Smith M. R., Saad F., Chowdhury S., Oudard S., Hadaschik B. A., Graff J. N., Olmos D., Mainwaring P. N., Lee J. Y., Uemura H., Lopez-Gitlitz A., Trudel G. C., Espina B. M., Shu Y., Park Y. C., Rackoff W. R., Yu M. K., Small E. J.   Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.  N. Engl. J. Med..  2018 ;378 :1408-1418

BACKGROUND: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. METHODS: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. RESULTS: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%). CONCLUSIONS: Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN number, NCT01946204 .).

Scherpereel A., Willemin M. C., Wasielewski E., Dhalluin X.   [Anti-tumor immunotherapy in malignant pleural mesothelioma].  Rev Mal Respir.  2018 ;35 :465-476

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a quite rare cancer, but with increasing incidence, that is usually induced by previous asbestos exposure. Its prognosis is poor and there is no validated curative therapy to date. Surgery of MPM, done only by few expert teams within a multimodal treatment is of limited and still disputed value. The standard treatment of MPM, relying on first-line chemotherapy by combined cisplatin-pemetrexed is often poorly effective, even if combination with bevacizumab anti-VEGF antibodies has slightly improved the results. Moreover, no second line treatment is recommended in case of failure of this chemotherapy. Therefore, the search of new therapies or strategies is crucial and the recruitment of patients in clinical trials is highly encouraged. BACKGROUND: Among the treatments under investigation, various anti-tumour immunotherapies, in particular immune checkpoints inhibitors (ICI), currently exhibit the most promising preliminary results. First data from the phase II, randomized "IFCT MAPS-2", recently presented during the 2017 ASCO meeting, confirmed the value of ICI in MPM patients in cases of chemotherapy failure. OUTLOOK AND CONCLUSIONS: However, several exciting immunotherapies other than ICI are presently being evaluated in MPM and are reported in this article. Moreover, many questions still need to be answered about immunotherapy: what is its potential value as first line treatment? How to target the best candidates for these treatments? Which combinations between immunotherapy and standard chemotherapy, targeted therapies, surgery or radiotherapy? Finally, it is now essential that every clinician has sufficient knowledge about the possible toxicities of immunotherapy.

Sauvan M., Chabbert-Buffet N., Canis M., Collinet P., Fritel X., Geoffron S., Legendre G., Wattier J. M., Fernandez H.   [Medical treatment for the management of painful endometriosis without infertility: CNGOF-HAS Endometriosis Guidelines].  Gynecol Obstet Fertil Senol.  2018 ;46 :267-272

OBJECTIVE: To provide clinical practice guidelines for the management of painful endometriosis in women without infertility. METHODS: Systematic review of the literature literature since 2006, level of evidence rating, external proofreading and grading of the recommendation grade by an expert group according to HAS methodology. RESULTS: Combined hormonal contraceptives (COP) and the levonorgestrel-releasing intra-uterin system (LNG-IUS) are recommended as first-line hormonal therapies for the treatment of painful endometriosis (grade B). Second-line therapy relies on oral desogestrel microprogestative, etonogestrel-releasing implant, GnRH analogs (GnRHa) and dienogest (grade C). It is recommended to use add-back therapy containing estrogen in association with GnRHa (grade B). After endometriosis surgery, hormonal treatment relying on COP or LNG-IUS is recommended to prevent pain recurrence (grade B). COP is recommended to reduce the risk of endometrioma recurrence after surgery (grade B) but the prescription of GnRHa is not recommended (grade C). Continuous COP is recommended in case of dysmenorrhea (grade B). GnRHa is not recommended as first line endometriosis treatment for adolescent girl because of the risk of bone demineralization (grade B). The management of endometriosis-induced chronic pain requires an interdisciplinary evaluation. Physical therapies improving the quality of life such as yoga, relaxation or osteopathy can be proposed (expert agreement). Promising medical alternatives are currently under preclinical and clinical evaluation.

Santulli P., Collinet P., Fritel X., Canis M., d''Argent E. M., Chauffour C., Cohen J., Pouly J. L., Boujenah J., Poncelet C., Decanter C., Borghese B., Chapron C.   [Management of assisted reproductive technology (ART) in case of endometriosis related infertility: CNGOF-HAS Endometriosis Guidelines].  Gynecol Obstet Fertil Senol.  2018 ;46 :373-375

The management of endometriosis related infertility requires a global approach. In this context, the prescription of an anti-gonadotropic hormonal treatment does not increase the rate of non-ART (assisted reproductive technologies) pregnancies and it is not recommended. In case of endometriosis related infertility, the results of IVF management in terms of pregnancy and birth rates are not negatively affected by the existence of endometriosis. Controlled ovarian stimulation during IVF does not increase the risk of endometriosis associated symptoms worsening, nor accelerate the intrinsic progression of endometriosis and does not increase the rate of recurrence. However, in the context of IVF management for women with endometriosis, pre-treatment with GnRH agonist or with oestrogen/progestin contraception improve IVF outcomes. There is currently no evidence of a positive or negative effect of endometriosis surgery on IVF outcomes. Information on the possibilities of preserving fertility should be considered, especially before surgery.

Saddiki N., Hennion S., Viard R., Ramdane N., Lopes R., Baroncini M., Szurhaj W., Reyns N., Pruvo J. P., Delmaire C.   Encoding and immediate retrieval tasks in patients with epilepsy: a functional MRI study of verbal and visual memory.  J Neuroradiol.  2018 ;45 :157-163

PURPOSE: Medial lobe temporal structures and more specifically the hippocampus play a decisive role in episodic memory. Most of the memory functional magnetic resonance imaging (fMRI) studies evaluate the encoding phase; the retrieval phase being performed outside the MRI. We aimed to determine the ability to reveal greater hippocampal fMRI activations during retrieval phase. MATERIALS AND METHODS: Thirty-five epileptic patients underwent a two-step memory fMRI. During encoding phase, subjects were requested to identify the feminine or masculine gender of faces and words presented, in order to encourage stimulus encoding. One hour after, during retrieval phase, subjects had to recognize the word and face. We used an event-related design to identify hippocampal activations. RESULTS: There was no significant difference between patients with left temporal lobe epilepsy, patients with right temporal lobe epilepsy and patients with extratemporal lobe epilepsy on verbal and visual learning task. For words, patients demonstrated significantly more bilateral hippocampal activation for retrieval task than encoding task and when the tasks were associated than during encoding alone. Significant difference was seen between face-encoding alone and face retrieval alone. CONCLUSIONS: This study demonstrates the essential contribution of the retrieval task during a fMRI memory task but the number of patients with hippocampal activations was greater when the two tasks were taken into account.

Rouvière O., Puech P., Renard-Penna R., Claudon M., Roy C., Mège-Lechevallier F., Decaussin-Petrucci M., Dubreuil-Chambardel M., Magaud L., Remontet L., Ruffion A., Colombel M., Crouzet S., Schott A. M., Lemaitre L., Rabilloud M., Grenier N.   Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study.  Lancet Oncol..  2018 ;20 :100-109
Raichi A., Marcq G., Fantoni J. C., Puech P., Villers A., Ouzzane A.   [Active surveillance in prostate cancer: Assessment of MRI in the selection and follow-up of patients].  Prog. Urol..  2018 ;28 :416-424

AIM: To evaluate the contribution of multiparametric MRI (MRI) and targeted biopsies (TB) in the selection and follow-up of patients under active surveillance (AS). METHODS: A single-center, retrospective cohort study on 131 patients in AS, with following criteria:6 and/or a maximum tumor length>5mm. RESULTS: Overall, 29 patients (22.1 %) were reclassified. Reclassification free survival rate was 93 % and 70 % at 1 year and 4 years respectively. Reclassification independent risk factors were: PSA density>0.15ng/mL/cm(3) (RR=2.75), PSA doubling time<3 years (RR=9.28), suspicious lesion on MRI diagnosis (RR=2.79) and occurrence of MRI progression during follow-up (RR=2). Sensitivity, specificity, PPV and NPV of MRI to assess progression for reclassification were 61 %, 69 %, 45 % and 81 %, respectively. CONCLUSION: For patients under AS, mpMRI decreases reclassification rates over time through better initial detection of significant cancers. Its high NPV makes it an efficient monitoring tool to distinguish patients with low risk of reclassification. LEVEL OF EVIDENCE: 4.

Quidet M., Zairi F., Boyle E., Facon T., Vieillard M. H., Machuron F., Lejeune J. P., Assaker R.   Evaluation of the relevance of surgery in patients with multiple myeloma harboring symptomatic spinal involvement: a retrospective case series.  World Neurosurg.  2018 ;114 :e356-e365

BACKGROUND: Multiple myeloma spinal involvement can lead to bone fractures and neurologic impairment that can severely alter quality of life. The role of surgery is controversial, given its high morbidity, and the lack of evidence. We hereby aim to evaluate efficacy and safety of surgery in the management of symptomatic spinal lesions in patients with multiple myeloma. METHODS: We included all patients operated on for a myeloma-related spinal lesion in our institution between 2007 and 2015. Demographic, clinical, and surgical data were collected as well as hematologic profiles. We retrospectively assessed the surgical success of the procedures, if at 3 months the patient fulfilled the following 4 criteria: pain relief, ability to walk, spinal stability, and no relevant morbidity. RESULTS: Thirty-six men and 19 women, with a median age of 62 years, were included. Seventeen patients underwent an emergency intervention, whereas 38 patients underwent elective surgery. At 3 months, 88.2% and 96.1%, respectively, of patients experienced pain relief and were able to walk. Spinal stability was considered satisfactory for 94.1% of patients. We reported 8 major complications in 8 patients. Altogether, 34 patients (61.8%) fulfilled all criteria for surgical success. An International Staging System score of 1 and the absence of previous chemotherapy were significantly associated with surgical success. CONCLUSIONS: Management of myeloma-related spine lesions requires a multidisciplinary approach. Surgery rapidly provides both decompression and stabilization. Using a strict patient-specific evaluation, we reported rewarding functional results, with acceptable morbidity. Surgery for multiple myeloma vertebral lesions seems to be a valuable option for carefully selected patients.

Ploteau S., Merlot B., Roman H., Canis M., Collinet P., Fritel X.   [Minimal and mild endometriosis: Impact of the laparoscopic surgery on pelvic pain and fertility. CNGOF-HAS Endometriosis Guidelines].  Gynecol Obstet Fertil Senol.  2018 ;46 :273-277

Minimal and mild endometriosis (stage 1 and 2 AFSR) can lead to chronic pelvic pain and infertility but can also exist in asymptomatic patients. The prevalence of asymptomatic patients with minimal and mild endometriosis is not clear but typical endometriosis lesions are found in about 5 to 10% of asymptomatic women and more than 50% of painful and/or infertile women. Laparoscopic treatment of minimal and mild endometriotic lesions is justified in case of pelvic pain because their destruction decrease significatively the pain compared with diagnostic laparoscopy alone. In this context, ablation and excision give identical results in terms of pain reduction. Moreover, literature shows no interest in uterine nerve ablation in case of dysmenorrhea due to minimal and mild endometriosis. Then, it is recommended to treat these lesions during a laparoscopy realised as part of pelvic pain. On the other hand, it is not recommended to treat asymptomatic patients. With regard to treatment of minimal and mild endometriosis in infertile patients, only two studies can be selected and both show that laparoscopy with excision or ablation and ablation of adhesions is superior to diagnostic laparoscopy alone in terms of pregnancy rate. However, it is not recommended to treat these lesions when they are asymptomatic because there is no evidence that they can progress with symptomatic disease. There is no study assessing the interest to treat these lesions when they are found fortuitously. Adhesion barrier utilisation permits to reduce post-operative adhesions, however literature failed to demonstrate the clinical profit in terms of reduction of the risk of pain or infertility.

Pierot L., Spelle L., Berge J., Januel A. C., Herbreteau D., Aggour M., Piotin M., Biondi A., Barreau X., Mounayer C., Papagiannaki C., Lejeune J. P., Gauvrit J. Y., Costalat V.   Feasibility, complications, morbidity, and mortality results at 6 months for aneurysm treatment with the Flow Re-Direction Endoluminal Device: report of SAFE study.  J Neurointerv Surg.  2018 ;10 :765-770

BACKGROUND AND PURPOSE: Flow diverters are increasingly used for the treatment of intracranial aneurysms. Evaluation of the first devices available for clinical use showed high efficacy of this treatment although safety results were worse compared with coiling or balloon-assisted coiling. The Safety and Efficacy Analysis of FRED Embolic Device in Aneurysm Treatment (SAFE) trial is a single-arm, multicenter, prospective study conducted to precisely analyze the safety and efficacy of the FRED and FRED Jr devices. METHODS: Unruptured and recanalized aneurysms located in the anterior circulation treated with FRED and FRED Jr were prospectively included. Adverse events were independently evaluated by a Clinical Event Committee with a vascular neurosurgeon and an interventional neuroradiologist. Primary safety outcome measures were morbidity and mortality rates at 6 months after treatment. RESULTS: A total of 103 patients/aneurysms were included in 13 interventional neuroradiology (INR) centers. Aneurysm locations were supraclinoid internal carotid artery (ICA) in 71 (68.9%), cavernous ICA in 15 (14.6%), anterior cerebral artery or anterior communicating artery in nine (8.7%), and middle cerebral artery in eight (7.8%). Aneurysms were small (<10 mm) in 71 patients (68.9%). Treatment was successfully performed in 98/103 patients (95.1%). Thromboembolic (TE) complications occurred in 5/103 patients (4.9%), intraoperative rupture in 2/103 patients (1.9%), delayed aneurysm rupture in 1/103 patient (1.0%), and delayed hematoma occurred in 1/103 patient (1.0%). Six-months' mortality and morbidity rates were 1/102 (1.0%) and 2/102 (2.0%), respectively. CONCLUSIONS: Aneurysm treatment with the FRED device is safe with low mortality (1.0%) and morbidity (2.0%). CLINICAL TRIAL REGISTRATION: NCT02921698.