This INDYGO trial assesses the feasibility of intraoperative 5-aminolevulinic acid PDT, a novel seamless approach to treat GBM. The technology is easily embeddable within the reference treatment at a low-incremental cost. The safety of this new treatment modality is a preliminary requirement before a multicenter randomized clinical trial can be further conducted to assess local control improvement by treating infiltrating and nonresected GBM cells.

Delineation of organs at risk (OARs) is a crucial step in surgical and treatment planning in brain cancer, where precise OARs volume delineation is required. However, this task is still often manually performed, which is time-consuming and prone to observer variability. To tackle these issues a deep learning approach based on stacking denoising auto-encoders has been proposed to segment the brainstem on magnetic resonance images in brain cancer context. Additionally to classical features used in machine learning to segment brain structures, two new features are suggested. Four experts participated in this study by segmenting the brainstem on 9 patients who underwent radiosurgery. Analysis of variance on shape and volume similarity metrics indicated that there were significant differences (p<0.05) between the groups of manual annotations and automatic segmentations. Experimental evaluation also showed an overlapping higher than 90% with respect to the ground truth. These results are comparable, and often higher, to those of the state of the art segmentation methods but with a considerably reduction of the segmentation time.

OBJECTIVE Ruptured arteriovenous malformations (AVMs) are often obliterated after emergency microsurgical treatment. However, some studies have reported AVM recurrence after the obliteration of ruptured AVMs. The authors report their experience with AVM recurrence after successful microsurgical treatment of ruptured AVMs. METHODS The authors reviewed the medical data of 139 consecutive patients who underwent microsurgery at the authors' institution for ruptured AVM between 2002 and 2012. Each patient underwent a conventional cerebral angiography examination immediately after the surgery. Subsequent follow-ups were performed with MR angiography after 6 months, and, if there was no indication of AVM recurrence, patients were followed up with conventional cerebral angiography between 1 and 2 years after the treatment; pediatric patients were followed up until age 18 years. Recurrence was defined as new radiological evidence of an AVM at the site of a ruptured AVM or a new hemorrhage in patients with angiographically documented AVM obliteration on postoperative angiograms. RESULTS The mean age of the patients at the time of ruptured AVM diagnosis was 30.8 years (SD ± 5, range 4-69 years), and 44 of the patients were younger than 18 years (the mean age at diagnosis in this pediatric subgroup was 11.4 years [range 4-17.9 years]). Complete AVM obliteration after the initial microsurgery was observed in 123 patients (89.5%). Reappearance of an AVM was noted in 7 patients between 12 and 42 months after the treatment, and all of these patients were younger than 18 years. The recurrent AVM was located in an eloquent zone in 4 patients, and deep venous drainage was noted in 3 patients. Radiosurgery was performed in 6 of these patients, and 1 patient underwent another microsurgical procedure. The authors noted only one rebleeding due to an AVM recurrence during the latency period after radiosurgery. CONCLUSIONS The recurrence of an AVM is fairly rare and affects mostly pediatric patients. Therefore, especially in children, long-term angiographic follow-up is required to detect AVM recurrence or an AVM remnant. The authors stress the need for discussion involving a multidisciplinary neurosurgical team to decide on treatment in cases of any AVM recurrence or remnant.

This article contains studies performed using animals. All applicable institutional and national guidelines for the care and use of animals were followed. The experimental design was declared to the French National Ethics Committee under reference number 04870.01. Authorship: M. Vermandel designed the study, cosupervised the study and wrote the manuscript; M. Quidet performed some of the experiments and helped write the manuscript; AS. Vignion-Dewalle performed the statistical analysis and helped write the manuscript; HA Leroy performed some of the experiments and read/corrected the manuscript; B. Leroux performed some of the experiments and reported results; and S. Mordon and N. Reyns cosupervised the study, designed the study and read/corrected the manuscript.

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Nowadays, Glioblastoma Multiform (GBM) remains an incurable brain tumour despite of recent advances in the standard of care. Patients harboring newly diagnosed GBM, de novo GBM, undergo to surgery for maximal tumour resection followed by radiation ther-apy and concomitant and adjuvant chemotherapy (Temozolomide). This protocol has raised the overall survival to 14.5 months. Promis-ing results have been documented concerning 5-ALA interstitial photodynamic therapies. However, interstitial PDT has always been delivered to treat recurrent or non-operable tumours. Because of heterogeneous population of patients with different care protocols in the context of their relapsing disease or the absence of controlled clinical trial, efficacy of 5-ALA PDT is not still evidenced and thus not included in the standard protocol.In order to prove the 5-PDT efficacy on patients harboring de novo GBM, our group has developed a specific medical device to deliver PDT intraoperatively in the surgical cavity.The main idea is to benefit from the course of 5-ALA Fluores-cence Guided Resection (FGR) to achieve an illumination with the suitable wavelength (635 nm). Treatment of the infiltrating cells by a PDT effect is expected in the first millimeters of the surgical cavity. In such manner, intraoperative PDT is a simple add-on to the standard protocol that is more ethically acceptable and more efficient to assess PDT efficacy.Ten patients will be enrolled. Each patient will undergo standard treatment protocol including PDT early after surgery. 25 J/cm 2 will be delivered at 5 mm of the surgical cavity borders. A fractionation scheme will be applied: 5 fractions of 5 J/cm 2 each with off-period of 2 min between each fraction. A first early post-operative MRI will be acquired on the intraoperative MRI of our department. Then, MRI will be acquired quarterly to monitor the treatment response.The primary endpoint is the feasibility of intraoperative PDT, estimated by the proportion of patients who undergone intraoper-ative PDT without unacceptable toxicity. The expected objective is 70%, 7 of 10 patients that we plan to include. Secondary endpoints are progression-free survival (PFS), overall survival, and evalua-tion at 3 months, 6 months and 12 months of radiation treatment response and patients' quality of life. Finally, after the feasibility and the absence of adverse effects, our protocol will be experienced through a controlled multicenter clinical trial (Phase II) which will focus on dose escalation (light and 5-ALA) and new biomarkers findings. This multicenter clinical trial will be set-up and performed with the support of the European network Synaps (http://www. synaps-project.eu).

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