Publications by authors named "Frederic Dhermain"

68 Publications

Cranial organs at risk delineation: heterogenous practices in radiotherapy planning.

Radiat Oncol 2021 Feb 4;16(1):26. Epub 2021 Feb 4.

Department of Radiation Oncology, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Sorbonne Université, Paris, France.

Background: Segmentation is a crucial step in treatment planning that directly impacts dose distribution and optimization. The aim of this study was to evaluate the inter-individual variability of common cranial organs at risk (OAR) delineation in neurooncology practice.

Methods: Anonymized simulation contrast-enhanced CT and MR scans of one patient with a solitary brain metastasis was used for delineation and analysis. Expert professionals from 16 radiotherapy centers involved in brain structures delineation were asked to segment 9 OAR on their own treatment planning system. As reference, two experts in neurooncology, produced a unique consensual contour set according to guidelines. Overlap ratio, Kappa index (KI), volumetric ratio, Commonly Contoured Volume, Supplementary Contoured Volume were evaluated using Artiview™ v 2.8.2-according to occupation, seniority and level of expertise of all participants.

Results: For the most frequently delineated and largest OAR, the mean KI are often good (0.8 for the parotid and the brainstem); however, for the smaller OAR, KI degrade (0.3 for the optic chiasm, 0.5% for the cochlea), with a significant discrimination (p < 0.01). The radiation oncologists, members of Association des Neuro-Oncologue d'Expression Française society performed better in all indicators compared to non-members (p < 0.01). Our exercise was effective in separating the different participating centers with 3 of the reported indicators (p < 0.01).

Conclusion: Our study illustrates the heterogeneity in normal structures contouring between professionals. We emphasize the need for cerebral OAR delineation harmonization-that is a major determinant of therapeutic ratio and clinical trials evaluation.
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http://dx.doi.org/10.1186/s13014-021-01756-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863275PMC
February 2021

Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients - a report of the PET/RANO group.

Neuro Oncol 2021 Feb 4. Epub 2021 Feb 4.

German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.

The management of patients with glioma usually requires multimodality treatment including surgery, radiotherapy, and systemic therapy. Accurate neuroimaging plays a central role for radiotherapy planning and follow-up after radiotherapy completion. In order to maximize the radiation dose to the tumor and to minimize toxic effects on the surrounding brain parenchyma, reliable identification of tumor extent and target volume delineation is crucial. The use of PET for radiotherapy planning and monitoring in gliomas has gained considerable interest over the last several years, but Class I data are not yet available. Furthermore, PET has been used after radiotherapy for response assessment and to distinguish tumor progression from pseudoprogression or radiation necrosis. Here, the RANO working group provides a summary of the literature and recommendations for the use of PET imaging for radiotherapy of patients with glioma based on published studies, constituting levels 1-3 evidence according to the Oxford Centre for Evidence-based Medicine.
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http://dx.doi.org/10.1093/neuonc/noab013DOI Listing
February 2021

Postoperative intracerebral haematomas following stereotactic biopsies: Poor planning or poor execution?

Int J Med Robot 2020 Dec 20. Epub 2020 Dec 20.

Service de Neurochirurgie, GHU Paris - Psychiatrie et Neurosciences - Hôpital Sainte-Anne, Paris, France.

Background: Postoperative intracerebral haematomas represent a serious complication following stereotactic biopsy. We investigated the possible underlying causes - poor planning or poor execution - of postoperative intracerebral haematomas following stereotactic biopsies.

Methods: We performed a technical investigation using a retrospective single-centre consecutive series of robot-assisted stereotactic biopsies for a supratentorial diffuse glioma in adults. Each actual biopsy trajectory was reviewed to search for a conflict with an anatomical structure at risk.

Results: From 379 patients, 12 (3.2%) presented with a postoperative intracerebral haematoma ≥20 mm on postoperative CT-scan (3 requiring surgical evacuation); 11 of them had available intraoperative imaging (bi-planar stereoscopic teleangiography x-rays at each biopsy site). The actual biopsy trajectory was similar to the planned biopsy trajectory in these 11 cases. In 72.7% (8/11) of these cases, the actual biopsy trajectory was found to contact a structure at risk (blood vessel and cerebral sulcus) and identified as the intracerebral haematoma origin.

Conclusions: Robot-assisted stereotactic biopsy is an accurate procedure. Postoperative intracerebral haematomas mainly derive from human-related errors during trajectory planning.
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http://dx.doi.org/10.1002/rcs.2211DOI Listing
December 2020

Prognostic relevance of adding MRI data to WHO 2016 and cIMPACT-NOW updates for diffuse astrocytic tumors in adults. Working toward the extended use of MRI data in integrated glioma diagnosis.

Brain Pathol 2020 Dec 17:e12929. Epub 2020 Dec 17.

Université de Paris, Sorbonne Paris Cité, Paris, France.

Assess the contribution of preoperative MRI data in improving grading of adult astrocytomas reclassified according to the WHO 2016 and cIMPACT-NOW update 3. Retrospective unicentric cohort study of 679 adult patients treated for newly diagnosed diffuse astrocytic and oligodendroglial tumors (January 2006-December 2016). We first systematically compared radiological (contrast enhancement present [CE+] vs. absent [CE-]) and histopathological findings (microvascular proliferation present [MPV+] vs. absent [MPV-]) to validate whether this comparing step of neoangiogenesis represents an efficient method to appreciate the representativity of the tumoral sampling. We focused on 629 cases of astrocytomas for radio-histological integrated analyses. In 598 cases (95.1%), neoangiogenesis evaluated by MRI or histology (CE+/MPV+ or CE-/MPV-) was identical. For the CE+/MPV- and CE-/MPV+ groups (23 cases), the radio-histological face-to-face evaluation allowed us to assess that for 13 cases (56.5%) the reason for this discrepancy was an undersampled tumor. We analyzed the group of CE+/MPV- (n = 8) and CE-/MPV+ (n = 2) in verified image-guided tumoral samples. Finally, we identified three new prognostic subgroups for molecular glioblastomas: (1) "non-representative sampling" (n = 9), (2) "Non neoangiogenic glioblastoma at the time of diagnosis, without contrast enhancement and microvascular proliferation" (n = 8), and (3) "contrast enhancing glioblastoma but without microvascular proliferation in a representative sample" (n = 4). Neoangiogenesis processes should be assessed to improve the prognosis accuracy of the current integrated diagnosis. We suggest adding imaging analyses during the neuropathological analysis of astrocytomas in adults.
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http://dx.doi.org/10.1111/bpa.12929DOI Listing
December 2020

Hippocampal Avoidance Whole-Brain Radiotherapy (WBRT) Versus WBRT in Patients With Brain Metastases: Were Hippocampi the Only Difference?

J Clin Oncol 2020 10 12;38(29):3453-3454. Epub 2020 Aug 12.

Antonin Levy, MD, PhD, Department of Radiation Oncology and INSERM U1030, Molecular Radiotherapy, Gustave Roussy, Université Paris-Saclay, Villejuif, France, and Université Paris Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France; and Frédéric Dhermain, MD, PhD; Angela Botticella, MD; Sofia Rivera, MD, PhD; and Cécile Le Péchoux, MD, Department of Radiation Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.

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http://dx.doi.org/10.1200/JCO.20.00548DOI Listing
October 2020

Standardization of brain MR images across machines and protocols: bridging the gap for MRI-based radiomics.

Sci Rep 2020 07 23;10(1):12340. Epub 2020 Jul 23.

Molecular Radiotherapy and Innovative Therapeutics, INSERM UMR1030, Gustave Roussy Cancer Campus, Paris-Saclay University, Villejuif, France.

Radiomics relies on the extraction of a wide variety of quantitative image-based features to provide decision support. Magnetic resonance imaging (MRI) contributes to the personalization of patient care but suffers from being highly dependent on acquisition and reconstruction parameters. Today, there are no guidelines regarding the optimal pre-processing of MR images in the context of radiomics, which is crucial for the generalization of published image-based signatures. This study aims to assess the impact of three different intensity normalization methods (Nyul, WhiteStripe, Z-Score) typically used in MRI together with two methods for intensity discretization (fixed bin size and fixed bin number). The impact of these methods was evaluated on first- and second-order radiomics features extracted from brain MRI, establishing a unified methodology for future radiomics studies. Two independent MRI datasets were used. The first one (DATASET1) included 20 institutional patients with WHO grade II and III gliomas who underwent post-contrast 3D axial T1-weighted (T1w-gd) and axial T2-weighted fluid attenuation inversion recovery (T2w-flair) sequences on two different MR devices (1.5 T and 3.0 T) with a 1-month delay. Jensen-Shannon divergence was used to compare pairs of intensity histograms before and after normalization. The stability of first-order and second-order features across the two acquisitions was analysed using the concordance correlation coefficient and the intra-class correlation coefficient. The second dataset (DATASET2) was extracted from the public TCIA database and included 108 patients with WHO grade II and III gliomas and 135 patients with WHO grade IV glioblastomas. The impact of normalization and discretization methods was evaluated based on a tumour grade classification task (balanced accuracy measurement) using five well-established machine learning algorithms. Intensity normalization highly improved the robustness of first-order features and the performances of subsequent classification models. For the T1w-gd sequence, the mean balanced accuracy for tumour grade classification was increased from 0.67 (95% CI 0.61-0.73) to 0.82 (95% CI 0.79-0.84, P = .006), 0.79 (95% CI 0.76-0.82, P = .021) and 0.82 (95% CI 0.80-0.85, P = .005), respectively, using the Nyul, WhiteStripe and Z-Score normalization methods compared to no normalization. The relative discretization makes unnecessary the use of intensity normalization for the second-order radiomics features. Even if the bin number for the discretization had a small impact on classification performances, a good compromise was obtained using the 32 bins considering both T1w-gd and T2w-flair sequences. No significant improvements in classification performances were observed using feature selection. A standardized pre-processing pipeline is proposed for the use of radiomics in MRI of brain tumours. For models based on first- and second-order features, we recommend normalizing images with the Z-Score method and adopting an absolute discretization approach. For second-order feature-based signatures, relative discretization can be used without prior normalization. In both cases, 32 bins for discretization are recommended. This study may pave the way for the multicentric development and validation of MR-based radiomics biomarkers.
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http://dx.doi.org/10.1038/s41598-020-69298-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378556PMC
July 2020

Dosimetry-Driven Quality Measure of Brain Pseudo Computed Tomography Generated From Deep Learning for MRI-Only Radiation Therapy Treatment Planning.

Int J Radiat Oncol Biol Phys 2020 Nov 14;108(3):813-823. Epub 2020 May 14.

U1030 Molecular Radiotherapy, Paris-Sud University - Gustave Roussy - Inserm - Paris-Saclay University, Villejuif, France; Department of Medical Physics, Gustave Roussy - Paris-Saclay University, Villejuif, France. Electronic address:

Purpose: This study aims to evaluate the impact of key parameters on the pseudo computed tomography (pCT) quality generated from magnetic resonance imaging (MRI) with a 3-dimensional (3D) convolutional neural network.

Methods And Materials: Four hundred two brain tumor cases were retrieved, yielding associations between 182 computed tomography (CT) and T1-weighted MRI (T1) scans, 180 CT and contrast-enhanced T1-weighted MRI (T1-Gd) scans, and 40 CT, T1, and T1-Gd scans. A 3D CNN was used to map T1 or T1-Gd onto CT scans and evaluate the importance of different components. First, the training set size's influence on testing set accuracy was assessed. Moreover, we evaluated the MRI sequence impact, using T1-only and T1-Gd-only cohorts. We then investigated 4 MRI standardization approaches (histogram-based, zero-mean/unit-variance, white stripe, and no standardization) based on training, validation, and testing cohorts composed of 242, 81, and 79 patients cases, respectively, as well as a bias field correction influence. Finally, 2 networks, namely HighResNet and 3D UNet, were compared to evaluate the architecture's impact on the pCT quality. The mean absolute error, gamma indices, and dose-volume histograms were used as evaluation metrics.

Results: Generating models using all the available cases for training led to higher pCT quality. The T1 and T1-Gd models had a maximum difference in gamma index means of 0.07 percentage point. The mean absolute error obtained with white stripe was 78 ± 22 Hounsfield units, which slightly outperformed histogram-based, zero-mean/unit-variance, and no standardization (P < .0001). Regarding the network architectures, 3%/3 mm gamma indices of 99.83% ± 0.19% and 99.74% ± 0.24% were obtained for HighResNet and 3D UNet, respectively.

Conclusions: Our best pCTs were generated using more than 200 samples in the training data set. Training with T1 only and T1-Gd only did not significantly affect performance. Regardless of the preprocessing applied, the dosimetry quality remained equivalent and relevant for potential use in clinical practice.
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http://dx.doi.org/10.1016/j.ijrobp.2020.05.006DOI Listing
November 2020

Role of neoadjuvant chemotherapy in metastatic medulloblastoma: a comparative study in 92 children.

Neuro Oncol 2020 11;22(11):1686-1695

Gustave Roussy Cancer Center, Department of Pediatric and Adolescent Oncology, Paris-Saclay University, Villejuif, France.

Background: Previous pilot studies have shown the feasibility of preoperative chemotherapy in patients with medulloblastoma, but benefits and risks compared with initial surgery have not been assessed.

Methods: Two therapeutic strategies were retrospectively compared in 92 patients with metastatic medulloblastoma treated at Gustave Roussy between 2002 and 2015: surgery at diagnosis (n = 54, group A) and surgery delayed after carboplatin and etoposide-based neoadjuvant therapy (n = 38, group B). Treatment strategies were similar in both groups.

Results: The rate of complete tumor excision was significantly higher in group B than in group A (93.3% vs 57.4%, P = 0.0013). Postoperative complications, chemotherapy-associated side effects, and local progressions were not increased in group B. Neoadjuvant chemotherapy led to a decrease in the primary tumor size in all patients; meanwhile 4/38 patients experienced a distant progression. The histological review of 19 matched tumor pairs (before and after chemotherapy) showed that proliferation was reduced and histological diagnosis feasible and accurate even after neoadjuvant chemotherapy. The 5-year progression-free and overall survival rates were comparable between groups. Comparison of the longitudinal neuropsychological data showed that intellectual outcome tended to be better in group B (the mean predicted intellectual quotient value was 6 points higher throughout the follow-up).

Conclusion: Preoperative chemotherapy is a safe and efficient strategy for metastatic medulloblastoma. It increases the rate of complete tumor excision and may improve the neuropsychological outcome without jeopardizing survival.

Key Points: 1. Preoperative chemotherapy increases the rate of complete tumor removal.2. No additional risk (toxic or disease progression) is linked to the delayed surgery.3. Preoperative chemotherapy could have a positive impact on the neuropsychological outcome of patients.
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http://dx.doi.org/10.1093/neuonc/noaa083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846143PMC
November 2020

Development of a disease-specific graded prognostic assessment index for the management of sarcoma patients with brain metastases (Sarcoma-GPA).

BMC Cancer 2020 Feb 12;20(1):117. Epub 2020 Feb 12.

Gustave Roussy Cancer Campus, Villejuif, France.

Background: Brain metastases from sarcomatous lesions pose a management challenge owing to their rarity and the histopathological heterogeneity. Prognostic indices such as the Graded Prognostic Assessment (GPA) index have been developed for several primary tumour types presenting with brain metastases (e.g. lung, breast, melanoma), tailored to the specifics of different primary histologies and molecular profiles. Thus far, a prognostic index to direct treatment decisions is lacking for adult sarcoma patients with brain metastases.

Methods: We performed a multicentre analysis of a national group of expert sarcoma tertiary centres (French Sarcoma Group, GSF-GETO) with the participation of one Canadian and one Swiss centre. The study cohort included adult patients with a diagnosis of a bone or soft tissue sarcoma presenting parenchymal or meningeal brain metastases, managed between January 1992 and March 2012. We assessed the validity of the original GPA index in this patient population and developed a disease-specific Sarcoma-GPA index.

Results: The original GPA index is not prognostic for sarcoma brain metastasis patients. We have developed a dedicated Sarcoma-GPA index that identifies a sub-group of patients with particularly favourable prognosis based on histology, number of brain lesions and performance status.

Conclusions: The Sarcoma-GPA index provides a novel tool for sarcoma oncologists to guide clinical decision-making and outcomes research.
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http://dx.doi.org/10.1186/s12885-020-6548-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014599PMC
February 2020

High-grade gliomas in adolescents and young adults highlight histomolecular differences from their adult and pediatric counterparts.

Neuro Oncol 2020 08;22(8):1190-1202

Paris Descartes University, Sorbonne Paris Cité, Paris, France.

Background: Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs).

Methods: We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification.

Results: Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of "rare adult IDH mutations" (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance.

Conclusions: HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.
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http://dx.doi.org/10.1093/neuonc/noaa024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594566PMC
August 2020

Imaging growth as a predictor of grade of malignancy and aggressiveness of IDH-mutant and 1p/19q-codeleted oligodendrogliomas in adults.

Neuro Oncol 2020 07;22(7):993-1005

Department of Neurosurgery, University Hospital Group for Psychiatry and Neurosciences (GHU)-Sainte-Anne Hospital, Paris, France.

Background: We quantified the spontaneous imaging growth rate of oligodendrogliomas. We assessed whether (i) it discriminates between World Health Organization (WHO) grade II and grade III oligodendrogliomas, and (ii) grade III oligodendrogliomas with neo-angiogenesis are associated with more fast growth rates (≥8 mm/y).

Methods: This work employed a retrospective bicentric cohort study (2010-2016) of adult patients harboring a newly diagnosed supratentorial oligodendroglioma, isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted (WHO 2016 classification), with a minimum of 2 available MRIs before any treatment (minimum 6-week interval) to measure the spontaneous tumor growth rate.

Results: We included 108 patients (age 44.7 ± 14.1 y, 60 males). The tumor growth rate was higher in grade III oligodendrogliomas with neo-angiogenesis (n = 37, median 10.4 mm/y, mean 10.0 ± 6.9) than in grade III oligodendrogliomas with increased mitosis count only (cutoff ≥6 mitoses, n = 18, median 3.9 mm/y, mean 4.5 ± 3.2; P = 0.004), and higher than in grade II oligodendrogliomas (n = 53, median 2.3 mm/y, mean 2.8 ± 2.2; P < 0.001). There was increased prevalence of fast tumor growth rates in grade III oligodendrogliomas with neo-angiogenesis (54.1%) compared with grade III oligodendrogliomas with increased mitosis count only (11.1%; P < 0.001), and in grade II oligodendrogliomas (0.0%; P < 0.001). The tumor growth rate trends did not differ between centers (P = 0.121). Neo-angiogenesis (P < 0.001) and mitosis count at ≥9 (P = 0.013) were independently associated with tumor growth rates ≥8 mm/year. A tumor growth rate ≥8 mm/year was the only predictor independently associated with shorter progression-free survival (P = 0.041).

Conclusions: The spontaneous tumor growth rate recapitulates oligodendroglioma aggressiveness, permits identification of grade III oligodendrogliomas preoperatively when ≥8 mm/year, and questions the grading by mitosis count.
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http://dx.doi.org/10.1093/neuonc/noaa022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339891PMC
July 2020

MRI Atlas of IDH Wild-Type Supratentorial Glioblastoma: Probabilistic Maps of Phenotype, Management, and Outcomes.

Radiology 2019 12 8;293(3):633-643. Epub 2019 Oct 8.

From the Department of Neurosurgery, Sainte-Anne Hospital, Paris, France (A.R., M.Z., E.D., J.P.); Paris Descartes University, Sorbonne Paris Cité, Paris, France (A.R., P.R., M.E., M.Z., J.F.M., F.C., E.L., P.V., C.O., J.P.); UMR 1266 INSERM, IMA-BRAIN, Institute of Psychiatry and Neurosciences of Paris, Paris, France (A.R., P.R., M.E., K.S., M.Z., P.G., S.L., A.F., J.F.M., P.V., C.O., J.P.); Department of Neuroradiology, Sainte-Anne Hospital, Paris, France (M.E., J.F.M., C.O.); Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan (K.S.); LTCI, Telecom ParisTech, Paris, France (P.G.); Department of Radiotherapy, Gustave Roussy University Hospital, Villejuif, France (F.D.); and Department of Neuropathology, Sainte-Anne Hospital, Paris, France (F.C., E.L., P.V.).

Background Tumor location is a main prognostic parameter in patients with glioblastoma. Probabilistic MRI-based brain atlases specifying the probability of tumor location associated with important demographic, clinical, histomolecular, and management data are lacking for isocitrate dehydrogenase (IDH) wild-type glioblastomas. Purpose To correlate glioblastoma location with clinical phenotype, surgical management, and outcomes by using a probabilistic analysis in a three-dimensional (3D) MRI-based atlas. Materials and Methods This retrospective study included all adults surgically treated for newly diagnosed IDH wild-type supratentorial glioblastoma in a tertiary adult surgical neuro-oncology center (2006-2016). Semiautomated tumor segmentation and spatial normalization procedures to build a 3D MRI-based atlas were validated. The authors performed probabilistic analyses by using voxel-based lesion symptom mapping technology. The Liebermeister test was used for binary data, and the generalized linear model was used for continuous data. Results A total of 392 patients (mean age, 61 years ± 13; 233 men) were evaluated. The authors identified the preferential location of glioblastomas according to subventricular zone, age, sex, clinical presentation, revised Radiation Therapy Oncology Group-Recursive Partitioning Analysis class, Karnofsky performance status, O-methylguanine DNA methyltransferase promoter methylation status, surgical management, and survival. The superficial location distant from the eloquent area was more likely associated with a preserved functional status at diagnosis (348 of 392 patients [89%], < .05), a large surgical resection (173 of 392 patients [44%], < .05), and prolonged overall survival (163 of 334 patients [49%], < .05). In contrast, deep location and location within eloquent brain areas were more likely associated with an impaired functional status at diagnosis (44 of 392 patients [11%], < .05), a neurologic deficit (282 of 392 patients [72%], < .05), treatment with biopsy only (183 of 392 patients [47%], < .05), and shortened overall survival (171 of 334 patients [51%], < .05). Conclusion The authors identified the preferential location of isocitrate dehydrogenase wild-type glioblastomas according to parameters of interest and provided an image-based integration of multimodal information impacting survival results. This suggests the role of glioblastoma location as a surrogate and multimodal parameter integrating several known prognostic factors. © RSNA, 2019 See also the editorial by Huang in this issue.
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http://dx.doi.org/10.1148/radiol.2019190491DOI Listing
December 2019

Repeatability and reproducibility of relative cerebral blood volume measurement of recurrent glioma in a multicentre trial setting.

Eur J Cancer 2019 06 9;114:89-96. Epub 2019 May 9.

University of Heidelberg, Germany.

Background: Measurement of relative cerebral blood volume (rCBV) with dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) is used extensively for brain tumour diagnosis and follow-up. The aim of this pilot study was to assess the robustness of rCBV measurement in patients with enhancing recurrent glioma in a European multicentre trial setting.

Methods: We included pre-treatment postcontrast T1 weighted (T1w) and DSC scans of 20 patients with recurrent glioma from 2 European Organisation for Research and Treatment of Cancer trials (26101 and 26091). Three reviewers independently placed a fixed circular region of interest of 70 mm in the tumour area of highest rCBV (rCBV). To calculate the normalised rCBV (nrCBV), three ROIs were placed in the anterior, middle and posterior centrum semiovale normal-appearing white matter of the contralateral hemisphere. After several months, each observer repeated the assessments blinded for initial findings. Repeatability and reproducibility were estimated with a mixed model. Each measurement was also classified according to 4 clinically meaningful categories.

Results: Three patients were post hoc excluded from analysis because of lack of enhancing tumour. The mean nrCBV repeatability was 49.5%, and reproducibility was 5.5%. In 14 of 17 patients, at least 2 reviewers classified the patient into the same category.

Conclusions: Our results indicate that a well-established review process needs to be applied upfront to assess perfusion in a multicentre trial setting. While awaiting further validation, we propose as a strategy to measure rCBV in the context of recurrent glioma trials to use two central reviewers and an adjudicator in case of disagreement.
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http://dx.doi.org/10.1016/j.ejca.2019.03.007DOI Listing
June 2019

Immunothérapie des glioblastomes.

Bull Cancer 2018 Dec;105 Suppl 1:S59-S67

Gustave-Roussy, université Paris-Saclay, Drug Development Department (DITEP), Villejuif, F-94805, France.

Immunotherapy In Glioblastomas: Targeting the immune system as a therapeutic strategy in solid tumors has shown great efficacy in various tumor types. However the role and success of this approach in glioblastomas remain to be determined. Recent studies demonstrated that central nervous system is no longer considered as an immunoprivileged sanctuary with impressive immune response without blood brain barrier's disruption. Improving our understanding of immune privilege in the central nervous system could lead to better treatment strategies in gliobastomas. This review focuses on describing the immune system in the central nervous system and immuno-therapeutic strategies under development in glioblastomas.
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http://dx.doi.org/10.1016/S0007-4551(18)30391-6DOI Listing
December 2018

The subventricular zone concept: ready for therapeutic implications?

Neuro Oncol 2018 10;20(11):1423-1424

Department of Radiation Oncology, Gustave Roussy University Hospital, Villejuif, France.

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http://dx.doi.org/10.1093/neuonc/noy147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176793PMC
October 2018

Brain Radiation Necrosis: Current Management With a Focus on Non-small Cell Lung Cancer Patients.

Front Oncol 2018 5;8:336. Epub 2018 Sep 5.

Department of Radiation Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.

As the prognosis of metastatic non-small cell lung cancer (NSCLC) patients is constantly improving with advances in systemic therapies (immune checkpoint blockers and new generation of targeted molecular compounds), more attention should be paid to the diagnosis and management of treatments-related long-term secondary effects. Brain metastases (BM) occur frequently in the natural history of NSCLC and stereotactic radiation therapy (SRT) is one of the main efficient local non-invasive therapeutic methods. However, SRT may have some disabling side effects. Brain radiation necrosis (RN) represents one of the main limiting toxicities, generally occurring from 6 months to several years after treatment. The diagnosis of RN itself may be quite challenging, as conventional imaging is frequently not able to differentiate RN from BM recurrence. Retrospective studies have suggested increased incidence rates of RN in NSCLC patients with oncogenic driver mutations [epidermal growth factor receptor (EGFR) mutated or anaplastic lymphoma kinase (ALK) positive] or receiving tyrosine kinase inhibitors. The risk of immune checkpoint inhibitors in contributing to RN remains controversial. Treatment modalities for RN have not been prospectively compared. Those include surveillance, corticosteroids, bevacizumab and local interventions (minimally invasive laser interstitial thermal ablation or surgery). The aim of this review is to describe and discuss possible RN management options in the light of the newly available literature, with a particular focus on NSCLC patients.
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http://dx.doi.org/10.3389/fonc.2018.00336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134016PMC
September 2018

Posterior Fossa Metastasis-Associated Obstructive Hydrocephalus in Adult Patients: Literature Review and Practical Considerations from the Neuro-Oncology Club of the French Society of Neurosurgery.

World Neurosurg 2018 Sep 20;117:271-279. Epub 2018 Jun 20.

Department of Neurosurgery, Sainte-Anne Hospital, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France; Inserm, U894, IMA-Brain, Centre de Psychiatrie et Neurosciences, Paris, France. Electronic address:

Background: There is no consensus concerning the management of adult patients with posterior fossa metastasis-associated obstructive hydrocephalus, especially regarding surgical procedures. A literature review was performed to assess the surgical strategy in the management of patients with metastatic brain tumor.

Methods: A literature search was conducted of PubMed in November 2017 to identify all studies concerning brain metastases and obstructive hydrocephalus in English. All studies (except case reports and pediatric studies) between December 1953 and November 2017 that were about posterior fossa metastasis-associated obstructive hydrocephalus in adult patients were eligible. Eligible studies were classified by level of evidence. We assessed epidemiology, clinical and imaging findings, neurosurgical management, and prognosis of adult patients with posterior fossa metastasis-associated obstructive hydrocephalus. We suggest some practical considerations and a management decision tree on behalf of the Neuro-oncology Club of the French Society of Neurosurgery, with evidence-based analysis.

Results: Direct surgical resection could be considered for patients with asymptomatic obstructive hydrocephalus, and endoscopic third ventriculostomy seems to be a reasonable procedure for patients with symptomatic obstructive hydrocephalus. A ventriculoperitoneal or atrial shunt seems to be a valid alternative when patients have a history of central nervous system infection or ventricular hemorrhage, leptomeningeal carcinomatosis, or unfavorable anatomy for an endoscopic third ventriculostomy to be performed.

Conclusions: The Neuro-oncology Club of the French Society of Neurosurgery suggests a prospective assessment of these neurosurgical procedures to compare their safety and efficacy.
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http://dx.doi.org/10.1016/j.wneu.2018.06.084DOI Listing
September 2018

Neutrophilia as a biomarker for overall survival in newly diagnosed high-grade glioma patients undergoing chemoradiation.

Clin Transl Radiat Oncol 2018 Mar 13;10:47-52. Epub 2018 Apr 13.

Radiation Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France.

Objective: To study the prognostic value of neutrophil disorders in a retrospective cohort of high-grade glioma patients receiving definitive concurrent temozolomide and radiation.

Materials And Methods: Clinical records of consecutive patients treated in our Institution between January 2005 and December 2010 with concurrent temozolomide (75 mg/m daily) and radiation were collected. The prognostic value of pretreatment neutrophilia on survival, defined as a neutrophil count exceeding 7 G/L, was examined.

Results: We identified 164 patients, all treated with concurrent temozolomide-based chemoradiotherapy. Initial surgery was achieved in most (75%), with resection > 90% in 55 patients (34%). Total 151 patients (92%) had glioblastoma, and 13 patients (8%) had WHO grade III glioma. Eighty-two patients (50%) displayed pretreatment neutrophilia. Neutrophilia was not associated with concurrent or adjuvant temodal discontinuation (p > 0.3). The 2-year actuarial overall survival was 45%. Steroid consumption, i.e. 60 mg or more of daily prednisolone, increased pretreatment neutrophil count (p = 0.005). In univariate analysis, neutrophilia was associated with worse overall survival (p = 0.019), as well as age ≥ 65 years (p = 0.009), surgical resection < 90% (p = 0.003) and prednisolone consumption ≥ 60 mg/day (p = 0.016). In multivariate analysis, neutrophilia (p = 0.013), age ≥ 65 (p = 0.001), and surgical tumor resection < 90% (p = 0.010) independently decreased overall survival, while, steroid consumption was not (p = 0.088).

Conclusion: In high-grade gliomas treated with concurrent temozolomide and radiation, pretreatment neutrophilia may be a significant prognosis factor for overall survival. In addition with previously available markers, this independent cost-effective biomarker could help identifying patients with worsened prognosis.
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http://dx.doi.org/10.1016/j.ctro.2018.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008628PMC
March 2018

Combined Diffuse Astrocytoma and Pleomorphic Xanthoastrocytoma Grade III Sharing IDH1 R132H Mutation.

World Neurosurg 2018 Aug 30;116:316-321. Epub 2018 May 30.

Department of Neuropathology, Sainte-Anne Hospital, Descartes University, Paris, France.

Background: Collision tumors are often difficult to distinguish from intratumoral heterogeneity in diffuse gliomas.

Case Description: We report the case of a 44-year-old woman admitted for intracranial hypertension. Magnetic resonance imaging revealed a right intra-axial frontal mass, composed of a hypervascular nodular portion contrasting with a large nonenhanced infiltrative and muliticystic portion. Histopathologic examination showed the occurrence of two morphologically different gliomas. The largest component corresponded to an anaplastic astrocytoma, IDH1-mutated. The second corresponded to a leptomeningeal nodule, reminiscent of a pleomorphic xanthoastrocytoma. Both tumoral components exhibited anaplastic features, World Health Organization grade III. Immunohistochemical and molecular studies showed that the 2 components were identical, IDH1 R132H mutated but without BRAF V600E mutation. Tumor progression was assessed 2 years after surgery, after radiotherapy and chemotherapy, showing supratentorial leptomeningeal dissemination.

Conclusions: Collision tumors and combined neoplasms have been rarely described in the brain and only 4 similar articles report the synchronous occurrence of 2 primary gliomas. A review of the literature is proposed, focusing on criteria that could be used to discriminate them.
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http://dx.doi.org/10.1016/j.wneu.2018.05.156DOI Listing
August 2018

The DNA methylome of DDR genes and benefit from RT or TMZ in IDH mutant low-grade glioma treated in EORTC 22033.

Acta Neuropathol 2018 04 24;135(4):601-615. Epub 2018 Jan 24.

Laboratory of Brain Tumor Biology and Genetics, Neuroscience Research Center, Lausanne University Hospital, Chemin des Boveresses 155, CLE-C306, 1066 Epalinges, Lausanne, Switzerland.

The optimal treatment for patients with low-grade glioma (LGG) WHO grade II remains controversial. Overall survival ranges from 2 to over 15 years depending on molecular and clinical factors. Hence, risk-adjusted treatments are required for optimizing outcome and quality of life. We aim at identifying mechanisms and associated molecular markers predictive for benefit from radiotherapy (RT) or temozolomide (TMZ) in LGG patients treated in the randomized phase III trial EORTC 22033. As candidate biomarkers for these genotoxic treatments, we considered the DNA methylome of 410 DNA damage response (DDR) genes. We first identified 62 functionally relevant CpG sites located in the promoters of 24 DDR genes, using the LGG data from The Cancer Genome Atlas. Then we tested their association with outcome [progression-free survival (PFS)] depending on treatment in 120 LGG patients of EORTC 22033, whose tumors were mutant for isocitrate dehydrogenase 1 or 2 (IDHmt), the molecular hallmark of LGG. The results suggested that seven CpGs of four DDR genes may be predictive for longer PFS in one of the treatment arms that comprised MGMT, MLH3, RAD21, and SMC4. Most interestingly, the two CpGs identified for MGMT are the same, previously selected for the MGMT-STP27 score that is used to determine the methylation status of the MGMT gene. This score was higher in the LGG with 1p/19q codeletion, in this and other independent LGG datasets. It was predictive for PFS in the TMZ, but not in the RT arm of EORTC 22033. The results support the hypothesis that a high score predicts benefit from TMZ treatment for patients with IDHmt LGG, regardless of the 1p/19q status. This MGMT methylation score may identify patients who benefit from first-line treatment with TMZ, to defer RT for long-term preservation of cognitive function and quality of life.
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http://dx.doi.org/10.1007/s00401-018-1810-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978935PMC
April 2018

Tolerance and outcomes of stereotactic radiosurgery combined with anti-programmed cell death-1 (pembrolizumab) for melanoma brain metastases.

Melanoma Res 2018 04;28(2):111-119

Radiation Oncology, Gustave Roussy, Villejuif, France.

Anti-programmed cell death-1 (anti-PD1) antibodies are currently the first-line treatment for patients with metastatic BRAF wild-type melanoma, alone or combined with the anti-CTLA4 monoclonal antibody, ipilimumab. To date, data on safety and the outcomes of patients treated with the anti-PD1 monoclonal antibodies, pembrolizumab (PB), or nivolumab, combined with stereotactic radiosurgery (SRS), for melanoma brain metastases (MBM) are scarce. We retrospectively reviewed all patients with MBM treated with PB combined with SRS between 2012 and 2015. The primary endpoint was neurotoxicity. The secondary endpoints were local, distant intracranial controls and overall survival (OS). Among 74 patients with MBM treated with SRS, 25 patients with a total of 58 MBM treated with PB combined with SRS within 6 months were included. Radiation necrosis, occurring within a median time of 6.5 months, was observed for four MBM (6.8%) in four patients. No other significant SRS-related adverse event was observed. After a median follow-up of 8.4 months, local control was achieved in 46 (80%) metastases and 17 (68%) patients. Perilesional oedema and intratumour haemorrhage appearing or increasing after SRS were associated with local progression (P<0.001). The median OS was 15.3 months (95% confidence interval: 4.6-26). The timing between SRS and PB administration did not seem to influence the risk of radiation necrosis, intracranial control or OS. SRS combined with PB was well tolerated and achieved local control in 80% of the lesions. Prolonged OS was observed compared with that currently yielded in this population of patients. Prospective studies are required to explore further the optimal ways to combine immunotherapy and SRS.
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http://dx.doi.org/10.1097/CMR.0000000000000413DOI Listing
April 2018

Intellectual, educational, and situation-based social outcome in adult survivors of childhood medulloblastoma.

Dev Neurorehabil 2019 Jan 16;22(1):19-26. Epub 2018 Jan 16.

e Département de Cancérologie de l'Enfant et de l'Adolescent , Gustave Roussy , Villejuif , France.

Purpose: To investigate intellectual and situation-based social outcome and educational achievement in adult survivors of childhood medulloblastoma and analyse factors influencing outcome Methods: We collected demographic, medical and cognitive data, and social and educational outcome at a mean time since the end of treatments of 14.9 years in 58 adults, aged 19-35 years, consecutively treated in a single cancer center between 1989 and 2005.

Results: Ten survivors had severe intellectual disability, 12 were still studying, 23 had a regular employment and 13 were unemployed. Full Scale Intellectual Quotient, assessed 6.6 years after the end of treatments, ranged from 46 to 131. It was strongly associated with educational achievement and significantly lower in patients who experienced postoperative cerebellar mutism, and when parental education level was low.

Conclusion: These factors should be systematically considered at diagnosis in order to offer adequate and timely assessments and interventions.
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http://dx.doi.org/10.1080/17518423.2018.1424262DOI Listing
January 2019

Anti-PD-1 Vasculitis of the central nervous system or radionecrosis?

J Immunother Cancer 2017 12 19;5(1):96. Epub 2017 Dec 19.

Department of Radiotherapy, Gustave Roussy Cancer Campus, 94800, Villejuif, France.

Commentary on « Cerebral vasculitis mimicking intracranial metastatic progression of lung cancer during PD-1 blockade » by Läubli H et al., J Immunother Cancer. 2017;5:46.The authors diagnosed a cerebral tumor-like lymphocytic vasculitis associated with anti-endothelial cell auto-antibodies secondary to anti-PD-1 therapy, treated by surgical resection and corticosteroids. We thought that this diagnosis should be discussed for at least two reasons. First, etiological explorations were not sufficient. Second, the diagnostic of radionecrosis should also be discussed.
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http://dx.doi.org/10.1186/s40425-017-0304-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735956PMC
December 2017

Cerebral blood flow changes after radiation therapy identifies pseudoprogression in diffuse intrinsic pontine gliomas.

Neuro Oncol 2018 06;20(7):994-1002

Hôpital Necker Enfants Malades, Pediatric Radiology Department, Paris, France.

Background: The interval between progression and death in diffuse intrinsic pontine glioma (DIPG) is usually <6 months. However, reports of longer patient survival following radiotherapy, in the presence of radiological signs of progression, suggest that these cases may be comparable to pseudoprogression observed in adult glioblastoma. Our aim was to identify such cases and compare their multimodal MRI features with those of patients who did not present the same evolution.

Methods: Multimodal MRIs of 43 children treated for DIPG were retrospectively selected at 4 timepoints: baseline, after radiotherapy, during true progression, and at the last visit. The patients were divided into 2 groups depending on whether they presented conventional MRI changes that mimicked progression. The apparent diffusion coefficient, arterial spin labeling cerebral blood flow (ASL-CBF), and dynamic susceptibility contrast perfusion relative cerebral blood volume (DSCrCBV) and flow (DSCrCBF) values were recorded for each tumor voxel, avoiding necrotic areas.

Results: After radiotherapy, 19 patients (44%) showed radiological signs that mimicked progression: 16 survived >6 months following so-called pseudoprogression, with a median of 8.9 months and a maximum of 35.6 months. All 43 patients exhibited increased blood volume and flow after radiotherapy, but the 90th percentile of those with signs of pseudoprogression had a greater increase of ASL-CBF (P < 0.001). Survival between the 2 groups did not differ significantly. During true progression, DSCrCBF and DSCrCBV values increased only in patients who had not experienced pseudoprogression.

Conclusions: Pseudoprogression is a frequent phenomenon in DIPG patients. This condition needs to be recognized before considering treatment discontinuation. In this study, the larger increase of the ASL-CBF ratio after radiotherapy accurately distinguished pseudoprogression from true progression.
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http://dx.doi.org/10.1093/neuonc/nox227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007230PMC
June 2018

Multimodal Magnetic Resonance Imaging of Treatment-Induced Changes to Diffuse Infiltrating Pontine Gliomas in Children and Correlation to Patient Progression-Free Survival.

Int J Radiat Oncol Biol Phys 2017 10 11;99(2):476-485. Epub 2017 Apr 11.

Pediatric Radiology Department, Hôpital Necker Enfants Malades, Paris, France; Institut National de la Santé et de la Recherche Médicale, Unité 1000, Paris, France; Imagine-Institut des Maladies Génétiques, UMR 1163, Paris, France; Université Paris Descartes, ComUE Sorbonne Paris Cité, Paris, France.

Purpose: To use multimodal magnetic resonance imaging (MRI) to quantify treatment-induced changes in the whole volume of diffuse infiltrating pontine gliomas and correlate them with progression-free survival (PFS).

Methods And Materials: This prospective study included 22 children aged 3.3 to 14.7 years (median, 5.9 years). Multimodal MRI was performed at 3 distinct time points: before treatment, the first week following radiation therapy (RT), and 2 months after RT. The imaging protocol included morphologic, multi b-value diffusion; arterial spin labeling; and dynamic susceptibility contrast-enhanced perfusion. Morphologic and multimodal data-lesion volume, diffusion coefficients, relative cerebral blood flow, and relative cerebral blood volume (rCBV)-were recorded at the 3 aforementioned time points. The Wilcoxon test was used to compare each individual parameter variation between time points, and its correlation with PFS was assessed by the Spearman test.

Results: Following RT, the tumors' solid component volume decreased by 40% (P<.001). Their median diffusion coefficients decreased by 20% to 40% (P<.001), while median relative cerebral blood flow increased by 60% to 80% (P<.001) and median rCBV increased by 70% (P<.001). PFS was positively correlated with rCBV measured immediately after RT (P=.003), and in patients whose rCBV was above the cutoff value of 2.46, the median PFS was 4.6 months longer (P=.001). These indexes tended to return to baseline 2 months after RT. Lesion volume before or after RT was not correlated with survival.

Conclusions: Multimodal MRI provides useful information about diffuse infiltrating pontine gliomas' response to treatment; rCBV increases following RT, and higher values are correlated with better PFS. High rCBV values following RT should not be mistaken for progression and could be an indicator of response to therapy.
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http://dx.doi.org/10.1016/j.ijrobp.2017.04.007DOI Listing
October 2017

Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study.

Lancet 2017 Oct 8;390(10103):1645-1653. Epub 2017 Aug 8.

Department of Pathology, Brain Tumour Centre at Erasmus MC Cancer Institute, Rotterdam, Netherlands.

Background: The role of temozolomide chemotherapy in newly diagnosed 1p/19q non-co-deleted anaplastic gliomas, which are associated with lower sensitivity to chemotherapy and worse prognosis than 1p/19q co-deleted tumours, is unclear. We assessed the use of radiotherapy with concurrent and adjuvant temozolomide in adults with non-co-deleted anaplastic gliomas.

Methods: This was a phase 3, randomised, open-label study with a 2 × 2 factorial design. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with WHO performance status scores of 0-2. The randomisation schedule was generated with the electronic EORTC web-based ORTA system. Patients were assigned in equal numbers (1:1:1:1), using the minimisation technique, to receive radiotherapy (59·4 Gy in 33 fractions of 1·8 Gy) alone or with adjuvant temozolomide (12 4-week cycles of 150-200 mg/m temozolomide given on days 1-5); or to receive radiotherapy with concurrent temozolomide 75 mg/m per day, with or without adjuvant temozolomide. The primary endpoint was overall survival adjusted for performance status score, age, 1p loss of heterozygosity, presence of oligodendroglial elements, and MGMT promoter methylation status, analysed by intention to treat. We did a planned interim analysis after 219 (41%) deaths had occurred to test the null hypothesis of no efficacy (threshold for rejection p<0·0084). This trial is registered with ClinicalTrials.gov, number NCT00626990.

Findings: At the time of the interim analysis, 745 (99%) of the planned 748 patients had been enrolled. The hazard ratio for overall survival with use of adjuvant temozolomide was 0·65 (99·145% CI 0·45-0·93). Overall survival at 5 years was 55·9% (95% CI 47·2-63·8) with and 44·1% (36·3-51·6) without adjuvant temozolomide. Grade 3-4 adverse events were seen in 8-12% of 549 patients assigned temozolomide, and were mainly haematological and reversible.

Interpretation: Adjuvant temozolomide chemotherapy was associated with a significant survival benefit in patients with newly diagnosed non-co-deleted anaplastic glioma. Further analysis of the role of concurrent temozolomide treatment and molecular factors is needed.

Funding: Schering Plough and MSD.
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http://dx.doi.org/10.1016/S0140-6736(17)31442-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806535PMC
October 2017

Evidence-based management of adult patients with diffuse glioma - Authors' reply.

Lancet Oncol 2017 08 26;18(8):e430-e431. Epub 2017 Jul 26.

Neurology Clinic and National Centre for Tumour Diseases, University Hospital Heidelberg, Heidelberg, Germany; German Consortium of Translational Cancer Research, Clinical Cooperation Unit Neurooncology, German Cancer Research Center, Heidelberg, Germany.

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http://dx.doi.org/10.1016/S1470-2045(17)30515-6DOI Listing
August 2017

Extent of resection and Carmustine wafer implantation safely improve survival in patients with a newly diagnosed glioblastoma: a single center experience of the current practice.

J Neurooncol 2017 Oct 1;135(1):83-92. Epub 2017 Jul 1.

Department of Neurosurgery, Service de Neurochirurgie, Sainte-Anne Hospital, 1, rue Cabanis, 75674, Paris Cedex 14, France.

For newly diagnosed glioblastomas treated with resection in association with the standard combined chemoradiotherapy, the impact of Carmustine wafer implantation remains debated regarding postoperative infections, quality of life, and feasibility of adjuvant oncological treatments. To assess together safety, tolerance and efficacy of Carmustine wafer implantation and of extent of resection for glioblastoma patients in real-life experience. Observational retrospective monocentric study including 340 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent surgical resection with (n = 123) or without (n = 217) Carmustine wafer implantation as first-line oncological treatment. Carmustine wafer implantation and extent of resection did not significantly increase postoperative complications, including postoperative infections (p = 0.269, and p = 0.446, respectively). Carmustine wafer implantation and extent of resection did not significantly increase adverse events during adjuvant oncological therapies (p = 0.968, and p = 0.571, respectively). Carmustine wafer implantation did not significantly alter the early postoperative Karnofsky performance status (p = 0.402) or the Karnofsky performance status after oncological treatment (p = 0.636) but a subtotal or total surgical resection significantly improved those scores (p < 0.001, and p < 0.001, respectively). Carmustine wafer implantation, subtotal and total resection, and standard combined chemoradiotherapy were independently associated with longer event-free survival (adjusted Hazard Ratio (aHR), 0.74 [95% CI 0.55-0.99], p = 0.043; aHR, 0.70 [95% CI 0.54-0.91], p = 0.009; aHR, 0.40 [95% CI 0.29-0.55], p < 0.001, respectively) and with longer overall survival (aHR, 0.69 [95% CI 0.49-0.96], p = 0.029; aHR, 0.52 [95% CI 0.38-0.70], p < 0.001; aHR, 0.58 [95% CI 0.42-0.81], p = 0.002, respectively). Carmustine wafer implantation in combination with maximal resection, followed by standard combined chemoradiotherapy is safe, efficient, and well-tolerated in newly diagnosed supratentorial glioblastomas in adults.
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http://dx.doi.org/10.1007/s11060-017-2551-4DOI Listing
October 2017

PET imaging in patients with meningioma-report of the RANO/PET Group.

Neuro Oncol 2017 Nov;19(12):1576-1587

Departments of Neurosurgery, Ludwig Maximilians-University of Munich, Munich, Germany.

Meningiomas are the most frequent nonglial primary brain tumors and represent about 30% of brain tumors. Usually, diagnosis and treatment planning are based on neuroimaging using mainly MRI or, rarely, CT. Most common treatment options are neurosurgical resection and radiotherapy (eg, radiosurgery, external fractionated radiotherapy). For follow-up after treatment, a structural imaging technique such as MRI or CT is used. However, these structural imaging modalities have limitations, particularly in terms of tumor delineation as well as diagnosis of posttherapeutic reactive changes. Molecular imaging techniques such as PET can characterize specific metabolic and cellular features which may provide clinically relevant information beyond that obtained from structural MR or CT imaging alone. Currently, the use of PET in meningioma patients is steadily increasing. In the present article, we provide recommendations for the use of PET imaging in the clinical management of meningiomas based on evidence generated from studies being validated by histology or clinical course.
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http://dx.doi.org/10.1093/neuonc/nox112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716194PMC
November 2017

Whole brain radiotherapy in patients with NSCLC and brain metastases.

Lancet 2016 Oct 4;388(10055):1960-1962. Epub 2016 Sep 4.

Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif 94800, France; Faculté de Médecine, Université Paris Sud, Le Kremlin-Bicêtre, France.

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http://dx.doi.org/10.1016/S0140-6736(16)31391-5DOI Listing
October 2016