Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2022­2023 : 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.

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2022­2023 : 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.

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2022­2023 : 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.

Pelvic insufficiency fractures after intensity modulated radiation therapy combined with chemotherapy for cervix carcinoma: Incidence and impact of bone mineral density.

Background and Purpose: The aim of this study was to evaluate the incidence and predictive factors of Pelvic Insufficiency Fractures (PIFs) occurring after Intensity Modulated Radiation Therapy (IMRT) combined with chemotherapy for locally advanced cervical cancer (CC). Material and methods: Medical records of patients receiving radio-chemotherapy with IMRT between 2010 and 2020 for advanced CC were reviewed. PIFs were detected during follow-up on pelvic Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). The cumulative incidence rate of PIFs and its confidence interval were calculated at 2 and 5 years of follow-up. Pre-therapeutic Bone Mineral Density (BMD) (g/cm3) was evaluated on CT simulation for sacrum and the fourth lumbar (L4) vertebrae. Sacrum dosimetric parameters (V30Gy, V40Gy, D50%, Dmean) were analyzed. Results: 136 patients were included. The median follow-up was 4.4 years. Median dose of D50% and V40Gy sacrum were 35.2 Gy (20.6-46.4) and 32.2% (7.2-73.4) respectively. The 2-year and 5-year cumulative incidence rates were 15.7% (95% CI: 9.88-22.71) and 22% (95% CI: 14.58-30.45) respectively. Median time interval between RT completion and PIFs' detection was 11.5 months (IQR: 7.4-22.3). Univariate analysis showed that older age (p < 0.01), postmenopausal status at baseline (p < 0.01), and lower sacral and spinal BMD at baseline (respectively p < 0.001 and p < 0.01) were significantly associated to all sites of PIFs, and lower sacral BMD with sacral fractures (p < 0.001). Conclusion: Post-IMRT PIFs were detected in 18.4% of patients with locally advanced CC. Individual predisposing factors as older age, postmenopausal status, decreased bone density on the CT simulation were mainly predictive.

[Treatments for rare ovarian tumors: What's new?] / 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.

Magnetic resonance imaging diagnosis of subependymal giant cell astrocytomas in follow-up of children with tuberous sclerosis complex: should we always use contrast enhancement?

BACKGROUND: Subependymal giant cell astrocytomas (SEGAs) arise in 10-26% of tuberous sclerosis complex (TSC) patients. SEGAs cause obstructive hydrocephalus and increase morbi-mortality. It is recommended that TSC patients be followed with contrast enhanced magnetic resonance imaging (CE-MRI), but repetitive use of gadolinium-based contrast-agents (GBCAs) may cause organ deposits. OBJECTIVE: To compare the diagnostic performances of non-CE- and CE-MRI to differentiate SEGAs from subependymal nodules in TSC patients during follow-up. MATERIALS AND METHODS: Thirty-five TSC patients (median age: 2.4 years) were enrolled in this retrospective single-center study from September 2007 to January 2019. Inclusion criteria were a certain diagnosis of TSC and at least three follow-up brain MRIs with GBCA injection. Two consecutive MRI scans per patient were selected and anonymized. Three radiologists performed a blinded review of non-enhanced and enhanced MRI sequences during different sessions. The diagnostic performances were compared (sensitivity, specificity, positive/negative predictive values, accuracy, inter/intra-observer agreements). RESULTS: The accuracies for detecting SEGAs were good and similar between the non-enhanced and enhanced MRI sequences. The sensitivity and specificity of non-CE-MRI to diagnose SEGA ranged from 75% to 100% and from 94% to 100%, respectively. The differences in numbers of false-positive and false-negative patients between non-CE- and CE-MRI never exceeded one case. Nodules size >10 mm, location near the Monro foramen, hydrocephalus and modifications between two consecutive MRI scans were significantly associated with the diagnosis of SEGA for the three readers (all P-values <0.05). Inter- and intra-observer agreements were also excellent for non-enhanced and enhanced MRI sequences (kappa=0.85-1 and 0.81-0.93, respectively). CONCLUSION: The performances of non-enhanced and enhanced MRI sequences are comparable for detecting SEGAs, questioning the need for systematic GBCA injections for TSC patients.