The association between oral contraceptive pills and ovarian cancer risk: A systematic review and meta-analysis.

INTRODUCTION: Previous study results have been inconclusive, so this meta-analysis aims to evaluate the association between ovarian cancer and oral contraceptive pills (OCPs). METHODS: PubMed, EMBASE, Scopus, and Web of Science were searched to identify studies on the association between OCPs and ovarian cancer from January 1, 2000 through February 5, 2023. The pooled relative risk (RR) and odds ratio (OR) were used to measure this relationship. RESULTS: A total of 67 studies were included. In the association between ever-use compared with never-use of OCPs and ovarian cancer risk, the pooled RR in cohort studies was 0.69 [95% CI: 0.61, 0.78]. For the relationship between duration of OCPs use and ovarian cancer in the cohort studies, no association between duration of use1-12 months 0.92 [95% CI: 0.82, 1.03] and duration of use 13-60 months 0.87 [95% CI: 0.73, 1.04], but there is a statistically significant inverse relationship between duration of use 61-120 months 0.62 [95% CI: 0.48, 0.81] and more than 120 months 0.51 [95% CI: 0.32, 0.80] and ovarian cancer. For the relationship between OCPs and histological subtype of epithelial ovarian cancer in the cohort studies, the pooled RR for invasive was 0.70 [95% CI: 0.56, 0.87], but no association between OCPs and borderline ovarian cancer 0.64 [95% CI: 0.31, 1.31]. CONCLUSION: Our analysis shows a statistically significant inverse relationship between ever-use compared to never-use of OCPs and ovarian cancer risk,and also between invasive cancer and OCPs. By increasing the duration of OCPs use, the risk of ovarian cancer decreased.

Kinetics of plasma cell-free DNA as a prospective biomarker to predict the prognosis and radiotherapy effect of esophageal cancer.

PURPOSE: The lack of reliable biomarkers for the prognosis and radiotherapy efficacy in esophageal cancer (EC) necessitates further research. The aim of our study was to investigate the predictive utility of plasma cell-free DNA (cfDNA) kinetics in patients with EC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and cfDNA levels (pre-radiotherapy [pre-RT] and post-radiotherapy [post-RT]) and the cfDNA kinetics (cfDNA ratio: post-RT cfDNA/pre-RT cfDNA) of 88 patients. We employed Kaplan-Meier curves to examine the relationship between cfDNA and overall survival (OS) as well as progression-free survival (PFS). Univariate and multivariate Cox regression analyses were executed to ascertain the independent risk factors in EC. RESULTS: The pre-RT cfDNA levels were positively correlated with clinical stage (P=0.001). The pre-RT cfDNA levels (cutoff value=16.915ng/mL), but not the post-RT cfDNA levels, were linked to a diminished OS (P<0.001) and PFS (P=0.0137). CfDNA kinetics (cutoff value=0.883) were positively associated with OS (P=0.0326) and PFS (P=0.0020). Notably, we identified independent risk factors for OS in EC treated with RT, including cfDNA ratio (high/low) (HR=0.447 [0.221-0.914] P=0.025), ECOG (0/1/2) (HR=0.501 [0.285-0.880] p=0.016), and histological type (esophagal squamous cell carcinoma [ESCC]/non-ESCC) (HR=3.973 [1.074-14.692] P=0.039). CONCLUSION: Plasma cfDNA kinetics is associated with prognosis and radiotherapy effect in EC undergoing RT, suggesting potential clinical application of a cheap and simple blood-based test.

[FRANCOGYN group: A brief history]. / Le groupe FRANCOGYN : bilan et avenir.

OBJECTIVES: Describing the constitution of the FRANCOGYN group (a national French research group in Oncological and Gynecological Surgery) and present its current and future development. METHODS: Literature review using PUBMed database with the keyword "FRANCOGYN". OBJECTIVES: Describing the constitution of the FRANCOGYN group (a national French research group in Oncological and Gynecological Surgery) and present its current and future development. RESULTS: The FRANCOGYN group was formed in December 2015, bringing together over the years more than 17 gynecological and oncological surgical department in France. The group carries out clinical research on gynecological pelvic cancers by constituting retrospective cohorts. Its legitimacy allows it to lead or co-lead the drafting of recommendations for clinical practice in the field of gynecological cancers. It now offers prospective randomized research funded by national grants. CONCLUSION: The FRANCOGYN network allows us to propose a national reflection on the surgical management of pelvic cancers in women, resulting in numerous international reference publications.

[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.

[HIPEC morbidity and implications for post-surgical treatment. A medical oncologist advice]. / Effets secondaires des CHIP et implications sur les traitements post-chirurgicaux. L'avis d'une oncologue médicale.

The fear that the medical oncologist may have is that HIPEC integrated into a multidisciplinary care pathway will negatively impact the treatments that will follow. This fear is largely related to the side effects, which are themselves dependent on the medication used. Cisplatin, most frequently used for epithelial ovarian cancers, has essentially renal toxicity, which can be avoided by the use of sodium thiosulfate. Oxaliplatin induces more severe toxicities post surgery than mitomycin C in colorectal cancers. However, the data from randomized trials are reassuring for the medical oncologist concerning the course of postoperative treatment, as long as HIPEC is performed according to a standardized protocol, within trained teams, and after multidisciplinary discussion concerning its modalities.

[Current post-surgical treatment strategies in first-line ovarian cancer]. / Stratégies thérapeutiques post-chirurgicales actuelles dans les cancers de l'ovaire en première ligne de traitement.

Although the management of epithelial ovarian cancer has evolved significantly over the past few years, it remains a public health issue, as most patients are diagnosed at an advanced stage and relapse after first line treatment. Chemotherapy remains the standard adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) stage I and II tumors, with some exceptions. For FIGO stage III/IV tumors, carboplatin- and paclitaxel-based chemotherapy are the standard of care, in combination with targeted therapies, especially bevacizumab and/or poly-(ADP-ribose) polymerase inhibitors, that have become a key milestone of first-line treatment. Our decision making for the maintenance therapy is based on the FIGO stage, tumor histology, timing of surgery (i.e. primary or interval debulking surgery), residual tumor, response to chemotherapy, BRCA mutation and homologous recombination (HR) status.

[State of results of HIPEC for epithelial ovarian cancer in the primary treatment or for relapse]. / État des lieux des résultats en termes de survie de la CHIP en primo-traitement et en récidive dans le cancer épithélial de l'ovaire.

Peritoneal carcinomatosis is an unavoidable development of ovarian cancer, from the first treatment to relapses, and is the main cause of patients death. Hyperthermic intraperitoneal chemotherapy (HIPEC), is a hope for cure for patients with ovarian cancer. HIPEC is based on direct application of chemotherapy on the perioneum with high concentration of chemotherapy enhanced with specific effects of hyperthermia. Theoretically, HIPEC could be proposed at different steps of ovarian cancer development. But the hypothesis of efficiency of a new treatment must be assessed before being routinely applied. Numerous clinical series are already published about HIPEC used in primary treatment of ovarian cancer or for relapses. These series are mostly retrospectives and based on heterogeneous parameters as inclusion criteria of patients, intra peritoneal chemotherapy, concentration, temperature, duration of HIPEC. Taking into account this heterogeneity it is not possible to draw strong scientific conclusions about HIPEC efficiency to treat ovarian cancer patients. We proposed a review allowing a better understanding of current recommendations of the use of HIPEC in ovarian cancer patients.

Place of radiotherapy for treatment of metastatic cervical, vaginal and endometrial uterine cancer.

Beyond classical palliative-intent irradiation schemes, there are increasing data suggesting a benefit for intensive locoregional treatments in metastatic gynecological cancers. Such approach aims at avoiding local symptoms related to tumor progression, but may also improve survival outcome by shrinking tumor burden to a microscopic state. This strategy is rarely considered upfront (in highly selected patients with very limited oligometastatic disease), but rather after systemic treatment. In case of tumor response (especially if complete response) of the metastatic sites, pelvic±para-aortic radiotherapy can be considered in combination with a brachytherapy boost to obtain long-term local control, in particular in cervical or vaginal cancer patients. Such approach seems particularly relevant when there is isolated persistence or progression of macroscopic disease within the pelvis. In parallel, there is also an increasing place for radiotherapy of oligo-metastatic sites. We review the literature on the place of radiotherapy in the management of cancers of the cervix and metastatic endometrial cancer.

[Immunotherapy in oncogynaecology]. / Immunothérapies validées en oncogynécologie.

Immune checkpoint inhibitors have deeply changed treatment paradigm of many tumor types, notably by providing long-term remissions, even in the metastatic setting. These immunotherapies aim to restore T-cells activity against tumour cells, in particular via the inhibition of PD1/PD-L1 interaction. As for lung or renal carcinomas, and melanomas, the management of endometrial and uterine cervical cancers has been disrupted by PD1/PD-L1 inhibitors efficacy. In locally advanced or metastatic cervical carcinomas, the combination of platinum-based chemotherapy with pembrolizumab demonstrated improved overall and progression-free survival in all subgroups of patients, and became the new standard of care. Regarding endometrial cancers, while single-agent immunotherapies have shown very limited activity in an unselected population, dostarlimab and pembrolizumab have been associated with remarkable antitumor activity in case of microsatellite instability (dMMR/MSI), detected in around 30% of patients. Finally, in endometrial cancer that has progressed after first-line chemotherapy, the association of pembrolizumab with an oral antiangiogenic kinase inhibitor (lenvatinib) has demonstrated its superiority over second-line chemotherapy regimens, regardless molecular subgroups, and has become the new standard of care in this indication.

[Impact of HPV status on nutritional status during radio chemotherapy for oropharyngeal cancer]. / Impact du statut HPV sur l'évolution nutritionnelle au cours de la chimioradiothérapie des patients atteints d'un cancer de l'oropharynx.

PURPOSE: Patients with oropharyngeal cancer are at high nutritional risk before and during treatment. Little is known about the influence of human papillomavirus (HPV) infection on nutritional status and its evolution during treatment. MATERIALS AND METHODS: A single-center retrospective study was conducted between August 2017 and December 2020 including 48 patients (14 HPV-induced: HPV+ and 34 non-HPV-induced: HPV-) with oropharyngeal squamous cell carcinoma treated by radiotherapy±chemotherapy (RT/CT). Nutritional risk at the time of tumor assessment (TA) was assessed by weight loss, swallowing ability, and the presence of digestive disorders in 4 stages of increasing severity. Nutritional status was assessed by weight and nutrition risk index (NRI) at the time of TA, before the start and at 3 months from the end of RT±CT. During RT±CT, the NRI and the systemic inflammatory response index (SIRI=neutrophils * monocytes/lymphocytes) were assessed weekly. RESULTS: HPV+patients were at lower nutritional risk at TA (50% grade ≥2 vs 85%, P=0.02), lost more weight (6% of their body weight vs 3%, P=0.05), and increased their SIRI by 7.5 points more than HPV- patients (P=0.04) during RT/CT. CONCLUSION: HPV+ oropharyngeal cancer patients are at high nutritional risk even in the absence of undernutrition at the outset of management.

Practice-changing clinical trials in radiation oncology for gastrointestinal malignancies in 2021-2023.

Gastrointestinal cancers are one of the most frequent cancers and a leading cause of cancer deaths worldwide. We provide an overview of the most important practice-changing trials that were either published or presented at the international scientific meetings in 2021-2023. Highlights included reports on three phase III trials (CONCORDE/PRODIGE 26, ARTDECO, and a study by Xu et al.) that evaluated dose escalation in the definitive setting for locally advanced oesophageal cancers, as well as two phase III trials that evaluated the role of chemotherapy (neo-AEGIS) and targeted therapy (NRG/RTOG 1010) in the neoadjuvant setting for adenocarcinoma oesophageal cancers or gastroesophageal junction cancer. CheckMate 577 evaluated nivolumab in patients who had residual pathological disease after neoadjuvant chemoradiation followed by complete resection. The use of radiation therapy for borderline and locally advanced pancreatic cancer is also discussed (SMART and CONKO-007 trials). Stereotactic body radiation therapy followed by sorafenib was compared to sorafenib alone in patients with hepatocellular carcinoma in the NRG/RTOG 1112 study. New options in the management of rectal cancer are emerging such as total neoadjuvant treatment (PRODIGE 23, RAPIDO, PROSPECT), organ preservation (OPRA, OPERA), and the role of immunotherapy in patients with DNA mismatch-repair deficient/microsatellite instability. Finally, preliminary results of the ACT 4 trial that evaluated de-escalation in anal cancer are presented.

[Practical management of PARP inhibitors: A French DELPHI consensus]. / Gestion pratique des inhibiteurs de PARP : Un consensus national DELPHI.

OBJECTIVE: Despite an increasing number of therapeutic indications, there are no specific recommendations regarding the management of PARP inhibitors other than what is specified in the SmPC of each substance. A Delphi French consensus was conducted to establish practical guidelines to meet the needs identified by healthcare professionals and patients. METHOD: Following the Delphi method, statements to optimize PARP inhibitor management were drafted by a multidisciplinary Steering Committee made up of 17 experts. These statements were submitted to the independent and anonymous vote of clinicians involved in treating patients on PARP inhibitors. RESULTS: This article presents 52 statements on the following topics: initiation and treatment; management of adverse events (hematological effects, gastrointestinal effects, renal effects, pulmonary effects, cutaneous effects, hypertension, insomnia, fatigue, dizziness); special populations and situations; communication with the patient; adherence. Forty-nine statements obtained voter consensus after 3 voting rounds. A hematologist and a nephrologist supplemented this task by drafting an expert opinion on the risk of occurrence of secondary leukemia and nephrological toxicity. CONCLUSIONS: This paper is the first Delphi consensus on the practical management of PARP inhibitors. The pragmatic recommendations resulting from this paper should make it possible to manage the side effects of PARP inhibitors better and thus prevent early treatment discontinuation and improve patient adherence by preserving quality of life.

[Dose-escalated radiotherapy in esophageal cancer: A review of the literature]. / Escalade de dose dans les cancers de l'œsophage : revue de la littérature.

For non-operable, localized esophageal cancer, definitive concurrent chemoradiotherapy is the standard treatment. Currently, the radiation dose recommended is 50 to 50,4Gy. However, the optimal radiation dose remains controversial. Many studies have demonstrated that locoregional failure remains a common failure pattern, most likely to occur within the original gross tumor volume. Several retrospective studies have indicated that higher radiation dose may improve local control and survival while others failed to demonstrate improved oucomes. In three randomized trials (INT0123, ARTDECO, and CONCORDE), dose escalation did not improve locoregional control nor survival, establishing 50Gy as the standard chemoradiation dose for patients who will not undergo surgery. Here, we reviewed the results of dose escalation in the literature in the neoadjuvant and definitive settings.

[Organ preservation in oropharyngeal cancers treatment: What arguments for radiotherapy?] / Préservation d'organe dans la prise en charge des cancers de l'oropharynx : quels arguments en faveur de la radiothérapie ?

Management of oropharyngeal cancer depends on several factors. Immediate surgery or radiotherapy may be considered. If the patient is operable, the choice depends on the extent of the disease, the contributing factors, and the expected functional results. For HPV-positive cancers, studies show comparable efficacy between surgery and radiotherapy. For early-stage cancers, unimodal treatment should be preferred. For HPV-negative cancers, the results of retrospective and observational studies are in favor of surgery. These studies have some limitations. In observational and/or retrospective studies, reclassification biases and the applicability of propensity scores weaken the validity of studies showing differences in management. Tumor and patient comparability are others majors interpretation biases. It is precipitate to conclude that surgery is superior for HPV-negative oropharyngeal cancers. Toxicity, therefore, becomes a criterion of choice for treatment. Unimodal management by surgery allows limited toxicity for the early stages. Surgery has less impact on salivation. Radiotherapy is rather less deleterious for swallowing in the early stages. For the advanced stages of HPV-induced tumors, the non-superiority of surgery should lead to the choice of radiochemotherapy. For oropharyngeal cancers, the possible benefit of surgery in HPV-negative oropharyngeal cancers must be confirmed in randomized studies. For the early stages of oropharyngeal cancer with unimodal treatment, management could be decided by shared decision making.

[Challenges and limits of therapeutic de-escalation for papillomavirus-related oropharyngeal cancer]. / Enjeux et limites de la désescalade thérapeutique dans la prise en charge du cancer de l'oropharynx lié au papillomavirus.

The incidence of HPV-related oropharyngeal cancers has been increasing in Western countries for several decades. If they are individualized within the latest TNM classification, the current standards of management do not authorize the management of these patients to be singled out. However, their distinct oncogenesis and their excellent prognosis compared to other patients has allowed the development of several clinical trials based on the question of therapeutic de-escalation. This review of the literature aims to take stock of the elements provided by clinical research in recent years.

[Molecular-integrated risk profile: An opportunity for therapeutic de-escalation in intermediate and high-intermediate risk endometrial cancer]. / Cancer de l'endomètre de stade localisé : la perspective d'une désescalade thérapeutique guidée par la classification moléculaire.

In Europe, endometrial cancer is the fourth most common cancer among women. The majority of patients are diagnosed at a localized stage. For these patients, the standard of care is based on an hysterectomy with salpingo oophorectomy±lymph node staging. Through the assessment of histopathologic features, risk groups are determined: low, intermediate, high-intermediate, and high risk. Adjuvant strategies are guided by these risk groups. While the prognosis of low-risk and high-risk is well known, that of intermediate and high-intermediate risk is more heterogeneous, and the therapeutic index of adjuvant treatments is more questionable. Several trials (PORTEC [Post Operative Radiation Therapy in Endometrial Carcinoma] I, GOG [Gynecologic Oncology Group] 99, ASTEC [A Study in the Treatment of Endometrial Cancer] EN.5, PORTEC II, Sorbe et al trial) have assessed observation, vaginal cuff brachytherapy and/or pelvic external beam radiotherapy in this population. Vaginal cuff brachytherapy reduces the local recurrence rate, and pelvic external beam radiotherapy the pelvic recurrence rate. However, no benefit in terms of overall survival or occurrence of distant metastases is highlighted. Compared to observation, brachytherapy and above all external beam radiotherapy are associated with an increased morbidity, and with a decreased quality of life. In order to improve the therapeutic ratio and to optimize medico-economic decisions, therapeutic de-escalation strategies, based on the molecular profiles, are emerging in clinical trials, and in the recommendations for the management of intermediate and high-intermediate risk endometrial cancers. The four main molecular profiles highlighted by the genomic analyzes of The Cancer Genome Atlas (TCGA) - POLE (polymerase epsilon) mutation, non-specific molecular profile, MMR (MisMatch repair) deficiency, and p53 mutation - but also the quantification of lymphovascular space invasion (absent, focal or substantial), and the assessment of L1CAM (L1 cell adhesion molecule) overexpression represent growing concerns. Thus, the use of molecular-integrated risk profile to determine the best adjuvant treatment represent a major way to personalize adjuvant treatment of endometrial cancers, with therapeutic de-escalation opportunity for around half of the high-intermediate risks. However, in the absence of prospective data, inclusion in clinical trials assessing molecular profile-based treatment remains the best therapeutic opportunity.