Davies M. A., Saiag P., Robert C., Grob J. J., Flaherty K. T., Arance A., Chiarion-Sileni V., Thomas L., Lesimple T., Mortier L., Moschos S. J., Hogg D., Márquez-Rodas I., Del Vecchio M., Lebbé C., Meyer N., Zhang Y., Huang Y., Mookerjee B., Long G. V.   Dabrafenib plus trametinib in patients with BRAF(V600)-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial.  Lancet Oncol..  2017 ;18 :863-873
Kluger N., Lebbe C., Grange F., Mortier L., Robert C.   Dermatological oncology: advanced melanoma, side effects of anti-PD1, place of monotherapy in the first line, treatment of metastatic melanoma.  Ann. Dermatol. Venereol..  2017 ;144 :S11-S14
Dupont C., Mordon S., Deleporte P., Reyns N., Vermandel M.   A novel device for intraoperative photodynamic therapy dedicated to glioblastoma treatment.  Future Oncol..  2017 ;13 :2441-2454

AIM: Photodynamic therapy (PDT) appears to be a valuable new treatment modality for cancer therapy. Studies have reported successful application of PDT for glioblastoma. Here, we introduce a new device dedicated to intraoperative PDT delivered early after fluoro-guided resection combined with a transfer function that determines the treatment time based on the size of the surgical resection cavity. MATERIALS & METHODS: First, we describe the device, which is composed of a trocar, a balloon filled with a diffusing solution, and a fiber guide in which a cylindrical light diffuser is inserted. Ex vivo experiments were performed to measure the fluence rate inside biological tissues. A calibration factor was defined to convert power measurements into fluence rate values. Calf brains were used to simulate light propagation in human brain tissue, and the photosensitizer administration effect on optical properties was discussed. The temperature elevation during illumination was evaluated. RESULTS: Light power was measured in tissues surrounding the device during ex vivo experiments. Using the previously characterized calibration factor, power measurements were converted to fluence rate values to obtain the transfer function. No thermal elevation was observed during a 2-h temperature test, and the impact of protoporphyrin IX on brain optical properties was considered negligible. CONCLUSION: A discussion of experimental precision is presented. The light duration determined by the abacus had a standard deviation of <1 min. This value is weak compared with the total illumination time necessary to treat one patient. The main advantage of our device lies in its straightforward implementation of intraoperative PDT for neurosurgery with acceptable dosimetry and easy treatment time.

Azais H., Canlorbe G., Kerbage Y., Grabarz A., Collinet P., Mordon S.   Image-guided surgery in gynecologic oncology.  Future Oncol..  2017 ;13 :2321-2328

Image-guided surgery is a relevant way to reduce surgical morbidity and maximize cytoreductive surgery approach especially in ovarian cancer. Sentinel lymph node detection is a promising approach to avoid radical lymph node dissection and is slightly becoming standard in daily practice in endometrial and cervical cancer surgery even if it needs to be evaluated more precisely. Regarding carcinomatosis of ovarian origin, detection and treatment of microscopic disease could be appropriate to avoid local recurrences. Photodiagnosis and photodynamic therapy are innovative techniques that allow to precise limits of excision (fluorescence-guided surgery) and to treat microscopic disease. Further developments of those strategies are necessary to become standard diagnosis tools and treatment options.

Ledu N., Rubod C., Piessen G., Roman H., Collinet P.   Management of deep infiltrating endometriosis of the rectum: Is a systematic temporary stoma relevant?.  J Gynecol Obstet Hum Reprod.  2017 ;47 :1-7

STUDY OBJECTIVE: To assess the value of performing a protective stoma in patients operated for rectal endometriosis. MATERIAL AND METHODS: From June 2009 to December 2011, 47 patients were operated for rectal endometriosis by segmental or discoid resection in 4 different centers. Two groups were formed: one with protective stoma (group S), n=33 and one without protective stoma (group NS), n=14. Data were collected from the CIRENDO database. MEASUREMENTS AND MAIN RESULTS: Postoperative complication rate of group NS was 57% against 48% in group S (P=0.75). There was an increasing trend of the rate of anastomotic leakage in group S as compared to group NS: 21% against 3% (P=0.073). All 3 patients of group NS with an anastomotic leakage were reoperated and the group S patient had medical treatment. In a center, digestive operative time was not necessarily performed in association with a gastrointestinal surgeon. All patients in group S had a restoration of continuity in about 3 months. Two of them had dilation of anastomotic stricture and 3 others showed a transient postoperative ileus during this recovery. Quality of life was assessed by the MOS SF-36 and significantly improved in both groups thanks to the intervention. CONCLUSION: Temporary digestive stoma in patients operated for rectal endometriosis has to be considered because in our study, it seems reducing complications such as anastomotic leakage. This must be confirmed with studies with larger numbers.

Ascierto P. A., Del Vecchio M., Robert C., Mackiewicz A., Chiarion-Sileni V., Arance A., Lebbé C., Bastholt L., Hamid O., Rutkowski P., McNeil C., Garbe C., Loquai C., Dreno B., Thomas L., Grob J. J., Liszkay G., Nyakas M., Gutzmer R., Pikiel J., Grange F., Hoeller C., Ferraresi V., Smylie M., Schadendorf D., Mortier L., Svane I. M., Hennicken D., Qureshi A., Maio M.   Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial.  Lancet Oncol..  2017 ;18 :611-622

BACKGROUND: A phase 2 trial suggested increased overall survival and increased incidence of treatment-related grade 3-4 adverse events with ipilimumab 10 mg/kg compared with ipilimumab 3 mg/kg in patients with advanced melanoma. We report a phase 3 trial comparing the benefit-risk profile of ipilimumab 10 mg/kg versus 3 mg/kg. METHODS: This randomised, double-blind, multicentre, phase 3 trial was done in 87 centres in 21 countries worldwide. Patients with untreated or previously treated unresectable stage III or IV melanoma, without previous treatment with BRAF inhibitors or immune checkpoint inhibitors, were randomly assigned (1:1) with an interactive voice response system by the permuted block method using block size 4 to ipilimumab 10 mg/kg or 3 mg/kg, administered by intravenous infusion for 90 min every 3 weeks for four doses. Patients were stratified by metastasis stage, previous treatment for metastatic melanoma, and Eastern Cooperative Oncology Group performance status. The patients, investigators, and site staff were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study treatment. This study is completed and was registered with ClinicalTrials.gov, number NCT01515189. FINDINGS: Between Feb 29, and July 9, 2012, 727 patients were enrolled and randomly assigned to ipilimumab 10 mg/kg (365 patients; 364 treated) or ipilimumab 3 mg/kg (362 patients; all treated). Median follow-up was 14.5 months (IQR 4.6-42.3) for the ipilimumab 10 mg/kg group and 11.2 months (4.9-29.4) for the ipilimumab 3 mg/kg group. Median overall survival was 15.7 months (95% CI 11.6-17.8) for ipilimumab 10 mg/kg compared with 11.5 months (9.9-13.3) for ipilimumab 3 mg/kg (hazard ratio 0.84, 95% CI 0.70-0.99; p=0.04). The most common grade 3-4 treatment-related adverse events were diarrhoea (37 [10%] of 364 patients in the 10 mg/kg group vs 21 [6%] of 362 patients in the 3 mg/kg group), colitis (19 [5%] vs nine [2%]), increased alanine aminotransferase (12 [3%] vs two [1%]), and hypophysitis (ten [3%] vs seven [2%]). Treatment-related serious adverse events were reported in 133 (37%) patients in the 10 mg/kg group and 66 (18%) patients in the 3 mg/kg group; four (1%) versus two (<1%) patients died from treatment-related adverse events. INTERPRETATION: In patients with advanced melanoma, ipilimumab 10 mg/kg resulted in significantly longer overall survival than did ipilimumab 3 mg/kg, but with increased treatment-related adverse events. Although the treatment landscape for advanced melanoma has changed since this study was initiated, the clinical use of ipilimumab in refractory patients with unmet medical needs could warrant further assessment. FUNDING: Bristol-Myers Squibb.

Alkeraye S., Nguyen T., Le Guern A., Alhaddad M., Mortier L.   Mucinous adenocarcinoma in association with hidradenitis suppurativa.  Clin. Exp. Dermatol..  2017 ;42 :550-551
Querleu D., Darai E., Lecuru F., Rafii A., Chereau E., Collinet P., Crochet P., Marret H., Mery E., Thomas L., Vifiefranque V., Floquet A., Planchamp F.   Primary management of endometrial carcinoma. Joint recommendations of the French society of gynecologic oncology (SFOG) and of the French college of obstetricians and gynecologists (CNGOF).  Gynecol. Obstet. Fertil. Senol..  2017 ;45 :715-725

OBJECTIVES: The management of endometrial carcinoma is constantly evolving. The SFOG and the CNGOF decided to jointly update the previous French recommendations (Institut national du cancer 2011) and to adapt to the French practice the 2015 recommendations elaborated at the time of joint European consensus conference with the participation of the three concerned European societies (ESGO, ESTRO, ESMO). MATERIAL AND METHODS: A strict methodology was used. A steering committee was put together. A systematic review of the literature since 2011 has been carried out. A first draft of the recommendations has been elaborated, with emphasis on high level of evidence. An external review by users representing all the concerned discipines and all kinds of practice was completed. Three hundred and four comments were sent by 54 reviewers. RESULTS: The management of endometrial carcinoma requires a precise preoperative workup. A provisional estimate of the final stage is provided. This estimation impact the level of surgical staging. Surgery should use a minimal invasive approach. The final pathology is the key of the decision concerning adjuvant therapy, which involves surveillance, radiation therapy, brachytherapy, or chemotherapy. CONCLUSION: The management algorithms allow a fast, state of the art based, answer to the clinical questions raised by the management of endometrial cancer. They must be used only in the setting of a multidisciplinary team at all stages of the management.

Frouin F., Melodelima D., de la Chapelle M. L., Vermandel M.   Reporting New Methods and New Results in Biomedical Engineering: Why Not Choosing IRBM?.  IRBM.  2017 ;38 :1-2
Leroy H. A., Vermandel M., Vignion-Dewalle A. S., Leroux B., Maurage C. A., Duhamel A., Mordon S., Reyns N.   Interstitial photodynamic therapy and glioblastoma: Light fractionation in a preclinical model.  Lasers Surg. Med..  2017 ;49 :506-515

BACKGROUND: Glioblastoma is a high-grade cerebral tumor with local recurrence and poor outcome. Photodynamic therapy (PDT) is a localized treatment based on the light activation of a photosensitizer (PS) in the presence of oxygen, which results in the formation of cytotoxic species. The delivery of fractionated light may enhance treatment efficacy by reoxygenating tissues. OBJECTIVE: To evaluate the efficiency of two light-fractionation schemes using immunohistological data. MATERIALS AND METHODS: Human U87 cells were grafted into the right putamen of 39 nude rats. After PS precursor intake (5-ALA), an optic fiber was introduced into the tumor. The rats were randomly divided into three groups: without light, with light split into 2 fractions and with light split into 5 fractions. Treatment effects were assessed using brain immunohistology. RESULTS: Fractionated treatments induced intratumoral necrosis (P < 0.001) and peritumoral edema (P = 0.009) associated with a macrophagic infiltration (P = 0.006). The ratio of apoptotic cells was higher in the 5-fraction group than in either the sham (P = 0.024) or 2-fraction group (P = 0.01). Peripheral vascularization increased after treatment (P = 0.017), and these likely new vessels were more frequently observed in the 5-fraction group (P = 0.028). CONCLUSION: Interstitial PDT with fractionated light resulted in specific tumoral lesions. The 5-fraction scheme induced more apoptosis but led to greater peripheral neovascularization. Lasers Surg. Med. 49:506-515, 2017. (c) 2016 Wiley Periodicals, Inc.