anti-PDL1 (PD1-ligand) monotherapy (18% vs. 0.9%) and anti-CTLA4+anti-PD(L)1 combination (20% vs. 8.9%). Anti-LAG3 (Lymphocyte-Activation-Gene-3) prescription was limited (<1%) in the studied timeframe. After 2020, over 14 different cancer types were treated vs. almost exclusively melanoma and lung cancers before 2016. Overall, the most reported irAE were skin reactions (22.9%), pneumonitis (18.5%), enterocolitis (14.4%) and thyroiditis (12.1%). ICI-myotoxicities (6.6%) included myositis, myocarditis and myasthenia-gravis like syndrome and were the most overlapping irAE (up to 30% overlap, vs. <3% in general for other inter-irAE overlap). The top factors associated with specific irAE (odds-ratio>5) were presence of thymic cancer for ICI-myotoxicities or hepatitis; presence of melanoma for vitiligo, uveitis or sarcoidosis; specific types of ICI regimen (anti-LAG3 for meningitis, anti-CTLA4 for hypophysitis); and specific reporting regions (eastern Asia for cholangitis). Median time-to-onset ranged from 31 to 273 days, being shortest for myotoxicities and most delayed for skin-bullous auto-immune reactions. Overall fatality was highest for myocarditis = 27.6%, myasthenia = 23.1%, severe cutaneous adverse reactions (SCAR) = 22.1%, myositis = 21.9%, pneumonitis = 21%, and encephalomyelitis = 18%; generally decreasing after 2020, except for myasthenia and SCAR. When reported, irAE recurrence rate after rechallenge was 28.9% (n = 275/951). Interpretation: This up-to-date comprehensive worldwide pharmacovigilance study defines the spectrum, characteristics, and evolution of irAE reporting summarizing over a decade of use. Multiple risk factors and clinical peculiarities for specific irAE have been identified as signals to guide clinical practice and future research. Funding: Paul Gougis was supported by the academic program: "Contrats ED: Programme blanc Institut Curie PSL" for the conduct of his PhD. Baptiste Abbar was supported by "the Fondation ARC Pour le Rechercher Sur le Cancer". The RT2L research group (Institut Curie) was supported by the academic program "SHS INCa", Sanofi iTech award, and by Monoprix∗.

Immune Checkpoint Inhibitor Use During Pregnancy and Outcomes in Pregnant Individuals and Newborns.

Importance: With the widespread use of immune checkpoint inhibitors (ICIs), concerns about their pregnancy outcomes through maternal exposure have emerged, and clinical comparative data are lacking. Objective: To assess the risk of pregnancy-, fetal-, and/or newborn-related adverse outcomes associated with exposure to ICIs compared with exposure to other anticancer agents. Design, Setting, and Participants: In this cohort study, all reports mentioning a pregnancy-related condition and an antineoplastic agent (Anatomical Therapeutic Chemical classification group L01) used for a cancer indication registered in the World Health Organization international pharmacovigilance database VigiBase up to June 26, 2022, were extracted. Exposure: Anticancer agents, including ICIs, used during pregnancy for a cancer indication. Immune checkpoint inhibitors included blockers of programmed cell death 1 (PD1) or its ligand (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Main Outcomes and Measures: The main outcome was the reporting odds ratio (ROR) for maternal, fetal, or newborn complications in patients treated with ICIs vs any other anticancer drug. Adverse events, categorized into 45 individual maternofetal adverse outcomes, were directly mapped to Medical Dictionary for Regulatory Activities preferred terms in VigiBase. Results: A total of 3558 reports (ICI: 91 [2.6%]; other anticancer drugs: 3467 [97.4%]) were included in the analysis. In the ICI group, most reports were from the US (60 [65.9%]), and the mean (SD) patient age was 28.9 (10.2) years; in 24 of 55 reports with data on cancer type (43.6%), patients were treated for melanoma. The molecules involved in the ICI group were anti-PD1 (58 reports [63.7%]), anti-PD1 plus anti-CTLA4 (15 [16.5%]), anti-CTLA4 (13 [14.3%]), anti-PD-L1 (4 [4.4%]), and anti-PD1 plus anti-lymphocyte activation gene 3 (1 [1.1%]). An ICI was used in combination with a non-ICI anticancer agent in 10 participants (11.0%). Compared with other anticancer drugs, none of the 45 adverse outcomes identified were overreported in the group exposed to ICIs. However, preterm birth was significantly overreported for the anti-PD1 plus anti-CTLA4 combination compared with other anticancer drugs (12 of 15 [80.0%] vs 793 of 3452 [23.0%]; ROR, 13.87; 95% CI, 3.90-49.28; P < .001) but not for anti-PD-L1 or anti-CTLA4 monotherapy. Three reports of possibly immune-related maternofetal events were identified: 1 case of maternal antiphospholipid syndrome leading to spontaneous abortion, 1 case of pneumonitis leading to neonatal respiratory distress syndrome and death, and 1 case of transient congenital hypothyroidism. Conclusions and Relevance: In this cohort study of 91 individuals exposed to ICIs during pregnancy, ICI exposure was not associated with overreporting of specific adverse pregnancy, fetal, and/or newborn outcomes compared with other anticancer treatments. However, due to possible rare immune-related neonatal adverse events, ICI use in pregnant women should be avoided when possible, especially the anti-PD1 plus anti-CTLA4 combination.

Concomitant medication, comorbidity and survival in patients with breast cancer.

Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of diagnosis. Preliminary epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this nationwide cohort study, we assessed the association between medication use at breast cancer diagnosis and survival. We included 235,368 French women with newly diagnosed non-metastatic breast cancer. In analyzes of 288 medications, we identified eight medications positively associated with either overall survival or disease-free survival: rabeprazole, alverine, atenolol, simvastatin, rosuvastatin, estriol (vaginal or transmucosal), nomegestrol, and hypromellose; and eight medications negatively associated with overall survival or disease-free survival: ferrous fumarate, prednisolone, carbimazole, pristinamycin, oxazepam, alprazolam, hydroxyzine, and mianserin. Full results are available online from an interactive platform ( https://adrenaline.curie.fr ). This resource provides hypotheses for drugs that may naturally influence breast cancer evolution.

Therapeutic role of para-aortic lymphadenectomy in patients with intermediate- and high-risk endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: Lymph nodal involvement is a prognostic factor in endometrial cancer. The added value of para-aortic lymphadenectomy compared with pelvic nodal evaluation alone remains a matter of debate in the management of patients with intermediate- and high-risk endometrial cancer. A systematic review and meta-analysis was conducted to assess the prognostic value of para-aortic lymphadenectomy in terms of overall survival and disease-free survival in patients with intermediate- and high-risk endometrial cancer. METHODS: The study adhered to the PRISMA guidelines. PubMed, Google Scholar and ClinicalTrials.gov were searched from January 2000 to April 2023. Studies on intermediate- and high-risk patients who underwent pelvic versus pelvic and para-aortic dissection were included in the analysis. The Methodological Index for Nonrandomized Studies (MINORS) and the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) were used for quality assessment of the selected articles. RESULTS: Fourteen studies were identified, encompassing 9415 patients with a median age of 62 years (IQR 56.5-66.5). The majority had International Federation of Gynecology and Obstetrics stage I-II disease (76%) and endometrioid histology (89%). The 72% of patients who underwent only pelvic nodal evaluation and the 87% who underwent pelvic and para-aortic lymphadenectomy received adjuvant treatment (p=0.44). Pelvic and para-aortic lymphadenectomy was associated with a significant improvement in 5-year overall survival (RR=0.71, 95% CI 0.57 to 0.88, p<0.01), translating to a 41% reduction in the risk of overall death. However, no significant differences were observed in the 5-year risk of recurrence (RR=1.12, 95% CI 0.94 to 1.34, p=0.15). Additionally, patients undergoing pelvic and para-aortic lymphadenectomy experienced a 26% increased risk of post-operative complications (RR=1.26, 95% CI 1.04 to 1.53, p=0.03) and prolonged operative times (MD=56.27, 95% CI 15.94 to 96.60, p<0.01). CONCLUSION: Pelvic and para-aortic lymphadenectomy appears to confer a prognostic benefit in patients with intermediate- and high-risk endometrial cancer. Robust prospective studies are needed to further validate these findings and elucidate the precise role of para-aortic lymphadenectomy in the optimal management of these patients.

[Arguments for centralization of surgical treatment of ovarian cancer in France based on morbidity and mortality data]. / Intérêts de la centralisation de la chirurgie du cancer de l'ovaire en France.

OBJECTIVE: To examine the current state for ovarian cancer surgery in France from 2009 to 2016 and to examine the impact of the volume of activity on morbidity and mortality by institution. MATERIAL AND METHOD: National retrospective study analyzing surgical sessions for ovarian cancer from the program of medicalization of information systems (PMSI), from January 2009 to December 2016. Institutions were divided according to the number of annual curative procedures into 3 groups: A<10; B: 10-19; C≥20. A propensity score (PS) and the Kaplan-Meier method were employed for statistical analyses. RESULTS: In total, 27,105 patients were included. The 1-month mortality rate in group A, B and C was 1.6; 1 and 0.7 %, respectively (P<0.001). Compared to group C, the Relative Risk (RR) of death within the first month was 2.22 for group A and 1.32 for group B (P<0.01). After MS, the 3- and 5-year survival in group A+B and group C were 71.4 and 60.3% (P<0.05) and 56.6, and 60.3% (P<0.05), respectively. The 1-year recurrence rate was significantly lower in group C (P<0.0001). CONCLUSION: An annual volume of activity>20 advanced stage ovarian cancers is associated with a decrease in morbidity, mortality, recurrence rate and improved survival.

Adenomyosis and obstetric complications: A retrospective case-control study.

OBJECTIVE: Adenomyosis is a uterine pathology affecting an increasing number of women of childbearing age. Its diagnosis is based upon histology or imaging [ultrasound or magnetic resonance imaging (MRI)]. Several studies have investigated the impact of adenomyosis on obstetric complications, with its diagnosis based on clinical symptoms, ultrasound or composite criteria. The aim of this study was to identify potential obstetric complications related to adenomyosis in women with an MRI-confirmed diagnosis. METHODS: A single centre retrospective case-control study was undertaken in pregnant patients with an MRI-confirmed diagnosis of adenomyosis between January 2013 and December 2017 at the University Hospitals of Strasbourg. Controls were matched in a 4:1 ratio for age, parity and body mass index. Multivariate analysis was performed to identify obstetric complications. RESULTS: In total, 291 women with an MRI-confirmed diagnosis of adenomyosis were identified during the study period. Of these, 89 patients achieved pregnancy after 24 weeks of gestation. The mean age of patients was 30.8 years. The adenomyosis group and the control group were comparable for matching criteria. Adenomyosis was found to be associated with increased risk of caesarean section [odds ratio (OR) 1.1, 95 % confidence interval (CI) 1.0-1.2; p = 0.03], intrauterine growth restriction (OR 1.3, 95 % CI 1.1-1.4; p < 0.001), postpartum haemorrhage (OR 1.2, 95 % CI 1.1- 1.4; p < 0.01), pre-eclampsia (OR 1.3, 95 % CI 1.0-1.6; p = 0.004) and previous spontaneous miscarriage (OR 2.09, 95 % CI 1.36-3.33; p < 0.001). Premature rupture of membranes, preterm delivery, severe intrauterine growth restriction and the risk of placenta praevia were not significantly higher in the adenomyosis group compared with the control group on multivariate analysis. CONCLUSION: This study demonstrates increased risk of several obstetric complications (caesarean section, intrauterine growth restriction, postpartum haemorrhage, pre-eclampsia, history of spontaneous miscarriage) in women with adenomyosis. To the authors' knowledge, this is the first study to use MRI as the sole criterion for diagnosis. These results could be complemented by larger-scale prospective studies in order to manage these patients more effectively during pregnancy.

Impact of guideline adherence and expert center referral on the early management and outcomes of uterine sarcoma patients: A retrospective analysis from the French NETSARC network.

OBJECTIVE: Uterine sarcomas are rare tumors with a poor prognosis. Their diagnosis is often incidental, following surgery. Our goal was to examine the early management strategies for uterine sarcomas, and to assess the impact of guideline adherence and expert center referral on both the management approaches and the clinical outcomes in patients with uterine sarcomas. METHODS: We retrospectively analyzed medical records from patients with uterine sarcoma referred to the Institut Curie and registered in the database of the French NETSARC network. RESULTS: In total, 100 patients, with a median age of 54 years, were included in the analyses. On MRI scans (n = 36), all patients had at least two signs suggestive of malignancy, and 77.8 % had four or more signs. No preoperative biopsy was performed in 65.6 % of cases. Only 14.1 % of patients underwent initial surgery at an expert center. Surgery performed outside the network was significantly associated with morcellation (32.9 % vs. 0 %; p = 0.036), fewer negative margins (R0 margins 52.4 % vs. 100 %; p = 0.006), and poor adherence to surgical guidelines (28.3 vs. 72.7 %; p = 0.013). Multivariate analysis showed that non-adherence to surgical recommendations was not significantly associated with relapse-free survival (HR = 0.54; 95 % CI [0.21-1.38]), but was an independent predictor of poor overall survival (HR = 0.12; 95 % CI [0.03-0.52]; p = 0.005). CONCLUSION: Despite a high frequency of suspicious clinical and radiological signs, a large proportion of women undergoing sarcoma surgery are treated outside of expert networks. We provide guidelines, integrating the clinical context and radiological signs to encourage early referral to reference centers for sarcoma.

Effects of gender and socio-environmental factors on health-care access in oncology: a comprehensive, nationwide study in France.

Background: Gender-based disparities in health-care are common and can affect access to care. We aimed to investigate the impact of gender and socio-environmental indicators on health-care access in oncology in France. Methods: Using the national health insurance system database in France, we identified patients (aged ≥18 years) who were diagnosed with solid invasive cancers between the 1st of January 2018 and the 31st of December 2019. We ensured that only incident cases were identified by excluding patients with an existing cancer diagnosis in 2016 and 2017; skin cancers other than melanoma were also excluded. We extracted 71 socio-environmental variables related to patients' living environment and divided these into eight categories: inaccessibility to public transport, economic deprivation, unemployment, gender-related wage disparities, social isolation, educational barriers, familial hardship, and insecurity. We employed a mixed linear regression model to assess the influence of age, comorbidities, and all eight socio-environmental indices on health-care access, while evaluating the interaction with gender. Health-care access was measured using absolute and relative cancer care expertise indexes. Findings: In total, 594,372 patients were included: 290,658 (49%) women and 303,714 (51%) men. With the exception of unemployment, all socio-environmental indices, age, and comorbidities were inversely correlated with health-care access. However, notable interactions with gender were observed, with a stronger association between socio-environmental factors and health-care access in women than in men. In particular, inaccessibility to public transport (coefficient for absolute cancer care expertise index = -1.10 [-1.22, -0.99], p < 0.0001), familial hardship (-0.64 [-0.72, -0.55], p < 0.0001), social isolation (-0.38 [-0.46, -0.30], p < 0.0001), insecurity (-0.29 [-0.37, -0.21], p < 0.0001), and economic deprivation (-0.13 [-0.19, -0.07], p < 0.0001) had a strong negative impact on health-care access in women. Interpretation: Access to cancer care is determined by a complex interplay of gender and various socio-environmental factors. While gender is a significant component, it operates within the context of multiple socio-environmental influences. Future work should focus on developing targeted interventions to address these multifaceted barriers and promote equitable health-care access for both genders. Funding: None.

Treatments During Pregnancy Targeting ERBB2 and Outcomes of Pregnant Individuals and Newborns.

Importance: Targeted therapies directed against ERBB2 are the cornerstone of medical treatment for ERBB2-positive breast cancers but are contraindicated during pregnancy. Objectives: To describe the association of exposure to anti-ERBB2 agents during pregnancy with pregnancy and fetal or newborn outcomes, and to compare the risk and types of adverse outcomes reported more frequently in this context than after exposure to other anticancer agents. Design, Setting, and Participants: For this case-control study, All reports with a pregnancy-related condition and an antineoplastic agent (Anatomical Therapeutic Chemical classification group L01) registered in the World Health Organization international pharmacovigilance database VigiBase up to June 26, 2022, were extracted. All reports with a pregnancy, an antineoplastic treatment during pregnancy, and a cancer were retained. Reports with anticancer agents prescribed for nononcologic purposes were not included. Exposure: The exposure group was defined as reports that mention anti-ERBB2 agents compared with exposure to other anticancer agents. Main Outcome and Measures: The main outcome was the reporting odds ratio (ROR) for maternofetal complications in the group exposed to anti-ERBB2 agents compared with other anticancer agents, as determined using a disproportionality analysis. Results: A total of 3558 reports (anti-ERBB2 agents, 328; other anticancer agents, 3230) were included in the analysis. In the group exposed to anti-ERBB2 agents, most reports were from the US (159 [48.5%]), the mean (SD) age of participants was 30.8 (10.4) years, and 209 patients (97.7%) were treated for breast cancers. The molecules most frequently involved in cases with anti-ERBB2 agents were trastuzumab (n = 302), pertuzumab (n = 55), trastuzumab-emtansine (n = 20), and lapatinib (n = 18). The outcomes overreported in these cases included oligohydramnios (ROR, 17.68 [95% CI, 12.26-25.52]; P < .001), congenital respiratory tract disorders (ROR, 9.98 [95% CI, 2.88-34.67]; P < .001), and neonatal kidney failure (ROR, 9.15 [95% CI, 4.62-18.12]; P < .001). Sensitivity and multivariable analyses found similar results. Toxic effects were also significantly overreported for trastuzumab-emtansine (cardiovascular malformation: ROR, 4.46 [95% CI, 1.02-19.52]) and lapatinib (intrauterine growth restriction: ROR, 7.68 [95% CI, 3.01-19.59]). Conclusions and Relevance: In this case-control study of 328 individuals exposed to anti-ERBB2 agents during pregnancy, exposure was associated with a severe specific adverse pregnancy and fetal or newborn outcomes compared with exposure to other anticancer treatments.

Management of patients with advanced epithelial ovarian cancer: a European survey.

BACKGROUND: The aim of this study was to assess current European practices in the management of patients with advanced epithelial ovarian cancer in 2021. METHODS: A 58-question electronic survey was distributed anonymously to the members of six European learned societies. Initial diagnostic workup and staging, pathological data, surgical data, treatments and follow-up strategies were assessed. RESULTS: A total of 171 participants from 17 European countries responded to emailed surveys. Most participants were experienced practitioners (superior than 15 years of experience) specializing in gynecology-obstetrics (29.8%), surgical oncology (25.1%), and oncogynecology (21.6%). According to most (64.8%) participants, less than 50% of patients were eligible for primary debulking surgery. Variations in the rate of primary debulking surgery depending on the country of origin of the practitioners were observed in this study. The LION study criteria were applied in 70.4% of cases during PDS and 27.1% after chemotherapy. In cases of BRCA1-2 mutations, olaparib was given by 75.0-84.8% of respondents, whereas niraparib was given in cases of BRCA wild-type diseases. CONCLUSIONS: This study sheds light on current practices and attitudes regarding the management of patients with advanced epithelial ovarian cancer in Europe in 2021.

[Application in France of the 2021 European recommendations on endometrial cancer]. / Application en France des recommandations européennes 2021 sur le cancer de l'endomètre.

The latest European recommendations of the European Societies of Gynecological Oncology (ESGO), Radiotherapy and Oncology (ESTRO) and Anatomopathology (ESP) concerning the management of patients with endometrial cancer were published in 2021. On behalf of the French Society of Gynecologic Oncology (SFOG) and the SFOG campus, we wish to summarize for the French-speaking readership the main measures with a more specific application for France. We also incorporate data from a Delphi survey conducted with a panel of French and French-speaking Swiss experts. The data presented in this article relate to histo-molecular characteristics, radiological data of endometrial cancer, and management of low-risk, intermediate-risk, intermediate-high-risk, and metastatic cancers. The aim of this review article is to show the application of the latest international recommendations to clinicians and pathologists for the implementation of these recommendations.

Impact of the Area of Residence of Ovarian Cancer Patients on Overall Survival.

Survival disparities persist in ovarian cancer and may be linked to the environments in which patients live. The main objective of this study was to analyze the global impact of the area of residence of ovarian cancer patients on overall survival. The data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. We included all the patients with epithelial ovarian cancers diagnosed between 2010 and 2016. The areas of residence were analyzed by the hierarchical clustering of the principal components to group similar counties. A multivariable Cox proportional hazards model was then fitted to evaluate the independent effect of each predictor on overall survival. We included a total of 16,806 patients. The clustering algorithm assigned the 607 counties to four clusters, with cluster 1 being the most disadvantaged and cluster 4 having the highest socioeconomic status and best access to care. The area of residence cluster remained a statistically significant independent predictor of overall survival in the multivariable analysis. The patients living in cluster 1 had a risk of death more than 25% higher than that of the patients living in cluster 4. This study highlights the importance of considering the sociodemographic factors within the patient's area of residence when developing a care plan and follow-up.

Management of Endometrial Cancer: French Society of Onco-Gynecology's Evaluation through a Delphi Survey.

Our aim was to assess the opinion of a panel of experts and obtain a consensus on the management of endometrial cancer in France and French Switzerland. A Delphi survey was carried out among a panel of French and French-speaking Swiss experts. The first questionnaire included 65 questions divided into eight categories: characterization of experts, histo-molecular characteristics and radiological data of endometrial cancer, and management of low-risk, intermediate-risk, intermediate-high-risk, high-risk, and metastatic cancers. The experts were asked to reply on a 9-point scale, both on the validity and the clarity of each question. After the answers were analyzed, a second questionnaire was sent to the same experts. The study took place between December 2021 and March 2022. Further, 58 (57.4%) of the 101 experts responded in the first round, and 39 recommendations were obtained (60%). Six questions were voted redundant and 20 discordant. These questions were reformulated, and, at the end of the second round, 17 recommendations were validated (85%). In total, the study presents an analysis of 56 questions and related responses. Expert advice helps to clarify non-consensual issues, standardize the management of endometrial cancer, and optimize clinical practices.

Surgical management of patients with advanced ovarian cancer: Results of a French National Survey.

INTRODUCTION: Desire to homogenize advanced stage ovarian cancer management has led to a debate on the need to centralize cares. The aim was to assess current practices to compare them with centralization motivation and to overview possible perspectives of evolution. METHODS: An anonymous questionnaire of 57 questions has been submitted from August 2021 to October 2021 to members of French gynecological oncological surgical societies. Questions encompassed all aspects of ovarian cancer surgical management, including institutions, technics, indications, and outcomes. RESULTS: Of the 40 responses, 77.5% managed less than 20 cases by themselves, but 67.5% practiced in institution managing more than 30 cases annually. Since the LION trial results' publication, 95% of practitioners have evolved their lymphadenectomy indications. More than 10% of surgery needed digestive resection for 90% of practitioners. Digestive resections rate was significantly higher for practitioners managing more than 20 cases (p<0.01), but it was not for institutions managing more than 30 cases annually (p=0,07). Surgeons performing more than 20 ovarian cancers annually reported less severe complications (p=0.04) compared to low-volume surgeons independently of institution volume. For more than a quarter of the practitioners, less than half of the patients can benefit from the enhanced recovery after surgery program despite benefits of such care. CONCLUSION: Our survey provides an overview of French practices in ovarian cancer management. This survey seems to confirm that minimum volume thresholds could lead to better outcomes. It also underlines that individual performances are as valuable as center volume.

No Impact of Seasonality of Diagnoses on Baseline Tumor Immune Infiltration, Response to Treatment, and Prognosis in BC Patients Treated with NAC.

Breast cancer (BC) is the most common cancer in women worldwide. Neoadjuvant chemotherapy (NAC) makes it possible to monitor in vivo response to treatment. Several studies have investigated the impact of the seasons on the incidence and detection of BC, on tumor composition, and on the prognosis of BC. However, no evidence is available on their association with immune infiltration and the response to treatment. The objective of this study was to analyze pre- and post-NAC immune infiltration as assessed by TIL levels, the response to treatment as assessed by pathological complete response (pCR) rates, and oncological outcomes as assessed by relapse-free survival (RFS) or overall survival (OS) according to the seasonality of BC diagnoses in a clinical cohort of patients treated with neoadjuvant chemotherapy. Out of 1199 patients, the repartition of the season at BC diagnosis showed that 27.2% were diagnosed in fall, 25.4% in winter, 24% in spring, and 23.4% in summer. Baseline patient and tumor characteristics, including notable pre-NAC TIL levels, were not significantly different in terms of the season of BC diagnosis. Similarly, the pCR rates were not different. No association for oncological outcome was identified. Our data do not support the idea that the seasonality of diagnoses has a major impact on the natural history of BC treated with NAC.

The French Early Breast Cancer Cohort (FRESH): A Resource for Breast Cancer Research and Evaluations of Oncology Practices Based on the French National Healthcare System Database (SNDS).

BACKGROUND: Breast cancer (BC) is the most frequent cancer and the leading cause of cancer-related death in women. The French National Cancer Institute has created a national cancer cohort to promote cancer research and improve our understanding of cancer using the National Health Data System (SNDS) and amalgamating all cancer sites. So far, no detailed separate data are available for early BC. OBJECTIVES: To describe the creation of the French Early Breast Cancer Cohort (FRESH). METHODS: All French women aged 18 years or over, with early-stage BC newly diagnosed between 1 January 2011 and 31 December 2017, treated by surgery, and registered in the general health insurance coverage plan were included in the cohort. Patients with suspected locoregional or distant metastases at diagnosis were excluded. BC treatments (surgery, chemotherapy, targeted therapy, radiotherapy, and endocrine therapy), and diagnostic procedures (biopsy, cytology, and imaging) were extracted from hospital discharge reports, outpatient care notes, or pharmacy drug delivery data. The BC subtype was inferred from the treatments received. RESULTS: We included 235,368 patients with early BC in the cohort (median age: 60 years). The BC subtype distribution was as follows: luminal (80.2%), triple-negative (TNBC, 9.5%); HER2+ (10.3%), or unidentifiable (n = 44,388, 18.9% of the cohort). Most patients underwent radiotherapy (n = 200,685, 85.3%) and endocrine therapy (n = 165,655, 70.4%), and 38.3% (n = 90,252) received chemotherapy. Treatments and care pathways are described. CONCLUSIONS: The FRESH Cohort is an unprecedented population-based resource facilitating future large-scale real-life studies aiming to improve care pathways and quality of care for BC patients.

Complete Laparoscopic Interval Debulking Surgery for Advanced Ovarian Cancer Achieves Similar Survival Outcomes to Open Approach: A Propensity-Matched Study.

To assess the laparoscopic interval debulking surgery (IDS) outcomes compared to laparotomy, by analyzing the overall survival (OS) and the progression free survival (PFS), as well as the intra- and post-operative morbidity.In this retrospective propensity-score-matched cohort study, all patients with stage III or IV FIGO (International Federation of Gynecology and Obstetrics) serous ovarian cancer, undergoing complete IDS after neoadjuvant chemotherapy, from January 1st of 2009 to June 1st 2019, were included.Thirty-seven patients were included in the laparoscopy group and 40 in the laparotomy group. There was no significant difference in terms of median OS between laparoscopy and laparotomy (23.1 months [95% CI 15.7-29.7] versus 26.3 months [95% CI 21.7-31.7], respectively, p = 0.17) and median PFS (14.8 months [95% CI 10.6-21.5] versus 12 months [95% CI 11-15.1], p = 0.057). After applying the propensity score, 25 patients were included in each group. Laparoscopy was associated with significantly less early postoperative complications (6 versus 17, p = 0.01) and shorter hospital stay (7.6 days versus 12.1, p < 0.001) and a significantly better OS (HR 0.45 [95% CI 0.19-0.95], p = 0.04), but with no significant difference in terms of PFS (HR 0.71 [95% CI 0.27-1.88], p = 0.49).In carefully-selected patients with advanced ovarian cancer, complete laparoscopic interval debulking surgery achieves similar survival outcomes to open laparotomy. Therefore, laparoscopy appears as a safe alternative to laparotomy for IDS after NACT in selected patients with advanced ovarian cancer and a low burden of disease.

Prospective evaluation of the connected biofeedback EMY Kegel trainer in the management of stress urinary incontinence.

INTRODUCTION: The aim of this study was to evaluate changes in the quality of life with the connected biofeedback EMY Kegel trainer in patients suffering from stress urinary incontinence. Materiel and methods: This was a prospective, single-center, non-comparative study, which took place between September 2019 and October 2020, in the University Hospitals of Strasbourg. Eligible patients were instructed to use the EMY probe for a minimum of 10 min per day for five days per week. To assess quality of life and urinary symptoms, the Contilife and ICIQ-SF scores were completed each month until the final visit (M3). The PGI-I was also completed at 3 months to assess the benefit of the EMY Kegel Trainer. RESULTS: A total of 55 patients were included. At the inclusion visit (M0), the mean Contilife and ICIQ-SF scores were respectively at 6.6 ± 1.5 and 10.5 ± 3.0 points. At the final visit (M3), the mean Contilife score increased to 9.2 ± 1.0, indicating an improvement in quality of life. The mean ICIQ-SF score decreased to 4.2 ± 4.0, indicating an improvement in urinary symptoms. The PGI-I questionnaire identified a positive assessement of the EMY Kegel trainer. On the 55 patients included, 35 (64%) reported completing at least 36 sessions during the study, i.e. an average of 3 sessions per week. CONCLUSIONS: This study suggests that perineal rehabilitation by biofeedback using the EMY Kegel trainer might be beneficial.

Bowel resection performed by gynecologists - Outcomes and learning curves. Activity profile in a Gynecology Department: 7-year observational cohort.

OBJECTIVE: Bowel resection is frequently used when performing oncological surgery to obtain complete cytoreduction or to remove endometriosis in case of intestinal invasion. Acquiring the surgical skills to perform this kind of procedure is crucial to offer to our patients an optimal management. The aim of this study is to describe a 7-years surgical experience in bowel resections of a gynecologic surgeon and to determine his learning curves. STUDY DESIGN: This is a monocentric retrospective cohort study reporting digestive resection performed between January 2013 and April 2020 in the Gynecology Department of Strasbourg University Hospital. Ninety-one consecutive patients were assigned in two groups: gynecological cancer (n = 44) and deep infiltrating endometriosis (DIE) (n = 47). The main outcome measure was the postoperative complications rate at 30 days, based on the modified Clavien-Dindo severity system. Learning curves were evaluated using cumulative sum (CUSUM) analysis of operative time and risk-adjusted cumulative sum (RA-CUSUM) analysis of severe perioperative complications. Identification of predictive factors for operation duration and severe perioperative complication occurrence was conducted using multivariate analysis. RESULTS: Minor complications were found in 25% of cases. Major complication rate (Clavien-Dindo ≥ IIIa) was 14% in total and only involved patients operated for cancer. The CUSUM curve for operative time peaked at the 35th case and showed a downward slope after the 45th case. Significant predictive factors of operating time were cytoreductive tumoral surgery, size of the bowel resection and laparoscopic surgery, while learning phase 3 significantly decreased it. The RA-CUSUM curve for severe perioperative complications (Clavien-Dindo ≥ IIIa) showed a progressive decrease in the complication rate as the number of interventions increases without showing clear inflection points. Only cardiopulmonary pathologies were found as significant predictive factor of severe complications. CONCLUSION: Proficiency in performing highly complex surgery was achieved after approximately 45 cases, cancer and DIE all together. Acceptable rates of severe perioperative complications were observed even during the initial learning period and are comparable with those found in the literature concerning bowel resection performed by gynecologic oncologists but also by general and digestive surgeons.

Adherence to European ovarian cancer guidelines and impact on survival: a French multicenter study (FRANCOGYN).

OBJECTIVE: The primary objective of the study was to validate the European Society for Medical Oncology (ESMO)-European Society of Gynecologic Oncology (ESGO) ovarian cancer guideline as a method of assessing quality of care, and to identify patient characteristics predictive of non-adherence to European guideline care. The secondary objectives were to analyze the evolution of practices over the years and to evaluate heterogeneity between centers. METHODS: This retrospective multicenter cohort study of invasive epithelial ovarian cancer reported to the FRANCOGYN database included data from 12 French centers between January 2000 and February 2017. The main outcome was adherence to ESMO-ESGO guidelines, defined by recommended surgical procedures according to the International Federation of Gynecology and Obstetrics (FIGO) stage and appropriate chemotherapy. Mixed multivariable logistic regression analysis with a random center effect was performed to estimate the probability of adherence to the guidelines. Survival analysis was carried out using the Kaplan-Meier method and a mixed Cox proportional hazards model. RESULTS: 1463 patients were included in the study. Overall, 317 (30%) patients received complete guideline adherent care. Patients received appropriate surgical treatment in 69% of cases, while adequate chemotherapy was administered to 44% of patients. Both patient demographics and disease characteristics were significantly associated with the likelihood of receiving guideline adherent care, such as age, performance status, FIGO stage, and initial burden of disease. In univariate and multivariate survival analysis, adherence to the guidelines was a statistically significant and independent predictor of decreased overall survival. Patients receiving suboptimal care experienced an increased risk of death of more than 100% compared with those treated according to the guidelines (hazard ratio 2.14, 95% confidence interval 1.32 to 3.47, p<0.01). In both models, a significant random center effect was observed, confirming the heterogeneity between centers (p<0.001). CONCLUSIONS: Adherence to ESMO-ESGO guidelines in ovarian cancer was associated with a higher overall survival and may be a useful method of assessing quality of care.