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Purpose: Glioblastoma remains incurable despite optimal multimodal management. The interim analysis of open label, single arm INDYGO pilot trial showed actuarial 12-months progression-free survival (PFS) of 60% (median 17.1 months), actuarial 12-months overall survival (OS) of 80% (median 23.1 months). We report updated, exploratory analyses of OS, PFS, and health-related quality of life (HRQOL) for patients receiving intraoperative photodynamic therapy (PDT) with 5-aminolevulinic acid hydrochloride (5-ALA HCl)., Methods: Ten patients were included (May 2017 - April 2021) for standardized therapeutic approach including 5-ALA HCl fluorescence-guided surgery (FGS), followed by intraoperative PDT with a single 200 J/cm 2 dose of light. Postoperatively, patients received adjuvant therapy (Stupp protocol) then followed every 3 months (clinical and cerebral MRI) and until disease progression and/or death. Procedure safety and toxicity occurring during the first four weeks after PDT were assessed. Data concerning relapse, HRQOL and survival were prospectively collected and analyzed., Results: At the cut-off date (i.e., November 1st 2023), median follow-up was 23 months (9,7-71,4). No unacceptable or unexpected toxicities and no treatment-related deaths occurred during the study. Kaplan-Meier estimated 23.4 months median OS, actuarial 12-month PFS rate 60%, actuarial 12-month, 24-month, and 5-year OS rates 80%, 50% and 40%, respectively. Four patients were still alive (1 patient free of recurrence)., Conclusion: At 5 years-follow-up, intraoperative PDT with surgical maximal excision as initial therapy and standard adjuvant treatment suggests an increase of time to recurrence and overall survival in a high proportion of patients. Quality of life was maintained without any severe side effects., Trial Registration Nct Number: NCT03048240. EudraCT number: 2016-002706-39., (© 2024. The Author(s).)

Independently, both 5-aminolevulinic acid (5-ALA) and intraoperative neuromonitoring (IONM) have been shown to improve outcomes with high-grade gliomas (HGG). The interplay and overlap of both techniques are scarcely reported in the literature. We performed a systematic review and meta-analysis focusing on the concomitant use of 5-ALA and intraoperative mapping for HGG located within eloquent cortex. Using PRISMA guidelines, we reviewed articles published between May 2006 and December 2022 for patients with HGG in eloquent cortex who underwent microsurgical resection using intraoperative mapping and 5-ALA fluorescence guidance. Extent of resection was the primary outcome. The secondary outcome was new neurological deficit at day 1 after surgery and persistent at day 90 after surgery. Overall rate of complete resection of the enhancing tumor (CRET) was 73.3% (range: 61.9-84.8%, p < .001). Complete 5-ALA resection was performed in 62.4% (range: 28.1-96.7%, p < .001). Surgery was stopped due to mapping findings in 20.5% (range: 15.6-25.4%, p < .001). Neurological decline at day 1 after surgery was 29.2% (range: 9.8-48.5%, p = 0.003). Persistent neurological decline at day 90 after surgery was 4.6% (range: 0.4-8.7%, p = 0.03). Maximal safe resection guided by IONM and 5-ALA for high-grade gliomas in eloquent areas is achievable in a high percentage of cases (73.3% CRET and 62.4% complete 5-ALA resection). Persistent neurological decline at postoperative day 90 is as low as 4.6%. A balance between 5-ALA and IONM should be maintained for a better quality of life while maximizing oncological control., (© 2023. The Author(s).)

Introduction: The combined use of intraoperative MRI and awake surgery is a tailored microsurgical resection to respect functional neural networks (mainly the language and motor ones). Intraoperative MRI has been classically considered to increase the extent of resection for gliomas, thereby reducing neurological deficits. Herein, we evaluated the combined technique of awake microsurgical resection and intraoperative MRI for primary brain tumours (gliomas, metastasis) and epilepsy (cortical dysplasia, non-lesional, cavernomas)., Patients and Methods: Eighteen patients were treated with the commonly used "asleep awake asleep" (AAA) approach at Lille University Hospital, France, from November 2016 until May 2020. The exact anatomical location was insular with various extensions, frontal, temporal or fronto-temporal in 8 (44.4%), parietal in 3 (16.7%), fronto-opercular in 4 (22.2%), Rolandic in two (11.1%), and the supplementary motor area (SMA) in one (5.6%)., Results: The patients had a mean age of 38.4 years (median 37.1, range 20.8-66.9). The mean surgical duration was 4.1 hours (median 4.2, range 2.6-6.4) with a mean duration of intraoperative MRI of 28.8 minutes (median 25, range 13-55). Overall, 61% (11/18) of patients underwent further resection, while 39% had no additional resection after intraoperative MRI. The mean preoperative and postoperative tumour volumes of the primary brain tumours were 34.7 cc (median 10.7, range 0.534-130.25) and 3.5 cc (median 0.5, range 0-17.4), respectively. Moreover, the proportion of the initially resected tumour volume at the time of intraoperative MRI (expressed as 100% from preoperative volume) and the final resected tumour volume were statistically significant (p= 0.01, Mann-Whitney test). The tumour remnants were commonly found posterior (5/9) or anterior (2/9) insular and in proximity with the motor strip (1/9) or language areas (e.g. Broca, 1/9). Further resection was not required in seven patients because there were no remnants (3/7), cortical stimulation approaching eloquent areas (3/7) and non-lesional epilepsy (1/7). The mean overall follow-up period was 15.8 months (median 12, range 3-36)., Conclusion: The intraoperative MRI and awake microsurgical resection approach is feasible with extensive planning and multidisciplinary collaboration, as these methods are complementary and synergic rather than competitive to improve patient oncological outcomes and quality of life.

Background: Cavernous malformations are clusters of abnormal and hyalinized capillaries without interfering brain tissue. Here, we present a cavernous malformation operated under awake conditions, due to location, in an eloquent area and using intraoperative magnetic resonance imaging due to patient's movement upon the awake phase., Case Presentation: We present the pre-, per-, and postoperative course of an inferior parietal cavernous malformation, located in eloquent area, in a 27-year-old right-handed Caucasian male, presenting with intralesional hemorrhage and epilepsy. Preoperative diffusion tensor imaging has shown the cavernous malformation at the interface between the arcuate fasciculus and the inferior fronto-occipital fasciculus. We describe the microsurgical approach, combining preoperative diffusion tensor imaging, neuronavigation, awake microsurgical resection, and intraoperative magnetic resonance imaging., Conclusion: Complete microsurgical en bloc resection has been performed and is feasible even in eloquent locations. Intraoperative magnetic resonance imaging was considered an important adjunct, particularly used in this case as the patient moved during the "awake" phase of the surgery and thus neuronavigation was not accurate anymore. Postoperative course was marked by a unique, generalized seizure without any adverse event. Immediate and 3 months postoperative magnetic resonance imaging confirmed the absence of any residue. Pre- and postoperative neuropsychological exams were unremarkable., (© 2023. The Author(s).)

Background: Gliomas are diffuse intra-axial lesions, which can be accessed by multiple surgical corridors for a same location depending on the surgeon's preference. 5-Aminolevulinic Acid use facilitates the extend of resection in case of high-grade gliomas, especially when differentiating normal brain from tumor periphery is challenging., Methods: Complete resection of glioblastoma via a supraorbital transciliary approach with 5-Aminolevulinic Acid use was performed without any complications, as demonstrated on postoperative MRI., Results: Patient was discharged on the third postoperative day. Wound follow-up shows good cosmetic result. Patient underwent concomitant chemo-radiation (Temozolomide- 60Gy) and adjuvant chemotherapy (Temozolomide). No tumor recurrence was noted at six months follow-up., Conclusion: In selected cases, supraorbital transciliary approach could be proposed as primary approach as it provides the advantage of full control over all the vasculo-nervous structures at skull base without the necessity of protective brain retractor use while the 5-Aminolevulinic Acid use allows a gross total resection., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Purpose: Targeted treatment for brainstem lesions requires above all a precise histopathological and molecular diagnosis. In the current technological era, robot-assisted stereotactic biopsies represent an accurate and safe procedure for tissue diagnosis. We present our center's experience in frameless robot-assisted biopsies for brainstem lesions., Methods: We performed a retrospective analysis of all patients benefitting from a frameless robot-guided stereotactic biopsy at our University Hospital, from 2001 to 2017. Patients consented to the use of data and/or images. The NeuroMate® robot (Renishaw™, UK) was used. We report on lesion location, trajectory strategy, histopathological diagnosis and procedure safety., Results: Our series encompasses 96 patients (103 biopsies) treated during a 17 years period. Mean age at biopsy: 34.0 years (range 1-78). Most common location: pons (62.1%). Transcerebellar approach: 61 procedures (59.2%). Most common diagnoses: diffuse glioma (67.0%), metastases (7.8%) and lymphoma (6.8%). Non conclusive diagnosis: 10 cases (9.7%). After second biopsy this decreased to 4 cases (4.1%). Overall biopsy diagnostic yield: 95.8%. Permanent disability was recorded in 3 patients (2.9%, all adults), while transient complications in 17 patients (17.7%). Four cases of intra-tumoral hematoma were recorded (one case with rapid decline and fatal issue). Adjuvant targeted treatment was performed in 72.9% of patients. Mean follow-up (in the Neurosurgery Department): 2.2 years., Conclusion: Frameless robot-assisted stereotactic biopsies can provide the initial platform towards a safe and accurate management for brainstem lesions, offering a high diagnostic yield with low permanent morbidity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Interstitial photodynamic therapy (iPDT), inserting optical fibers inside brain tumors, has been proposed for more than 30 years. While a promising therapeutic option, it is still an experimental treatment, with different ways of application, depending on the team performing the technique., Objective: In this systematic review, we reported the patient selection process, the treatment parameters, the potential adverse events and the oncological outcomes related to iPDT treatment applied to brain tumors., Methods: We performed a search in PubMed, Embase and Medline based on the following Mesh terms: "interstitial" AND "photodynamic therapy" AND "brain tumor" OR "glioma" OR glioblastoma" from January 1990 to April 2020. We screened 350 studies. Twelve matched all selection criteria., Results: 251 patients underwent iPDT. Tumors were mainly de novo or recurrent high-grade gliomas (171 (68%) of glioblastomas), located supratentorial, with a median volume of 12 cm 3 . Hematoporphyrin derive agent (HpD) or protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (5-ALA) was used as a photosensitizer. Up to 6 optical fibers were introduced inside the tumor, delivering 200 mW/cm at a wavelength of 630 nm. Overall mortality was 1%. Transient and persistent morbidity were both 5%. No permanent deficit occurred using 5-ALA PDT. Tumor response rate after iPDT was 92% (IQR, 67; 99). Regarding glioblastomas, progression-free-survival was respectively 14.5 months (IQR, 13.8; 15.3) for de novo lesions and 14 months (IQR, 7; 30) for recurrent lesions, while overall survival was respectively 19 months (IQR, 14; 20) and 8 months (IQR, 6.3; 8.5). In patients harboring high-grade gliomas, 33 (13%) were considered long-term survivors (> 2 years) after iPDT., Conclusion: Regardless of heterogeneity in its application, iPDT appears safe and efficient to treat brain tumors, especially high-grade gliomas. Stand-alone iPDT (i.e., without combined craniotomy and intracavitary PDT) using 5-ALA appears to be the best option in terms of controlling side effects: it avoids the occurrence of permanent neurological deficits while reducing the risks of hemorrhage and sepsis., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Gangliogliomas (GG) are considered WHO grade I rare tumors. While they commonly manifest as temporal lobe epilepsy, they can be located anywhere in the brain. Primary treatment is complete microsurgical resection. Remnant or recurrent GG can benefit from radiation therapy. Here, we present a series of GG who received Gamma Knife radiosurgery (GKR) after initial microsurgery., Methods: Between October 2009 and February 2020, four patients benefitted from such approach. The median age at surgery was 16 years (mean 17, 11-25) and at the time of GKR was 22.5 years (mean 23, 19-28). Initial clinical symptom was epilepsy in 3 cases and incidental in one. Biopsy was firstly performed in one case. One patient had stereotactic electroencephalography. The respective anatomical locations were right parieto-occipital, sylvian, left paraventricular and left inferior parietal., Results: Gamma Knife radiosurgery was performed after a median time of 3.5 years after initial gross total microsurgical resection (GTR). The median follow-up after GKR was 54 months (mean 58.5, 6-120). The median marginal dose was 18 Gy (mean 17.5, 16-18). The median target volume was 0.5 mL (mean 0.904, 0.228-2.3). The median prescription isodose volume was 0.6 mL (mean 0.9, 0.3-2.4). At last follow-up, GG majorly decreased in 3 patients, remained stable in one., Conclusion: Gamma Knife radiosurgery is safe and effective for remnant GG after GTR. Primary treatment remains microsurgical resection, especially in cases with symptomatic mass effect or with epilepsy. Single fraction GKR can be a valuable option for remnant or recurrent tumors after initial resection., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The unfavorable prognosis despite maximal therapy relates to high propensity for recurrence. Thus, overall survival (OS) is quite limited and local failure remains the fundamental problem. Here, we present a safety and feasibility trial after treating GBM intraoperatively by photodynamic therapy (PDT) after 5-aminolevulinic acid (5-ALA) administration and maximal resection., Methods: Ten patients with newly diagnosed GBM were enrolled and treated between May 2017 and June 2018. The standardized therapeutic approach included maximal resection (near total or gross total tumor resection (GTR)) guided by 5-ALA fluorescence-guided surgery (FGS), followed by intraoperative PDT. Postoperatively, patients underwent adjuvant therapy (Stupp protocol). Follow-up included clinical examinations and brain MR imaging was performed every 3 months until tumor progression and/or death., Results: There were no unacceptable or unexpected toxicities or serious adverse effects. At the time of the interim analysis, the actuarial 12-months progression-free survival (PFS) rate was 60% (median 17.1 months), and the actuarial 12-months OS rate was 80% (median 23.1 months)., Conclusions: This trial assessed the feasibility and the safety of intraoperative 5-ALA PDT as a novel approach for treating GBM after maximal tumor resection. The current standard of care remains microsurgical resection whenever feasible, followed by adjuvant therapy (Stupp protocol). We postulate that PDT delivered immediately after resection as an add-on therapy of this primary brain cancer is safe and may help to decrease the recurrence risk by targeting residual tumor cells in the resection cavity. Trial registration NCT number: NCT03048240. EudraCT number: 2016-002706-39.

Fronto-temporo-insular (FTI) gliomas continue to represent a surgical challenge despite numerous technical advances. Some authors advocate for surgery in awake condition even for non-dominant hemisphere FTI, due to risk of sociocognitive impairment. Here, we report outcomes in a series of patients operated using intraoperative magnetic resonance imaging (IoMRI) guided surgery under general anesthesia, using no cortical or subcortical mapping. We evaluated the extent of resection, functional and neuropsychological outcomes after IoMRI guided surgery under general anesthesia of FTI gliomas located in the non-dominant hemisphere. Twenty patients underwent FTI glioma resection using IoMRI in asleep condition. Seventeen tumors were de novo, three were recurrences. Tumor WHO grades were II:12, III:4, IV:4. Patients were evaluated before and after microsurgical resection, clinically, neuropsychologically (i.e., social cognition) and by volumetric MR measures (T1G+ for enhancing tumors, FLAIR for non-enhancing). Fourteen (70%) patients benefited from a second IoMRI. The median age was 33.5 years (range 24-56). Seizure was the inaugural symptom in 71% of patients. The median preoperative volume was 64.5 cm 3 (min 9.9, max 211). Fourteen (70%) patients underwent two IoMRI. The final median EOR was 92% (range 69-100). The median postoperative residual tumor volume (RTV) was 4.3 cm 3 (range 0-38.2). A vast majority of residual tumors were located in the posterior part of the insula. Early postoperative clinical events (during hospital stay) were three transient left hemiparesis (which lasted less than 48 h) and one prolonged left brachio-facial hemiparesis. Sixty percent of patients were free of any symptom at discharge. The median Karnofsky Performance Score was of 90 both at discharge and at 3 months. No significant neuropsychological impairment was reported, excepting empathy distinction in less than 40% of patients. After surgery, 45% of patients could go back to work. In our experience and using IoMRI as an adjunct, microsurgical resection of non-dominant FTI gliomas under general anesthesia is safe. Final median EOR was 92%, with a vast majority of residual tumors located in the posterior insular part. Patients experienced minor neurological and neuropsychological morbidity. Moreover, neuropsychological evaluation reported a high preservation of sociocognitive abilities. Solely empathy seemed to be impaired in some patients.

Purpose: Intraoperative MRI (iMRI) offers the possibility of acquiring intraoperatively real-time images that will guide neurosurgeons when removing brain tumors. The objective of this study was to report the existence of FLAIR abnormalities on iMRI that may occur on the margin of a brain resection and may lead to misdiagnosis of residual tumor., Methods: We retrospectively analyzed intraoperative MRI (iMRI) in 21 consecutive patients who underwent surgery for a low-grade glioma. Two readers independently reviewed iMRI images to search for the presence of a FLAIR hyperintensity surrounding the surgical cavity. For each patient, they were instructed to characterize FLAIR abnormalities on the margins of the resected area as (1) no FLAIR abnormality; (2) "linear FLAIR hyperintensity (LFH)", when a<5mm linear FLAIR hyperintensity was present; or (3) "nodular FLAIR hyperintensity (NFH)", in the case of a thick and nodular FLAIR hyperintensity., Results: LFH were present on at least one surgical margin of one third of the patients analyzed with iMRI, and vanished on follow-up MRI, confirming its transient condition; whereas NFH were linked to persistence of pre-surgical abnormalities, such as residual tumor as confirmed or by histopathological analysis of a second surgery or by its remnant on follow-up MRI., Conclusion: Linear FLAIR hyperintensities can be present on surgical margins analyzed by iMRI and should not be mistaken for residual tumor., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: For glial tumor management, the extent of resection (EOR) is the key to enhance tumor control and improve patient outcomes. Intraoperative MRI (IoMRI) neuronavigated microsurgery emerged as a useful neuroimaging tool for performing optimal and safe tumor resection., Method: Here, we present the different steps of the microsurgical resection of a challenging deeply located right fronto-temporal glioma, using intraoperative MRI in an integrated IoMRI imaging platform., Conclusion: Intraoperative MRI neuronavigated microsurgery helps to enhance the tumor resection, while reducing unintended area damages. The use of IoMRI fosters a "staged volume resection," to keep safe, taking into account the progressive intraoperative brain shift.

Background: The optimal sequence of stereotactic radiotherapy (SRT) and immune checkpoint inhibition (ICI) and assessment of response in patients with brain metastases from melanoma remain challenging., Methods: We reviewed clinical and neuroimaging data of 62 patients with melanoma, including 26 patients with BRAF-mutant tumours, with newly diagnosed brain metastases treated with ICI alone (n=10, group 1), SRT alone or in combination with other systemic therapies (n=20, group 2) or ICI plus SRT (n=32, group 3). Response was assessed retrospectively using response evaluation criteria in solid tumours (RECIST) V.1.1, response assessment in neuro-oncology (RANO) and immunotherapy RANO (iRANO) criteria. MRI follow-up from 43 patients was available for central review., Results: Patients treated with ICI alone showed no objective responses and had worse outcome than patients treated with SRT without or with ICI. RECIST, RANO and iRANO criteria were concordant for complete response (CR) and partial response (PR). RANO called progression earlier than RECIST for clinical deterioration without MRI progression in some patients. Progression was called later when using iRANO criteria because of the need for a confirmatory scan. Pseudoprogression was documented in seven patients: three patients in group 2 and four patients in group 3. Radionecrosis was documented in seven patients: two patients in group 2 and five patients in group 3. Regression of non-irradiated lesions was seen neither in two patients treated with SRT alone nor in five patients treated with SRT plus ICI, providing no evidence for rare abscopal effects., Conclusions: Pseudoprogression is uncommon with ICI alone, suggesting that growing lesions in such patients should trigger an intervention. Pseudoprogression rates were similar after SRT alone or SRT in combination with ICI. Abscopal effects are rare or do not exist. Response assessment criteria should be considered carefully when designing clinical studies for patients with brain metastases who receive SRT., Competing Interests: Competing interests: None declared., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background and Purpose: The challenge of the neurosurgical management of gliomas lies in achieving a maximal resection without persistent functional deficit. Diffusion tensor imaging (DTI) allows non-invasive identification of white matter tracts and their interactions with the tumor. Previous DTI validation studies were compared with intraoperative cortical stimulation, but none was performed based on the tumor anatomopathological analysis. This preliminary study evaluates the correlation between the preoperative subcortical DTI tractography and histology in terms of fiber direction as well as potential tumor-related fiber disruption., Methods: Eleven patients harboring glial tumors underwent preoperative DTI images. Correlations were performed between the visual color-coded anisotropy (FA) map analysis and the tumor histology after "en bloc" resection. Thirty-one tumor areas were classified according to the degree of tumor infiltration, the destruction of myelin fibers and neurofilaments, the presence of organized white matter fibers, and their orientation in space., Results: After histologic comparison, the DTI sensitivity and specificity to predict disrupted fiber tracts were respectively of 89% and 90%. The positive and negative predicted values of DTI were 80% and 95%. The DTI data were in line with the histologic myelin fiber orientation in 90% of patients. In our series, the prevalence of destructed fiber was 31%. Glioblastoma WHO grade IV harbored a higher proportion of destructed white matter tracts. Lower WHO grades were associated with higher preservation of subcortical fiber tracts., Conclusion: This DTI/histology study of "en bloc"-resected gliomas reported a high and reproducible concordance of the visual color-coded FA map with the histologic examination to predict subcortical fiber tract disruption. Our series brought consistency to the DTI data that could be performed routinely for glioma surgery to predict the tumor grade and the postoperative clinical outcomes.

Objective: To determine the efficacy of the thrombopoietin receptor agonist romiplostim for the prevention of temozolomide-induced thrombocytopenia in newly diagnosed glioblastoma., Methods: In the PLATUM phase II open-label, multicenter, single-arm trial, patients diagnosed with Common Terminology Criteria for Adverse Events grade 3 or 4 thrombocytopenia during chemoradiotherapy received weekly subcutaneous romiplostim injections. PLATUM aimed at demonstrating that the percentage of thrombocytopenic patients treated with romiplostim able to complete 6 cycles of maintenance temozolomide chemotherapy exceeded 10% ( p 0 = 0.10; p A = 0.35). Using type I error equal to 0.05% and 95% power, 31 patients had to be recruited. According to a Fleming 2-step design with a preplanned interim analysis after recruitment of 20 patients (step 1), the trial was terminated early for success., Results: Twenty patients were enrolled in step 1. Median age was 61 years (range 33-73). Twelve patients received 6 temozolomide cycles, corresponding to a success rate of 60% (95% confidence interval 36%-81%). Four patients discontinued temozolomide because they did not respond to romiplostim, 2 for progression, and 2 for adverse events unrelated to romiplostim., Conclusion: The thrombopoietin receptor agonist romiplostim improves exposure to chemotherapy in patients with glioblastoma experiencing temozolomide-induced thrombocytopenia., Clinicaltrialsgov Identifier: NCT02227576., Classification of Evidence: This study provides Class IV evidence that for patients with glioblastoma and thrombocytopenia, romiplostim is effective for the secondary prophylaxis of temozolomide-induced thrombocytopenia., (© 2019 American Academy of Neurology.)

Background: The postoperative outcomes and the predictors of seizure control are poorly studied for supratentorial cavernous angiomas (CA) within or close to the eloquent brain area., Objective: To assess the predictors of preoperative seizure control, postoperative seizure control, and postoperative ability to work, and the safety of the surgery., Methods: Multicenter international retrospective cohort analysis of adult patients benefitting from a functional-based surgical resection with intraoperative functional brain mapping for a supratentorial CA within or close to eloquent brain areas., Results: A total of 109 patients (66.1% women; mean age 38.4 ± 12.5 yr), were studied. Age >38 yr (odds ratio [OR], 7.33; 95% confidence interval [CI], 1.53-35.19; P = .013) and time to surgery > 12 mo (OR, 18.21; 95% CI, 1.11-296.55; P = .042) are independent predictors of uncontrolled seizures at the time of surgery. Focal deficit (OR, 10.25; 95% CI, 3.16-33.28; P < .001) is an independent predictor of inability to work at the time of surgery. History of epileptic seizures at the time of surgery (OR, 7.61; 95% CI, 1.67-85.42; P = .003) and partial resection of the CA and/or of the hemosiderin rim (OR, 12.02; 95% CI, 3.01-48.13; P < .001) are independent predictors of uncontrolled seizures postoperatively. Inability to work at the time of surgery (OR, 19.54; 95% CI, 1.90-425.48; P = .050), Karnofsky Performance Status ≤ 70 (OR, 51.20; 95% CI, 1.20-2175.37; P = .039), uncontrolled seizures postoperatively (OR, 105.33; 95% CI, 4.32-2566.27; P = .004), and worsening of cognitive functions postoperatively (OR, 13.71; 95% CI, 1.06-176.66; P = .045) are independent predictors of inability to work postoperatively., Conclusion: The functional-based resection using intraoperative functional brain mapping allows safe resection of CA and the peripheral hemosiderin rim located within or close to eloquent brain areas., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background: High-field intraoperative MRI (IoMRI) is part of the neurosurgical armamentarium to improve the extent of glioma resection (EOR)., Objective: To report our oncological and functional outcomes using IoMRI for neuronavigated glioma surgery., Methods: In this prospective monocentric study, we reported 100 consecutive adult patients operated on for glioma using IoMRI with neuronavigation, under general anesthesia without intraoperative stimulation, from July 2014 to April 2017. The volumetric evaluation was based on the FLAIR hypersignal for non-enhancing tumors after Gadolinium infusion and on the T1 hypersignal after Gadolinium infusion for enhancing tumors. We evaluated the surgical workflow, the EOR and the clinical outcomes (using Karnofsky performance score (KPS))., Results: Sixty-nine patients underwent one IoMRI, and 31 from two IoMRI controls. At first IoMRI, the median tumor residue was higher in the FLAIR group than in the T1G+ group whereas no more difference was reported after the second IoMRI between the 2 groups (p = 0.56). Additional resection was performed 6 times more frequently in the FLAIR group (OR = 5.7, CI (1.9-17)). The median EOR was 100% (IQR, 93.6-100) whatever the tumor type (first surgery or recurrence) and location. Higher residues were reported only in the insula area (p = 0.004). The median KPS was 90 (IQR, 80-100) at discharge, 3, 6 and 12 months after surgery, with no statistical difference between low- and high-grade gliomas (p = 0.34)., Conclusion: IoMRI neuronavigated surgery provided maximal EOR whatever the type of glioma and location. IoMRI was all the more useful for non- or minimally enhancing tumors. The step by step surgical resection, introducing the concept of "staged volume" surgery, ensured a high security for the surgeon and low permanent morbidity for the patients.

Purpose: The practical management of cavernous angioma located within eloquent brain area before, during and after surgical resection is poorly documented. We assessed the practical pre-operative, intra-operative, and post-operative management of cavernous angioma located within eloquent brain area., Method: An online survey composed of 61 items was sent to 26 centers to establish a multicenter international retrospective cohort of adult patients who underwent a surgical resection as the first-line treatment of a supratentorial cavernous angioma located within or close to eloquent brain area., Results: 272 patients from 19 centers (mean 13.6 ± 16.7 per center) from eight countries were included. The pre-operative management varied significantly between centers and countries regarding the pre-operative functional assessment, the pre-operative epileptological assessment, the first given antiepileptic drug, and the time to surgery. The intra-operative environment varied significantly between centers and countries regarding the use of imaging systems, the use of functional mapping with direct electrostimulations, the extent of resection of the hemosiderin rim, the realization of a post-operative functional assessment, and the time to post-operative functional assessment. The present survey found a post-operative improvement, as compared to pre-operative evaluations, of the functional status, the ability to work, and the seizure control., Conclusions: We observed a variety of practice between centers and countries regarding the management of cavernous angioma located within eloquent regions. Multicentric prospective studies are required to solve relevant questions regarding the management of cavernous angioma-related seizures, the timing of surgery, and the optimal extent of hemosiderin rim resection., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Glioblastoma (GBM) is characterized by marked proliferation, major infiltration, and poor prognosis. Despite current treatments, including surgery, radiation oncology, and chemotherapy, the overall median survival is 15 mo and the progression-free survival is 7 to 8 mo. Because of systematic relapse of the tumor, the improvement of local control remains an issue. In this context, photodynamic therapy (PDT) may offer a new treatment modality for GBM., Objective: To assess the feasibility of intraoperative PDT early after surgical resection of GBM without unacceptable and unexpected toxicities., Methods: The INDYGO clinical trial (INtraoperative photoDYnamic Therapy for GliOblastomas) treatment will be carried out in addition to the current standard of care (SOC) of glioblastoma: maximum resection surgery followed by concomitant radio-chemotherapy and adjuvant chemotherapy. PDT treatment will be delivered during surgery early, after the fluorescence-guided resection. Immunological responses and biomarkers will also be investigated during the follow-up. A total of 10 patients will be recruited during this study., Expected Outcomes: Clinical follow-up after the SOC with PDT is expected to be similar (no significant difference) to the SOC alone., Discussion: 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., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Background: There is currently no therapy that prevents high-grade glioma recurrence. Thus, these primary brain tumors have unfavorable outcomes. Recently, 5-ALA photodynamic therapy (PDT) has been proposed to delay relapse and is highly expected to have potential synergistic effects with the current standard of care. However, PDT treatment delivery needs to be optimized by evaluating the impact of both the number of fractions and the light power used., Objectives: Previous studies have reported MRI examination-based outcomes for PDT in glioblastoma. Our study aimed to compare MRI markers across different treatment schemes that use interstitial PDT in high-grade glioma in a preclinical model., Materials and Methods: Forty-eight "nude" rats were grafted with human U87 cells into the right putamen and subsequently submitted to interstitial PDT. The rats were randomized into six groups, including two different sham groups and four different treated groups (5 fractions at 5 mW or 30 mW and 2 fractions at 5 mW or 30 mW). After photosensitizer (PS) precursor (5-ALA) intake, an optical fiber was introduced into the tumor. Treatment effects were assessed with early high-field MRI to acquire T1 and T2 diffusion and perfusion images., Results: There was no difference in the variation of the diffusion coefficient among the six groups (p = 0.0549, Kruskal-Wallis test). However, a significant difference was identified among the six groups in terms of variation in perfusion (p = 0.048, Kruskal-Wallis test), supporting a lesional effect in the treated groups. Additionally, the sham groups had significantly smaller edema volumes than were observed in the treated groups. Moreover, the 5-fraction group treated with 30 mW was associated with edema volumes that were significantly greater than those in the 5-fraction group treated with 5 mW (p = 0.019)., Conclusion: Based on observations of MRI data and considering treatment effects, the 5-fraction group treated at 5 mW was not significantly different from the other treated groups in terms of cell deaths, characterized by diffusion imaging, or necrosis level. However, the significantly lower level of edema observed in this group indicated that this treatment scheme had limited toxicity., (Copyright © 2018. Published by Elsevier B.V.)

Background: High-grade gliomas are primary brain tumors that have shown increasing incidence and unfavorable outcomes. Local control is crucial to the management of this pathology. Photodynamic therapy (PDT), based on the light-induced activation of a photosensitizer (PS), achieves local treatment by inducing selective lesions in tumor tissue., Objectives: Previous studies have reported the outcomes of PDT for glioblastoma via immunohistological data. Our study aimed to evaluate MRI findings, including diffusion, and perfusion sequences, compared with immunohistological data from the same population to address the efficiency of light fractionation., Materials and Methods: Twenty-six "nude" rats grafted with human U87 cells into the right putamen underwent PDT. After PS precursor (5-ALA) intake, an optical fiber was introduced into the tumor. The rats were randomized into the following groups: those without illumination and those that received two or five fractions of light. Treatment effects were assessed with early high-field MRI to measure the volume of necrosis and edema using diffusion and perfusion sequences; the MRI results were compared with immunohistology results, including necrosis and apoptosis markers., Results: Elevated diffusion values were observed on MRI in the centers of the tumors of the treated animals, especially in the 5-fraction group (P < 0.01). Perfusion was decreased around the treatment site, especially in the 5-fraction group (P = 0.024). The MRI findings were consistent with previously published histological data. The median volume of necrosis was significantly different between the sham group and treated groups, 0 mm 3 versus 2.67 mm 3 , P < 0.001. The same trend was previously observed in histology data when grading the absence or presence of necrosis and when the presence of necrosis was significantly more predominant for the treated group than for the untreated group (P < 001). Additionally, cell death represented by apoptosis marker data (TUNEL method) was significantly higher in the 5-fraction group than in the 2-fraction group (P = 0.01)., Conclusion: Diffusion and perfusion MRI revealed histological lesions. Interstitial PDT (iPDT) induced specific lesions in the tumor tissue, which were observed with MRI and confirmed by histopathological analysis. Thus, MRI may provide a non-invasive and reliable tool to assess treatment outcomes after PDT. Lasers Surg. Med. 50:460-468, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Purpose: Photodynamic therapy (PDT) is a promising treatment modality to be added in the management of glioblastoma multiforme (GBM). Light distribution modeling is required for planning and optimizing PDT. Several models have been developed to predict the light propagation inside biological tissues. In the present study, two analytical methods of light propagation emitted from a cylindrical fiber source were evaluated: a discrete and a continuous method., Methods: The two analytical approaches were compared according to their fluence rate results. Several cylindrical diffuse lengths were evaluated, and the relative deviation in the fluence rates was estimated. Moreover, a sensitivity analysis was conducted to compute the variance of each analytical model., Results: The discrete method provided fluence rate estimations closer to the Monte-Carlo simulations than the continuous method. The sensitivity study results did not reveal significant differences between the variance of the two analytical models., Conclusions: Although the discrete model provides relevant light distribution, the heterogeneity of GBM tissues was not considered. With the improvement in parallel computing that drastically decreased the computing time, replacing the analytical model by a Monte-Carlo GPU-accelerated code appeared relevant to the GBM case. Nonetheless, the analytical modeling may still function in the optimization algorithms, which might be used in the Photodynamic treatment planning system. Lasers Surg. Med. 50:523-534, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: High-field intraoperative MRI (IoMRI) is a useful tool to improve the extent of glioma resection (EOR)., Objective: To compare the interest of 1.5T IoMRI in glioma surgery between enhancing and non-enhancing tumors, based on volumetric analysis., Methods: A prospective single-center study included consecutive adult patients undergoing glioma surgery with IoMRI. Volumetric evaluation was based on FLAIR hypersignal after gadolinium injection in non-enhancing tumors and T1 hypersignal after gadolinium injection in enhancing tumors. Endpoints comprised: residual tumor volume (RTV), EOR, workflow and clinical outcome on Karnofsky performance score (KPS)., Results: Fifty-three surgeries were performed from July 2014 to January 2016. Thirty-four patients underwent one IoMRI, and 19 two IoMRIs. In non-enhancing tumors, intraoperative RTV on 1st IoMRI T2/FLAIR was higher than in enhancing tumors on T1 sequences (7.25cm 3 vs. 0.74cm 3 , respectively; P=0.008), whereas the RTV on 2nd IoMRIs and final RTV were no longer significantly different. After IoMRI, 72% of patients underwent additional resection. In non-enhancing tumors, EOR increased from 77.3% on 1st IoMRI to 97.4% on last MRI (P<0.001). Taking all tumors together, final RTV values were: median=0cm 3 , mean=3.9cm 3 . Mean final EOR was 94%. In 25% of patients, KPS was reduced during early postoperative course; at 3 and 6 months postoperatively, median KPS was 90., Conclusion: Intraoperative MRI guidance significantly enhanced the extent of glioma resection, especially for non- or minimally enhancing tumors, while preserving patient autonomy., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: In 30% of patients with brain metastasis (BM), neurological symptoms are the first clinical manifestation of systemic malignancy, referred to as BM from cancer of unknown primary site (BM-CUPS). Here, we define the diagnostic value of 18 F-fluordesoxyglucose positron emission tomography (FDG-PET/CT) in the workup of BM-CUPS., Methods: We screened 565 patients operated for BM at the University Hospital Zurich and identified 64 patients with BM-CUPS with data on both FDG-PET/CT and contrast-enhanced chest/abdomen computed tomography (CT) available at BM diagnosis. A cohort of 125 patients with BM-CUPS from Lille and Vienna was used for validation., Results: FDG-PET/CT was not superior to chest/abdomen CT in localising the primary lesion in the discovery cohort, presumably because most primary tumours were lung cancers. However, FDG-PET/CT identified additional lesions suspicious of extracranial metastases in 27 of 64 patients (42%). The inclusion of FDG-PET/CT findings shifted the graded prognostic assessment (GPA) score from 3 with CT alone to 2.5 for PET/CT (p = 3.8 × 10 -5 , Wilcoxon's test), resulting in a predicted survival of 5.3 versus 3.8 months (p = 6.1 × 10 -5 ; Wilcoxon's test). All observations were confirmed in the validation cohort., Conclusions: Lung cancers are the most common primary tumour in BM-CUPS; accordingly, CT alone shows similar overall sensitivity for detecting the primary tumour as FDG-PET/CT. Yet, FDG-PET/CT improves the accuracy of staging by detecting more metastases, reflected by decreased GPA scores and decreased predicted survival. Therefore, randomised trials on patients with BM should standardise methods of staging, notably when stratifying for GPA., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

An integrated diagnosis using molecular features is recommended in the 2016 World Health Organization (WHO) classification. Our aim was to explore non-targeted molecular classification using MALDI mass spectrometry imaging (MALDI MSI) associated to microproteomics in order to classify anaplastic glioma by integration of clinical data. We used fresh-frozen tissue sections to perform MALDI MSI of proteins based on their digestion peptides after in-situ trypsin digestion of the tissue sections and matrix deposition by micro-spraying. The generated 70μm spatial resolution image datasets were further processed by individual or global segmentation in order to cluster the tissues according to their molecular protein signature. The clustering gives 3 main distinct groups. Within the tissues the ROIs (regions of interest) defined by these groups were used for microproteomics by micro-extraction of the tryptic peptides after on-tissue enzymatic digestion. More than 2500 proteins including 22 alternative proteins (AltProt) are identified by the Shotgun microproteomics. Statistical analysis on the basis of the label free quantification of the proteins shows a similar classification to the MALDI MSI segmentation into 3 groups. Functional analysis performed on each group reveals sub-networks related to neoplasia for group 1, glioma with inflammation for group 2 and neurogenesis for group 3. This demonstrates the interest on these new non-targeted large molecular data combining both MALDI MSI and microproteomics data, for tumor classification. This analysis provides new insights into grade III glioma organization. This specific information could allow a more accurate classification of the biopsies according to the prognosis and the identification of potential new targeted therapeutic options. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: The aim of our study was to report the usefulness of intraoperative MRI guidance in the resection of brain lesions adjacent to eloquent areas., Patients and Methods: A single center prospective series of gliomas amenable to optimized resection with intraoperative MRI between September 2014 and December 2015., Results: The study included 56 patients. The median duration of the first intraoperative MRI was 38min, interquartile range (IQR 30-46). Fourteen patients (40%) underwent a second intraoperative MRI, which had a median duration of 26min (IQR, 18-30). The median total operative time was 265min (IQR, 242-337). After the first intraoperative MRI, the median residual glioma volume of the 35 gliomas adjacent to eloquent areas was 7.04cm 3 (IQR, 2.22-13.8), which did not significantly differ from the other gliomas (P=0.07). After the second intraoperative MRI, the median residual glioma volume was 3.86cm 3 (IQR, 0.82-6.99), which did not significantly differ from the other patients (P=0.700). On the postoperative MRI, the median extent of the glioma resections adjacent to eloquent areas was 99.78% (IQR, 88.9-100), which was not significantly different from the rest of the population (P=0.290). At 6 months after surgery, the median Karnofsky Performance Score was 90, and 2.8% of the patients presented a permanent new neurological deficit., Conclusion: Our results suggest that intraoperative MRI is an effective and safe technique to improve the extent of brain lesion resections close to eloquent areas., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Introduction: Surgical resection of supratentorial cavernous angiomas located in eloquent areas poses a significant risk to the patient of postoperative neurological impairment and justifies intraoperative functional monitoring., Methods: Multicentre retrospective series of adult patients with cavernous angiomas located within eloquent areas and treated with functional-based surgical resection according to functional boundaries under intraoperative functional cortico-subcortical monitoring under awake conditions., Results: Fifty patients (18 males, mean 36.3±10.8 year-old) underwent surgical resection with intraoperative cortico-subcortical functional mapping using direct electrostimulation under awake conditions for a cavernous angioma located in eloquent areas with a mean postoperative follow-up of 21.0±21.2 months. At presentation, the cavernous angioma had previously resulted in severe impairment (neurological deficit in 34%, seizures in 70%, uncontrolled seizures in 34%, reduced Karnofsky Performance Status score of 70 or less in 24%, inability to work in 52%). Functional-based surgical resection allowed complete removal of the cavernous angioma in 98% and of the haemosiderin rim in 82%. Postoperative seizures and other complications were rare, and similarly so across all centres included in this series. Postoperatively, we found functional improvement in 84% of patients (reduced Karnofsky Performance Status score of 70 or less in 6%, uncontrolled seizures in 16%, and inability to work in 11%)., Conclusion: Functional-based surgical resection aids the safe and complete resection of cavernous angiomas located in eloquent areas while minimizing the surgical risks. Functional mapping has to be considered in such challenging cases., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Radionecrosis (RN) represents the main complication of stereotactic radiotherapy (SRT) for brain metastases. It may be observed in up to 34% of cases at 24 months after treatment and associated with significant morbidity in 10-17%., Areas Covered: Our aim is to discuss the results of original studies on RN related to SRT for brain metastases. Expert commentary: Although the development of RN is unpredictable, larger volume of the lesion, prior whole brain irradiation, and higher dose of radiation represent the major risk factors. RN appears on MRI as contrast-enhancing necrotic lesions, surrounded by edema, occurring at least 3 months after SRT, localized within fields of irradiation. No firm criteria are established. Surgery can provide symptomatic relief but is associated with a risk of complications. Corticosteroids are considered the standard of care treatment, despite limited efficacy and many adverse effects. Bevacizumab represents another interesting option that needs to be validated.

Objective: Photodynamic therapy (PDT) has become a well-established modality for the treatment of many cancers. Photodynamic eradication of tumor cells depends on the presence of a photosensitizer, oxygen and light. However, oxygen depletion during PDT is a well known problem. Modulation of light delivery could address this issue by counteracting tumor hypoxia, thereby improving tumor cell killing. This preclinical study was designed to validate an animal model incorporating 5-aminolaevulinic acid (5-ALA)-PDT using U87 glioblastoma cells. We aimed to evaluate the effects of light modulation for inducing specific tumoral lesions in this model (i.e., necrosis or apoptosis)., Materials and Methods: U87 glioblastoma cells were stereotactically engrafted into the brains of male fox1 rnu/rnu rats. Light delivery was studied after 5-ALA injection (100 mg/kg i.p.). 26J of 635 nm light was interstitially delivered to U87 tumor-bearing rats at a radiant power of either 30 mW (high fluence rate) or 4.8 mW (low fluence rate). In each group, half of the population received illumination in 2 fractions with a refractory interval of 120 s, whereas the other half received continuous illumination., Results: Twenty-two animals received 5-ALA-PDT, and the level of necrosis was scored. In the high-fluence-rate group, we observed a greater degree of tumor necrosis in rats receiving fractionated delivery than in rats receiving continuous illumination. Similar differences were not observed in the low-fluence-rate group, which exhibited only sparse necrosis. Higher morbidity and mortality rates were observed in the high-fluence-rate group., Conclusion: We have developed a reproducible and reliable rodent model for interstitial 5-ALA PDT. We found that the effects of 5-ALA-PDT are dependent on light delivery conditions. Although the low-fluence-rate treatment was better tolerated, 5-ALA-PDT induced more necrosis using fractionated delivery at a high fluence rate. These results require confirmation with further studies involving larger populations and additional fractionation schemes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: To constrain the risk of severe toxicity in radiotherapy and radiosurgery, precise volume delineation of organs at risk is required. This task is still manually performed, which is time-consuming and prone to observer variability. To address these issues, and as alternative to atlas-based segmentation methods, machine learning techniques, such as support vector machines (SVM), have been recently presented to segment subcortical structures on magnetic resonance images (MRI)., Methods: SVM is proposed to segment the brainstem on MRI in multicenter brain cancer context. A dataset composed by 14 adult brain MRI scans is used to evaluate its performance. In addition to spatial and probabilistic information, five different image intensity values (IIVs) configurations are evaluated as features to train the SVM classifier. Segmentation accuracy is evaluated by computing the Dice similarity coefficient (DSC), absolute volumes difference (AVD) and percentage volume difference between automatic and manual contours., Results: Mean DSC for all proposed IIVs configurations ranged from 0.89 to 0.90. Mean AVD values were below 1.5 cm(3), where the value for best performing IIVs configuration was 0.85 cm(3), representing an absolute mean difference of 3.99% with respect to the manual segmented volumes., Conclusion: Results suggest consistent volume estimation and high spatial similarity with respect to expert delineations. The proposed approach outperformed presented methods to segment the brainstem, not only in volume similarity metrics, but also in segmentation time. Preliminary results showed that the approach might be promising for adoption in clinical use.

High-grade gliomas represent a widely heterogeneous group of tumors, the most frequent of which is glioblastoma multiforme. Its annual incidence has risen over the last decades, particularly amongst elderly people. The actual standards of care allow for a 15-month median survival rate for WHO grade IV gliomas. As recurrence occurs in more than 85% of patients at the surgical margins, the initial resection extent is a cornerstone of disease control. Fluorescence guided resection (FGR) aims at increasing complete resections and, thus, local control. This technique uses 5-aminolevulinic acid (5-ALA), a natural intermediate substance in the heme-porphyrin biosynthesis pathway, and a protoporphyrin IX (PpIX) precursor. PpIX is fluorescent under blue light exposure. Recent studies reported a significant increase in complete resections using FGR, which were associated with prolonged progression free survival, fewer reinterventions, and delayed neurological deterioration. Here, we depict the principles of this surgical technique, its actual outcomes, and future developments., (© 2015 Wiley Periodicals, Inc.)

Numerous tumour types can occur in the pineal region. Because these tumours are uncommon and heterogeneous, it is often difficult to establish optimal treatment strategies based on comparative clinical trials. To date, the role of radiosurgery for the treatment of pineal region tumours remains controversial. This report of a 10-year single-department experience and review of the literature focuses on the spectrum of pathologic features found in these pineal parenchymal tumours and on the interest of radiosurgery in their management. Considering pineocytomas, although these tumours have been considered to be radioresistant to fractionated radiotherapy, our results are in agreement with similar results reported in the literature in suggesting that radiosurgery may be an alternative to surgical resection or an adjuvant therapy when the resection is not optimal. When dissemination occurs after radiosurgery, however, craniospinal radiation and chemotherapy are necessary. Radiosurgery has also proven its interest in the treatment of germinomas as an alternative to encephalic radiotherapy with limited long-term damage. Regarding the other pathologies, radiosurgery can be considered as part of a multimodal treatment including surgery, chemo-radiotherapy and its role still has to be clearly defined., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Pineal tumours account for 1% to 4% of brain tumours in adults and for around 10% in children. Except in a few cases where germ cell markers are elevated, accurate histological samples are mandatory to initiate the treatment. Open surgery still has a high morbidity and is often needless. Biopsies can either be obtained by endoscopic or stereotactic procedures., Methods: Following an extensive review of the literature (PubMed 1970-2013; keywords pineal tumour, biopsy; English and French), 33 studies were analysed and relevant data compared regarding the type of procedure, diagnosis rate, cerebrospinal fluid diversion type and rate, perioperative mortality, morbidity., Results: Endoscopic and stereotactic biopsies showed a diagnosis rate of 81.1% (20%-100%) and 93.7% (82%-100%), respectively. Endoscopic biopsies involved 21.0% of minor and 2.0% of major complications whereas stereotactic biopsies involved 6.4% of minor and 1.6% of major complications. The most frequently reported complication was haemorrhage for both endoscopic and stereotactic procedures, accounting for 4.8% and 4.3%, respectively. Mortality rate was low for both endoscopic and stereotactic procedures, equal to 0.4% and 1.3%, respectively. Local experience of stereotactic biopsies was also reported and corroborated the previous data., Conclusions: The difference between both procedures is not statistically significant (p>0.05) across large series (≥20patients). Nevertheless, tissue diagnosis appears less accurate with endoscopic procedures than with stereotactic procedures (81.1% versus 93.7%, weighted mean across all series). In our opinion, the neuroendoscopic approach is the best tool for managing hydrocephalus, whereas stereotactic biopsies remain the best way to obtain a tissue diagnosis with accuracy and low morbidity., (Copyright © 2014. Published by Elsevier Masson SAS.)

Stereotactic radiotherapy of brain metastases is increasingly proposed after polydisciplinary debates among experts. Its definition and modalities of prescription, indications and clinical interest regarding the balance between efficacy versus toxicity need to be discussed. Stereotactic radiotherapy is a 'high precision' irradiation technique (within 1mm), using different machines (with invasive contention or frameless, photons X or gamma) delivering high doses (4 to 25Gy) in a limited number of fractions (usually 1 to 5, ten maximum) with a high dose gradient. Dose prescription will depend on materials, dose constraints to organs at risk varying with fractionation. Stereotactic radiotherapy may be proposed: (1) in combination with whole brain radiotherapy with the goal of increasing (modestly) overall survival of patients with a good performance status, 1 to 3 brain metastases and a controlled extracranial disease; (2) for recurrence of 1-3 brain metastases after whole brain radiotherapy; (3) after complete resection of a large and/or symptomatic brain metastases; (4) after diagnosis of 3-5 asymptomatic new or progressing brain metastases during systemic therapy, with the aim of delaying whole brain radiotherapy (avoiding its potential neurotoxicity) and maintaining a high focal control rate. Only a strict follow-up with clinical and MRI every 3 months will permit to deliver iterative stereotactic radiotherapies without jeopardizing survival. Simultaneous delivering of stereotactic radiotherapy with targeted medicines should be carefully discussed., (Copyright © 2015. Published by Elsevier SAS.)

Brain metastases management has evolved over the last fifteen years and may use varying strategies, including more or less aggressive treatments, sometimes combined, leading to an improvement in patient's survival and quality of life. The therapeutic decision is subject to a multidisciplinary analysis, taking into account established prognostic factors including patient's general condition, extracerebral disease status and clinical and radiological presentation of lesions. In this article, we propose a management strategy based on the state of current knowledge and available therapeutic resources., (Copyright © 2015. Published by Elsevier SAS.)

Surgical excision of brain metastases has been well evaluated in unique metastases. Two randomized phase III trial have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful. Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, to rule out a differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system or radionecrosis). Finally, the biological documentation of brain metastatic disease might be useful in situations where a specific targeted therapy can be proposed. Selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved overall survival of cancer patients partially due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to the local treatment of brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients., (Copyright © 2015. Published by Elsevier SAS.)

The incidence of brain metastases is increasing because of the use of new therapeutic agents, which allow an improvement of overall survival, but with only a poor penetration into the central nervous system brain barriers. The management of brain metastases has changed due to a better knowledge of immunohistochemical data and molecular biological data, the development of new surgical, radiotherapeutic approaches and improvement of systemic treatments. Most of the time, the prognosis is still limited to several months, nevertheless, prolonged survival may be now observed in some sub-groups of patients. The main prognostic factors include the type and subtype of the primitive, age, general status of the patient, number and location of brain metastases, extracerebral disease. The multidisciplinary discussion should take into account all of these parameters. We should notice also that treatments including surgery or radiotherapy may be proposed in a symptomatic goal in advanced phases of the disease underlying the multidisciplinary approach until late in the evolution of the disease. This article reports on the ANOCEF (French neuro-oncology association) guidelines. The management of brain metastases of breast cancers and lung cancers are discussed in the same chapter, while the management of melanoma brain metastases is reported in a separate chapter due to different responses to the brain radiotherapy., (Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background and Purpose: Stereotactic radiosurgery (SRS) followed by close follow-up is becoming a popular strategy for the management of brain metastases as cancer patients live longer and late adverse effects of whole brain radiotherapy (WBRT) are increasingly reported. The authors report their experience in consecutively treated patients with limited brain metastases from non-small cell lung cancer (NSCLC), who underwent SRS alone followed by a close follow-up., Methods: This study is the retrospective analysis of prospectively collected data. We included of 89 consecutive patients (80 men; mean age 59.7 years) with a KPS score of 60 or greater, who underwent Gamma Knife SRS for 1-4 metastases, at Lille University Hospital between January 2004 and December 2010. The mean radiation dose was 23.41Gy (range 18-26Gy) and the mean tumour volume was 2.47cm(3) (range 0.3-6.7cm(3)). After treatment, clinical and radiological (MRI) monitoring was scheduled at 2, 4, 8 and 12 months in the first year and at 4-month intervals thereafter., Results: Overall survival was 70.8% at 1 year and 50% at 2 years. The actuarial local control rate was 91.5% at 1 year and 85.5% at 2 years. Ten of 89 patients experienced a local failure, which required a salvage treatment. The distant brain control rate was 79.2% at 1 year, and 67.1% at 2 years. A total of 25 patients developed new metastases, 10 patients were treated with a new radiosurgical procedure, 12 patients underwent a WBRT while 3 patients developed a leptomeningeal disease. We reported an overall complication rate of 10.1% per patient and 7.8% per treated tumour; all complications were classified grade 1 or 2., Conclusion: In patients with limited brain metastases from NSCLC, SRS is an effective treatment associated with high local control rate with low morbidity. When performed in isolation, close follow-up is mandatory and radiosurgery can be renewed as salvage treatment for distant brain progression, limiting the use of WBRT., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT) consists of a laser light exposure of tumor cells photosensitized by general or local administration of a pharmacological agent. Nowadays, PDT is a clinically established modality for treatment of many cancers. 5-Aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven its rational in fluoro-guided resection of malignant gliomas due to a selective tumor uptake and minimal skin sensitization. Moreover, the relatively specific accumulation of photosensitizing PPIX within the tumor cells has gained interest in the PDT of malignant gliomas. Several experimental and clinical studies have then established ALA-PDT as a valuable adjuvant therapy in the management of malignant gliomas. However, the procedure still requires optimizations in the fields of tissue oxygenation status, photosensitizer concentration or scheme of laser light illumination. In this extensive review, we focused on the methods and results of ALA-PDT for treating malignant gliomas in experimental conditions. The biological mechanisms, the effects on tumor and normal brain tissue, and finally the critical issues to optimize the efficacy of ALA-PDT were discussed., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background and Purpose: Biopsies of brain stem lesions are useful for histopathological analysis, which guide appropriate treatment. The frame-based stereotactic procedure is the gold standard technique for biopsies of the brain stem. For the past few years, a frameless stereotactic robot, the NeuroMate robot (Renishaw, UK) has also been used for brain biopsies. We report a retrospective study of 15 patients who underwent NeuroMate robot-guided biopsies of brain stem lesions to evaluate the efficiency and safety of the system., Methods: From January 2004 to March 2006, 15 patients (five children and ten adults) underwent 17 biopsies of brain stem lesions. The lesions were located in the mesencephalon in two cases, in the pons in seven cases, in the pons and the medulla oblongata in five cases, and in the whole midbrain in one case. The biopsy procedure comprised four stages: image acquisition, preoperative planning, patient-to-image registration, and operative procedure. A transcerebellar approach was used in 12 cases and a double oblique anterior frontal approach in five cases., Results: Two adults underwent a second procedure because the first biopsy was not contributive. There was no operative mortality. We observed two cases of transient morbidity and one case of permanent morbidity., Conclusions: The frameless NeuroMate robot is an efficient and safe instrument for biopsies of brain stem lesions. We believe that the use of frameless stereotactic techniques for brain stem biopsies could increase the number of biopsies and therefore improve the diagnostic yield and accuracy of the technique., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Unlabelled: Isolated brain relapse is uncommon in Hodgkin's lymphoma and often linked with advanced or refractory disease., Case Reports: We report two patients with stage IV Hodgkin's disease, previously treated with chemotherapy, who later developed neurological symptoms. Brain MRI demonstrated two different types of lesions. Histological findings were consistent with intracranial location of Hodgkin lymphoma. Both of the patients presented only with isolated CNS relapse of the lymphoma., Conclusion: The two cases demonstrated the MRI appearance of intracranial involvement can be varied and mimic other disease processes in patients with a previous history of Hodgkin's lymphoma. Thus, a biopsy is necessary for diagnosis and correct treatment.

Introduction: Memory impairment caused by bilateral hippocampal primitive brain tumor is rarely reported. Clinical and MRI features can mimic paraneoplastic limbic encephalitis (PLE), and the differential diagnosis between these 2 entities may be difficult., Case Report: We report the case of a 42-year-old woman presenting with amnesia without neurologic focal signs at clinical examination. The neuroimaging features consisted of bilateral limbic hyperintensities on T2-weighted and FLAIR brain MRI. Despite exhaustive biologic and radiologic investigations, no specific etiology was found. The diagnosis of paraneoplastic limbic encephalitis was suspected, although antineuronal antibodies were negative and no cancer was detected after the first evaluation. Eight months after onset, the memory complaint of the patient increased along with disability in activities of the daily living, the neurologic examination slightly changed with frontal neurologic signs and the brain MRI showed a new cystic lesion in the left hippocampus with enhancement after contrast administration. The left temporal tumor was resected and the neuropathological examination was consistent with gliomatosis cerebri with a focal high grade astrocytoma., Conclusions: This case highlights the need to consider the possibility of infiltrative gliomatosis in patients presenting with features of paraneoplastic limbic encephalitis.

The anatomy of the supratentoriel midline structures of the brain is complex: corpus callosum, third ventricle, trigone, choroid plexus, pineal gland, falx cerebri. Different types of tumors can arise from these structures including tumors of the trigone and septum, tumors of the falx, third ventricular tumors and pinal region tumors. These tumors share similar features: minimal clinical symptoms despite their occasional large size, mild non-specific intracranial hypertension syndrome, value of MRI for depiction of tumor location, stereotactic biopsy, relative difficulty of surgical management.

Object: The aim of this study was to document the possible role of Gamma Knife radiosurgery, suitable for the treatment of deep and well limited tumors, in the management of pineal parenchymal tumors (PPT)., Population and Methods: We reviewed retrospectively a series of 13 patients with PPT treated by Gamma Knife radiosurgery during 16 procedures. Mean age was 31 (range 10 to 74). Eight patients had pineocytomas (61.5%), and 5 had pineoblastomas (38.5%). Radiosurgery was performed alone in 6 cases, after partial microsurgical resection in 3 cases, in association with chemotherapy in 3 cases and following conventional fractionated radiotherapy in 1 case. The marginal dose to these tumors ranged from 11 to 20 Gy (mean 15 Gy)., Results: With a mean follow-up of 34 months (range 6 to 88), all tumors responded to treatment and disappeared or ceased growing. Two patients with pineoblastoma had tumor size progression out of the initial target requiring several radiosurgery procedures. At the end of the follow-up period, 10 out of 12 patients were alive. Two patients with pineoblastoma died because of carcinomatous meningitis or tumor size progression. We observed no mortality or major morbidity related to radiosurgery., Conclusion: This study confirms that radiosurgery can be an effective and safe primary treatment modality for patients with pineocytomas. It should have a role in multimodality therapy which includes microsurgical resection, fractionated radiotherapy and chemotherapy for the management of malignant pineal tumors.