Long term follow-up of patients with newly diagnosed glioblastoma treated by intraoperative photodynamic therapy: an update from the INDYGO trial (NCT03048240).

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/cm2 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.

Impact of biologically effective dose on tremor decrease after stereotactic radiosurgical thalamotomy for essential tremor: a retrospective longitudinal analysis.

Stereotactic radiosurgery (SRS) is one of the surgical alternatives for drug-resistant essential tremor (ET). Here, we aimed at evaluating whether biologically effective dose (BEDGy2.47) is relevant for tremor improvement after stereotactic radiosurgical thalamotomy in a population of patients treated with one (unplugged) isocenter and a uniform dose of 130 Gy. This is a retrospective longitudinal single center study. Seventy-eight consecutive patients were clinically analyzed. Mean age was 69.1 years (median 71, range 36-88). Mean follow-up period was 14 months (median 12, 3-36). Tremor improvement was assessed at 12 months after SRS using the ET rating assessment scale (TETRAS, continuous outcome) and binary (binary outcome). BED was defined for an alpha/beta of 2.47, based upon previous studies considering such a value for the normal brain. Mean BED was 4573.1 Gy2.47 (median 4612, 4022.1-4944.7). Mean beam-on time was 64.7 min (median 61.4; 46.8-98.5). There was a statically significant correlation between delta (follow-up minus baseline) in TETRAS (total) with BED (p = 0.04; beta coefficient - 0.029) and beam-on time (p = 0.03; beta coefficient 0.57) but also between TETRAS (ADL) with BED (p = 0.02; beta coefficient 0.038) and beam-on time (p = 0.01; beta coefficient 0.71). Fractional polynomial multivariate regression suggested that a BED > 4600 Gy2.47 and a beam-on time > 70 min did not further increase clinical efficacy (binary outcome). Adverse radiation events (ARE) were defined as larger MR signature on 1-year follow-up MRI and were present in 7 out of 78 (8.9%) cases, receiving a mean BED of 4650 Gy2.47 (median 4650, range 4466-4894). They were clinically relevant with transient hemiparesis in 5 (6.4%) patients, all with BED values higher than 4500 Gy2.47. Tremor improvement was correlated with BED Gy2.47 after SRS for drug-resistant ET. An optimal BED value for tremor improvement was 4300-4500 Gy2.47. ARE appeared for a BED of more than 4500 Gy2.47. Such finding should be validated in larger cohorts.

Microsurgical resection of gliomas of the cingulate gyrus: a systematic review and meta-analysis.

Cingulate gyrus gliomas are rare among adult, hemispheric diffuse gliomas. Surgical reports are scarce. We performed a systematic review of the literature and meta-analysis, with the aim of focusing on the extent of resection (EOR), WHO grade, and morbidity and mortality, after microsurgical resection of gliomas of the cingulate gyrus. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we reviewed articles published between January 1996 and December 2022 and referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical studies of microsurgical series reporting resection of gliomas of the cingulate gyrus. Primary outcome was EOR, classified as gross total (GTR) versus subtotal (STR) resection. Five studies reporting 295 patients were included. Overall GTR was 79.4% (range 64.1-94.7; I2= 88.13; p heterogeneity and p < 0.001), while STR was done in 20.6% (range 5.3-35.9; I2= 88.13; p heterogeneity < 0.001 and p= 0.008). The most common WHO grade was II, with an overall rate of 42.7% (24-61.5; I2= 90.9; p heterogeneity, p< 0.001). Postoperative SMA syndrome was seen in 18.6% of patients (10.4-26.8; I2= 70.8; p heterogeneity= 0.008, p< 0.001), postoperative motor deficit in 11% (3.9-18; I2= 18; p heterogeneity= 0.003, p= 0.002). This review found that while a GTR was achieved in a high number of patients with a cingulate glioma, nearly half of such patients have a postoperative deficit. This finding calls for a cautious approach in recommending and doing surgery for patients with cingulate gliomas and for consideration of new surgical and management approaches.

Resection of the contrast-enhancing tumor in diffuse gliomas bordering eloquent areas using electrophysiology and 5-ALA fluorescence: evaluation of resection rates and neurological outcome-a systematic review and meta-analysis.

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.

Frameless robot-assisted stereotactic biopsies for lesions of the brainstem-a series of 103 consecutive biopsies.

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.

Gamma Knife radiosurgery for acromegaly: Evaluating the role of the biological effective dose associated with endocrine remission in a series of 42 consecutive cases.

INTRODUCTION: Stereotactic radiosurgery (SRS) is a valuable treatment option for persistent and/or recurrent acromegaly secondary to growth hormone (GH) secreting pituitary adenoma (PA). Here, we assess the role of biological effective dose (BED) received by PA treated with SRS in relation with endocrine remission. METHODS: Forty-two patients (minimum 6 months follow-up) were included. Mean marginal dose was 27.7 (median 28, 20-35), and mean BED received by tumour was 193.1 Gy2.47 (median 199.7, 64.1-237.1). Based on the median values, we divided the patients in high tumour BED group (H-BEDtm, 199.7-237.1 Gy2.47, n = 12) and low BED one (L- BEDtm, 64.1-199.7 Gy2.47 , n = 10). The two groups did not differ by pretherapeutic IGF-1 levels (p = .1) or by the prescribed dose (p = .6). RESULTS: Mean follow-up period was 62.5 months (median 60.5, 9-127). Probability of IGF-1 normalization was 65% at 3 years and 72.4% at 4 years, remaining stable until last follow-up. Twenty-two (52.4%) patients had complete endocrine remission in absence of any Somatostatin analogues. Actuarial rates were 33% at 3 years and 57.4% at 7 years, further remaining stable during follow-up course. In univariate analysis, only statistically significant parameter was pretherapeutic serum IGF-1 and IGF-1 index (p = .01). Five patients (5/26, 19.3%) without previous hypopituitarism developed new pituitary insufficiency. H-BEDtm was associated with higher rates of endocrine remission compared with L-BEDtm, with actuarial probability of 70.2% versus 48.2% at 9 years, although this did not reach statistical significance (p > .05). CONCLUSION: Our study confirms that SRS by Gamma Knife is safe and effective for GH-secreting PA. Pretherapeutic serum levels of IGF-1 were only statistically significant parameter for endocrine remission.

Standardized intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial.

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.

Trigeminal Neuralgia Secondary to Meningiomas and Vestibular Schwannoma Is Improved after Stereotactic Radiosurgery: A Systematic Review and Meta-Analysis.

INTRODUCTION: Trigeminal neuralgia (TN) secondary to tumors is encountered in up to 6% of patients with facial pain syndromes and is considered to be associated with tumors affecting the trigeminal nerve pathways. The most frequent are meningiomas and vestibular schwannomas (VS). Stereotactic radiosurgery (SRS) has emerged as a valuable treatment, with heterogeneity of clinical results. We sought to review the medical literature on TN treated with SRS for meningiomas and VS and investigate the rates of improvement of TN symptoms. METHODS: We reviewed articles published between January 1990 and December 2019 in PubMed. Pain relief after SRS, the maintenance of pain relief, and TN recurrence and complications were evaluated with separate meta-analyses, taking into account the data on individual patients. RESULTS: Pain relief after SRS was reported as Barrow Neurological Institute (BNI) pain intensity scores of BNI I in 50.5% (range 36-65.1%) of patients and BNI I-IIIb in 83.8% (range 77.8-89.8%). There was no significant difference in series discussing outcomes for tumor targeting versus tumor and nerve targeting. Recurrences were described in 34.7% (range 21.7-47.6; tumor targeting). Maintenance of BNI I was reported in 36.4% (range 20.1-52.7) and BNI I-IIIb in 41.2% (range 29.8-52.7; tumor targeting series). When both the nerve and the tumor were targeted, only 1 series reported 86.7% with BNI I-IIIb at last follow-up. Complications were encountered in 12.6% (range 6.3-18.8; tumor targeting series) of patients; however, they were much higher, as high as 26.7%, in the only study reporting them after targeting both the nerve and the tumor. The most common complication was facial numbness. CONCLUSION: SRS for TNB secondary to benign tumors, such as meningiomas and VS, is associated with favorable clinical course, but less favorable than in idiopathic TN. There was, however, heterogeneity among reports and targeting approaches. Although targeting both the nerve and the tumor seemed to achieve better long-term results, the rate of complications was much higher and the number of patients treated was limited. Future clinical studies should focus on the standard reporting of clinical outcomes and randomization of targeting methods.

Tumor control and trigeminal dysfunction improvement after stereotactic radiosurgery for trigeminal schwannomas: a systematic review and meta-analysis.

Trigeminal nerve schwannomas (TS) are uncommon intracranial tumors, frequently presenting with debilitating trigeminal and/or oculomotor nerve dysfunction. While surgical resection has been described, its morbidity and mortality rates are non-negligible. Stereotactic radiosurgery (SRS) has emerged with variable results as a valuable alternative. Here, we aimed at reviewing the medical literature on TS treated with SRS so as to investigate rates of tumor control and symptomatic improvement. We reviewed manuscripts published between January 1990 and December 2019 on PubMed. Tumor control and symptomatic improvement rates were evaluated with separate meta-analyses. This meta-analysis included 18 studies comprising a total of 564 patients. Among them, only one reported the outcomes of linear accelerators (Linac), while the others of GK. Tumor control rates after SRS were 92.3% (range 90.1-94.5; p < 0.001), and tumor decrease rates were 62.7% (range 54.3-71, p < 0.001). Tumor progression rates were 9.4% (range 6.8-11.9, p < 0.001). Clinical improvement rates of trigeminal neuralgia were 63.5% (52.9-74.1, p < 0.001) and of oculomotor nerves were 48.2% (range 36-60.5, p < 0.001). Clinical worsening rate was 10.7% (range 7.6-13.8, p < 0.001). Stereotactic radiosurgery for TS is associated with high tumor control rates and favorable clinical outcomes, especially for trigeminal neuralgia and oculomotor nerves. However, patients should be correctly advised about the risk of tumor progression and potential clinical worsening. Future clinical studies should focus on standard reporting of clinical outcomes.

Impact of combined use of intraoperative MRI and awake microsurgical resection on patients with gliomas: a systematic review and meta-analysis.

Microsurgical resection of primary brain tumors located within or near eloquent areas is challenging. Primary aim is to preserve neurological function, while maximizing the extent of resection (EOR), to optimize long-term neurooncological outcomes and quality of life. Here, we review the combined integration of awake craniotomy and intraoperative MRI (IoMRI) for primary brain tumors, due to their multiple challenges. A systematic review of the literature was performed, in accordance with the Prisma guidelines. Were included 13 series and a total number of 527 patients, who underwent 541 surgeries. We paid particular attention to operative time, rate of intraoperative seizures, rate of initial complete resection at the time of first IoMRI, the final complete gross total resection (GTR, complete radiological resection rates), and the immediate and definitive postoperative neurological complications. The mean duration of surgery was 6.3 h (median 7.05, range 3.8-7.9). The intraoperative seizure rate was 3.7% (range 1.4-6; I^2 = 0%, P heterogeneity = 0.569, standard error = 0.012, p = 0.002). The intraoperative complete resection rate at the time of first IoMRI was 35.2% (range 25.7-44.7; I^2 = 66.73%, P heterogeneity = 0.004, standard error = 0.048, p < 0.001). The rate of patients who underwent supplementary resection after one or several IoMRI was 46% (range 39.8-52.2; I^2 = 8.49%, P heterogeneity = 0.364, standard error = 0.032, p < 0.001). The GTR rate at discharge was 56.3% (range 47.5-65.1; I^2 = 60.19%, P heterogeneity = 0.01, standard error = 0.045, p < 0.001). The rate of immediate postoperative complications was 27.4% (range 15.2-39.6; I^2 = 92.62%, P heterogeneity < 0.001, standard error = 0.062, p < 0.001). The rate of permanent postoperative complications was 4.1% (range 1.3-6.9; I^2 = 38.52%, P heterogeneity = 0.123, standard error = 0.014, p = 0.004). Combined use of awake craniotomy and IoMRI can help in maximizing brain tumor resection in selected patients. The technical obstacles to doing so are not severe and can be managed by experienced neurosurgery and anesthesiology teams. The benefits of bringing these technologies to bear on patients with brain tumors in or near language areas are obvious. The lack of equipoise on this topic by experienced practitioners will make it difficult to do a prospective, randomized, clinical trial. In the opinion of the authors, such a trial would be unnecessary and would deprive some patients of the benefits of the best available methods for their tumor resections.

Repeat stereotactic radiosurgery for progressive vestibular schwannomas after previous radiosurgery: a systematic review and meta-analysis.

Vestibular schwannomas (VS) are slow-growing intracranial extraaxial benign tumors, developing from the vestibular part of the eight cranial nerves. Stereotactic radiosurgery (SRS) has now a long-term scientific track record as first intention treatment for small- to medium-sized VS. Though its success rate is very high, SRS for VS might fail to control tumor growth in some cases. However, the literature on repeat SRS after previously failed SRS remains scarce and reported in a low number of series with a limited number of cases. Here, we aimed at performing a systematic review and meta-analysis of the literature on repeat SRS for VS. Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2020 and referenced in PubMed. Tumor control and cranial nerve outcomes were evaluated with separate meta-analyses. Eight studies comprising 194 patients were included. The overall rate of patients treated in repeat SRS series as per overall series with first SRS was 2.2% (range 1.2-3.2%, p < 0.001). The mean time between first and second SRS was 50.7 months (median 51, range 44-64). The median marginal dose prescribed at first SRS was 12 Gy (range 8-24) and at second SRS was 12 Gy (range 9.8-19). After repeat SRS, tumor stability was reported in 61/194 patients, i.e., a rate of 29.6% (range 20.2-39%, I2 = 49.1%, p < 0.001). Tumor decrease was reported in 83/194 patients, i.e., a rate of 54.4% (range 33.7-75.1%, I2 = 89.1%, p < 0.001). Tumor progression was reported in 50/188 patients, i.e., a rate of 16.1% (range 2.5-29.7%, I2 = 87.1%, p = 0.02), rarely managed surgically. New trigeminal numbness was reported in 27/170 patients, i.e., a rate of 9.9% (range 1.4-18.3%, p < 0.02). New facial nerve palsy of worsened of previous was reported in 8/183 patients, i.e., a rate of 4.3% (range 1.4-7.2%, p = 0.004). Hearing loss was reported in 12/22 patients, i.e., a rate of 54.3% (range 24.8-83.8%, I2 = 70.7%, p < 0.001). Repeat SRS after previously failed SRS for VS is associated with high tumor control rates. Cranial nerve outcomes remain favorable, particularly for facial nerve. The rate of hearing loss appears similar to the one related to first SRS.

Intraoperative MRI and FLAIR Analysis: Implications for low-grade glioma surgery.

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.

Reversible Focal Dystonia Secondary to Giant Perivascular Spaces.

Giant perivascular spaces (PVS) are rare, CSF-filled, dilated cavities lined by the pia mater that are most often asymptomatic radiological findings but can sometimes cause neurological symptoms. We present two exceptional cases of secondary focal dystonia induced by the mass effect on the basal ganglia caused by giant diencephalic PVSs. In both cases, we chose a surgical stereotactic drainage approach as a treatment strategy that allowed controlling the movement disorders. The beneficial therapeutic effect was sustained at long-term follow-up. We believe that similar cases could be addressed successfully with this method.

Intraoperative MRI guidance for right deep fronto-temporal glioma resection: how I do it.

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.

Impact of the skull contour definition on Leksell Gamma Knife® Icon™ radiosurgery treatment planning.

INTRODUCTION: The Gamma Knife® planning software (TMR 10, Elekta Instruments, AB, Sweden) affords two ways of defining the skull volume, the "historical" one using manual measurements (still perform in some centers) and the new one using image-based skull contours. Our objective was to assess the potential variation of the dose delivery calculation using consecutively in the same patients the two above-mentioned techniques. MATERIALS AND METHODS: We included in this self-case-control study, 50 patients, treated with GKRS between July 2016 and January 2017 in Lausanne University Hospital, Switzerland, distributed among four groups: convexity targets (n = 18), deep-seated targets (n = 13), vestibular schwannomas (n = 11), and trigeminal neuralgias (n = 8). Each planning was performed consecutively with the 2 skull definition techniques. For each treatment, we recorded the beam-on time (min), target volume coverage (%), prescription isodose volume (cm3), and maximal dose (Gy) to the nearest organ at risk if relevant, according to each of the 2 skull definition techniques. The image-based contours were performed using CT scan segmentation, based upon a standardized windowing for all patients. RESULTS: The median difference in beam-on time between manual measures and image-based contouring was + 0.45 min (IQR; 0.2-0.6) and was statistically significant (p < 0.0001), corresponding to an increase of 1.28% beam-on time per treatment, when using image-based contouring. The target location was not associated with beam-on time variation (p = 0.15). Regarding target volume coverage (p = 0.13), prescription isodose volume (p = 0.2), and maximal dose to organs at risk (p = 0.85), no statistical difference was reported between the two skull contour definition techniques. CONCLUSION: The beam-on time significantly increased using image-based contouring, resulting in an increase of the total dose delivery per treatment with the new TMR 10 algorithm. Other dosimetric parameters did not differ significantly. This raises the question of other potential impacts. One is potential dose modulation that should be performed as an adjustment to new techniques developments. The second is how this changes the biologically equivalent dose per case, as related to an increased beam on time, delivered dose, etc., and how this potentially changes the radiobiological effects of GKRS in an individual patient.

High-field intraoperative MRI and glioma surgery: results after the first 100 consecutive patients.

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.

Photodynamic therapy for glioblastoma: A preliminary approach for practical application of light propagation models.

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.

MRI assessment of treatment delivery for interstitial photodynamic therapy of high-grade glioma in a preclinical model.

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 mm3 versus 2.67 mm3 , 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.

Radiosurgery and fractionated radiotherapy for cavernous sinus meningioma: a systematic review and meta-analysis.

INTRODUCTION: Radiosurgery (RS) and fractionated radiotherapy (FRT) are part of the therapeutic armamentarium for the management of cavernous sinus meningiomas. We propose a systematic review of the local tumor control and clinical outcomes after monofractionated radiosurgical treatment, including gamma knife radiosurgery (GKRS) and linear accelerator (Linac RS), or fractionated radiotherapy. MATERIALS AND METHODS: The current review and meta-analysis adhered to the PRISMA guidelines. We performed a search in PubMed, Embase, and Medline based on the following mesh terms, used alone or in diverse combinations, in both title and abstract: "cavernous sinus," "meningioma," "radiosurgery," "gamma knife," "linac," "cyberknife," and "radiotherapy". We screened 425 studies. We selected 36 studies, matching all selection criteria: 24 for GK, 5 for Linac, and 7 for FRT. RESULTS: Were included 2817 patients (GKRS, n = 2047, LinacRS, n = 350, FRT, n = 420). Half of patients benefited from upfront RS or FRT; the other half benefited from adjuvant RS or FRT (combined approach or tumor recurrence). The mean gross target volume (GTV) was smaller for RS as compared to FRT (p = 0.07). The median marginal doses were 13.9 Gy (range, 11 to 28) for GKRS and 14 Gy (range, 12.8 to 17.7) for LinacRS. For FRT, patients received a mean dose of 51.2 Gy (25.5 fractions, 1.85 Gy each). The mean overall follow-up values were 48 months (range, 15 to 89) for GKRS, 69 months (range, 46 to 87) for Linac, and 59.5 months (range, 33 to 83) for FRT. PFS at 5 years for GKRS, LinacRS, and FRT were respectively 93.6%, 95.6%, and 97.4% (p = 0.32, the Kruskal-Wallis). Monofractionated treatments (GKRS and LinacRS) induced more tumor volume regression than FRT (p = 0.001). Tumor recurrence or progression ranged between 3 and 5.8%, without statistically significant differences between modalities (p > 0.05). Trigeminal symptoms improved in approximately 54%, and III-IV-VI cranial nerves (CN) palsies improved in approximately 45%. After GKRS, visual acuity improved in 21% (not enough data available for other modalities). De novo deficits occurred in 5 to 7.5%. Adverse radiation effects appeared in 4.6 to 9.3% (all techniques pooled). CONCLUSION: RS achieved a twice-higher rate of tumor volume regression than FRT. GKRS series reported an improvement in visual acuity in 21% of the cases. GKRS, Linac, and FRT provided similar clinical post therapeutic outcomes for the trigeminal and oculomotor CN.

Encoding and immediate retrieval tasks in patients with epilepsy: A functional MRI study of verbal and visual memory.

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