Bulletin du Cancer

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2022–2023 : Prise en charge du cancer du col de l'utérus avancé

French recommendations for clinical practice, Nice/Saint-Paul-de-Vence 2022-2023: Management of advanced cervical cancer The prognosis of cervical cancer remained pejorative until recently, first-line treatment consisting of platinum-based chemotherapy, associated with bevacizumab whenever possible, without any other therapeutic innovation for several years. However in 2022, immunotherapy appeared in the therapeutic landscape. Pembrolizumab can now be prescribed, thanks to the early access status granted by the HAS in September 2022, in patients with PD-L1 positive tumors. In parallel, bevacizumab generic is now reimbursed, allowing its association with chemotherapy on top of pembrolizumab, if indicated. For patient relapsing after platinium salts, and who never received immunotherapy, cemiplimab could be delivered and reimboursed since spring 2023, whatever could be PD-L1 status. Pretherapeutic work-up includes imaging combining MRI and PET/CT or CT of the chest, abdomen and pelvis, as well as evaluation of PD-L1 status on tumor and immune cells to define the CPS score that will determine eligibility to pembrolizumab treatment (CPS > 1). Possibilities of locoregional treatment depend on individual situations and are discussed on a case-by-case basis in multidisciplinary meetings. Early supportive care is always recommended and inclusion in clinical trials must be systematically considered.

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2024–2025 : prise en charge du cancer épithélial de l’ovaire de haut grade

« Comment traiter histologiquement un ganglion sentinelle ? »

Sentinel node is defined as the first node to receive drainage from a primary tumor and seems to reflect the nodal status in the lymphatic drainage of the tumor. Sentinel node technique has modified the pathological examination of lymph nodes, with intraoperative evaluation of sentinel node, allowing immediate lymph node dissection in case of positive sentinel node, and histological ultrastratification to detect occult metastases. This is a literature review of different histological protocols of sentinel node according to different organs. Except for sentinel node in breast cancer and melanoma, intraoperative examination of sentinel node is helpful using frozen section, more sensitive than touch imprint cytology. Sentinel node should be embedded in paraffin block entirely after gross sectioning at two millimeters intervals parallel to the long axis of the node. Histological ultrastaging with serial sections can be helpful, but the number of sections and the interval between them is not codified. Three sections at 200-250 microns can identify the majority of micrometastases (200 microns). Systematic immunohistochemistry of sentinel node is not necessary for breast cancers, since isolated tumor cells do not modify the therapeutic strategy, but remains useful in other organs.

Stratégies ganglionnaires dans les cancers de l’endomètre

In 2018, around 382,100 new cases of endometrial cancer (EC) were reported worldwide, accounting for about 4.4% of all new cases of cancer in women. In France, in 2018, the EC is the first gynecological cancer in incidence and the fourth cancer in women. The rationale for the therapeutic management of EC is based on the estimation of a theoretical risk of recurrence and lymph node metastasis using MRI and preoperative biopsy criteria. However, lymph node status remains the determining factor of adjuvant treatment. In order to reduce the morbidity of lymphadenectomy, the concept of sentinel lymph node biopsy (SLN) has been developed. The SLN technique has evolved in recent years, thanks to the advent of robotics and the creation of fluorescence detection cameras. It has been shown that detection of SLN with Indocyanine Green (ICG) allows for more frequent bilateral migration of 88 to 100% and better detection of pelvic GS in 97% of cases with a decrease in morbidity. Recently, in view of the absence of a therapeutic role of lymph node staging, the operational risks and the delay of adjuvant treatments, in case of pelvic lymph node metastasis on definitive histological examination, the question of secondarily performing paraaortic lymphadenectomy arises. The SLN procedure, extended to all early-stage endometrial cancers, should lead to a major reduction in the use of secondary staging and better adaptation of adjuvant therapy.

Cancer du sein chez la femme en âge de procréer : problématiques autour du rôle des hormones

Gynecological carcinosarcomas: Overview and future perspectives

Gynecologic carcinosarcoma (CS) are rare and aggressive tumors composed of high-grade carcinoma and sarcoma. Carcinosarcoma account for less than 5% of uterine and ovarian carcinoma and patients have poor outcome with a 5-year overall survival of less than 30%. In early-stage setting, the treatment mainstay is surgery and adjuvant chemoradiotherapy or adjuvant chemotherapy in uterine (UCS) and ovarian CS (OCS), respectively. In metastatic or advanced stage disease, chemotherapy is the rule with a lower response rate and poorer prognosis compared to other high-grade carcinomas. Although very few treatment options are available, CS are often excluded from the clinical trials precluding therapeutic improvement. However, recent molecular advances are paving the way for new therapeutic strategies. In the current proposal, we extensively review the uterine and ovarian carcinosarcomas including epidemiology, pathology, genomic landscape, as well as current therapies and future perspectives.

Prise en charge du cancer du col de l’utérus à la Réunion de 2016 à 2020

In Réunion Island, the standardized mortality rate for cervical cancer is 4.8/100,000 women, while it is 2.2/100,000 in France. A previous study, before 2016, showed that the absence of brachytherapy and non-compliance with recommendations could contribute to this increased mortality. The objective of the study was to analyze the management of invasive cervical cancers since 2016 in Reunion. Women diagnosed with invasive cervical cancer in one of our health centers in La Réunion, between January 1st, 2016, and December 31st, 2020. The recommendations of the French society of onco-gynecologists (SFOG) were considered as the reference to assess professional practices. During the study period, 236 women were diagnosed with cervical cancer, 94% of whom underwent an MRI and 54.8% a PET scan during the initial assessment. Compared to previous years, there has been an improvement in the management of these patients with 99% of the files presented in multidisciplinary consultation meetings and more than 80% of the treatments administered which complied with the recommendations including with the use of brachytherapy. Since the implementation of brachytherapy in Reunion in 2016, the treatment of invasive cervical cancer in Reunion has improved. Soon, a shared medical file should harmonize the transmission of information between the care centers of Reunion and contribute to improve our practices.

Prise en charge des carcinomes ovariens de haut grade séreux et/ou endométrioïdes de stades avancés (III-IV) et testing HRD-BRCA en 2023 : actualisation selon les données publiées et/ou présentées en 2022

Management of high grade, serous and/or endometrioid, advanced (stages III-IV) ovarian carcinomas and HRD-BRCA testing in 2023: update according to data published/presented in 2022 Molecular analysis of ovarian carcinomas must be now systematically performed to determine BRCA1 and BRCA2 status as well as genomic instability score. Several types of tests are available. From a clinical perspective, new data from phase III clinical trials presented in 2022 confirm the key role of PARP inhibitors in first-line medical treatment of high-grade serous ovarian cancers. A new algorithm that includes all new evidence is proposed for selection of first-line therapy.

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.

Current and future trials about HIPEC in ovarian cancer

Due to the typical peritoneal spread of the disease, together with cytoreductive surgery and adjuvant platinum-based chemotherapy, the role of hyperthermic intraperitoneal chemotherapy (HIPEC) is gainig more interest in advanced ovarian cancer (AOC) treatment. Indeed, the addition of hyperthemia seems to enhance the cytotoxic effect of chemotherapy directly delivered on peritoneal surface. So far, data on HIPEC administration during the primary debulking surgery (PDS) have been controversial. Indeed, despite flaws and biases, a survival advantage in a subgroup analysis of a prospective randomized trial of PDS+HIPEC treated patients was not demonstrated, whilst positive results are coming from a large retrospective cohort of patients treated with HIPEC after upfront surgery. In this setting, larger prospective data from an ongoing trial are expected by 2026. Contrariously, the addition of HIPEC with cisplatin 100mg/m

Déficit de la recombinaison homologue dans les cancers épithéliaux de l’ovaire : de la caractérisation moléculaire au parcours des patientes

High-grade serous ovarian carcinoma (HGSOC), the most frequent and aggressive form of epithelial ovarian cancer is characterized in half of cases by homologous recombination deficiency (HRD). This molecular alteration is defined by distinct causes and consequences. The main and most characterized cause is the presence of an alteration affecting BRCA1 and BRCA2 genes. Regarding consequences, a specific genomic instability leads to increased sensitivity to platinum salts and poly (ADP-ribose) polymerase (PARPi) inhibitors. This latter point enabled the advent of PARPi in first and second line maintenance. As such, the initial and rapid evaluation of HRD status with molecular tests is a key step in the management of HGSOC. Until recently, the range of tests offered proved to be very limited and suffered from technical and medical limitations. This has recently led to the development and validation of alternatives, including academic ones. This "state of the art" review will bring a synthesis concerning the assessment of HRD status in HGSOCs. After a brief introduction of HRD (including main causes and consequences) and of its predictive value regarding PARPi, we will discuss the limitations of current molecular tests and the existing alternatives. Finally, we will contextualize this to the situation in France, with special consideration concerning the positioning and the financial coverage of these tests, with the perspective of optimizing patient management .

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.

Place des thérapies innovantes dans la prise en charge des cancers du col de l’utérus

Despite optimized screening and prevention strategies, cervical cancer remains a major public health problem, even in developed countries. In France, the incidence is estimated at 3159 cases per year in 2023. While the management of early-stage cases is now highly standardized, few therapeutic advances were made in the treatment of metastatic stages before 2021, before the therapeutic arsenal that we know today took off. The aim of this review is to summarize these advances.

Real-world dostarlimab use in advanced/recurrent endometrial cancer in France

In October 2020, the French Health Authority granted early access outside of the clinical trial setting for dostarlimab, a programmed death-1 inhibitor. Dostarlimab was approved by the European Medicines Agency (in April 2021) as monotherapy for patients with post-platinum mismatch repair deficient/microsatellite instability-high advanced/recurrent endometrial cancer, based on the results of the GARNET trial (NCT02715284). This was a real-world descriptive analysis of patients granted cohort temporary authorization of use to receive dostarlimab between November 2020 and June 2021. Physicians could complete follow-up forms at each treatment cycle to provide clinical information, safety, and efficacy data. Safety and disease progression data were also captured through pharmacovigilance reports. Of 95 temporary authorization of use requests made by 80 oncologists in 59 French hospitals, 87 patients were eligible, and 80 received≥1 dose of dostarlimab. Based on treatment response assessments received (n=43), the mean (standard deviation) time from treatment initiation to response evaluation was 11 (6) weeks. The disease control rate (complete plus partial responses plus stable disease rates) was 56% (n=24/43), and the overall response rate was 35% (n=15/43); both consistent with those reported in the GARNET trial. No new safety signals were reported. The enrolment of 80 patients in an 8-month period highlights the need for access to novel treatment regimens in France for these patients post-platinum. Prospective randomized studies are ongoing to assess the efficacy and safety of dostarlimab and other checkpoint inhibitors as first-line treatment in patients with endometrial cancer.

Detailed overview on rare malignant ovarian tumors

The group of rare malignant ovarian tumors includes the group of germ cell tumors, sex cords stromal ovarian tumors, small cell carcinoma, malignant Brenner tumors, rare epithelial tumors such as mucinous carcinoma, clear cell carcinoma, or low-grade serous carcinoma, as well as ovarian carcinosarcoma. Together they comprise about 10% of all ovarian tumors. Due to their low prevalence and their heterogeneity, data and treatment recommendations are limited. Even though all ovarian tumors are staged according to the FIGO staging of epithelial ovarian tumors, treatment differs especially in germ cell tumors and sex cords stromal ovarian tumors. Non-epithelial ovarian tumors can arise from a variety of ovarian precursor cells such as germ cells, granulosa cells, theca cells, or stromal fibroblasts. As can be expected already due to their divergent precursor lesions, these malignancies are substantially different but united by their rarity. This overview article gives a comprehensive summary on the pathology and clinical presentation, as well as therapy recommendations of a selection of those rare ovarian tumors, based on the latest national guidelines and related important publications.

Les inhibiteurs de PARP s’installent en première ligne des cancers de l’ovaire

Étude rétrospective : chirurgie d’intervalle tardive post chimiothérapie versus après 3–4 cures dans le cadre de la prise en charge d’un cancer de l’ovaire localement avancé non opérable d’emblée

Treatment in locally advanced ovarian cancer is optimal surgery followed by chemotherapy. Patients with significant tumor spread, OMS>2, age>75 years old are poor candidates for aggressive primary surgery. Interval surgery, after neo-adjuvant chemotherapy, aims to achieve more complete surgery, increase survival, and reduce surgical morbidity. The primary endpoint was progression-free survival. Secondary outcomes were overall survival and postoperative morbidity and mortality. This is a retrospective study conducted in 2 French referral centers between January 2000 and December 2015. Patients who could not benefit from a complete initial surgery were operated after 3 cures of chemotherapy at the François Baclesse center and after least 5 cures at the center René Gauducheau. The population analyzed included 104 patients, 43 (41.0%) patients treated at the René Gauducheau center (group 1) and 61 (59.0%) patients treated at the François Baclesse center (group 2). Progression-free and overall survival were similar between the 2 groups, they were, respectively, 15.9 months and 34 months in group 1 vs. 15.4 months and 37.6 months in group 2 (P=0.72; P=0.65). Mean hospital stay and postoperative morbidity were similar in both groups. For weak patients, to limit invasive surgery, doing more than 5 courses of chemotherapy may be a reasonable option.

Stratégies ganglionnaires dans les cancers vulvaires. Recommandations de l’ESGO

The European Society of Gynaecologic Oncology (ESGO) guidelines cover the whole field of common clinical situations in gynecologic oncology. Their elaboration follows a strict process including a systematic review of the literature, the setting up of a group of expert on the basis of scientific production, geographical balance, and multidisciplinarity, and an external review by users and patients. The recommendations for the management of vulvar cancer were elaborated in 2015 and published in 2017. They are available in open access on the ESGO website, and can be incorporated in clinical practice using the free ESGO guidelines smartphone application. This review is a selection of the sections addressing the diagnostic and strategical aspects of the management of lymph nodal disease in vulvar cancer. An additional review of the recent literature published since 2015 has been carried out. The management of nodal disease in vulvar cancer encompasses a diagnostic and a therapeutic component. Clinical and imaging assessment still play a major role, whilst the identification of the sentinel node is currently a mainstay of assessment of the nodal status in early vulvar cancer. The therapeutic component is based on the rational use of full lymph node dissection and (chemo)radiation.

Reste-t-il des indications de curage ganglionnaire dans les cancers épithéliaux de l’ovaire après l’essai LION ?

In March 2019, Harter et al. published the results of the LION study (Lymphadenectomy in patients with advanced ovarian neoplasms) which raises the question of pelvic and para-aortic lymphadenectomy for patients with advanced-stage epithelial ovarian cancer (EOC). These results influenced the new French recommendations published in December 2018 by the French National Cancer Institute (INCa). Thus, it no longer seems consistent to perform a systematic lymphadenectomy for patients for whom there is no argument for nodal involvement, when a macroscopic complete peritoneal cytoreductive surgery has been performed. The question of preoperative lymph node assessment is therefore essential, whereas more than half of the patients in the LION study had metastatic lymph node involvement that was histologically proven. For the assessment of lymph node status by imaging, superior sensitivity for Positron Emission Tomography is demonstrated in comparison with CT-scan or Magnetic Resonance Imaging. Nevertheless, thoraco-abdomino-pelvic CT-scan with contrast injection remains the gold standard for this indication. In the absence of suspected involvement, supra-renal, mesenteric, coelio-hepatic, and cardio-phrenic lymphadenectomy are not recommended. Lymphadenectomies should always be performed in the other situations of EOC management apart from the rare case of stage 1 expansile subtype mucinous carcinoma. The aim of this review is to discuss lymphadenectomy indications for the surgical management of EOC by taking into account new data from the scientific literature.

Mise à jour 2021 des recommandations pour la pratique clinique de Nice/Saint-Paul-de-Vence dans le cancer de l’ovaire épithélial de haut grade

Since the previous 2013 and 2016 recommendations for clinical practice (RPC) Nice/Saint-Paul-de-Vence for gynecological cancers, the management of ovarian cancer has become more complex with the evolution of the quality criteria recommended for surgery and the integration of molecular biology for the decision of medical treatments, especially for high grade epithelial ovarian cancers. Surgical indications have become more precise both in the first line and in the context of relapse. Treatments with PARP inhibitors is a major advance in medical management with significant efficacy in maintenance after response to platinum-based chemotherapy. The benefit already known in the case of late relapse has also been demonstrated in first-line treatment with progression-free survival never observed in this pathology with patients with very long responses, especially in the case of BRCA gene abnormalities (somatic or constitutional). In 2021, medical and surgical strategies in front line including PARP inhibitors associated or not with bevacizumab as a maintenance complement after platinum chemotherapy are guided by both response to platinum agents and molecular profiling including BRCA (somatic or constitutional) genetic status and homologous recombination pathway (HRD) abnormalities, that should be early tested. On behalf of the GINECO national oncologist group, we have updated the guidelines for high grade ovarian epithelial cancer (excepted rare tumors) in order to allow rapid dissemination of the latest advances to the medical community and improve daily practice.

Traitement médical de première ligne du cancer épithélial de l’ovaire de haut grade

In early stages, standard treatment is adjuvant chemotherapy, consisting of platinum-based combination for 6 cycles, especially in serous and endometrioid high grade carcinomas. In advanced stages, indication of neoadjuvant chemotherapy must be discussed on a case-by-case basis in multidisciplinary meetings (MDM). Bevacizumab can also be considered in the neoadjuvant setting in some circumstances, always after discussion in MDM. Carboplatin plus paclitaxel every 21 days, with or without bevacizumab remains the standard of care for first-line chemotherapy. Inhibitors of poly-(ADP-riboses) polymerases (PARPi) have been approved and are reimbursed as maintenance monotherapy in tumors carrying BRCA1 or BRCA2 mutation after complete or partial response to chemotherapy. Two recent studies demonstrated the efficacy of PARPi on progression free survival, one for niraparib single-agent in patients with high-grade ovarian carcinoma regardless of BRCA status, the other one for the combination of bevacizumab and olaparib in patients with high grade carcinoma, with positive test for homologous recombination DNA repair deficiency (regardless of BRCA status). These two new modalities of maintenance therapy are now available in compassionate use programs or post compassionate use programs. Depending on pending decisions upon reimbursement, these indications might be somewhat modified.

Diagnostic histologique et moléculaire des cancers de l’ovaire – recommandations pour la pratique clinique Saint-Paul 2021

Oncogenetic testing is now part of standard management in high grade ovarian cancer, including at least mutational status of BRCA1/BRCA2 genes. If necessary, tumor genetic testing is followed by constitutional testing to either confirm the constitutional origin of variants identified in BRCA1/2 genes or detect variants in other predisposition genes. The whole process including prescription of tumoral testing, retrieval of analysis report and communication of results must be formalized, as well as information on possible consequences of the results for the patient and her family. Tumor material must meet criteria of size and cellularity to allow high-quality analysis. These samples are processed during the preanalytical phase with two major steps : time of cold ischemia and fixation. Only pathogenic (Class V) and likely pathogenic (Class IV) variants shown in tumor tissue are mentioned in the report. Currently, only BRCA1 and BRCA2 genes are routinely studied but, in the future, analysis will be extended to other genes involved in homologous recombination repair. In patients without BRCA mutation, other biomarkers reflecting sensitivity to PARP inhibitors, such as HRD scores (homologous recombination deficiency) that appeared recently, will have to be implemented in routine practice in order to better select patients for these treatments and choose optimal therapy.

Prise en charge chirurgicale du cancer épithélial de l’ovaire – première ligne et première rechute

Based on recently published data, these recommendations present some evolutions in the surgical management of high grade epithelial ovarian cancers. In apparently early stages (FIGO I and II), surgical staging must be undertaken to confirm the absence of both peritoneal lesions and lymph node involvement (that might change stage and management). Neoadjuvant chemotherapy is not indicated, surgical exploration should be performed upfront, by laparotomy, to reduce the risk of rupture of the primary tumor. In advanced stages, the first step is to evaluate the feasibility of primary surgery with complete tumor cytoreduction. If it appears unfeasible, 3 or 4 cycles of neoadjuvant chemotherapy are administered before interval surgey. Whether it is implemented in the primary or interval setting, surgery must be performed by experimented teams, in an approved facility, having developed a rehabilitation program. Lymph node dissection is not mandatory if no adenopathies have been identified by imaging and by peroperative palpation. At first relapse, the surgical decision must be made by a multidisciplinary team, using scores predictive of complete cytoreduction (AGO or iMODEL criteria). Similarly as in first line, the objective is to achieve resection without any residual disease. Surveillance after first-line treatment must be adapted, according to the probability of another complete cytoreduction in case of late relapse, especially in patients who benefited from primary complete surgery and maintained good performance status.

Certification nationale pour la chirurgie des cancers gynécologiques

In France, we are lacking an identified pathway for training in gynaecological cancer surgery. The four competent French learned societies: the SFOG, the CNGOF, the SFCO and the SCGP supported by the CNU of Obstetrics & Gynaecology, and UNICANCER agreed to materialize this course and attest it by a certification awarded by a national jury. The national committee of certification in gynaecological oncology made up of ten members, representing the 6 concerned organizations, set itself five objectives: the definition of the eligibility criteria for training centres; the determination of a check-list to be filled by the candidate; the determination of a targeted curriculum for the training in gynecological oncological surgery; the determination of the assets necessary for the certification of a candidate already in practice; and the practical organization of the certification. Criteria for approval of centres for training included 150 gynaecological cancer cases per year, among which 100 excisional surgeries, including twenty advanced-stage ovarian cancers. For certification of candidate who followed the curriculum established by the committee or by validation of prior experience for an actual practitioner, a candidate must validate a logbook and fill out a checklist including four parts: theoretical and practical training; research and publications; teaching and subscription to a continuing education program. The accomplished elements of the logbook and the checklist will be evaluated by a score. The first certification session is planned for the end of 2021.

COVID arm and PET/FDG imaging

Severe carcinoid syndrome revealing a primary ovarian carcinoid tumor

Toxicity profile of taxanes in Tunisian cancer patients: A retrospective study of 90 cases

Taxanes are widely used in medical oncology. The aim of our study was to report and analyze the toxicity features of these drugs in Tunisian patients and to determine their impact on treatment response. Our retrospective study concerned 90 patients treated by taxanes in a medical oncology unit, from January 2014 to January 2017. We collected their epidemiologic and anatomo-clinical data and we detailed toxicity features including types grades and impact on tumor response. Median age was 46 years. 80% of patients had breast cancer. Tumors were metastatic in 23.3% of cases. Nail toxicity was observed in 100% of patients. Grade I-II digestive toxicity was observed in 54.4% of cases. Hematological toxicity was noted in 42.2% of patients and it reached grade III-IV in five patients. Neurological toxicity occurred in 31% of patients and was grade III-IV in 6 cases. Alopecia was observed in 60% of patients. Fatigue was noted in 57.8% of patients. Myalgia was observed in 42.2% of patients. Toxicity did not affect the response to treatment. The taxanes' toxicity profile in Tunisian patients is characterized by more frequent digestive and nail toxicities and less frequent hematological toxicities, dose reduction and treatment delays than other populations.

Épidémiologie des cancers en Algérie, 1996–2019

Cancer is a major public health problem in Algeria. The aim of this article was to estimate trends in cancer incidence in Oran, Algeria, over the period 1996-2019. Nine cancer sites were analyzed. Incidence data over the 1996-2019 period were collected from the Oran cancer registry. The annual percent changes in incidence rates were evaluated with Joinpoint analysis. Between 1996 and 2019, unfavorable trends in incidence were observed for lung and colorectal cancers in both sexes, as well as female breast cancer. In contrast, a continuous decrease in incidence rates of cervical cancer were observed. As for the prostate, no corresponding trend was emerged for this cancer. The upward trend in incidence rates for some cancers underscores the need to strengthen prevention efforts.

Health, illness and cancer in Reunion Island: Health services in a diverse but aging French territory

The major social, cultural, economic and demographic changes in Reunion Island in the last 70 years have had effects on its population and the evolution of its public health issues. The demographic transition and changes in lifestyle have led to a rapidly aging population with increased needs for care for dependency and chronic illness such as cancers. The aim of this paper is to offer a review of the literature and ongoing research on health and cancer in Reunion Island. It reviews the recent literature on these changes, including the socio-demography of the population, the medical demography and cancer care infrastructure. It highlights the significant social inequalities of the island, and shows its medical demography and healthcare services are close to national averages. It then offers a review of publications on the experiences of health and illness in Reunion Island in a multicultural and postcolonial context, between medical pluralism and biomedicine. It then offers a focus on the epidemiology of three cancers, namely breast, cervical and prostate cancers. It concludes with a review of known ongoing research, and calls for a rapid adaptation of the organization of the medico-social system, in order to face Reunion Island's most pressing healthcare issues: chronic illnesses such as cancers, and dependency.

Hormonothérapie en situation adjuvante en fonction du risque

De la biologie des tumeurs de la granulosa de l’ovaire à la perspective de nouvelles thérapeutiques au-delà de la chimiothérapie

Granulosa cell tumors (GCTs) are rare ovarian neoplasms, accounting for 2-5% of all ovarian cancers. Two histological types have been described: juvenile (JGCT) and adult (AGCT), the latter accounting for around 95% of the GCTs. AGCTs are mostly diagnosed at an early stage and commonly have a good prognosis. However, GCTs tend to be associated with late recurrence in about a third of cases which are a major concern. These recurrences often require repeated surgical interventions. Systemic treatments, for their part, show limited effectiveness in this context, highlighting the need to identify new therapeutic targets. Thus, better biological characterization of these tumors would enable us to propose more targeted treatments. To achieve this, the molecular characteristics of GCTs have been explored. Most AGCTs harbor a mutation in the FOXL2 transcription factor sequence, therefore allowing to investigate therapeutic perspectives targeting its signalling, as well as setting the first steps towards immunotherapy in these tumors. Knowledge of JGCTs is more limited due to their rarity. However, molecular analysis revealed that ∼60% of the JGCTs bore a genetic mutation in the AKT1 oncogene. However, its clinical significance has still to be explored. For both GCTs subtypes, the CDK4/6-Rb1 axis is promising. Consequently, exploring the molecular features and their role in the biology of these tumors could open up new avenues for targeted and personalized therapies, thereby improving patient care.

Prospects of the therapeutic approaches of ketogenic diet on the clinical outcomes of cancer: A scoping review

The scientific community has become more enthusiastic about ketogenic diet (KD) to improve the outcomes in medical conditions, including cancer by exploiting the reprogramed metabolism of cancer cells, making the diet a promising candidate as an adjuvant cancer therapy. From this perspective, the aim of this study was to provide a broad overview covering the therapeutic effects, evaluating the clinical evidence of clinical studies underlying the implementation of the KD in the context of cancer treatment and prognosis. A scoping literature search between the years 1990 and 2023 was carried out by using PRISMA guidelines and searching through different databases of the clinical studies supporting the effectiveness and benefits of KD in various carcinomas that could provide findings of evidence on the prognosis and clinical outcomes of cancer treatment. A total of 23 cancer-related publications were included, 12 of which focused on brain cancer particularly glioblastoma multiforme (GBM), 4 on both breast and ovarian cancers, and 3 on pancreatic cancer. A total of 10 publications were reported as clinical trials regarding cancers of the brain (4 studies), breast (2 studies), and ovarian (4 studies). Case report studies were reported in 3 publications for brain cancer, and 2 publications for breast cancer. Nearly almost of the studies found that there was a potential role of KD in the prognosis of cancer treatment. The current review suggests that cancer patients may get favorable effects from the implementation of KD to support clinical outcomes of cancer treatment.

Ovarian mature teratomas: Differences in management and outcomes in adolescents cared for by gynecologic and pediatric surgeons

Ovarian mature teratomas (OMTs) are the most common benign ovarian tumors in pediatric patients. Management in adolescents can be performed by pediatric (PSs) or gynecologic surgeons (GSs). The aim of this study was to assess the differences in OMT management and the repercussions according to the risk of secondary events. Based on a multicentric study, we compared patients aged 14 to 18 who underwent surgery for OMT between 2009 and 2022 from the French national pediatric database of OMTs with patients managed by GSs. In total, 119 patients were included (80 by PSs, 39 by GSs). Differences between teams were noted: (i) tumor marker analysis is systematic by PSs (80%, n=72) but rare by GSs (18%, n=7) (P<0.001), (ii) PSs mostly carried out a laparotomy (78%, n=62), whereas GSs preferred laparoscopy (90%, n=35) (P<0.001), (iii) peroperative rupture was more frequent by GSs (56%, n=22) than PSs (10%, n=8) (P<0.001), (iv) median duration of follow-up increased by PSs (20months) versus 1month by GSs (P=0.001). Ten second events (13% by GSs [n=5], 6% by PSs [n=5]) occurred in nine patients, without significant differences (P=0.151). A notable difference exists in the management of OMTs between PSs and GSs in our study, GSs may overlook a malignant component in germ cell tumors in adolescents and the risk of metachronous recurrence, reported up to 10-20%. We recommend a compliance to SIOPE 2020 guidelines (Sessa et al., 2020) to avoid rupture of potential malignant tumor and to preserve fertility.

Formes familiales de cancer du sein – dépistage génétique et surveillance en fonction du risque

In France breast cancer is the most common cancer among women and the leading cause of cancer deaths. Identifying women with a "high" or "very high" breast cancer risk, according to the terminology of the Haute Autorité de santé 2014 guidelines, is essential to offer them special cares in term of screening and prevention. Women genetically predisposed have a very high risk of breast cancer. During the oncogenetic specialist consultation, familial and personal history of cancer is considered to evaluate the risk of hereditary Breast/Ovarian syndrome and thus the need of a genetic screening. In 2017 a list of 13 genes involved in hereditary ovarian or breast cancer has been established in France (Genetic and Cancer Group - Unicancer). Women carrying a BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN mutation have a higher risk of breast cancer and are considered as "high risk". Therefore medical breast surveillance similar to carriers of BRCA1/BRCA2 mutation is recommended for these patients (INCa guidelines 2017). However a mutation in one of those genes is only identified in approximatively 10% of the screened families. The oncogenetic specialist's assessment distinguishes families in which women remain at a "high" risk of breast cancer (HAS 2014 for screening) from those where women have a "very high" risk (INCa guidelines 2017 for screening and prevention).

Y a-t-il une place pour la fimbriectomie radicale prophylactique suivie d’une ovariectomie différée ?

Risk reducing salpingo-oophorectomy has long been the gold standard for preventing the development of tubo-ovarian cancers in high-risk population such as BRCA1/2 mutation carriers. Although a clear survival benefit has been demonstrated of these prophylactic procedures, important side effect from the associated surgical menopause have been described. Given that recent evidence suggests that most high-grade serous carcinomas (HGSC), the majority of all ovarian carcinomas, and especially for patients with a genetic predisposition originate in the fallopian tube, where also precursor lesions such as STIC can be found, an alternative risk reduction strategy has emerged, the prophylactic fimbriectomy with delayed oophorectomy. Multiple studies have already investigated the acceptability, side effects and safety of this procedure, with promising results. And currently multiple studies are ongoing to investigate the long-term effects on sexuality and the risk of developing subsequent tubo-ovarian carcinomas. A long-term follow-up in a large population is essential given the latency of 4-5 years between precursor lesions and HGSC. In this review, we provide an overview of the current knowledge on the origin, screening, and risk-reducing surgery for the prevention of tubo-ovarian cancers in high-risk women.

Hystérectomie prophylactique (syndrome de Lynch, BRCA et autres)

Endometrial cancer is the 4th most common cancer in women in France, with an increasing incidence partly due to the increase in diabetes and obesity. A genetic predisposition is found in approximately 5% of cases, notably Lynch syndrome, Peutz-Jeghers syndrome, hamartomatous tumor syndrome (Cowden syndrome), and BRCA1/2 mutations. Although no organized screening is in place for endometrial cancer in the general population, individual screening is recommended for most of these at-risk populations. Prophylactic surgery is a key strategy to reduce the risk of endometrial cancer in high-risk women. For patients with Lynch syndrome, recommendations favor a total hysterectomy with bilateral salpingo-oophorectomy starting at age 40, after childbearing is complete. Hormonal supplementation with natural estrogens is important until the physiological age of menopause to reduce bone and cardiovascular risks and to improve the quality of life, including sexual health, for these women. In Cowden syndrome and Peutz-Jeghers syndrome, the lack of data limits surgical recommendations, although prophylactic hysterectomy may be considered starting at age 40, once childbearing is complete. For patients with BRCA1/2 mutations, while risk-reducing adnexal surgery is recommended, hysterectomy remains debated. It requires a personalized assessment with patients based on the benefit/risk balance.

Utilisation en pratique de la classification FIGO 2023 du cancer de l’endomètre

Since the last FIGO classification in 2009, numerous studies and recommendations have contributed to improving the management of endometrial cancer. The introduction of molecular classification (including POLE, MMR, and P53 status) has enabled better categorization of these cancers by defining specific patient groups, thus allowing for more tailored surgical management and adjuvant treatment. The data and analyses on molecular and histological classification developed in the 2021 guidelines from the European Societies of Gynecologic Oncology (ESGO), Radiation Therapy and Oncology (ESTRO), and Anatomical Pathology (ESP) have been utilized to develop the new 2023 FIGO classification for endometrial cancer. We are witnessing an evolution of the FIGO classification, shifting from a purely anatomical classification to a risk-based classification. It is important in pathology reports to specify the histological type of the tumor, the grade for endometrioid tumors, the presence or absence of lymphovascular space invasion, and the extent of the tumor (myometrial invasion, involvement of the serosa, cervix, vagina, adnexa, or neighboring organs). These essential points are included in the 2023 FIGO classification and will enable precise staging of the tumor. This article aims to clarify and simplify the classification of patients according to the new 2023 FIGO classification for endometrial cancer.

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

Previous study results have been inconclusive, so this meta-analysis aims to evaluate the association between ovarian cancer and oral contraceptive pills (OCPs). 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. 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]. 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.

Intérêts de la centralisation de la chirurgie du cancer de l’ovaire en France

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. 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: A20 advanced stage ovarian cancers is associated with a decrease in morbidity, mortality, recurrence rate and improved survival.

Prise en charge médicale de la récidive du cancer épithélial de l'ovaire

The panel of therapeutic options available for medical treatment of relapsed ovarian cancer increased over the last years. In late, platinum-sensitive relapse, standard treatment remains platinum-based polychemotherapy. The choice between bevacizumab added to chemotherapy followed by maintenance and inhibitors of poly-(ADP-riboses) polymerases (PARPi) after response to platinum-based therapy should be discussed, taking into account prior treatment, contraindications, and disease characteristics (biology, symptoms…). The addition of bevacizumab at first platinum-sensitive relapse can be considered if it has not been administered in first line, and it is optional (rechallenge) if previously administered (but without Marketing Authorization in this setting). PARPi are indicated for maintenance therapy after response to platinum-based chemotherapy (whatever the treatment line), regardless of BRCA mutational status, in case of no prior administration. Early relapses are associated with poor prognosis and therapeutic options are more limited. They are treated by monochemotherapy without platinum agents, associated with bevacizumab if not administered previously. Beyond first early relapse, there is no standard and inclusion in a clinical trial should be proposed if possible. Several clinical studies assessing associations of immunotherapy and chemotherapy and/or antiangiogenic drugs and/or targeted therapies (such as PARPi) are ongoing in early or late relapse.

CAR-T cells, from principle to clinical applications

Chimeric antigen receptors (CAR)-T cells are genetically engineered T-lymphocytes redirected with a predefined specificity to any target antigen, in a non-HLA restricted manner, therefore combining antibody-type specificity with effector T-cell function. This strategy was developed some thirty years ago, after extensive work established the key role of the immune system against cancer. The first-engineered T-cell with chimeric molecule was designed in 1993 by Israeli immunologist Zelig Eshhar. Since then, several modifications took place, including the addition of co-stimulatory domain, to further improve CAR-T cell anti-tumor potency. The first clinical application of CAR-T cell was done in Rotterdam in 2005 for metastatic renal cell carcinoma and simultaneously at the National Cancer Institute (NCI) for metastatic ovarian cancer. These pioneered studies failed to demonstrate a therapeutic benefit, but warning emerged concerning their safety of use. The real clinical success came with anti-CD19 CAR-T cells, used since 2009 by Steven Rosenberg at the NCI in a patient with refractory follicular lymphoma and in 2011 by Carl June and David Porter from the University of Pennsylvania in patients with chronic lymphocytic leukemia and B-cell acute lymphoblastic leukemia. From that time, large centers in North America have embarked in several early phase and pivotal trials that have demonstrated unprecedent response rate in heavily pretreated chemo refractory patient with B-cell malignancies. Theses clinical success have led to the approval of three anti-CD19 CAR-T cells products for the management of B-cell malignancies in the United States and in Europe as of December 2020.

Défauts de la recombinaison homologue et inhibiteurs de PARP en thérapeutique

PARP inhibitors are effective in different types of tumors such as ovarian, breast, prostate and pancreatic cancer. Many studies are in progress and may lead to prescription evolution. PARP inhibitors prescription is almost reserved to patients with a constitutional BRCA mutation or a somatic BRCA alteration or a tumor with a deficiency in homologous recombination. Nowadays, the diagnosis of homologous recombination deficit, HRD, is possible with the prescription of a myChoice CDx (Myriad) test. PARP inhibitors are studied in association with chemotherapy and targeted therapies but also with radiotherapy and with immune checkpoint inhibitors. Access to PARP inhibitors is challenged with the emergence of resistance mechanism. Various trials are now studying the possibility of reversing these resistance mechanisms.

Nouvelles AMMs : niraparib et olaparib en première ligne dans les cancers de l’ovaire

Combinaison de la chirurgie et du traitement médical du cancer de l’ovaire : y a-t-il une stratégie optimale ?

The objective of this review is to evaluate the optimal positioning of cytoreduction surgery and perioperative medical treatments in the initial management and relapse of advanced-stage epithelial ovarian carcinoma. In the initial management, primary surgery should be proposed if the absence of tumor residue is feasible with reasonable surgery (extensive surgical resections to be considered and their complications, but also the general condition of the patient). Guidelines recommend 3 to 4 cycles of neoadjuvant chemotherapy before interval surgery for patients not eligible for primary surgery. Late interval surgery (i.e. after≥5-6 cycles of chemotherapy) is not a standard of care and should only be proposed in case of poor tumor response after 3-4 cycles and when complete interval surgery seems feasible. At first tumor recurrence in platinum-sensitive patients, a primary cytoreduction surgery can be considered if complete surgery can be managed. Predictive scores (AGO score; i-model score) can be used to select eligible patients. Given the lack of strong evidence, performing cytoreduction surgery at first recurrence in platinum-resistant patients or in the event of subsequent recurrence cannot be recommended. Nevertheless, obtaining a complete surgery in these clinical situations seems to provide a benefit in terms of overall survival and its application should be based on the expertise of specialized teams.

Health, illness and cancer in Mayotte: Multicultural experiences in a medically underserved French Territory

The island of Mayotte is part of the French territory and one of the European Union's Outermost Regions but there is a significant lack of data and research on health and cancers in Mayotte. This article reviews the literature on health, disease and cancer in Mayotte, from the perspectives of social science and epidemiology. It starts by shedding light on the specificities of Mahoran demography and society, and shows the healthcare infrastructure is insufficient to meet the population's needs. It then reviews social science studies on health and illness in Mayotte and shows that the political issue of migration permeates the management and the experiences of health on the island. It ends with a focus on the epidemiology of cervical cancer and a review of the available data on screening, treatment and prevention. The article concludes with a quick review of ongoing research and urgently calls for more data and research on this critical public health issue.

Diagnostic des sarcomes utérins et tumeurs mésenchymateuses utérines rares à potentiel de malignité. Référentiels du Groupe Sarcome Français et des Tumeurs Rares Gynécologiques

The landscape of uterine sarcomas is becoming more complex with the description of new entities associated with recurrent driver molecular alterations. Uterine sarcomas, in analogy with soft tissue sarcomas, are distinguished into complex genomic and simple genomic sarcomas. Leiomyosarcomas and undifferentiated uterine sarcomas belong to complex genomic sarcomas group. Low-grade and high-grade endometrial stromal sarcomas, other rare tumors associated with fusion transcripts (such as NTRK, PDGFB, ALK, RET ROS1) and SMARCA4-deficient uterine sarcoma are considered simple genomic sarcomas. The most common uterine sarcoma are first leiomyosarcoma and secondly endometrial stromal sarcomas. Three different histological subtypes of leiomyosarcoma (fusiform, myxoid, epithelioid) are identified, myxoid and epithelioid leiomyosarcoma being more aggressive than fusiform leiomyosarcoma. The distinction between low-grade and high-grade endometrial stromal sarcoma is primarily morphological and immunohistochemical and the detection of fusion transcripts can help the diagnosis. Uterine PEComa is a rare tumor, which is distinguished into borderline and malignant, according to a risk assessment algorithm. Embryonal rhabdomyosarcoma of the uterine cervix is more common in children but can also occur in adult women. Embryonal rhabdomyosarcoma of the uterine cervix is almost always DICER1 mutated, unlike that of the vagina which is wild-type DICER1, and adenosarcoma which can be DICER1 mutated but with less frequency. Among the emerging entities, sarcomas associated with fusion transcripts involving the NTRK, ALK, PDGFB genes benefit from targeted therapy. The integration of molecular data with histology and clinical data allows better identification of uterine sarcomas in order to better treat them.

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2024–2025 : prise en charge du cancer de l’endomètre métastatique et/ou en rechute

Prise en charge du cancer de l’endomètre métastatique et/ou en rechute. Recommandations 2020 pour la pratique clinique (Colloque de Nice-Saint Paul de Vence)

Endometrial cancer is a common cancer in older women and is often associated with comorbidities. Management of metastatic disease and/or relapse requires a multidisciplinary approach. Recent advances in the understanding of oncogenesis and molecular classification of endometrial cancers offer new therapeutic perspectives. These first recommendations, established following the methodology of Nice-Saint-Paul recommendations for clinical practice (RPC), aims to integrate molecular advances in diagnostic and therapeutic management. In 2020, the histological diagnosis of endometrial cancer is based on morphology and immunohistochemistry, including at least p53, oestrogen and progesterone receptors. Deficiency in the DNA mismatch repair system (MMR) must be assessed in all advanced endometrial tumors for oncogenetic and theranostic purposes. It can be sought initially by an analysis in immunohistochemistry with the 4 markers (MLH1, MSH2, MSH6, PMS2). Medical treatment depends on histological type, presence of hormone receptors and patient's profile to refer to chemotherapy (carboplatin-paclitaxel) or hormone therapy (for example of the progestogen type); in the event of MMR-deficiency, immunotherapy trial is the best option. As part of overall management of advanced endometrial cancer, radiotherapy (and surgery in rare cases) must be discussed, in particular in the event of loco-regional only relapse or oligometastatic disease.

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2024–2025 : prise en charge du cancer du col de l’utérus avancé

During decades, first-line treatment of advanced cervical cancer solely consisted of platinum-based chemotherapy, associated with bevacizumab whenever possible. Since 2022, immunotherapy is part of standard therapeutic strategy with pembrolizumab on the one hand, associated with chemotherapy and bevacizumab in patients with PD-L1 positive tumors (CPS≥1), and cemiplimab on the other hand, in patients who did not receive prior immunotherapy and progress after first line regardless of PD-L1 expression. Pretherapeutic work-up includes CT of the chest, abdomen and pelvis potentially associated with

Impact of preoperative conization on treatment outcomes in cervical cancer patients undergoing abdominal radical hysterectomy

The optimal surgical treatment for early-stage cervical cancer has been reevaluated in the light of the LACC trial, revealing poorer outcomes with minimally invasive surgery due to inevitable tumor spillage. Preoperative conization contributed to longer disease-free survival, improved overall survival, and reduced recurrence rates in patients undergoing minimally invasive radical hysterectomy (RH). This research evaluated the impact of preoperative conization on recurrence and survival in cervical cancer patients undergoing abdominal RH. A study retrospectively analyzed 274 patients with cervical cancer who underwent abdominal RH. Treatment outcomes were compared based on whether preoperative conization was performed. While no difference in recurrence was evident, a slight, albeit nonsignificant difference in mortality rates indicated that conization neither improves nor worsens survival. In cases with equal depth of invasion, conization did not affect survival. In comparison to other studies, this research offers insights into conization's role in the treatment of a wider range of tumor stages, affirming its diagnostic significance without adverse effects on survival, particularly in cases of equal invasion depth during abdominal RH.

La formation spécialisée transversale en cancérologie pour les internes en gynécologie médicale : retour sur cinq ans d’existence

The transversal specialized formation (TSF) in oncology has been enabling non-oncologist physicians to acquire oncology skills for five years. This study aims to assess the TSF for medical gynecology residents. A 23-item questionnaire was sent to physicians from the specialized medical degree (SMD) in medical gynecology who completed the TSF between 2020 and 2023. The data were analyzed using Student's t-tests, Fischer tests, and Chi Of the 22 residents identified, 20 (90.9%) responded to the questionnaire. Nine residents (40.9%) were from the Paris region. The reasons for undertaking the TSF included interest in gynecological and breast cancers (81.8%), clinical richness (50.0%), and scientific dynamism (50.0%). Of the 11 respondents who had completed the SMD or had a defined post-residency project, all reported working in a hospital setting. The main activity was gyneco-oncology (n=6, 55.0%), including sexology, monitoring at-risk women, post-cancer care, and medical oncology (n=5, 45.0%). The average satisfaction with the TSF was 7.2/10, with no significant regional difference (P=0.62). Suggested areas for improvement included harmonizing theoretical courses, offering specialized internships in gynecological oncology, and providing mentorship. Five years after its implementation, medical gynecologists are satisfied with the TSF in oncology. The main requests are for strengthening national courses and expanding the range of internships, all focused on the original specialty.

Claudine 18.2 : nouvelle cible thérapeutique dans les cancers digestifs

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2024–2025 : prise en charge du cancer du col de l’utérus localisé

Localized or locally advanced cervical cancer is treated with a curative intent. Its management requires multidisciplinary expertise and a rigorously structured approach to optimize the probability of success. Initial workup (clinical examination, imaging, pathology) allows precise characterization of the tumour and staging according to TNM and FIGO classifications. Surgical management of early stage cancers, ranging from conization for small tumour to hysterectomy, sometimes including sentinel lymph node biopsy, is based on therapeutic algorithms that take into account stage, pathological criteria (invasion, margins, node involvement) and risk category. Postoperative treatment, when required, includes radiochemotherapy, that can be followed by brachytherapy. In locally advanced cancers, treatment consists of radiochemotherapy followed by uterovaginal brachytherapy and immunotherapy that has recently demonstrated its benefits. Since cervical cancer often develops in young women, its management raises important questions related to fertility and sometimes, to the management of cancer during pregnancy. Finally, although it is not the topic of these recommendations, it is important to highlight the major role of vaccination to avoid the vast majority of these cancers.

Correlation between HPV-16 integration status and cervical intraepithelial neoplasia and cervical cancer in patients infected with HIV

This study aimed to explore the mechanism by which HIV infection promotes cervical cancer and precancerous lesions. This was a retrospective observational study including 96 patients with high-risk HPV-16 infection who underwent cervical biopsy, cervical conization, or hysterectomy. Among them, 43 patients were diagnosed with both HIV and cervical cancer or precancerous lesions. High-risk HPV infection (HPV16+) positive samples were collected, and total RNA was extracted and amplified by fluorescence quantitative PCR. The expression of HPV E2 and E6 in cervical tissues of HIV-infected and non-HIV-infected patients with high-risk HPV was determined. As the degree of cervical tissue lesions increased, the proportions of integrated HPV-16 increased significantly within both HIV-negative (P=0.008) and HIV-positive groups (P=0.027). In comparison to the HIV-positive group, although the HIV-negative group had a higher proportion of free type HPV-16 infection (64.3% vs. 35.7%) and a lower proportion of integrated type infection (41.7% vs. 58.3%), the differences were not statistically significant (P=0.117). The lower the CD4+ T lymphocyte level, the greater the possibility of HPV-16 integrated infection. Patients with HIV and HPV-16 infection exhibit a significantly higher rate of integrated HPV-16 infection, which is closely linked to HIV-induced immunosuppression, particularly the depletion of CD4+ T lymphocytes. This integration accelerates the progression of cervical lesions, increasing the risk of developing high-grade cervical intraepithelial neoplasia or cervical cancer. These findings underscore the need for targeted screening and therapeutic strategies in HIV-positive women to prevent HPV-related malignancies.

Therapeutic effect of haploidentical peripheral blood stem cell treatment on relapsed/refractory ovarian cancer

The traditional immunotherapy is limited on relapsed/refractory metastatic ovarian cancer because tumors cause immunosuppression. Since new therapeutic strategies to improve clinical outcomes for patients with relapsed/refractory metastatic ovarian carcinoma are needed, the aim of this study was to evaluate the therapeutic effect of haploidentical peripheral blood stem cells (haplo-PBSCs) adoptive treatment on relapsed/refractory ovarian cancer. Thirteen patients with advanced stage of ovarian cancer and refractory history after surgery and chemotherapy were treated with interleukin-2 activated haplo-PBSCs donated by their parents or children. Clinical outcomes including therapeutic response by measuring tumor size changes using CT scanning, CA-125 levels and survival times were evaluated. T and NK cell population in patients before and after treatment was detected by flow cytometry analysis. The median follow-up time after haplo-PBSCs adoptive treatment was 14 months. At the time of the last follow-up, the median overall survival after haplo-PBSCs adoptive treatment was 9.1 months. Ten patients (76.9%) achieved a relief of symptoms, including abdominal distention, ache, fatigue, and poor appetite. During the first 2 months after treatment, CA125 levels decreased in 10 patients (76.9%). Five patients (38.5%) had a stable disease and 1 patient (8%) had partial response. T cell population (CD3

Impact of complete surgical staging on survival of patients with early-stage (FIGO I or II) ovarian cancer: Data from the Cote d’Or Registry of Gynecological Cancers from 1998 to 2015

Early-stage ovarian cancer represents 20 to 33% of all ovarian cancers and is thus quite rare in France, with around 1200 new cases per year. No study to date has convincingly demonstrated the utility of lymphadenectomy in early-stage ovarian cancer. We sought to evaluate the impact on overall survival of complete surgical staging in patients management for FIGO stage I and II ovarian cancer. We performed a retrospective observational study using data from the Cote d'Or Registry of Gynecological Cancers. We included patients with invasive early stage epithelial ovarian cancer (FIGO stages I and II), diagnosed between 1 January 1998 and 31 December 2015. A total of 179 patients were included in the study. Patients who had lymphadenectomy were younger on average (P<0.001) and had fewer comorbidities (P=0.03). Lymphadenectomy was performed during the first surgery in 59.2% of cases (58 patients) and during a second, re-staging surgery in 40.8% (n=40). When complete surgical staging was performed, the rate of up-staging (to at least FIGO stage III) was 11.2% (11/98). The median follow-up was 8.4 years. At the study, 31.6% patients with complete surgical staging had died and 48.4% patients also died in the group without lymphadenectomy, HR 0.59 CI [0.36-0.97] P<0.04. In patients with early-stage ovarian cancer, complete surgical staging appears to yield a benefit in terms of overall survival. In 10 to 15% of cases, it leads to upstaging, with the resultant indication for maintenance therapy, which has also shown a survival benefit.

Les avancées actuelles de l’immunothérapie dans le cancer de l’ovaire

Ovarian cancers express highly immunogenic tissue-specific antigens. The resulting immune infiltration is a major prognostic factor. There is therefore a strong biological rationale for the development of immunotherapy in ovarian cancer. However, based on Phase I and II clinical trials data, the efficacy of anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors (ICPIs) remains limited in monotherapy in heavily pre-treated patients. Currently, the identification of predictive biomarkers of response and resistance is one of the major areas of research. Identifying effective combination of anti-PD-1 or anti-PD-L1 with other anticancer agents is another clinical need. Several combinations were evaluated. The association of ICPIs with chemotherapy (anthracyclines or carboplatin+paclitaxel) is disappointing (JAVELIN studies). The association with PARP inhibitors, anti-angiogenic agents and CTLA-4 inhibitors seems promising. Other immune therapies such as cell therapies (adoptive transfer of intra-tumor lymphocytes, CAR T cells or vaccines from dendritic cells) could be the future of immunotherapy in ovarian cancer but only early phase studies clinical data is available at this time.

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2024–2025 : prise en charge cardio-oncologique des principaux schémas thérapeutiques en onco-gynécologie

New therapeutic options for gynecological cancers (in particular, targeted therapies and immunotherapies) are associated with potential cardiovascular toxicities that oncologists should be able to identify, detect and manage together with a cardiologist. The first step consists of evaluating the patient's individual cardiovascular risk, regardless of planned oncologic treatment, to determine whether this treatment can be initiated immediately or if cardiological advice is required. In a second step, the risk of cardiovascular toxicity of the selected treatment must be assessed, considering its intrinsic risk and the patient's comorbidities. Once treatment has started, appropriate monitoring should be implemented during administration, and after discontinuation. Beyond general recommendations, specific situations are detailed for initial workup and surveillance relating to most common protocols of chemotherapy, immunotherapy, targeted therapy and associations used in gynecological oncology. If cardiotoxicity occurs (hypertension, QT interval increase, left ventricular dysfunction, troponin increase, myocarditis), the oncologist must be aware of the principles of management, and distinguish between what he can manage on his own and what requires referring to specialists. Prior to rechallenge after cardiotoxicity, multidisciplinary discussion is mandatory to assess the patient's benefit/risk ratio.

Results of a National French Survey on use of KELIM model for management of patients with advanced stage epithelial ovarian cancer (SFOG Campus)

Ovarian cancer, predominantly epithelial, is the ninth most common and fifth most lethal cancer among women in France, with late diagnosis and poor prognosis despite curative treatments. The KELIM model, built according to Ca125 kinetics, given its proven predictive and prognostic characteristics, has been implemented online to aid therapeutic decision-making. This study assessed the use of the KELIM score among French gynecological oncology experts using a survey sent from 13 December 2023 to 30 January 2024, through Google forms to all member of French Society of Gynecological Oncology (SFOG), Young of French Society of Gynecological Oncology (SFOG campus) and National Investigators Group for Ovarian and Breast Cancer Studies in France (GINECO-ARCAGY). Fifty-two respondents, mainly gynecology and medical oncologists, revealed that 58% of them have used KELIM score, primarily in neoadjuvant settings. Participants considered that the KELIM score was mainly used to define the chemosensitivity (79%) and to identify patients who could then receive bevacizumab (82%). In the maintenance setting, the KELIM score was reported as quite frequently used (41%). It was inconsistently used to help the surgical procedure decision (37%). The KELIM score predictive value for chemosensitivity, is acknowledged, especially for bevacizumab indications. However, its adoption into routine practice is dependent on the level of familiarity of practitioners. The findings suggest that while KELIM is seen as a potential useful tool for reinforcing therapeutic strategies, including choice of maintenance therapy or sequence of cytoreduction surgery, its broader adoption requires enhanced education and prospective validation.

Therapeutic advances and molecular insights in low-grade serous ovarian carcinoma

Low-grade serous ovarian carcinoma is a rare subtype of epithelial ovarian cancer, accounting for less than 10% of serous malignancies. Compared to high-grade serous ovarian carcinoma, it follows an indolent course, often affects younger women, and demonstrates resistance to conventional cytotoxic chemotherapy. Low-grade serous ovarian is characterized by recurrent MAPK pathway alterations (KRAS, BRAF, NRAS) and frequent expression of functional hormone receptors, supporting the rationale for targeted and endocrine strategies. Optimal management relies on complete surgical cytoreduction. Endocrine therapy has shown promise, particularly in maintenance settings, and is being investigated in frontline strategies. MEK inhibitors, especially trametinib and avutometinib in combination with defactinib, have recently demonstrated improved outcomes in recurrent disease, while new combination strategies are under active evaluation to overcome resistance mechanisms. Immunotherapy remains of limited efficacy, though biomarker-driven combinations are explored. Ongoing biomarker-guided trials are expected to refine treatment paradigms.

Annexectomie bilatérale de réduction de risque : pour qui, comment et quels résultats ?

Currently, the main means of diagnosing ovarian cancer at an early stage involve risk prediction, prevention and screening in patients identified as being at genetic risk. Our aim is to identify patients who may benefit from bilateral salpingo-oophorectomy for risk reduction purposes, as well as the modalities for its realization. We list the genes associated with ovarian cancer predisposition, their frequency in the general population, the risk of patients carrying these genes developing ovarian cancer, and the risk-reducing surgical procedures associated with each gene.

Avancées thérapeutiques dans la prise en charge des tumeurs rares malignes ovariennes

Even if each rare ovarian tumor (ROT) has a low incidence, the sum of all these entities represents almost the half of all ovarian neoplasms. Thus, development of dedicated clinical trial emerged as a prerequisite to improve their managements. Owing to the spreading of dedicated institutional networks and (supra)national collaborations, the number of clinical trials has increased the past few years, with different types of trials; while some focused on specific molecular features, others assessed innovative molecules. Furthermore, relevant randomized clinical trials were designed as a mean to position new treatment options. Currently, innovative molecular-driven trials, based on master protocol trials are emerging and may shed light towards the improvement of personalized medicine regarding ROT.

Statement of the AGO Kommission Ovar, AGO Study Group, NOGGO, AGO Austria, Swiss AGO, BGOG, CEEGOG, GEICO, and SFOG regarding the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in epithelial ovarian cancer

An international joint statement about the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer was published in 2016, warning about the uncritical use of HIPEC outside controlled studies. This statement has now been updated after the most recent literature was reviewed by the participating study groups and societies. HIPEC became a treatment option in patients with advanced colon cancer after positive results of a randomized trial comparing surgery and HIPEC versus palliative treatment alone. Although this trial did not compare the added value of HIPEC to surgery alone, HIPEC for the treatment of peritoneal metastases was in the subsequent years generalized to many other cancer types associated with peritoneal carcinomatosis including epithelial ovarian cancer (EOC). In the meantime, new evidence from prospective randomized trials specifically for EOC-patients emerged, with however contradicting results and several quality aspects that made the interpretation of their findings critical. Moreover, three additional trials in colorectal cancer failed to confirm the previously presumed survival benefit through the implementation of HIPEC in peritoneally disseminated colorectal cancers. Based on a still unclear and inconsistent landscape, the authors conclude that HIPEC should remain within the remit of clinical trials for EOC-patients. Available evidence is not yet sufficient to justify its broad endorsement into the routine clinical practice.

HJURP inhibits proliferation of ovarian cancer cells by regulating CENP-A/CENP-N

High expression of Holliday Junction-Recognizing Protein (HJURP) has been shown to be a marker of poor prognosis in ovarian cancer. The objective of this study was to investigate the molecular mechanisms of HJURP in ovarian cancer (OC) progression. Gene Expression Profiling Interactive Analysis (GEPIA) was used to analyze the gene expression profile. Real-time quantitative PCR (qRT-PCR) was used to detect the expression level and correlation of HJURP and centromere protein-A (CENP-A) in OC tissues and cell lines. CCK-8 assay was used to detect cell proliferation. The expression level of apoptosis-related proteins and cell cycle-related proteins were detected by western blotting. Cell cycle and mitochondrial content were determined by flow cytometry. The results showed that HJURP was up-regulated in OC tissues and cell lines, while the cell proliferation was inhibited after transfecting by si-HJURP. Knockdown of HJURP promoted cell apoptosis. Meanwhile, low-expression of HJURP could down-regulate cell replication cycle-related proteins (Cyclin-dependent kinase 2, cyclinD1 and Cyclin-dependent kinase 4) and make cell replication stay in the S phase. Moreover, further studies showed that HJURP was positively correlated with CENP-A in OC tissues. Finally, the rescue experiment further verified that HJURP targeted regulation of CENP-A in OC. The study indicated that HJURP plays a significant role in OC and could target CENP-A to regulate OC cell growth. These findings provide a clue to the diagnosis and treatment of OC.

Impact de l’étude LACC. Une enquête de la SFOG

The LACC (Laparoscopic Approach to Cervical Cancer Trial) study, released in 2018, described oncological findings in favour of open surgery compared to the minimally invasive pathway in the management of early stage cervical cancers. Our aim was to assess the impact of this study on surgical practices in France. Online questionnaire, consisting of 13 questions addressed to gynecology oncology french society (SFOG) surgeons. Forty questionnaires were collected. The median annual number of radical hysterectomy was 5 (0-20). Prior to the study, 92.5 % of cervical cancer patients had radical hysterectomy by minimally invasive surgery. In case of laparoscopy or robot, the uterine manipulator was used in 67.6 % and the colpotomy was performed intra-abdominally (78.4 %). After the LACC study, 60 % changed their practice. Open surgery was favored by 75 % of those who modified their practice. Among those continuing to perform minimally invasive surgeries, the manipulator and the intracorporeal colpotomy were discontinued. One-third of surgeons have changed their surgical practice for endometrial cancer in parallel. The results of the LACC study led to a change in surgical practices with an increase in open surgery and a stop in the use of the uterine manipulator and the laparoscopic/robotic intracorporeal colpotomy in the surgical management of early stage of cervical cancer.

Situation professionnelle à long terme après un cancer : étude réalisée à partir de registres de population

Few studies have explored the long-term occupational situation after cancer. The aim of our study were to study the employment status among long-term cancer survivors and to compare it to cancer-free controls from the general population at 5, 10 or 15 years after cancer diagnosis. From data of a registry-based study, long-term survivors from breast,cervical and colorectal cancer, randomly selected from three tumor registries in France, were compared to cancer-free controls randomly selected from electoral lists. We selected active cancer survivors and cancer-free controls aged less than 60 at the time of the survey. We have studied the employment status of cases vs. controls and the factors associated with employment status. At 5, 10 or 15 years after diagnosis, we did not observe any significant difference in employment status between cases and controls. Among cases, 17% had lost their jobs. Older age, lower incomes, lower education, a short-term employment contract, the presence of co-morbidities, fatigue and a worse quality of life were associated with job loss. Although the employment status of the cases was comparable to that of the controls, efforts should be intensified to make it easier for patients diagnosed with cancer to return to work.

Comment pouvons-nous améliorer le dépistage du cancer du col de l’utérus : que pouvons-nous apprendre des erreurs ?

Cervical cancer screening is considered one of the most significant public health interventions that can reduce not only the incidence, but also the mortality of the disease. One of the most important factors for screening effectiveness is coverage defined as the number of women tested within a recommended interval. In the first years of the cervical screening, the participation rate in National Screening Program in Romania was 14.2% with slight difference in different region of the country. In the northeastern part of the country, in the first four years of the program, the rate was 16.9% with an alarmingly continuous decrease. Thus, increasing the rate of uptake of cervical screening is essential. The policy-makers should take new measures to increase women's participation in this screening program. The objective of this paper was to review situation of the screening program and to identify gaps and needs in the system and to bring or suggest solution.

Prévenir les cancers : place de la vaccination Papillomavirus en population générale

Papillomavirus (HPV), the first sexually transmitted disease in the world, is the main infectious agent responsible for cancer (6300 per year, in France). The cycle of HPV infection - >precancerous lesions - >cancer is well documented with regard to the cervix (cf. Nobel Prize in 2008). While this area is the most frequent (3000), it is far from being the only one. Other cancers include the anus, oropharyngeal sphere, glans and vulva. The sum of these other induced HPV cancers is greater than the total number of cervical cancers and also concerns boys. Screening is essential but insufficient and only concerns the cervix. Only vaccination can provide primary and general prevention. Since 2007, there have been many studies demonstrating its excellent efficacy and tolerance. However, France lags behind other countries with a vaccination coverage (<30 %) that does not allow for an epidemiological impact.

Place du ganglion sentinelle dans les cancers du col utérin débutants

Lymph node status is the most important prognostic factor of survival in women with early stage cervical cancer. Sentinel lymph node (SLN) biopsy is an accurate method for the assessment of lymph nodal involvement in early-stages cervical cancer and has been increasingly used instead of systematic pelvic lymph node dissection (PLND). Less-radical lymph node dissection decreases the associated morbidity of PLND, especially the risk of lower-leg lymphoedema, which affects severely patient quality of life. SLN biopsy allows nodes ultrastaging and provides supplementary histological information by increasing the detection of tumor low-volume (isolated tumors cells and micrometastases). Moreover, SLN biopsy provides accurate anatomical information on pelvic lymphatic drainage pathway by identifying nodes outside of routine lymphadenectomy areas. Selection of a population at low-risk of nodal metastasis, a minimal training, and simple rules may ensure a low false negative rate. Several studies have shown that SLN mapping in these patients is feasible, with excellent detection rates and sensitivity. Combined detection with technetium-99 and blue dye has been widely used but recently, there has been increasing interest in the use of fluorescent dies such as indocyanine green (ICG) which would improve SLN detection. Although recent international guidelines recommend performing SLN biopsy in addition to PLND, SLN biopsy alone is not the gold-standard yet due to lack of prospective evidence, especially on long-term oncological safety. Some points remain controversial such as the low accuracy of intraoperative SLN status assessment by frozen section and the impact of micrometastasis on prognostic. The prospective randomized clinical trial SENTICOL III will answer to these problematics.

Evaluation of tumor response three months after concomitant chemoradiotherapy with high dose rate brachytherapy as a definitive treatment modality for locally advanced cervical cancer

Radiotherapy remains an essential part of the management of locally advanced cervical cancer. Post-treatment surveillance allows for tumor response assessment and early detection of progressive prosecutions or local recurrences that may benefit from salvage treatment. The objective of this work is to assess the effectiveness of this therapeutic modality. This is a retrospective study of 69 patients treated with concomitant radiation chemotherapy followed by high dose rate intracavitary brachytherapy. The tumor response was assessed by gynecologic physical examination at three months after the end of treatment. Median age of patients is 54.9 years (33-78 years). The most common histological type is squamous cell carcinoma (89.9%). The average dose received during external radiotherapy is 52.2Gy (46-60Gy). The average dose received during brachytherapy is 27.5Gy (18-28Gy). Three months after completion of treatment, 95.6% of patients had complete tumor remission, and only 4.4% had a tumor residue of 1cm. Radiation chemotherapy with brachytherapy allows for improved short-term local control in cervical cancer.

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2022–2023 : Prise en charge du cancer de l'endomètre métastatique et/ou en rechute

Recommendations for clinical practice Nice/Saint-Paul-de-Vence 2022-2023 : Management of advanced/relapsing endometrial cancer Since the first recommendations in 2020 concerning metastatic and/or relapsed endometrial cancer, new treatment options have shown a benefit on patients' life expectancy, justifying their update. In first line, the choice will be made between chemotherapy with carboplatin/paclitaxel or hormone therapy with progestin, depending on tumor characteristics (histological type, grade, expression of hormone receptors, rate of progression). In case of a dMMR tumors, the use of immunotherapy within the framework of a therapeutic trial is an option. Beyond first-line chemotherapy, current standard treatment consists of the combination of pembrolizumab and lenvatinib, regardless of MMR status. Close clinical and biological monitoring is however necessary given the potential toxicity. Chemotherapy retains its place either as monotherapy (paclitaxel or doxorubicin) in the event of failure or contraindication to pembrolizumab-lenvatinib, or in combination with carboplatin in the event of a long free interval and pMMR tumor. The numerous ongoing clinical trials evaluating new therapeutic targets or strategies adapted to molecular or histological types should allow further improvements the prognosis of patients with metastatic endometrial cancer.

Dostarlimab associé à la chimiothérapie dans le cancer endométrial en rechute ou avancé

Nouvelle AMM : dostarlimab – cancer de l’endomètre en deuxième ligne dMMR/MSI

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2022–2023 : Diagnostic histomoléculaire des carcinomes de l'endomètre

French recommendations for clinical practice Nice-Saint-Paul de Vence 2022-2023: histomolecular diagnosis of endometrial carcinomas The characterisation of endometrial carcinomas has been recently modified and enriched by molecular classification, the integration of which now impacts therapeutic decisions on whether adjuvant therapy should be administered or not in localized tumors, and influences treatment selection in advanced disease. Mandatory information includes histological type according to WHO 2020 classification, histological grade, hormone receptors status and molecular classification, the main new elements to provide being analysis of MMR proteins, p53 status and POLE status in selected cases. Sampling and preparation of material must be performed adequately to allow complete analysis. Numerous markers can be used to better define histological type, distinguish between primary lesion or metastases, or provide prognostic information. Determination of MMR/MSI profile is complex but well defined by guidelines that precisely describe techniques to be used and interpretation rules. Knowledge of POLE status is useful to guide therapeutic strategy, especially to consider de-escalation in stages I and II, in particular in case of high grade and/or p53 mutated tumors. This is why indications of POLE determination must be well defined. Finally, oncogenetics consultation is recommended in dMMR tumors (except in case or MLH1 promoter methylation) and in patients with evocative familial history.

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2022–2023 : prise en charge du cancer de l'endomètre localisé

Recommendations for clinical practice, Nice/Saint-Paul-de-Vence 2022-2023: Management of localized endometrial cancer Endometrial cancer is the most frequent gynecological cancers in industrialized countries and its incidence increases. The newmolecularclassification allows determination of the risk of recurrence and helps orienting therapeutic management. Surgery remains the cornerstone of treatment. Minimally invasive approach must be preferred for stages I and II. Surgery includes hysterectomy with bilateral adnexectomy, sentinel lymph node biopsy even in high risk diseases and omentectomy for non-endometrioid tumors (except in case of clear cells tumors). Fertility preservation can be proposed in low grade, stage I tumors without myometrial involvement. In stage III/IV disease, lymph node debulking without totallymphadenectomy is indicated. In case of peritoneal carcinomatosis, first-line cytoreductive surgery is recommended if complete resection can be achieved. Adjuvant therapy is not recommended in low risk tumors. In intermediate risk tumors, curietherapy is indicated. In tumors with high-intermediate risk, curietherapy and external radiotherapy are indicated according to prognostic factors (stage II, lymphovascular invasion); adjuvant chemotherapy can be considered on a case-by-case basis. In high risk tumors, chemotherapy and external radiotherapy are recommended using a concomitant or sequential approach.

Sarcomes du stroma endométrial de bas grade : référentiels de prise en charge du GSF-GETO/NETSARC+ et du groupe TMRG

Low-grade endometrial stromal sarcoma (LG-ESS) accounts for approximately 15% of all uterine sarcomas. Median age of patients is around 50 years and half of the patients are premenopausal. In all, 60% of cases present with FIGO stage I disease. Preoperatively radiologic findings of ESS are not specific. Pathological diagnosis remains essential. This review aimed to present the French guidelines for low grade ESS treatment within the Groupe sarcome français - Groupe d'étude des tumeurs osseuse (GSF-GETO)/NETSARC+ and tumeur maligne rare gynécologique (TMRG) networks. Treatments should be validated in multidisciplinary team involved in sarcomas or rare gynecologic tumors. Hysterectomy is the cornerstone of treatment for localized ESS, and morcellation should be avoided. Systematic lymphadenectomy in ESS does not improve the outcome and is not recommended. Leaving the ovaries in situ in stage I tumors could be discussed for young women. Adjuvant hormonal treatment could be considered, for two years for stage I with morcellation or stage II and livelong for stages III or IV. Nevertheless, several questions remain, such as optimal doses, regimens (progestins or aromatase inhibitors) and duration of therapy. Tamoxifen is contraindicated. Secondary cytoreductive surgery if feasible for recurrent disease, appears to be an acceptable approach. Systemic treatment for recurrent or metastatic disease is mainly hormonal, with or without surgery.

Place des inhibiteurs de PARP dans le traitement des cancers de l’endomètre et du col de l’utérus

New molecular therapeutic approaches have emerged in recent years for advanced gynaecological cancers, including targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi). These have demonstrated efficacy in high-grade serous ovarian cancers in patients carrying a mutation in the BRCA gene, which predisposes them to breast and ovarian cancers. Clinical and pre-clinical data suggest that the activity of PARPi inhibitors may not be limited to BRCA mutated tumours and may involve the homologous recombination pathway. These data raise the question of the potential efficacy of PARPi in advanced endometrial and cervical cancers where treatment options are currently limited. At present, there are few data available on the activity of PARPi in endometrial and cervical cancers, but some results seem promising. In this review, we present a synthesis of the available studies concerning PARPi in endometrial and cervical cancer.

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.

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.

Nouvelle AMM : pembrolizumab et lenvatinib en deuxième ligne dans l’endomètre

Gestational trophoblastic diseases and neonatal choriocarcinoma

Trophoblastic diseases include benign pre-tumor entities (hydatidiform moles) and malignancies called gestational trophoblastic tumors. Most of the latter arise after a hydatidiform mole and are referred to as post-molar trophoblastic tumors. Their diagnosis relies on elevated human chorionic gonadotrophin (hCG) levels following a mole, without the need for histological confirmation. Other forms, including choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT), require histology; notably, PSTT and ETT are relatively resistant to chemotherapy and usually necessitate surgery. The management of post-molar tumors and choriocarcinomas is guided by the International Federation of Gynecology and Obstetrics prognostic score: low-risk cases are treated with monochemotherapy, whereas high-risk forms by polychemotherapy. In refractory disease, immune checkpoint inhibitors represent an emerging option. Gestational choriocarcinoma is characterized by its marked malignancy, aggressiveness, and ability to spread to the mother and fetus. Diagnosis is based on histology combined with abnormally elevated circulating or urinary levels of hCG. Neonatal choriocarcinoma, resulting from transplacental transmission, is exceptionally rare yet life-threatening. It typically manifests early in life, with hemorrhagic visceral metastases. Management, although non-standardized, generally involves platinum-based chemotherapy followed by possible surgical removal of residual lesions. Therapeutic intervention must be prompt and adapted to neonatal pharmacokinetics, while addressing the significant risk of hemorrhagic complications. This review summarizes current knowledges on the diagnosis and treatment of gestational trophoblastic diseases, with particular emphasis on gestational choriocarcinoma and its neonatal counterpart.

L’année 2021 dans tous ses états : une synthèse digérée

Once again this year, the Editorial Board presents here a summary of the most important advances in treatment and patient care in oncology over the past year. Some of the most important results in breast and gynecological cancers (endometrium and cervix), lung, brain, urologic and digestive cancers. Are also presented progresses in hematological malignancies, pediatric oncology, and of course supportive care essential for our patients.

Désescalade chirurgicale en oncologie gynécologique

The evolution of knowledge in gynecologic oncology is leading to surgical de-escalation in several areas, particularly in lymph node staging. Sentinel lymph node biopsy that was initially used in low and intermediate risk endometrial cancer, has now been extended to high-intermediate and high-risk endometrial cancer. Sentinel lymph node biopsy plays also an important role in the nodal staging of early-stage cervical cancer. The radicality of hysterectomies in patients with early cervical cancer is under debate. Similarly, surgical staging with para-aortic lymphadenectomy in locally advanced cervical cancer should be performed only for few cases. Systematic pelvic and para-aortic lymphadenectomy in patients with advanced ovarian cancers is not recommended anymore.

Évaluation de l’application des recommandations des cancers de l’endomètre de type 2 : étude rétrospective multicentrique

Non endometrioid endometrial cancer are infrequent and have poor prognosis. The aim of the study was to evaluate non endometrioid endometrial cancer managment by evaluating endometrial cancer guidelines application. This multicentric retrospective study enrolled non endometrioid endometrial cancer between January 2009 to December 2019. Analyses adapted at last French guidelines applicated corresponding of year management. Seventy-four non endometrioid endometrial cancer analysed in 10 centers: 34 carcinosarcoma (45,9 %), 29 serous carcinoma (39,2 %), 9 clear cells carcinoma (12,2 %) and 2 undifferentiated carcinoma (2,7 %). For initial management, endometrial cancer guidelines applicated to 45,9 %. First reason of initial guidelines « non-application » was lack of surgical lymph node stadification (57,1 %). For adjuvant management, endometrial cancer guidelines applicated to 38.7 %. First reason of adjuvant guidelines « non-application » was lack lymph node stadification to complete staging when it previously incompletly operated (67,6 %). Non endometrioid endometrial cancer guidelines applicability is difficult. This explicated by high age and comorbidity when surgical lymph node stadification is necessary. Using new staging technic will allow target management and better select lymph node staging indication.