Publications

OBJECTIVE: This study aims to describe the clinical and molecular presentation of pediatric neurofibromatosis type 2 (NF2) and the subsequent management of vestibular schwannomas (VS) and hearing rehabilitation. METHODS: This is a single-center retrospective study of neurofibromatosis type 2 diagnosed before the age of 18 years old from 1997. Natural history of vestibular schwannomas and surgical outcomes were evaluated using volumetric MRI, hearing, and facial nerve assessment. Patients included in chemotherapy protocols were excluded. RESULTS: From a database of 80 patients followed up for NF2 on a regular basis, 25 patients were eligible (11 sporadic cases, 14 inherited in five families). The mean age at diagnosis was 11.6 years old. The average clinical follow-up was 6.5 years. NF2 mutation was identified in 81 % of the probands. The average growth rate based on the maximum linear diameter (DGR) was 1.68 mm/year (n = 33, average follow-up 4.22 years) and 545 mm(3)/year in volumetric assessment (VGR) for VS larger than 1 cm (n = 21, average follow-up 3.4 years). In unoperated ears, hearing was stable in about 50 % of ears. The mean change in dB HL was 9.5 dB/year for pure-tone average and 3.5 for speech-recognition threshold (n = 34, 5.5 years 1-12). Eight children required removal through a translabyrinthine approach (mean follow-up was 4.5 years), six patients were operated on for hearing preservation (mean postoperative follow-up 4.3 years). Six patients were eligible for hearing rehabilitation with cochlear implantation (I), and five received placement of an auditory brainstem implant. CONCLUSION: Early diagnosis and treatment of small growing VS should be carefully discussed considering familial history and possible rehabilitation with a CI.

OBJECTIVES: The receptor tyrosine kinase MET is essential to embryonic development and organ regeneration. Its deregulation is associated with tumorigenesis. While MET gene amplification and mutations leading to MET self-activation concern only a few patients, a high MET level has been found in about half of the non-small cell lung cancers (NSCLCs) tested. How this affects MET activation in tumors is unclear. Also uncertain is the prognostic value, in cancer, of a phenomenon well described in cell models: MET shedding, i.e. its cleavage by membrane proteases leading to release of a soluble fragment into the medium. MATERIALS AND METHODS: A prospective cohort of 39 NSCLC patients was constituted at diagnosis or soon after. Normal tissues, tumor tissues, and blood samples were obtained. This allowed, for the same patient, synchronous determination of (i) the MET level in the tumor, (ii) receptor phosphorylation, and (iii) the concentration of soluble MET fragment (sMET) in the serum. RESULTS: After confirming the adequacy of an ELISA for measuring the serum level of sMET, we found no correlation between this level and the concentration of MET in tumors, as evaluated by immunohistochemistry and western blotting. Nevertheless, all but one tumor displaying a high MET level also displayed receptor phosphorylation, restricted to a small number of tumor cells. CONCLUSION: Our results thus demonstrate that the serum level of sMET is not indicative of the amount of MET present in the tumor cells and cannot be used as a biomarker for therapeutic purposes. However, MET scoring of tumor biopsies could be a first step prior to determination of MET receptor activation in high-MET tumors.

PURPOSE: To obtain an overview of the degree of discrepancy between current clinical practice of prostate magnetic resonance imaging (MRI) in France and recommendations. MATERIALS AND METHODS: A brief survey was sent to 1229 members of the French society of urology in order to identify their indications of prostate MRI and its impact on patient management. The urologists were asked to answer several questions regarding age, practice modality, prostate MRI examinations (technique, indication before first biopsy, second biopsy, cancer staging, active surveillance, recurrence, focal therapy) and quality of reports. RESULTS: A total of 445 responses were received (participation rate of 36%). The mean delay for obtaining an appointment for prostate MRI ranged between 15-30 days in 54%. Fifty-four percent of MRI reports contained a PIRADS score and 23% a Likert score. The indications of multiparametric-MRI were tumor detection/location prior to repeat biopsy (90%), cancer staging (85%), management of patients under active surveillance (85%), selection of candidates to focal therapy (63%), tumor detection/location in biopsy naive patients (53%), detection of local recurrence after radical (51%). Only 119 urologists (28.6%) had access to image fusion (MRI and transrectal ultrasound) and 351 (85.4%) used cognitive fusion. Mostly, targeted biopsies are done by urologists alone (nearly 80%), a very few are done by radiologists (8%) or by the two of them in collaboration (12%). CONCLUSION: The majority of urologists consider that prostate MRI is essential for the management of patients with prostate cancer. Practices are ahead of recommendations particularly before the first biopsy and in active surveillance.

BACKGROUND: Complete and homogeneous illumination of the pleural cavity is essential to the success of photodynamic therapy (PDT) for mesothelioma, but remains a challenge. Knowing the repartition and propagation of light around the light applicator could be the first step towards optimizing dosimetry. Here we propose a characterization method of the illumination profile of a specific light device. METHODS: The light wand, made of a cylindrical diffuser located inside an endotracheal tube, was fixed in a tank filled with dilute 0.01% intralipid. Light dosimetry was performed around the tip of the wand using two complementary methods: direct measurements of light power with an isotropic probe and measurements of light distribution characterization. RESULTS: Dosimetry with the isotropic probe showed an ellipse-shaped illumination. An optimized effective attenuation coefficient was deduced. Combined with the spatial representation, a theoretical illumination profile was established with iso-surfaces of fluence rate, defining a gradient light dose according to the distance from the diffuser. CONCLUSION: A theoretical illumination profile of a light device was established and could be part of an intra-operative dosimetry system to improve light delivery during intrapleural PDT.

BACKGROUND: On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma. METHODS: After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety. RESULTS: At a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). The rate of overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo group (hazard ratio for death, 0.72; 95.1% CI, 0.58 to 0.88; P=0.001). The rate of distant metastasis-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo group (hazard ratio for death or distant metastasis, 0.76; 95.8% CI, 0.64 to 0.92; P=0.002). Adverse events of grade 3 or 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo group. Immune-related adverse events of grade 3 or 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab group, 5 patients (1.1%) died owing to immune-related adverse events. CONCLUSIONS: As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00636168 , and EudraCT number, 2007-001974-10 .).

We report an additional case of a ruptured basilar trunk perforator aneurysm, for which an endovascular treatment was initially planned, but aborted due to the spontaneous regression of the aneurysm. Thus, a conservative management consisting on a close follow-up was decided that confirmed the favorable radiological outcome. Spontaneous regression of such aneurysm should be well-known by neurosurgeons and neuroradiologists in order to prevent the potential iatrogenic effects of the related treatment modalities.