Real-World Data on Newly Diagnosed BRCA-Mutated High-Grade Epithelial Ovarian Cancers: The French National Multicenter ESME Database.

BACKGROUND: In spite of the frequency and clinical impact of BRCA1/2 alterations in high-grade epithelial ovarian cancer (HGEOC), real-world information based on robust data warehouse has been scarce to date. METHODS: Consecutive patients with BRCA-mutated HGEOC treated between 2011 and 2016 within French comprehensive cancer centers from the Unicancer network were extracted from the ESME database. The main objective of the study was the assessment of clinicopathological and treatments parameters. RESULTS: Out of the 8021 patients included in the ESME database, 266 patients matching the selection criteria were included. BRCA1 mutation was found in 191 (71.8%) patients, while 75 (28.2%) had a BRCA2 mutation only; 95.5% of patients received a cytoreductive surgery. All patients received a taxane/platinum-based chemotherapy (median = six cycles). Complete and partial response were obtained in 53.3% and 20.4% of the cases, respectively. Maintenance therapy was administered in 55.3% of the cases, bevacizumab being the most common agent. After a median follow up of 51.7 months, a median progression-free survival of 28.6 months (95% confidence interval (CI) [26.5; 32.7]) and an estimated 5-year median overall survival of 69.2% (95% CI [61.6; 70.3]) were reported. Notably, BRCA1- and BRCA2-mutated cases exhibited a trend towards different median progression-free survivals, with 28.0 (95% CI [24.4; 32.3]) and 33.3 months (95% CI [26.7; 46.1]), respectively (p-value = 0.053). Furthermore, five-year OS for BRCA1-mutated patients was 64.5% (95% CI [59.7; 69.2]), while it was 82.5% (95% CI [76.6; 88.5]) for BRCA2-mutated ones (p-value = 0.029). CONCLUSIONS: This study reports the largest French multicenter cohort of BRCA-mutated HGEOCs based on robust data from the ESME, exhibiting relevant real-world data regarding this specific population.

Major impact of COVID-19 national containment on activities in the French northern comprehensive cancer center.

The SARS-CoV-2 pandemic has significantly impacted cancer patient management. National and local recommendations to reduce SARS-CoV-2 transmission have been applied in a comprehensive cancer center located in Northern France. We prospectively measured key indicators for three successive eight-week periods: directly before, during, and right after the containment (from 16 March to 10 May 2020). Overall, the number of newly diagnosed and referred cancer patients in our hospital steadily increased (1027; 1135 and then 1704; +11% during containment and +50% just after). To reduce patient transportation, teleconsultations were implemented. Teleconsulting activity steadily increased during the three periods (5, 2025, and 2351). However, a marked decrease in the number of surgical procedures was observed (448; 330 and 288; -26% during containment and -13% just after). We observed a slight decrease in the number of radiation therapy sessions (7761; 7328 and 7075; -6% during containment and -3% just after) and in day-hospital cycles of IV systemic treatment (2891; 2736 and 2717; -5% during containment and -1% just after). We observed an increase in the number of patients admitted to palliative care and a dramatic reduction in clinical trial enrollment. During this 24-week period, organizational changes were mainly characterized by an increase in newly diagnosed cancer patient referral and the implementation of protective measures, such as teleconsultations. Activities in cancer surgery have decreased while radiotherapy and chemotherapy activities were stable.

[Management of epithelial ovarian cancer. Short text drafted from the French joint recommendations of FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa]. / Texte court rédigé à partir de la recommandation nationale de bonnes pratiques cliniques « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa ¼.

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). In case of ovarian, Fallopian tube or primitive peritoneal cancer of FIGO III-IV stages, thoraco-abdomino-pelvic CT scan with injection (grade B) is recommended. Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A).

Magnetic resonance imaging after external beam radiotherapy and concurrent chemotherapy for locally advanced cervical cancer helps to identify patients at risk of recurrence.

OBJECTIVE: Tumor volume and regression after external beam radiotherapy have been shown to be accurate parameters to assess treatment response via magnetic resonance imaging (MRI). The aim of the study was to evaluate the prognostic value of tumor size reduction rate after external beam radiotherapy and chemotherapy prior to brachytherapy. METHODS: Patients with locally advanced cervical cancer treated at two French comprehensive cancer centers between 1998 and 2010 were included. Treatment was pelvic external beam radiotherapy with platinum based chemotherapy followed by brachytherapy. Records were reviewed for demographic, clinical, imaging, treatment, and follow-up data. Anonymized linked data were used to ascertain the association between pre-external and post-external beam radiotherapy MRI results, and survival data. RESULTS: 185 patients were included in the study. Median age at diagnosis was 45 years (range 26-72). 77 patients (41.6%) were International Federation of Gynecology and Obstetrics stage IB2-IIA disease and 108 patients (58.4%) were stage IIB-IVA. Median tumor size after external beam radiotherapy and chemotherapy was 2.0 cm (range 0.0-8.0) and median tumor size reduction rate was 62.4% (range 0.0-100.0%). Tumor size and tumor reduction rate at 45 Gy external beam radiotherapy MRI were significantly associated with local recurrence free survival (P<0.001), disease free survival, and overall survival (P<0.05). Tumor reduction rate ≥60% was significantly associated with a decreased risk of relapse and death (HR (95% CI) 0.21 (0.09 to 0.50), P=0.001 for local recurrence free survival; 0.48 (0.30 to 0.77) P=0.002 for disease free survival; and 0.51 (0.29 to 0.88), P=0.014 for overall survival). CONCLUSIONS: Tumor size reduction rate >60% between pre-therapeutic and post-therapeutic 45 Gy external beam radiotherapy with concurrent chemotherapy was associated with improved survival. Future studies may help to identify patients who may ultimately benefit from completion surgery, adjuvant chemotherapy, and closer follow-up.

Treatment and follow-up of malignant struma ovarii: Regarding two cases.

Malignant struma ovarii (SO) is a rare tumor, and as a consequence, treatments and follow-up procedures are not clearly established. Presented in this study are two cases of suspicious ovarian masses, resected and corresponding to malignant SO on histopathology. Similar to thyroid cancer, we proposed complementary radioiodine therapy ((131)I) after total thyroidectomy (no malignancy was observed at this level in our two patients). Patients underwent treatment with 3.7 GBq (131)I followed by post-therapy whole-body scintigraphy, which can detect residual disease or occult metastases. Thyroid remnant ablation increases the sensitivity and specificity of follow-up testing using serum thyroglobulin levels as a tumor marker. Our two patients remained disease-free for 3 and 5 years, respectively, after treatment.

Prospective multicenter study evaluating the survival of patients with locally advanced cervical cancer undergoing laparoscopic para-aortic lymphadenectomy before chemoradiotherapy in the era of positron emission tomography imaging.

PURPOSE: The aim of this prospective study conducted in three French comprehensive cancer centers was to evaluate the therapeutic impact on survival of laparoscopic para-aortic (PA) staging surgery in locally advanced cervical cancer (LACC) before chemoradiotherapy. PATIENTS AND METHODS: We conducted a prospective multicenter study of 237 patients treated from 2004 to 2011 for LACC with negative positron emission tomography (PET) imaging of the PA area and undergoing laparoscopic PA lymphadenectomy. Radiation fields were extended to the PA area when PA nodes were involved. Chemoradiotherapy modalities were homogeneous across institutions. Patients with a poor prognosis histologic subtype or peritoneal carcinosis were excluded. RESULTS: Patients had clinical International Federation of Gynecology and Obstetrics stages IB2 (n = 79), IIA (n = 10), IIB (n = 121), III (n = 22), or IVA (n = 5). One hundred ninety-nine patients had squamous carcinoma, and 38 had adenocarcinoma/adenosquamous lesions. Twenty-nine patients (12%) had nodal involvement (false-negative PET-computed tomography [CT] results)-16 with a PA nodal metastasis measuring more than 5 mm and 13 with a nodal metastasis measuring ≤ 5 mm. Event-free survival rates at 3 years in patients without PA involvement or with PA metastasis measuring ≤ or more than 5 mm were 74% (SE, 4%), 69% (SE, 21%), and 17% (SE, 14%; P < .001). CONCLUSION: To our knowledge, this is the largest series of patients reported undergoing such a strategy. We obtained the same survival rate for patients with PA nodal metastasis ≤ 5 mm and patients without PA lymph node involvement, suggesting that this strategy is highly efficient in such patients. Conversely, the survival of patients with PA nodal involvement greater than 5 mm remained poor, despite the absence of extrapelvic disease on PET-CT imaging in this subgroup.

Identification of novel androgen receptor antagonists using structure- and ligand-based methods.

Androgen receptor (AR) plays a critical role in the development and progression of prostate cancer (PCa). The AR hormone-binding site (HBS) is intensively studied and represents the target area for current antiandrogens including Bicalutamide and structurally related Enzalutamide. As resistance to antiandrogens invariably emerges in advanced prostate cancer, there exists a high medical need for the identification and development of novel AR antagonists of different chemotypes. Given the wealth of structural information on the AR in complex with a variety of ligands, we have applied an integrated structure- and ligand-based virtual screening methodology to identify novel AR antagonists. Virtual hits generated by a consensus voting approach were experimentally evaluated and resulted in the discovery of a number of structurally diverse submicromolar antagonists of the AR. In particular, one identified compound demonstrated anti-AR potency in vitro that is comparable to the clinically used Bicalutamide. These results set a ground for the development of novel classes of PCa drugs that are structurally different from current AR antagonists.

Laparoscopic radical hysterectomy after preoperative brachytherapy for stage IB1 cervical cancer: feasibility, results, and surgical implications in a large bicentric study of 162 consecutive cases.

PURPOSE: To examine the feasibility and to report the results of laparoscopic radical hysterectomy (LRH) after initial uterovaginal brachytherapy (BT) for stage IB1 cervical cancer. METHODS: We retrospectively reviewed patients at 2 comprehensive cancer centers who underwent initial BT followed 6-8 weeks later by LRH and lymph node dissection. RESULTS: Between 2003 and 2010, a total of 162 patients underwent LRH. The procedure was feasible via this approach in 160 cases (98.8%) (2 conversions to laparotomy). Eight perioperative complications occurred. Nineteen patients had nodal involvement. Peri- or postoperative ureteral morbidity occurred in 10 patients (6%). Twenty-four patients (15%) experienced postoperative dysuria. Histologically, only 9 patients had residual cervical disease ≥5 mm, and only 1 patient had parametrial lymphovascular space involvement (associated with nodal spread). No patient had vaginal disease or involved surgical margins. After a median follow-up of 39 (range 3-118) months, 9 patients experienced relapse. Five-year overall survival was 95% (range 88.2-97.9%). CONCLUSIONS: Radical hysterectomy using a laparoscopic approach is feasible and reproducible after initial BT for stage IB1 cervical cancer and is associated with excellent survival. Morbidity is close to that reported in patients treated with up-front surgery. In this large series, the morbidity associated with parametrial dissection and the fact that parametrial spread was observed in only 0.6% of the patients suggest that a simple extrafascial hysterectomy is perhaps sufficient in this context; the rate of urinary tract morbidity would then be reduced.

[What is new in the surgical treatment of pelvic gynecologic cancers?]. / Actualités chirurgicales dans les cancers gynécologiques pelviens.

General tendency of modern cancerology is the research of adequacy between extent of disease and treatments. This concept is of course valid for gynaecology and we saw these last months the promising results of fertility-sparing surgery: in initial cervical cancers and in ovarian cancer with good prognosis. Actual Studies should define a clear attitude in patient less than 40 with initial endometrial cancer. At the same time, the development of laparoscopic surgery has continued in cervical cancer staging. If use of sentinel node in endometrial or vulvar cancers remains discussed as for its reliability, importance of staging was stressed for cervical cancer and initial ovarian cancer. Laparoscopic surgery is confirmed in patient at risk with endometrial cancer but it is necessary to stress efforts of French teams which still push back the technical limits of laparoscopic approach like pelvic exenteration or intra-peritoneal chemohyperthermia in advanced ovarian cancer. The adventure continues....

[The choice of approach in the surgical management of endometrial carcinoma: a retrospective serie of 155 cases]. / Places respectives des différentes voies d'abord chirurgicales dans le traitement du cancer de l'endomètre au stade I clinique: étude de 155 cas.

SETTING: Retrospective study of patients consecutively managed surgically for apparent stage I endometrial carcinoma in a comprehensive cancer center, using a standardized protocol for the choice of surgical approach: laparoscopically assisted vaginal hysterectomy (LAVH) as standard procedure, vaginal surgery in apparent stage IA grade 1 or in patients in poor medical condition, laparotomy in the case of subserous myometrial involvement at imaging or in patients with enlarged uteri or in the presence of a contra-indication to laparoscopy. MATERIALS AND METHODS: Excluding 2 patients in whom laparoscopy was converted in laparotomy, and 1 patient who had a full laparoscopic hysterectomy, the records of 155 patients were reviewed. All patients had a preoperative sonogram, and 74% had a preoperative MRI. Preoperative data, preoperative staging, operative data, pathological staging, postoperative complications, recurrence and survival were recorded. RESULTS: 69 patients (43.6%) had a LAVH procedure (group LAVH), 58 patients (36.7%) were treated by laparotomy (group TAH), and 28 patients (18%) were treated by simple vaginal hysterectomy (group VH). Patients in the vaginal group were significantly heavier (VH 91.3 kg 33, range 53-175) than those of the other two groups (TAH 76.5 12.7, range 48-142; LAVH 71.1 18.5, range 47-102). The number of large (> 10 cm) uteri was significantly greater in the TAH group (46.5%) than the LAVH group (26.1%, p = 0.02) or the VH group (14.3%, p = 0.007). Myometrial invasion was suspected in 53.6% of the VH group, 72.6% of the LAVH group, and 71.4% of the TAH group. Deep myometrial invasion was suspected in no patient of the VH group, 14.5% of the LAVH group and 70.7% of the TAH group. The LAVH group had a significantly longer mean operative time than the TAH group or the VH group. The number of perioperative complications was significantly higher in the TAH group (22.4%) compared to the LAVH group (5.6%) and the VH group (0%). Blood loss was significantly elevated in the laparotomy group compared to the other two groups. The mean number of nodes removed was significantly higher in the LAVH group (15.8 7.8, range 4-37) compared to the TAH group (11 5.3, range 2-25, p = 0.002). Of 155 patients, 100 (64.5%) had correct preoperative staging. In 19 (12.3%), FIGO stage was overestimated preoperatively, and in 36 (23.2%) the FIGO stage was underestimated preoperatively. Survival curves were not found significantly different between groups.