Microbiological epidemiology and antibiotic susceptibility of infected meshes after prosthetic abdominal wall repair.

INTRODUCTION: Infectious complications of parietal mesh after prosthetic abdominal wall repair are rare. Their management is complex. Furthermore, the emergence of bacterial resistance, the presence of a foreign material, the need to continue an extended antibiotic therapy, and the choice of an appropriate treatment are crucial. The objective of this study is to access the microbiological epidemiology of infected parietal meshes in order to optimize the empirical antibiotic therapy. METHODS: Between January 2016 and December 2021, a monocentric and retrospective study was performed in patients hospitalized for infected parietal meshes at Avicenne hospital, in Paris area. Clinical and microbiological data such as antibiotic susceptibility were collected. RESULTS: Twenty-six patients with infected parietal meshes have been hospitalized during this period. Meshes were in preaponevrotic positions (n=10; 38%), retromuscular (n=6; 23%) and intraperitoneal (n=10; 38%). Among the 22 (84.6%) documented cases of infections, 17 (77.3%) were polymicrobial. A total of 54 bacteria were isolated, 48 of which had an antibiogram available. The most frequently isolated bacteria were: Enterobacterales (n=19), Enterococcus spp. (n=11) and Staphylococcus aureus (n=6), whereas anaerobes were poorly isolated (n=3). Concerning these isolated bacteria, amoxicillin-clavulanic acid, metronidazole-associated cefotaxime, piperacillin-tazobactam and meropenem were susceptible in 45.5%, 68.2%, 63.6%, 77.2%, of cases, respectively. CONCLUSION: This work highlights that infections of abdominal parietal meshes may be polymicrobial and the association amoxicillin-clavulanic acid cannot be used as a probabilist antibiotic therapy because of the high resistance rate in isolated bacteria. The association piperacillin-tazobactam appears to be a more adapted empirical treatment to preserve carbapenems, a broad-spectrum antibiotic class.

Long-term fatigue and quality of life among epithelial ovarian cancer survivors: a GINECO case/control VIVROVAIRE I study.

BACKGROUND: Few data are available on long-term fatigue (LTF) and quality of life (QoL) among epithelial ovarian cancer survivors (EOCS). In this case-control study, we compared LTF, symptoms and several QoL domains in EOCS relapse-free ≥3 years after first-line treatment and age-matched healthy women. PATIENTS AND METHODS: EOCS were recruited from 25 cooperative GINECO centers in France. Controls were randomly selected from the electoral rolls. All participants completed validated self-reported questionnaires: fatigue (FACIT-F), QoL (FACT-G/O), neurotoxicity (FACT-Ntx), anxiety/depression (HADS), sleep disturbance (ISI), and physical activity (IPAQ). Severe LTF (SLTF) was defined as a FACIT-F score <37/52. Univariate and multivariate logistic regressions were conducted to analyze SLTF and its influencing factors in EOCS. RESULTS: A total of 318 EOCS and 318 controls were included. EOCS were 63-year-old on average, with FIGO stage I/II (50%), III/IV (48%); 99% had received platinum and taxane chemotherapy, with an average 6-year follow-up. There were no differences between the two groups in socio-demographic characteristics and global QoL. EOCS had poorer FACIT-F scores (40 versus 45, P < 0.0001), lower functional well-being scores (18 versus 20, P = 0.0002), poorer FACT-O scores (31 versus 34 P < 0.0001), and poorer FACT-Ntx scores (35 versus 39, P < 0.0001). They also reported more SLTF (26% versus 13%, P = 0.0004), poorer sleep quality (63% versus 47%, P = 0.0003), and more depression (22% versus 13%, P = 0.01). Fewer than 20% of EOCS and controls exercised regularly. In multivariate analyses, EOCS with high levels of depression, neurotoxicity, and sleep disturbance had an increased risk of developing SLTF (P < 0.01). CONCLUSION: Compared with controls, EOCS presented similar QoL but persistent LTF, EOC-related symptoms, neurotoxicity, depression, and sleep disturbance. Depression, neuropathy, and sleep disturbance are the main conditions associated with severe LTF.

Neoadjuvant chemotherapy (NACT) increases immune infiltration and programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC).

Background: Lymphocytic infiltration at diagnosis is prognostic in EOC, however, the impact of NACT on tumour infiltrating lymphocytes (TILs) or PD-L1 expression remains poorly described. Patients and methods: Patients with EOC and sequential samples (pre-NACT, post-NACT or relapse) were retrospectively identified. TILs were evaluated on whole sections; stromal TILs (sTILs) scored as percentage of stromal area with high sTILs defined as ≥50%; intra-epithelial TILs (ieTILs) scored semi-quantitatively (0-3) with high ieTILs ≥2. A smaller number were available for PD-L1 evaluation, cut-off for positivity was ≥5% staining. Results: sTILs were detected in all tumours at diagnosis (range 2-90%, median 20%), with 22% (25/113) showing high sTILs. Among evaluable paired pre/post-NACT samples (N = 83), an overall increase in median sTILs from 20% to 30% was seen following NACT (P = 0.0005); individually the impact of NACT varied with sTILs increasing in 51% (42/83), decreasing in 25%, and stable in 24%. Post-NACT sTILs were predictive of platinum-free interval (PFI), patients with PFI ≥6 months had significantly higher post-NACT sTILs (sTILs 28% versus 18% for PFI <6 months, P = 0.026); pre-NACT sTILS were not predictive. At diagnosis, 23% showed high ieTILs, and following NACT 33% showed increasing ieTILs. Proportion of tumours with PD-L1-positive immune cells was 30% (15/50) pre-NACT and 53% (27/51) post-NACT (P = 0.026). Among paired tumours, 63% of PD-L1-negative tumours became positive after NACT, furthermore cisplatin induced PD-L1 expression in PD-L1-negative EOC cell lines. On multivariate analysis, high sTILs both pre- and post-NACT were independent prognostic factors for progression-free survival (PFS) (HR 0.49, P = 0.02 and HR 0.60, P = 0.05, respectively). No prognostic impact of ieTILs or PD-L1 expression was detected. Conclusions: In EOC, sTILs levels are prognostic at diagnosis and remain prognostic after NACT. TILs and PD-L1 expression increase following NACT. Evaluation of immune parameters in the post-NACT tumour may help select patients for immunotherapy trials.

Health-related quality of life in women with recurrent ovarian cancer receiving paclitaxel plus trebananib or placebo (TRINOVA-1).

BACKGROUND: To evaluate the influence of treatment on health-related quality of life (HRQoL) in 919 women with recurrent ovarian cancer enrolled in the TRINOVA-1 study, a randomized, placebo-controlled phase III study that demonstrated that trebananib 15 mg/kg QW plus weekly paclitaxel significantly improved progression-free survival (PFS) compared with placebo plus weekly paclitaxel (7.2 versus 5.4 months; hazard ratio, 0.66; 95% confidence interval 0.57-0.77; P < 0.001). PATIENTS AND METHODS: HRQoL was assessed with the Functional Assessment of Cancer Therapy-Ovary [FACT-O; comprising FACT-G and the ovarian cancer-specific subscale (OCS)] and EuroQOL EQ-5D instruments before treatment on day 1 of weeks 1, 5, 9, 13, 17, and every 8 weeks thereafter and at the safety follow-up visit. A pattern-mixture model was used to evaluate the influence of patient dropout on FACT-O and OCS scores over time. RESULTS: Of 919 randomized patients, 834 (91%) had a baseline and ≥1 post-baseline HRQoL assessment. At baseline, scores for all instruments were similar for both arms. At 25 weeks, mean ± SD changes from baseline were negligible, with mean ± SD changes typically <1 unit from baseline: -2.4 ± 16.6 in the trebananib arm and -1.6 ± 15.2 in the placebo arm for FACT-O, -0.71 ± 5.5 in the trebananib arm and -0.86 ± 4.9 in the placebo arm for OCS, and -0.02 ± 0.22 in the trebananib arm and 0.02 ± 0.19 in the placebo arm for EQ-5D. Distribution of scores was similar between treatment arms at baseline and over the course of the study. In pattern-mixture models, there was no evidence that patient dropout affected differences in mean FACT-O or OCS scores. Edema had limited effect on either FACT-O or OCS scores in patients with grade ≥2 edema or those with grade 1 or no edema. CONCLUSIONS: Our results demonstrate that the improvement in PFS among patients in the trebananib arm in the TRINOVA-1 study was achieved without compromising HRQoL. CLINICALTRIALSGOV IDENTIFIER: NCT01204749.

Novel membrane-based targets - Therapeutic potential in gynecological cancers.

Recent advances have been made in the molecular profiling of gynecological tumors. These discoveries have led to the development of targeted therapies that have the potential to disrupt molecular pathways involved in the oncogenesis or tumor progression. In this review, we highlight areas of recent progress in the field of membrane receptor inhibitors in gynecological malignancies and describe the biological rationale underlying the inhibition of these receptors. We will introduce drug immuno-conjugates, and give an update on the biological rationale and the clinical studies involving agents directed against EGFR, HER3, IGFR, MET, FGFR, NOTCH, and TRAIL. We also discuss the challenge facing these new therapies.

Actinomycin D, cisplatin, and etoposide regimen is associated with almost universal cure in patients with high-risk gestational trophoblastic neoplasia.

BACKGROUND: Patients with high-risk gestational trophoblastic neoplasia (GTN) need multi-agent chemotherapy to be cured. The most common regimen is etoposide (E), methotrexate (M) and actinomycin D (A), alternating weekly with cyclophosphamide (C) plus vincristine (O) (EMA/CO). Cisplatin (P) is a very active drug, but it is usually restricted to second-line therapies. Herein, we report the results of a cisplatin-based therapy: APE (actinomycin D, cisplatin, and etoposide). PATIENTS AND METHODS: The efficacy and safety of APE for high-risk GTN (defined by Institut Gustave-Roussy (IGR) criteria and/or an International Federation of Gynaecology and Obstetrics (FIGO) score >6) are reported. Patients with brain metastasis or placental-site trophoblastic tumour were excluded. RESULTS: Between 1985 and 2013, 95 patients were treated with APE for high-risk GTN: 59 patients as first-line, 36 as ⩾ 2nd-line therapy. There was 94.7% complete remission, though five patients relapsed. One patient died from GTN after multiple lines of chemotherapy. The five-year overall survival rate (median follow-up 5.7 years) was 97% (95% confidence interval (CI): 91-99%). No death from toxicity occurred. Long-term, six grade-1 neuro-toxicities, three grade-1 and two grade-2 oto-toxicities, and one grade-1 renal toxicity were recorded. One patient developed AML-M4 after APE and EMA/CO. Thirty-four of 35 women, who wished to become pregnant, succeeded and all had at least one live birth. CONCLUSION: With a 97% long-term overall survival rate, limited long-term toxicity, and an excellent reproductive outcome, APE could be regarded as an alternative option to EMA/CO as a standard therapy for high-risk GTN.

[Chemotherapy in epithelial ovarian cancer]. / Chimiothérapie des cancers épithéliaux de l'ovaire.

Chemotherapy is fundamental in the management of epithelial ovarian carcinomas both for early and advanced stages (rarely surgical treatment alone) and in almost every step of the disease. The reference schema combines carboplatin and paclitaxel intravenously. Intraperitoneal chemotherapy also proved its efficacy after complete surgery for advanced disease and should be reserved to trained teams due to its technical constraints and toxicity issues. Modalities of treatment in relapsed and progressive disease depend mainly on the free interval between this diagnosis and the last dose of platinum. Bevacizumab has proven its effectiveness in prolonging progression-free survival in 1st line setting in association with chemotherapy followed by maintenance and in case of relapse or progression both fore platinum sensitive or resistant disease. Finally, a better understanding of ovarian cancer biology will allow us to consider new molecular-targeted agents guided by the specific characteristics of each patient and each tumor.

Quality indicators in ovarian cancer surgery: report from the French Society of Gynecologic Oncology (Societe Francaise d'Oncologie Gynecologique, SFOG).

BACKGROUND: Based on registries, the European experience has been that <50% of patients are treated according to protocols and/or benefit from the minimum required surgery for ovarian cancer. The French Cancer Plan 2009-2013 considers the definition of qualitative indicators in ovarian cancer surgery in France. This endeavour was undertaken by the French Society of Gynaecologic Oncology (SFOG) in partnership with the French National College of Obstetricians and Gynecologists and all concerned learned societies in a multidisciplinary mindset. METHODS: The quality indicators for the initial management of patients with ovarian cancer were based on the standards of practice determined from scientific evidence or expert consensus. RESULTS: The indicators were divided into structural indicators, including material (equipment), human (number and qualification of staff), and organizational resources, process indicators, and outcome indicators. CONCLUSIONS: The enforcement of a quality assurance programme in any country would undoubtedly promote improvement in the quality of care for ovarian cancer patients and would result in a dramatic positive impact on their survival. Such a policy is not only beneficial to the patient, but is also profitable for the healthcare system.

A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group.

BACKGROUND: There is no proven benefit of adjuvant treatment of uterine sarcoma (US). SARCGYN phase III study compared adjuvant polychemotherapy followed by pelvic radiotherapy (RT) (arm A) versus RT alone (arm B) conducted to detect an increase ≥ 20% of 3-year PFS. METHODS: Patients with FIGO stage ≤ III US, physiological age ≤ 65 years; chemotherapy: four cycles of doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/day d1-2, cisplatin 75 mg/m² d3, (API) + G-CSF q 3 weeks. Study was stopped because of lack of recruitment. RESULTS: Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16 stage II, 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, 19 carcinosarcomas. Gr 3-4 toxicity during API (/37 patients): thrombopenia (76%), febrile neutropenia (22%) with two toxic deaths; renal gr 3 (1 patient). After a median follow-up of 4.3 years, 41/81 patients recurred, 15 in arm A, 26 in arm B. The 3 years DFS is 55% in arm A, 41% in arm B (P = 0.048). The 3-year overall survival (OS) is 81% in arm A and 69% in arm B (P = 0.41). CONCLUSION: API adjuvant CT statistically increases the 3 year-DFS of patients with US.

[Outcome of cervical carcinoma with locoregional lymph node involvement by FDG-PET]. / Modalités d'évolution des cancers du col utérin avec atteinte ganglionnaire locorégionale à la TEP-FDG.

PURPOSE: To assess the outcome of cervical carcinoma with positive nodes on fluorodesoxyglucose positon emission tomography scans (FDG-PET). PATIENTS AND METHODS: Patients with cervical carcinoma who had pelvic and/or para-aortic lymph nodes involvement by FDG-PET and treated with a curative intent from 2003 to 2007 were retrospectively studied. All patients received pelvic (and possibly para-aortic) radiotherapy with chemotherapy, followed by brachytherapy, and possibly surgery. The first site of relapse was classified as follows: local, nodal (pelvic or para-aortic) or metastatic. RESULTS: Forty patients were included the study. Median age was 47 years (range: 28-78). Thirty patients had nodal involvement limited to pelvic area and ten had a para-aortic involvement. Median follow-up was 42.5 months (range: 11-85). There were 22 relapses and 20 deaths: 20 due to relapse and one due to late toxicity. Three-year survival is 50 % (95 % confidence interval [CI]: 36-65). First relapse was: metastatic for 33 % (13/40), local for 20 % (8/40) and isolated nodal for 5 % (2/40). Multivariate analysis has revealed that only staging according to International Federation of Gynecology and Obstetrics (FIGO) and para-aortic involvement had a significant impact on survival. Three-year survival was 58 % (CI: 39-74) and 24 % (CI: 7-57) (P=0.009) in patient without and with para-aortic involvement, respectively. CONCLUSION: Para-aortic involvement by FDG-PET is a significant prognostic factor for overall survival. Local control at primary site remains of paramount importance for patient with nodal involvement. Isolated nodal failures are scarce.

How to follow up advanced-stage borderline tumours? Mode of diagnosis of recurrence in a large series stage II-III serous borderline tumours of the ovary.

BACKGROUND: The aim of this study was to describe how recurrences were diagnosed in the largest series of patients treated for an advanced-stage serous borderline ovarian tumour. PATIENTS AND METHODS: From 1973 to 2006, 45 patients with a serous borderline tumour and peritoneal implants relapsed among 162 patients with a follow-up exceeding 1 year. Data concerning recurrences and the mode of diagnosis were reviewed. RESULTS: The median follow-up interval was 8.2 years (range 19-286 months). The mode of diagnosis of recurrences was imaging (n = 19), clinical symptoms (n = 8), cancer antigen (CA) 125 elevation (n = 7), secondary surgery (n = 5) and unknown (n = 6). The median time to recurrence was 31 months (range 4-242 month). The type of recurrence was invasive low-grade serous carcinoma in 14 patients. Five patients died of recurrent tumour. Among the 39 patients with a known mode of diagnosis of recurrence, the most frequent diagnostic method for invasive recurrences was blood CA 125 elevation (6 of 13) and the majority of noninvasive recurrences were diagnosed by imaging (16 of 23). CONCLUSIONS: This study demonstrates that ultrasound is the most relevant follow-up procedure in this context. Nevertheless, the blood CA 125 test is of particular interest for detecting invasive recurrent disease, which is the most crucial event.

[Postoperative morbidity after completion surgery following homogeneous chemoradiation therapy in locally advanced cervical cancer]. / Morbidité de la chirurgie de clôture après radio-chimiothérapie chez des patientes atteintes d'un cancer du col de stade avancé.

OBJECTIVE: To evaluate the morbidity rate in patients following completion surgery (hysterectomy±lymphadenectomy) after chemoradiation therapy (CRT) for an advanced stage cervical cancer. PATIENTS AND METHODS: Patients fulfilling the following inclusion criteria were studied: (1) stage IB2-IVA cervical carcinoma; (2) tumor initially confined to the pelvic cavity; (3) pelvic external radiation therapy with delivery of 45Gy with concomitant chemotherapy (cisplatin 40mg/m(2)/week) followed by utero-vaginal brachytherapy; (4) completion surgery after the end of radiation therapy including at least a hysterectomy. RESULTS: One-hundred and fifty patients treated between 1998 and 2007 fulfilled inclusion criteria. Thirty-seven (25%) patients had 55 post-operative complications (17 had severe complications requiring surgical or radiological treatment). Two deaths related to postoperative morbidity had occurred. The risk of complications was increased with a radical hysterectomy (OR=2.4; P=0.04) and the presence of residual cervical disease (≤1cm: OR=4.3, >1cm: OR=2.5; P=0.01). CONCLUSION: In the present study, the morbidity of completion surgery (based on hysterectomy with or without lymphadenectomy) is very high in patients treated with initial CRT for locally advanced cervical cancer whereas the therapeutic value of such surgery remains unproven.

Hyperthermic intra-peritoneal chemotherapy using oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma. Results of a phase II prospective multicentre trial. CHIPOVAC study.

INTRODUCTION: The aim of the present study was to prospectively evaluate morbidity of intra-peritoneal hyperthermic chemotherapy (HIPEC) using Oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma and, secondly, to study peritoneal recurrence. METHODS: Between 2004 and 2007, 31 patients from 18 to 65 years with FIGO stage IIIC epithelial ovarian carcinoma were treated by surgery and a total of 6 cycles of platinum based chemotherapy. Those patients were eligible for consolidation therapy. We performed a second look laparotomy operation with intra-peritoneal hyperthermic chemotherapy. We used Oxaliplatin 460 mg/m(2) with 2 l/m(2) of dextrose in an open medial laparotomy for a total of 30 min at a temperature of 42-44 degrees C. RESULTS: The grade 3 morbidity rate was 29% (95 CI: 14-45%). Nine patients experienced a total of 13 exploratory laparotomies for intra-abdominal bleeding after HIPEC. Two-year disease free and overall survival were 27% and 67% respectively. As a result of this high level of morbidity the trial was closed. CONCLUSION: Using intra-peritoneal Oxaliplatin associated with hyperthermia as consolidation therapy for advanced ovarian cancer results in a high risk of grade 3 morbidities with only a small benefit on survival.

Impact of adjuvant treatment modalities on the management of patients with stages I-II endometrial stromal sarcoma.

PURPOSE: To explore whether adjuvant treatment options may impact on the prognosis in localized endometrial stromal sarcomas (ESSs; stages I and II). The historical options usually discussed in addition to hysterectomy and bilateral salpingoophorectomy (BSO) are active surveillance, pelvic radiotherapy, chemotherapy and hormonal therapy, alone or in combination. PATIENTS AND METHODS: Among 84 consecutive patients treated for ESS at a single referral center, 54 with localized stage disease were identified. Recurrence-free survival and overall survival were estimated and patterns of recurrences described. Univariate and multivariate analyses were carried out. RESULTS: With a median follow-up of 58 months, only one patient had died. None of the 23 patients who had received adjuvant therapy relapsed compared with 13 of 31 patients who had not received any adjuvant therapy. Adjuvant treatments were hormonal therapy (n = 10) and brachytherapy with/without pelvic radiotherapy (n = 13). Almost the majority of relapses were local (92%) and extra-pelvic metastasis was observed in nearly half of the patients (46%). In the multivariate analysis, the major determinants of relapse-free survival were adjuvant treatment, myometrial invasion (P = 0.005) and no BSO (P = 0.005). CONCLUSIONS: In this series, adjuvant treatment of localized ESSs was associated with the absence of recurrence.

Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes.

BACKGROUND: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer. PATIENTS AND METHODS: Patients had a maximum of three prior chemotherapy lines with no more than two prior platinum-containing regimens and a progression-free interval after the last dose of platinum <12 months. A total dose of 4 mg/m(2)/cycle (0.8 mg/m(2)/day from day 1 to day 5) was administered, repeated every 28 days. RESULTS: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less. CONCLUSION: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity.

[Rare ovarian tumours: therapeutic strategies in 2010, national website observatory for rare ovarian cancers and delineation of referent centers in France]. / Les tumeurs rares de l'ovaire: stratégies thérapeutiques en 2010, Observatoire francophone des tumeurs rares de l'ovaire et émergence des centres de références.

Majorities of the rare ovarian cancers were represented by germ cell tumours and sex cords ovarian tumours with borderline tumours, clear cell carcinoma and mucinous carcinoma and are extremely rare malignant diseases of the ovaries. Tumors of the stromal (Leydig cells) and/or sex cords (Sertoli cells) represent approximately 7% of ovarian cancers and develop from the conjunctive tissue (respectively, interstitial and nurse cells) of the ovaries. All together, they represented less than 5% of the adult malignant and non malignant ovarian tumours. Treatment of rare ovarian tumors is currently as follows. Surgery is the same as that for ovarian adenocarcinoma, with one major difference: conservation of reproductive function in women of reproductive age is usual case for this type of tumor. Chemotherapy for germ cell and sex cords tumors, based on data reported in the literature is the same as that prescribed for testicular germ-cell tumors. For rare epithelial carcinoma, carboplatin plus paclitaxel remains the standard attitude with a well-known less efficiency than for other epithelial subtypes. Surgery, chemotherapy and possible surgical intervention for residual lesions are highly complex. Too rare to be included in randomized studies, treatment of these tumors has benefited from the therapeutic advancements made against testicular germ-cell tumors or with publications using retrospective data. Effectively, some prognostic factors such stage, histology, number of managed patients seems to be prognostic for survival. Because of the rarity of these tumours a specialized website (www.ovaire-rare.org) was developed in France in 2002. Objectives were: to delineate prognostic factors of these very rare diseases, to favour patient inclusion in a clinical trial available online, to provide access to online medical expert forum (disease-related) for complex cases, and finally to demonstrate the impact of these tools on improving medical practice. The website provides very interesting data for a better knowledge of these rare tumors and will possibly help improve medical practice. Since 2008, referent centers were delineated to promote optimal management of these tumors, organization of clinical and molecular research at a national or international level and to elaborate guidelines. The other new scientific data concern surgical procedures for sex cords tumors, evidence for presence of FOXL2 mutation in adult granulosa cell tumors, the use of paclitaxel plus carboplatin for sex cords tumors.

[First line chemotherapy of advanced epithelial ovarian cancer]. / Chimiothérapie de première ligne des adénocarcinomes ovariens de stades avancés.

The treatment of the advanced ovarian adenocarcinoma, most frequently stage at diagnostic, relies on association of surgery and chemotherapy. The current standard is the association carboplatine-paclitaxel. In spite of this treatment, relapses are frequent, and the prognosis thus remains very reserved. Presently the current areas of research aim at both improving the efficiency of treatments and decreasing their toxicity. So the various trials dealt with the use of the other cytotoxics having proved efficiency against relapses either in double-agent therapy or in association in the current standard, or in the administration of the chemotherapy by intra peritoneal way. They also investigated the possibility of pursuing the therapeutic sequence by a treatment of maintenance or consolidation. As for numerous cancerous pathologies, the targeted therapies, notably the antiangiogenic one, represent an important hope in the treatment of the ovarian cancer.

[New drugs and targeted therapeutic agents in ovarian cancer]. / Nouvelles molécules et thérapeutiques moléculaires ciblées dans les adénocarcinomes ovariens de stades avancés.

Ovarian cancers are the leading cause of death from gynaecological malignancies in Western countries. Despite optimal treatment combining surgery and chemotherapy, relapse is observed in the majority of patients. This review aims to present the results of trials having evaluated new drugs in ovarian cancers. Advances in the understanding of cancer biology and more specifically of cell signalling pathways have led to the identification of several potential molecular targets and to the development of new agents directed against these targets. The assessment of targeted therapies is relatively recent in this field. So far, only the results of phase II trials have been published, but many phase III trials are underway. Some targets (HER-2, EGFR) initially regarded as promising have already been abandoned due to the lack of results. The most advanced molecular therapies target angiogenesis (VEGF, VEFGR). PARP and mTOR inhibitors may also represent a significant therapeutic improvement. It remains to confirm the interest of these new approaches by assessing the benefit on overall survival. The goal remains to individualize and to tailor the drugs to the tumour biology, in order to provide personalized treatment to each patient.

[Three-dimensional brachytherapy optimization techniques in the treatment of patients with cervix cancer]. / Apport des techniques de curiethérapie optimisée grâce à l'imagerie tridimensionnelle dans la prise en charge des patientes atteintes d'un cancer du col utérin.

Traditionally, prescription and treatment planning in intracavitary brachytherapy for cervix cancer have used either reference points (mainly points A and B) or reference isodoses (60Gy according to ICRU recommendations) to report doses to the target volume. Doses to critical organs were reported at bladder and rectum ICRU points. This practice has been supported by a long-standing clinical experience that has yielded an acceptable therapeutic ratio. The recent development of imaging has contributed to the improvement in target and organs at risk knowledge. In 2005 and 2006, GEC-ESTRO recommendations publications on 3-D based image brachytherapy have defined the different volumes of interest. These recommendations have been validated with intercomparison delineation studies. With the concomitant development of remote after-loading projectors, provided with miniaturized sources, it is now possible to plan radiation doses by adjusting dwell positions and relative dwell time values. These procedures allow better coverage of the targets while sparing OAR. The recent literature data evidence a significant improvement in local control with no increase in complications. Further studies are needed to better define the dose recommended in both tumour and organs at risk. This is one of the goals of the European study on MRI-guided brachytherapy in locally advanced cervical cancer (EMBRACE) protocol.

[French recommendations for ovarian cancer management during pregnancy]. / Recommandations pour la prise en charge du cancer de l'ovaire pendant la grossesse.

Evaluation of the fetus using prenatal ultrasound has resulted in increased detection of asymptomatic adnexal masses during pregnancy. Such masses are rarely malignant (1/10 000 to 1/50 000 pregnancies), but the possibility of borderline or cancer must be considered. It is a common assumption by both patients and physicians that if an ovarian cancer is diagnosed during pregnancy, treatment necessitates sacrificing the well-being of the fetus. However, in most cases, it is possible to offer appropriate treatment to the mother without placing the fetus at serious risk. The care of a pregnant woman with cancer involves evaluation of sometimes competing maternal and fetal risks and benefits. These recommendation approaches attempt to balance these risks and benefits; however, they should be considered advisory and should not replace specific interdisciplinary consultation with specialists in maternal-fetal medicine, gynecologic oncology, and pediatrics, as well as imaging and pathology, as needed. Second level ultrasound including Doppler is needed. MRI is not often necessary, and CA 125 is of low contribution. We suggest surgery be performed after 15 SA for ovarian masses which (1) persist into the second trimester, (2) are greater than 5 to 10 cm in diameter, or (3) have solid or mixed solid and cystic ultrasound characteristics. During antepartum surgical staging and debulking, homolateral salpingo-oophorectomy and peritoneal cytology and exploration are necessary. Women found to have advanced stage epithelial ovarian cancer should consider having completion of the debulking of the reproductive organs at the conclusion of the pregnancy. If chemotherapy is indicated, we recommend delaying administration, if possible, after the delivery or at least after 20 SA in order to minimize the potential fetal toxicity.