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. 2011 Jul 25;21(6):633–644. doi: 10.1111/j.1750-3639.2011.00491.x

French Brain Tumor DataBase: 5‐Year Histological Results on 25 756 Cases

Valérie Rigau 1,, Sonia Zouaoui 2, Hélène Mathieu‐Daudé 2, Amélie Darlix 3, Aurélie Maran 1, Brigitte Trétarre 2, Faiza Bessaoud 2, Fabienne Bauchet 2, Redha Attaoua 2, Pascale Fabbro‐Peray 4, Michel Fabbro 5, Christine Kerr 5, Luc Taillandier 3, Hugues Duffau 7, Dominique Figarella‐Branger 6, Valérie Costes 1, Luc Bauchet 7; with the participation of Société Française de Neuropathologie (SFNP), Société Française de Neurochirurgie (SFNC) and the Club de Neuro‐Oncologie of the Société Française de Neurochirurgie (CNO‐SFNC), and Association des Neuro‐Oncologues d'Expression Française (ANOCEF)
PMCID: PMC8094058  PMID: 21554472

Abstract

This work aimed to prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis is available. The objectives were to (i) create a national registry and a network to perform epidemiological studies; (ii) implement clinical and basic research protocols; and (iii) harmonize the health care of patients affected by PCNST. For 5 years, 25 756 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included glioma (48.9%), all other neuroepithelial tumors (5%), meningioma (28.8%), nerve sheath tumors (8.4%), lymphoma (3.2%) and others (5.7%). Cryopreservation was reported for 6018 PCNST specimens. Tumor resections (R) were performed in 78% cases, while biopsies accounted for 22%. Median age (MA), sex, percentage R and number of cryopreserved tumors were detailed for each histology; for example, out of 6053 glioblastomas (MA 63 years, male 59.4%, R 62%, 1611 were cryopreserved), and out of 37 atypical teratoid/rhabdoid tumors (MA 2 years, male 56.8%, R 94%, 17 were cryopreserved). This database or databank dedicated to PCNST cases contains detailed data on clinical, histological and other characteristics, such as the inclusion of data on cryopreserved specimens that are not available in other European registries. Therefore, this is a valuable resource that can be used for planning future epidemiological and clinical research.

Keywords: brain tumor, database, epidemiology, neuro‐oncology, neuropathology, neurosurgery

INTRODUCTION

Primary central nervous system tumors (PCNSTs) represent a complex heterogeneous group of pathological entities that may be benign, malignant or of unpredictable evolution 2, 8, 24, 28, 30, 31, 42. These tumors represent a major public health problem (16), and the French epidemiological data are fragmentary 17, 20, 26, 32, 33, as a national registry for these tumor cases does not exist. The main objective of this project was to prospectively record all PCNST cases in France, for which histological diagnosis is available. The long‐term goals in creating the French Brain Tumor DataBase (FBTDB) were to: (i) create a national registry and a national network to perform epidemiological studies; (ii) implement a new database and use it for setting up both clinical and basic research protocols; (iii) allow the evaluation of the medical practices of an area or of the entire country; and (iv) harmonize the health care of patients affected by PCNST at the higher level. The French societies involved in the management of patients diagnosed with PCNST [ie, Association des Neuro‐Oncologues d'Expression Française (ANOCEF), Société Française de Neurochirurgie (SFNC), Société Française de Neuropathologie (SFNP)] were linked to initiate this work at a countrywide level through the use of a national survey on the medical practices in neuro‐oncology and a census of the protocols of fundamental research existing in France 3, 21. The methodology and initial results of the FBTDB, clinical epidemiology for childhood PCNST and a specific work concerning oncological patterns of care for patients with glioblastoma have already been published by the FBTDB 4, 5, 6, 7, 36.

Here, we report the histological results of the FBTDB on 25 756 cases of newly diagnosed and histologically confirmed PCNST, and discuss a few perspectives of such database.

MATERIALS AND METHODS

Patients with newly diagnosed and histologically confirmed PCNSTs (since 1 January 2004) were identified in the FBTDB, and initial data were prospectively collected. All neurosurgeons and neuropathologists in France who participated in creating the FBTDB were instructed to complete a data file card for each patient that underwent surgery. Histological diagnosis was always made by experienced neuropathologists; more than 90% of these neuropathologists worked in public academic centers. The methodology for the FBTDB accrual was previously described in detail (4). In summary, the data file card was placed in all operating rooms where surgery for PCNST is performed, and was systematically sent along with the sample to the pathology lab. The easy‐to‐complete card contains questions on sociodemographic, clinical, radiological, surgical and pathological data (an optional question about cryopreservation of the samples was included). The first part of the card (ie, sociodemographic, clinical, radiological and surgical data) was completed by the neurosurgeon. The second part was completed by the pathologist. All completed cards were mailed to the Tumor Registry from Herault (TRH) [Registre des Tumeurs de l'Hérault (RTH), Montpellier, France], which has extensive expertise in working with tumor data and has the required authorization for recording data with personal identifiers. The TRH compiled all cards and analyzed the data in collaboration with the University Institute of Clinical Research of Montpellier‐Nîmes (IURC, Institut Universitaire de Recherche Clinique, Montpellier‐Nîmes, France). A new data file card has been used since 2007 (Figure 1). The data presented here include age, sex, histological diagnosis according to the ICD‐0‐3 [World Health Organization (WHO) classification] and Systematized Nomenclature of Medicine (SNOMED) codes from Louis et al (28) and French nomenclature Association for the Development of Information Technology in Cytology, Anatomy and Pathology (ADICAP) (1) (a list of included codes is presented in Table 1), cryopreservation of samples and surgery (biopsy/resection).

Figure 1.

Figure 1

The pathological, neuroradiological and clinical card contains all the data asked for recording the primary central nervous system tumor (PCNST). It is systematically filled up for each patient by the neurosurgeon in the operating room and by the pathologist if the diagnosis of PCNST is confirmed.

Table 1.

Histological repartition of the 25 756 cases with clinical and surgical data from the French Brain Tumor Database, 2004 to 2008. Abbreviations: T = total; B = biopsy; R = resection; M = male; F = female; N = number; Med = median age at diagnosis; m = mean age at diagnosis; CRYO =  cryopreservation; MPNST = malignant peripheral nerve sheath tumor.

ICD‐O ADICAP N M F m Med CRYO Reported surgery
T R (%) B (%)
Tumors of neuroepithelial tissue
Glioma NOS 9380/3 N7R0 205 114 91 49.96 56.0 37 192 30.7 69.3
Astrocytic tumors
Astrocytoma NOS 9400/3 N7S0 205 127 78 42.82 46.0 23 171 46.2 53.8
Pilocytic astrocytoma 9421/1 N0S8 718 367 351 16.26 12.0 201 617 86.7 13.3
Pilomyxoïd astrocytoma 9425/3 (0001) 4 1 3 10.50 10.0 2 2 50.0 50.0
Subependymal giant cell astrocytoma 9384/1 N0T2/3 50 24 26 16.90 16.5 25 39 92.3 7.7
Pleomorphic xantho‐astrocytoma 9424/3 N7S9 56 30 26 36.73 34.0 14 50 84.0 16.0
Fibrillary astrocytoma 9420/3 N7S2 115 68 47 38.48 40.0 36 102 40.2 59.8
Gemistocytic astrocytoma 9411/3 N7S4 41 26 15 45.61 48.0 11 35 45.7 54.3
Protoplasmic astrocytoma 9410/3 N7S6 12 7 5 47.42 43.5 1 10 40.0 60.0
Anaplastic astrocytoma 9401/3 N7T6 372 204 168 57.16 60.0 105 352 35.2 64.8
Glioblastoma 9440/3 N7X0 6053 3593 2460 61.61 63.0 1611 5212 61.9 38.1
Giant cell glioblastoma 9441/3 N7X2 115 63 52 55.90 60.0 43 109 67.9 32.1
Gliosarcoma 9442/3 N7X4 62 40 22 55.77 57.0 17 54 92.6 7.4
Gliomatosis cerebri 9381/3 N7R9 25 15 10 48.08 52.0 4 21 23.8 76.2
8033 4679 3354 55.50 60.0 2130 6966
58.2% 41.8% 26.5% 61.6 38.4
Oligodendroglial tumors
Oligodendroglioma 9450/3 N7V0 1271 731 540 43.24 42.0 346 1064 61.7 38.3
Anaplastic oligodendroglioma 9451/3 N7V4 1313 733 580 52.68 54.0 456 1202 69.3 30.7
2584 1464 1120 47.90 48.0 802 2266
56.7% 43.3% 31.0% 65.7 34.3
Oligoastrocytic tumors
Oligoastrocytic tumors NOS 9382/3 N7R4 8 5 3 47.75 46.0 2 6 50.0 50.0
Oligoastrocytoma 9382/3 N7V2 416 223 193 43.92 42.0 106 370 58.9 41.1
Anaplastic oligoastrocytoma 9382/3 N7V3 831 475 356 52.24 55.0 224 771 60.7 39.9
1255 703 552 49.42 51.0 332 1147
56.0% 44.0% 26.5% 60.1 39.9
Ependymal tumors
Subépendymoma 9383/1 N0W6 57 40 17 51.81 55.0 14 46 87.0 13.0
Myxopapillary ependymoma 9394/1 N7W2 87 53 34 37.47 35.0 14 71 97.2 2.8
Ependymoma, NOS 9391/3 N7W0 388 217 171 41.46 43.0 88 305 92.5 7.5
Cellular ependymoma 9391/3 N7W1 30 16 14 33.70 33.0 9 28 92.9 7.1
Papillary ependymoma 9393/3 N7W4 15 8 7 44.67 50.0 4 12 91.7 8.3
Clear cell ependymoma 9391/3 N7W5 18 11 7 26.67 20.0 3 14 85.7 14.3
Ependymoma, anaplastic 9392/3 N7W8 128 62 66 26.33 13.5 50 112 90.2 9.8
Tanicytic ependymoma 9391/3 (0002) 10 8 2 40.10 42.0 3 8 50.0 50.0
733 415 318 38.52 41.0 185 596
56.6% 43.4% 25.2% 91.4 8.6
Total 12 605 7261 5344 52.35 56.0 3449 10 975
Gliomes 57.6% 42.4% 27.4% 63.9 36.1
Choroid plexus tumors
Choroid plexus papilloma 9390/0 N0Z0 89 42 47 26.70 22.0 19 76 92.1 7.9
Atypical choroid plexus papilloma 9390/1 (0003)
Choroid plexus carcinoma 9390/3 N7Z0 14 9 5 23.43 13.0 4 14 85.7 14.3
103 51 52 26.25 20.0 23 90
49.5% 50.5% 22.3% 91.1 8.9
Other neuroepithelial tumors
Astroblastoma 9430/3 N7T4 1 0 1 24.00 24.0 1 1 100.0 0.0
Chordoid glioma of the third ventricle 9444/1 (0004) 3 2 1 41.66 46.0 1 2 50.0 50.0
Angiocentric glioma 9431/1 (0005)
Esthesioneuroblastoma 9522/3 B7F2 20 15 5 49.05 47.0 2 18 94.4 5.6
24 17 7 47.08 47.0 4 21
70.8% 29.2% 16.7% 95.0 5.0
Neuronal and mixed neuronal–glial tumors
Dysplastic gangliocytoma of cerebellum (Lhermitte–Duclos) 9493/0 N0L2 4 3 1 40.75 42.5 1 4 100.0 0.0
Desmoplastic infantile astrocytoma/ganglioma 9412/1 N0N0 5 1 4 16.40 2.0 0 5 100.0 0.0
Dysembryoplastic neuroepithelial tumor 9413/0 N0N2 128 71 57 20.52 18.0 37 117 92.3 7.7
Gangliocytoma 9492/0 N0L0 12 4 8 33.25 32.5 3 11 81.8 18.2
Ganglioglioma 9505/1 N7N0 287 159 128 22.83 18.0 87 212 87.7 12.3
Anaplastic ganglioglioma 9505/3 N7N1 34 19 15 45.56 50.0 10 28 89.3 10.7
Central neurocytoma 9506/1 N4L0 74 37 37 35.16 31.0 23 62 90.3 9.7
Extraventricular neurocytoma 9506/1 (0006)
Cerebellar liponeurocytoma 9506/1 (0007)
Papillary glioneuronal tumor 9509/1 (0008) 3 2 1 22.00 16.0 2 3 100.0 0.0
Rosette‐forming glioneuronal tumor of the fourth ventricle 9509/1 (0009) 4 2 2 35.50 30.0 2 3 100.0 0.0
Paraganglioma 8680/1 P0A0 22 10 12 47.77 44.0 4 17 100.0 0.0
Paraganglioma malignant 8680/3 P7A0 3 1 2 52.66 55.0 0 2 50.0 50.0
576 309 267 26.72 23.0 169 464
53.6% 46.4% 29.3% 89.9 10.1
Tumor of the pineal region
Pinealoma, NOS 9360/1 P7P0 11 9 2 39.73 44.0 3 11 36.4 63.6
Pineocytoma 9361/1 P7P2 28 11 17 48.93 47.5 4 25 80.0 20.0
Pineal parenchymal tumor of intermediate differentiation 9362/3 P7P6 3 2 1 26.33 28.0 2 3 33.3 66.7
Pineoblastoma 9362/3 P7P4 24 12 12 23.08 18.0 5 21 61.9 38.1
Papillary tumor of the pineal region 9395/3 (0010) 2 1 1 53.00 53.0 0
68 35 33 37.44 39.5 14 60
51.5% 48.5% 20.6% 63.3 36.7
Embryonal tumors
Medulloblastoma, NOS 9470/3 N7P0 314 186 128 17.90 11.5 111 290 90.0 10.0
Desmoplastic medulloblastoma 9471/3 N7P2 53 35 18 12.23 9.0 22 45 93.3 6.7
Medulloblastoma with extensive nodularity 9471/3 (0011) 3 1 2 10.33 7.0 1 2 100.0 0.0
Anaplastic medulloblastoma 9474/3 (0012) 4 4 0 19.00 15.5 1 3 100.0 0.0
Large‐cell medulloblastoma 9474/3 (0013) 1 1 0 2.00 2.0 1 1 100.0 0.0
CNS primitive neuroectodermal tumor 9473/3 N7M2 68 33 35 22.25 12.5 16 63 79.4 20.6
CNS Neuroblastoma 9500/3 N7M0 14 9 5 16.36 5.0 6 13 76.9 23.1
CNS Ganglioneuroblastoma 9490/3 N7M1 8 4 4 34.50 36.5 0 6 100.0 0.0
Medulloepithélioma 9501/3 N7Q0 3 0 3 2.66 3.0 1 2 50.0 50.0
Ependymoblastoma 9392/3 N7X8 1 0 1 25.00 25.0 0
Atypical teratoid/rhabdoid tumor 9508/3 X7R8 37 21 16 9.32 2.0 17 32 93.8 6.3
506 294 212 17.33 10.0 176 457
58.1% 41.9% 34.8% 88.8 11.2
Tumors of the cranial and paraspinal nerves
Schwannoma (neurilemnoma, neurinoma) 9560/0 N0A0 1894 900 994 51.75 53.0 360 1634 97.9 2.1
Schwannoma (neurofibromatosis type1) 9560/0 N0B0 101 50 51 53.55 55.0 6 87 97.7 2.3
Cellular schwannoma 9560/0 N4A0 16 8 8 46.62 52.5 2 13 76.9 23.1
Plexiform schwannoma 9560/0 N0A6 8 2 6 47.25 48.5 0 7 100.0 0.0
Mélanotic schwannoma 9560/0 N0C4 5 2 3 52.60 47.0 0 4 100.0 0.0
Neurofibroma 9540/0 N0C0 78 40 38 39.89 39.0 8 65 100.0 0.0
Plexiform neurofibroma 9550/0 N0C1 9 5 4 35.11 29.0 1 6 100.0 0.0
Granular cells neurofibroma 9540/0 N0C8 3 0 3 57.66 62.0 1 2 100.0 0.0
Neurofibroma (neurofibromatosis type 1) 9540/0 N0D0 13 7 6 34.70 29.0 2 10 100.0 0.0
Neurofibrosarcoma (SAI) 9540/3 N7C0 6 3 3 43.83 38.5 2 6 83.3 16.7
Perineurioma 9571/0 N0G0 3 1 2 58.33 59.0 0 2 100.0 0.0
Intraneural perineurioma 9571/0 N0G4
Malignant perineurioma 9571/3 (0014)
Malignant peripheral nerve sheath tumor 9540/3 N7A0 16 4 12 44.44 40.0 2 8 100.0 0.0
Epithelioid MPNST 9540/3 N7A3
MPNST with mesenchymal differentiation 9540/3 N7H0
Melanotic MPNST 9540/3 N7A5 1 0 1 35.00 35.0 0 1 100.0 0.0
MPNST with glandular differentiation 9540/3 N7A6 1 1 0 28.00 28.0 0 1 100.0 0.0
2154 1023 1131 51.07 53.0 384 1846
47.5% 52.5% 17.8% 97.8 2.2
Tumors of the meninges
Tumors of meningothelial cells
Meningioma, NOS 9530/0 N0J0 1507 374 1133 57.19 57.0 264 1337 97.5 2.5
Meningothelial meningioma 9531/0 N0K2 2397 626 1771 57.46 57.0 517 2029 97.8 2.2
Fibrous (fibroblastic) meningioma 9532/0 N0J4 754 144 610 57.67 58.0 141 628 97.1 2.9
Transitional (mixed) meningioma 9537/0 N0K4 1168 267 901 57.24 57.0 218 1013 97.3 2.7
Psammomatous meningioma 9533/0 N0K8 302 39 263 62.29 63.0 44 246 96.7 3.3
Angiomatous meningioma 9534/0 N0J2 151 61 90 58.96 58.5 29 136 96.3 3.7
Rare variety meningioma (NOS) 9530/0 N0K9* 65 14 51 57.71 57.0 7 64 89.1 10.9
Microcystic meningioma 9530/0 N0K9 71 17 54 55.23 56.0 19 62 100.0 0.0
Secretory meningioma 9530/0 N0K9 89 13 76 58.23 57.0 11 70 97.1 2.9
Lymphoplasmacyte‐rich meningioma 9530/0 N0K9
Clear‐cell meningioma 9538/1 N0K9 38 11 27 51.39 50.5 11 35 100.0 0.0
Chordoid meningioma 9538/1 N0K9 58 17 41 52.92 52.5 8 53 98.1 1.9
Rhabdoid meningioma 9538/3 N0K9 5 2 3 64.40 66.0 2 4 100.0 0.0
Metaplastic meningioma 9530/0 N0K3 40 10 30 56.25 54.0 3 33 93.9 6.1
Atypical meningioma 9539/1 N4J0 624 299 325 59.60 62.5 128 482 97.5 2.5
Papillary meningioma 9538/3 N7K6 8 5 3 47.12 45.0 3 7 100.0 0.0
Anaplastic meningioma 9530/3 N7J0 134 66 68 61.23 62.5 22 101 99.0 1.0
Meningiomatosis 9530/1 N4J9 8 4 4 51.00 53.5 3 7 100.0 0.0
7419 1969 5450 57.76 58.0 1430 6307
26.5% 73.5% 19.3% 97.4 2.6
Mesenchymal tumors
Benign mesenchymal tumor (NOS) X0H0
Lipoma 8850/0 L0L0 19 14 5 31.79 30.0 1 16 93.8 6.3
Angiolipoma 8861/0 L0P1 5 3 2 53.20 55.0 1 3 100.0 0.0
Hibernoma 8880/0 L0M4
Liposarcoma 8850/3 L7L0 2 2 0 49.50 49.5 0 2 100.0 0.0
Solitary fibrous tumor 8815/0 F0A1 33 14 19 54.00 57.0 11 30 93.3 6.7
Fibrosarcoma 8810/3 F7A0
Histiocytome fibreux malin 8830/3 F7M0
Leiomyoma 8890/0 L0A0
Leiomyosarcoma 8890/3 L7A0 3 1 2 62.66 57.0 1 3 100.0 0.0
Rhabdomyoma 8900/0 R0C0
Rhabdomyosarcoma 8900/3 R7C0 3 1 2 11.66 13.0 0 3 100.0 0.0
Chondroma 9220/0 C0A0 4 3 1 20.75 16.0 0 2 100.0 0.0
Chondrosarcoma 9220/3 C7A0 14 5 9 38.50 36.5 1 11 90.9 9.1
Osteoma 9180/3 Q0A0 14 3 11 40.14 37.5 1 11 100.0 0.0
Osteosarcoma 9180/3 Q7A0 6 5 1 32.33 31.5 2 5 100.0 0.0
Osteochondroma 9210/0 C0G0 6 2 4 37.67 40.0 0 4 100.0 0.0
Hemangioma 9120/0 V0A0 251 125 126 39.57 41.0 13 190 96.3 3.7
Epithelioid hemangioendothelioma 9133/1 V7N0 3 1 2 68.33 69.0 0 3 100.0 0.0
Hemangiopericytoma benign 9150/1 V0K0 30 16 14 53.27 54.5 8 26 100.0 0.0
Uncertain malignancy hemangiopericytoma V4K0 19 11 8 55.31 58.0 5 11 100.0 0.0
Infantile hemangiopericytoma V0K1
Anaplastic hemangiopericytoma 9150/3 V7K0 29 15 14 57.21 56.0 3 26 96.2 3.8
Angiosarcoma 9120/3 V7A0 3 3 0 49.00 44.0 0 2 100.0 0.0
Kaposi sarcoma 9140/3 V7R0
Ewing's sarcoma—PNET 9364/3 X7L0 8 5 3 23.75 23.5 2 8 100.0 0.0
452 229 223 42.49 45.0 49 356
50.7% 49.3% 10.8% 96.6 3.4
Primary melanocytic lesions
Diffuse melanocytoma 8728/0 (0015)
Melanocytoma 8728/1 (0016)
Malignant melanoma 8720/3 M7A0 11 6 5 65.00 69.0 1 7 100.0 0.0
Meningeal melanomatosis 8728/3 (0017)
11 6 5 65.00 69.0 1 7
100.0 0.0
Other neoplasms related to the meninges
Hemangioblastoma 9161/1 V0G0 394 208 186 45.91 45.0 81 342
52.8% 47.2% 20.6% 98.2 1.8
Lymphomas and hematopoietic neoplasms
Malignant lymphoma 9590/3 K7G0 321 172 149 62.09 66.0 57 178 25.3 74.7
Diffuse large B cell lymphoma 9680/3 K7G7 513 263 250 64.67 67.0 106 394 20.3 79.7
Plasmacytoma 9731/3 J7D8 16 7 9 55.87 56.0 1 9 100.0 0.0
Granulocytic sarcoma 9930/3 (0018)
850 442 408 63.05 66.0 164 581
52.0% 48.0% 19.3% 23.1 76.9
Germ cell tumors
Germinoma 9064/3 G7K0 54 46 8 20.39 17.5 9 48 37.5 62.5
Embryonal carcinoma 9070/3 G7H5 1 1 0 14.00 14.0 0 1 100.0 0.0
Yolk sac tumor 9071/3 G7H6 1 1 0 15.00 15.0 0 1 0.0 100.0
Choriocarcinoma 9100/3 T7C0
Teratoma (NOS) 9080/1 D0V0 2 2 0 20.50 20.5 0 2 100.0 0.0
Mature teratome 9080/0 G0G0 27 15 12 25.11 17.0 4 23 95.7 4.3
Immature germ cell tumors (NOS) 9080/3 G7H0 4 2 2 19.00 18.0 0 4 75.0 25.0
Immature teratoma 9080/3 G7H1 7 4 3 8.71 8.0 2 6 100.0 0.0
Teratoma with malignant transformation 9084/3 G7G0
Mixed germ cell tumor 9085/3 T7H0
Immature teratoma and seminoma 9080/3 G7M6 1 0 1 8.00 8.0 0 1 100.0 0.0
Malignant germ cell tumors (NOS) 9064/3 G7A0 9 8 1 15.22 13.0 3 9 55.6 44.4
106 79 27 20.10 17.0 18 95
74.5% 25.5% 17.0% 61.1 38.9
Tumors of the sellar region
Craniopharyngioma 9350/1 D0N2 255 144 111 35.64 36.0 26 225 92.4 7.6
Adamantinous craniopharyngioma 9351/1 (0019) 37 19 18 38.46 35.0 5 22 100.0 0.0
Papillary craniopharyngioma 9352/1 (0020) 3 1 2 49.66 45.0 0 2 100.0 0.0
Granular cell tumor 9582/0 (0021)
Pituicytoma 9432/1 (0022) 2 1 1 59.00 59.0 0 1 100.0 0.0
Spindle cell oncocytoma (adenohypophysis) 8291/0
297 165 132 36.29 36.0 31 250
55.6% 44.4% 10.4% 93.2 6.8
Miscellaneous
Chordoma 9370/3 D4N4 61 40 21 50.88 56.0 10 50 92.0 8.0
Uncategorized 130 64 66 46.26 52.0 15 97 41.2 58.8
191 104 87 47.74 53.0 25 147
54.5% 45.5% 13.1% 58.5 41.5
Total 25 756 12 192 13 564 52.15 56.0 6018 21 997
47.3% 52.7% 23.4% 77.9 22.1

The italicized ICD‐O numbers are provisional codes proposed for the fourth edition of ICD‐O.

Note that from 2004 to 2006, pathologists used The WHO 2000 Classification (24). Since 2007, the new WHO classification (28) has been applied, and rare mesenchymal tumors of the meninges have been recorded only since 2007.

The study was approved by the French legislation, and by all the French societies involved in the neuro‐oncology field: ANOCEF, SFNC and SFNP.

RESULTS

From 2004 to 2008, a total of 25 756 cases of newly diagnosed histologically confirmed PCNSTs was recorded in the FBTDB. Of the 60 participating centers (coupled neurosurgical department/pathological lab) located throughout France, 50 were public centers (45 academic centers and 5 general hospitals) and 10 were private institutions. However, with regard to the number of patients, the proportions were 94% from public centers and 6% from private institutions.

Of the 25 756 PCNST cases, 12 192 were men (47.3%), 13 564 were women (52.7%), 1601 were children (age: <15 years) (6.2%) and 521 were teenagers (15 ≤ age < 20 years) (2%).

Tumor localizations were specified in 17 199 cases and included supratentorial (77.7%), infratentorial (15.7%), spinal cord or cauda equina (5.3%) and mixed (1.3%). Surgery was specified in 21 997 cases. Tumor resections represented 78% of surgical operations, while biopsies represented 22%. For each histological type and subtype, percentages of biopsy and resection are detailed in Table 1.

Histological results

The distribution by each histology, sex, mean/median age (MA) at diagnosis and surgery, for the 25 756 PCNST cases, is shown in Table 1. Gliomas accounted for about half of all PCNST cases, while meningiomas accounted for about one‐third. Gliomas were more frequent in men (57.6%), while meningiomas in women (73.5%). The MAs of gliomas/all other neuroepithelial tumors/meningiomas/nerve sheath tumors/lymphomas were 56, 18, 58, 53 and 66 years, respectively.

According to the new WHO classification 27, 28, the new entities encountered in our series were: three papillary glioneuronal tumors, four rosettes forming glioneuronal tumor of the fourth ventricle, two papillary tumors of the pineal region, two pituicytomas and no spindle cell oncocytoma of the ante hypophysis. Concerning the new variants, we counted four pilomyxoid astrocytomas, four anaplastic medulloblastomas and three medulloblastomas with extensive nodularity recorded over 2 years.

Formaldehyde was used as a fixative, alone or in association, in 68% of the case samples. Cryopreservation was reported for 6018 PCNST specimens.

DISCUSSION

This work detailed all histological types and subtypes for 25 756 cases of newly diagnosed and histologically confirmed PCNST in France from 2004 to 2008. This work was made possible, thanks to the cooperation of a large number of neurosurgeons and pathologists from all over France, and the methodological support of epidemiologists. Above all, this work shows the importance of multidisciplinary networks and databases that involve clinicians, pathologists and epidemiologists (8).

However, this discussion is mainly focused on: (i) methodology; (ii) comparison of our results (histological distribution, age, sex, surgery) with a small number of publications that detailed all types and subtypes of PCNST in a large population; and (iii) current applications and perspectives of such database for scientific and public communities.

Methodology

The primary difficulty in building a tumor registry is defining the type of tumor to be recorded. Recent publications 11, 12, 17, 30, 31, 41, the classification system of the WHO 24, 28 and the European recommendations for coding tumors of the brain and central nervous system (CNS) (18) include all primary benign and malignant tumors located in the CNS, including the envelopes of the CNS and the origin of the nerves localized in the skull and the spine. Second, a registry has to record all cases of the defined tumors. The ascertainment system could influence the selection of tumor types to be included in the registry definition. As our registration system was based on the neurosurgical French network, we decided to record tumors that are always seen in neurosurgery. At the beginning of this work in 2004, we did not include mesenchymal non‐meningothelial tumors (except hemangiopericytoma), which were not considered as primary brain tumors by the French community at that time. Except for these differences, we selected the types of tumors that are included in the WHO 2000 (24) and Central Brain Tumor Registry of the United States (CBTRUS) classification schemes. In addition, we used the French nomenclature (1) in combination with the WHO (24).

Since 2007, all the codes included in the WHO 2007 (28) have been used in the FBTDB, and we started to record pituitary tumors. However, we still had some difficulties recording some cases of pituitary tumors. So, we decided to exclude pituitary tumors in the present work.

In the future, we could adopt a complementary strategy. It has been established by the Brain Tumor Epidemiology Consortium (BTEC) that glioblastomas and meningiomas have enough general agreement over time, across regions and between individual pathologists that one can consider using existing diagnostic data without further review [ie, as long as uniform guidelines, such as those provided by the WHO, are used (15)]. This would limit the number of cases to review and would mainly concern the rare PCNSTs. Moreover, some specific studies on rare PCNSTs will soon begin in France, and in these cases, the review will be part of the projects.

Comparison of our results

To our knowledge, there is no publication that detailed the distribution of all histological types and subtypes of PCNST according to the WHO 2007 Classification, by number of cases, sex, MA, number of cryopreserved samples and surgery for all ages in a large population.

First, in most countries, brain tumor registration is restricted to malignant tumor types (13). Only a few countries (eg, USA, Canada, Scandinavian countries, Austria) report incidence rates on benign and borderline brain tumors 9, 10, 12, 38, 39, 41. These tumors constitute approximately 45.5% to 70% of all brain tumors (11). However, benign and borderline lesions may be associated with significant neurological deficits, and may show malignant biological progression over time. Therefore, increasing attempts to register all brain tumor cases have been made. In the USA, it has already become legally mandatory to report all brain tumor types (Benign Brain Tumor Cancer Registries Amendment Act; Public Law 107‐260). Second, even in publications that included primary nonmalignant tumors, the details of all histological types and subtypes are very rarely presented. Therefore, our results are mainly compared to the CBTRUS results.

The sex ratios (male/female) for the CBTRUS (11) and for the FBTDB are very similar (eg, all neuroepithelial tumors: 1.28/1.34, all gliomas: 1.29/1.36, glioblastomas: 1.37/1.46, pilocytic astrocytomas: 1.14/1.05, oligodendrogliomas: 1.21/1.35, all ependymomas: 1.13/1.30, nonmalignant and malignant neuronal/glial tumors: 1.24/1.16, embryonal/primitive/medulloblastoma: 1.46/1.39, tumors of cranial and spinal nerves: 0.94/0.91, meningiomas: 0.35/0.36, lymphomas: 1.19/1.08, etc., for CBTRUS/FBTDB, respectively).

For many tumors, the MA at diagnosis is similar in the CBTRUS (11) and in the FBTDB (eg, pilocytic astrocytoma: 13/12, oligodendroglioma: 41/42, glioblastoma: 64/63, choroid plexus tumors: 17/20, nonmalignant and malignant neuronal/glial tumors: 26/23, embryonal tumors: 9/10, tumors of cranial and spinal nerves: 53/53, craniopharyngioma: 38/36, lymphoma: 63/66 years old for CBTRUS/FBTDB, respectively). In addition, it is important to note that the MA at diagnosis is often lower in clinical trials (eg, for glioblastoma, 56 years in Stupp et al (37) and 53 years in Westphal et al (40)) and in some single‐institution studies (eg, 58 years in Filippini et al (19)). Age is an important prognostic factor for most of all PCNSTs; this underlines the importance of population studies to compare oncological management and survival between two different countries or areas.

Before comparing the percentages of each PCNST between the CBTRUS and the FBTDB, it is important to note few important points. First, CBTRUS reported more than 10% of pituitary tumors (10.7% in the 2009–2010 CBTRUS statistical report in 18 states in 2002–2006 (11), and 12.7% in CBTRUS statistical report in the USA in 2004–2006 (12)), whereas FBDTB did not include pituitary tumors in the present report. Second, unspecified neoplasm accounted for 5.1% in the CBTRUS (11), while it accounted for only 0.5% in the FBTDB. This difference could be explained by the fact that in the FBTDB, histological coding comes directly from pathologists, while the CBTRUS includes cases without histological diagnosis. Third, the percentage of meningioma is smaller in the FBTDB (28.8%) than in the CBTRUS (37.7%, when considering without pituitary tumors) (11). This difference could also be explained by the fact that in the FBTDB, only cases with histological confirmation have been recorded. In 2011, reporting of all cases of PCNST is still a challenge, specifically for nonmalignant tumors and tumors without histological confirmation. In the last report of the CBTRUS, it was stated that “the cancer registry incidence rates for the malignant tumors (cancer registry range: 4.62 to 8.69 per 100 000 person‐years) are again seen as being much less variable than the reported incidence rates for the non‐malignant tumors (cancer registry range: 6.13 to 16.74 per 100 000 person–years)”(12).

When we take into account these three points, we can consider that our results (Table 1) show a distribution by histology, MA at diagnosis and sex comparable to the recent literature 11, 12, 17, 41, even by specific histology 23, 35. The distribution of the different subtypes of PCNST is similar in France and in the USA, except for oligodendroglial tumors. Two main reasons may explain this difference: (i) the US data were collected between 2002 and 2006 (11), while the French data were collected between 2004 and 2008. Indeed, most studies (for a review, see (22)) have reported a recent increase of oligodendroglial tumors in comparison to astrocytic tumors. (ii) French neuropathologists are more influenced by the classification proposed by Daumas‐Duport et al (14) than American neuropathologists.

New entities and variants have been published by the last WHO classification in 2007 (28). As our work included the year 2008, French pathologists included few such cases. These new entities began to be described in 2008, 1 year after the new classification has been published. But, it is too early to be representative of a population study. Moreover, only few specific cases have been reported in the literature.

To our knowledge, this work is the first in Europe, and probably in the world, that specifies the surgery (biopsy or resection) for all histological types and subtypes of PCNST in a large population. Over 97% of tumors of the meninges, and cranial and paraspinal nerves are resected. Regarding gliomas, the proportion of biopsy appears to vary by country and/or studies. For example, the Glioma Outcomes Project described a biopsy rate for glioblastoma of 20% (25), and in the San Francisco Bay Area SEER registry, during the period 1991–2001, 27.3% of glioblastoma patients had a biopsy (43). In an Italian single‐institution study, biopsy was performed in 12% of all the glioblastoma cases (19), and in an Italian consortium study, the percentage of biopsies was 25% for all astrocytoma grades that were treated with RT (29). In France, the biopsy rate for glioblastoma was 44% in the year 2004 (7), and now it decreases. For the years 2004 to 2008, the biopsy rate was 38%.

Current applications and perspectives

Epidemiological data from the FBTDB already helped to build two ongoing French Hospital Clinical Research Programs (PHRCs) (one randomized multicenter phase II trial for patients with de novo unresectable glioblastoma, and one national, prospective phase II study for adult patients with medulloblastoma). The FBTDB also helped to identify and recruit patients for two other ongoing “PHRCs” (one for children with craniopharyngioma, and one for adult patients with intracranial ependymoma). Other specific projects are in progress (eg, oncological management and survival for all French glioblastoma patients newly diagnosed and histologically confirmed in 2008 in all French territory; histologically confirmed grade II glioma distribution in all French territory).

To contribute to a better completeness of reported cases, a second source for recording histologically confirmed PCNST is in progress. In agreement with the French Society of Neuropathology (SFNP), a comprehensive annual listing of all cases analyzed by each pathology lab will be sent securely to the RTH. A clinical research technician will track the missing listings, verify the registered cases, complete the database and check discordant cases with each lab. Then, the clinical research technician will complete the main clinical data for cases not registered yet, by contacting the relevant department of neurosurgery. The FBTDB recently received grants from the French cancer institute [Institut National du Cancer (INCa)] to analyze and compare oncological management and survival between the different French areas.

Apart from some specific cases, the causes of PCNST are unknown 8, 26, 34. Epidemiological studies of PCNST have examined many risk factors over the past several decades; however, there are few consistent findings. The inconclusive results may be caused by small sample sizes in individual studies and differences between studies in patients, tumor types and methods of classification. That is why the FBTDB would like to collect a huge number of cases, and study each histological type and subtype separately, and then participate in international studies with, for example, the BTEC and the International Agency for Research on Cancer (IARC).

Virtual tumor bank is one of the major interests of such database. Recording cryopreservation of samples, to our knowledge, has not been previously reported and is original in our study. More than 6000 identified PCNSTs are cryopreserved. For these cryopreserved tumors, we know the histological diagnosis, and the main clinical and radiological features. This represents the first virtual tumor bank of PCNST in Europe, and holds great potential for future biological and clinical investigations. Many specific retrospective or prospective studies will use the FBTDB to identify patients and get initial data. Collaborative studies have already been initiated.

CONCLUSION

This database or databank dedicated to PCNST contains detailed data on clinical, histological and other characteristics, such as availability of cryopreserved specimens that are not available in other European registries. Thus, it is a valuable resource that can be used for planning future epidemiological and clinical research.

ACKNOWLEDGMENTS

The authors wish to acknowledge all the doctors and professors who helped and completed the cards for the record of PCNSTs in France: Abbey Toby A. (Clichy), Adle‐Biassette H. (Paris), Adreux (Brest), Albagnac V. (Limoges), Algros M.P. (Besancon), Amat C. (Saint Pierre), Ansart F. (Besancon), Arbez‐Gindre F. (Besancon), Arbion F. (Tours), Arrivets P. (Saint Pierre), Aubriot Lorton M.H. (Dijon), Auvigne I. (Toulouse), Averous G. (Strasbourg), Badsi A. (Perpignan), Baldet P. (Montpellier), Barbey C. (Tours), Bazille C. (Paris), Bedgedjian I. (Besancon), Benabidallah S. (Bron), Benali A. (Orléans), Bergemer Fouquet A.M. (Tours), Bertocchi C. (Paris), Beuvon F. (Paris), Billotet C. (Perpignan), Blechet C. (Tours), Bondoin (Brest), Bonneau C. (Orleans), Bonyhay G. (Clichy), Bordier (Saint Pierre), Borrelly C. (Montpellier), Boudjadi S. (Reims), Bouvier C. (Marseille), Branquet D. (Clamart), Bressenot A. (Nancy), Broche C. (Nîmes), Brouchet A. (Toulouse), Brousset P. (Toulouse), Bruniau A. (Amiens), Cahn V. (Reims), Calvet P. (Toulon), Camo J. (Perpignan), Camparo P. (Paris), Carloz E. (Toulon), Cassagnau E. (Nantes), Cathelineau D. (Lille), Caulet S. (Rennes), Caveriviere P. (Toulouse), Cazals‐Hatem D. (Clichy), Charlotte F. (Paris), Chapon F. (Caen), Charpin C. (Marseille), Chatelain D. (Amiens), Chenard M.P. (Strasbourg), Chretien F. (Creteil), Clairotte A. (Besancon), Colombat M. (Clichy), Conan V. (Brest), Concha (Brest), Costa K. (Perpignan), Costes V. (Montpellier), Costes‐Charlet N. (Clermont‐Ferrand), Coulon A. (Poitiers), Couvelard A. (Clichy), Cremades (Paris), Croue A. (Angers), Cruel T. (Pringy), Danjoux M. (Toulouse), Daumas‐Duport C. (Paris), Degano‐Valmarx S. (Toulouse), Delage Corre M. (Limoges), Delattre C. (Lille), Delisle M.B. (Toulouse), Delsol M. (Toulouse), Deschamps L. (Clichy), Diebold M.D. (Reims), Donsbeck A.V. (Chambery), Dosda A. (Clichy), Duga I. (Toulouse), Dumollard J.M. (Saint Etienne), Durand L. (Montpellier), Duval H. (Rennes), Eimer S. (Bordeaux), Etchandy M.P. (Pau), Eyremandi (Pau), Fallet C. (Paris), Faraut (Nîmes), Felce Dachez M. (Clichy), Felix S. (Besancon), Fernandez C. (Marseille), Fetissof F. (Tours), Feutry C. (Pringy), Figarella‐Branger D. (Marseille), Figuccio M. (Toulon), Fornes P. (Reims), Fouet B. (Toulon), Fregeville M. (Saint Pierre), Fromont G. (Poitiers), Gaspard C. (Montpellier), Gay G. (Pau), Gontier M.F. (Amiens), Goujon J.M. (Poitiers), Gray F. (Paris), Grignon Y. (Nancy), Gros (Paris), Guillou (Reims), Guymar S. (Paris), Gyenes C. (Dijon), Hassoun J. (Marseille), Haudebourg J. (Nice), Heitzmann A. (Orleans), Henin D. (Paris), Hennequin V. (Nancy), Heymann M.F. (Nantes), Istier L. (Pringy), Jaubert F. (Paris), Jouan H. (Rennes), Jourdan F. (Tours), Jouvet A. (Bron), Justrabo E. (Dijon), Kaci R. (Paris), Kantelip B. (Besancon), Kemeny J.L. (Clermont‐Ferrand), Kerdraon O. (Lille), Kerdraon R. (Orleans), Kermanac H.P. (Pringy), Khaddage A. (Saint Etienne), Kleinclaus I. (Colmar), Kopp N. (Bron), Krzisch S. (Colmar), Kujas M. (Paris), Labrousse F. (Limoges), Lacroix C. (Le Kremlin Bicetre), Lamant L. (Toulouse), Lannes B. (Strasbourg), Laquerriere A. (Rouen), Laurent C. (Toulouse), Le Gall F. (Rennes), Le Houcq M. (Saint Pierre), Lechapt E. (Caen), Leclair F. (Nantes), Leduc (Lille), Leger F. (Bordeaux), Lerintiu F. (Colmar), Levillain P. (Poitiers), Lhermitte B. (Saint Pierre), Lhermitte B. (Strasbourg), Loussouarn D. (Nantes), Maitre F. (Orleans), Majek‐Zakine E. (Reims), Manent A.M. (Pau), Maran A. (Montpellier), Marcon N. (Nancy), Mareel A. (Pointe A Pitre), Marie B. (Nancy), Martin L. (Dijon), Maues De Paula A. (Marseille), Maurage C.A. (Lille), Mazerolles C. (Toulouse), Mergey E. (Pau), Meyronnet D. (Bron), Michalak S. (Angers), Michenet P. (Orleans), Michiels J.F. (Nice), Milin S. (Poitiers), Miquel C. (Paris), Mohr M. (Strasbourg), Mohra (Clermont‐Ferrand), Mokhtari K. (Paris), Monpon C. (Toulouse), Morand Dusserre I. (Pringy), Moreau A. (Nantes), Moreau M. (Toulouse), Moreno S. (Rouen), Musso Rigal C. (Toulouse), Neuville A. (Strasbourg), Oksman A. (Toulouse), Oukabli M. (Tours), Palasse J. (Toulouse), Parent M. (Douai), Patey M. (Reims), Pellissier J.F. (Marseille), Peoc'h M. (Saint Etienne), Philippe A. (Tours), Pialat J. (Limonest), Pluot M. (Reims), Polivka M. (Paris), Pommepuy I. (Limoges), Ponnelle T. (Dijon), Pradere Labat M. (Toulouse), Pradere M. (Toulouse), Quintana M. (Nimes), Quintin I. (Brest), Quintyn M.L. (Toulouse), Ranfaing E. (Besancon), Raynaud P. (Montpellier), Reis Borges R. (Nîmes), Renjard L. (Tours), Reyre J. (Toulouse), Richard S. (Le Kremlin Bicetre), Rigau V. (Montpellier), Ringenbach F. (Besancon), Rouquette I. (Toulouse), Rousseau A. (Nancy), Rousseau A. (Paris), Rousselet M.C. (Angers), Rousselot C. (Tours), Ruchoux M.M. (Lille), Sabourin J.C. (Rouen), Saïkali S. (Rennes), Saingra B. (Montpellier), Saint‐ Andre J.P. (Angers), Saint Blancard P. (Clamart), Saint Pierre G. (Bron), Saint‐Paul M.C. (Nice), Sarrouy J. (Pointe A Pitre), Savin C. (Nîmes), Sawan B. (Bordeaux), Schill H. (Montargis), Selves J. (Toulouse), Seurat P. (Saint Pierre), Sevestre H. (Amiens), Sorbara R. (Toulouse), Soulard P. (Paris), Soulard R. (Toulon), Souraud J.B. (Toulon), Straub P. (Colmar), Streichenberger N. (Bron), Talagas M. (Brest), Terrier P. (Toulon), Toquet C. (Nantes), Tortel M.C. (Colmar), Trouillas J. (Tours), Tubiana A. (Paris), Uro‐Coste E. (Toulouse), Valmary S. (Toulouse), Vandenbos F. (Nice), Varlet P. (Paris), Vasiljevic A. (Marseille), Vaunois B. (Saint Etienne), Verdier D. (Tours), Veresezon L. (Rouen), Vic P. (Montpellier), Viennet G. (Besancon), Vignaud J.M. (Nancy), Villa C. (Paris), Vital A. (Bordeaux), Warter A. (Fort De France), Weinbreck N. (Nancy), Yacoub M. (Poitiers), Yaziji N. (Reims), Yriarte‐Laurent M.C. (Toulouse), Yver M. (Poitiers).

Abi Lahoud G. (Paris), Achim V. (Clermont‐Ferrand), Adetchessi T. (Marseille), Aesch B. (Tours), Agha M. (Dijon), Aghakhani N. (Le Kremlin‐Bicetre), Akkhabar (Angers), Al Hallak R. (Lyon), Aldea S. (Paris), Alfieri A. (Limoges), Ali Benali M. (Limoges), Aliamus A. (Saint Pierre), Allano V. (Brest), Allaoui M. (Lille), Alliez B. (Marseille), Alliez J.R. (Marseille), Amlashi S.F.A. (Rennes), Aouad N. (Toulon), Arthuis F. (Paris), Assaker R. (Lille), Atta (Rennes), Auque J. (Nancy), Autricque A. (Pau), Ayache D. (Paris), Barat J.L. (Marseille), Baroncini M. (Lille), Barrey C. (Lyon), Bataille B. (Poitiers), Bauchet L. (Montpellier), Baussart (Le Kremlin‐Bicetre), Bayram M. (Rouen), Bazin A. (Reims), Beauchesne P. (Nancy), Beaudic Y. (Besancon), Beaurain J. (Dijon), Bedou G. (Perpignan), Belliard H. (Lyon), Bellow F. (Rouen), Beltechi R. (Strasbourg), Ben Hamouda H. (Saint Etienne), Ben Ismaïl M. (Tours), Ben Yahia M. (Rennes), Benezech J. (Montpellier), Benhima H. (Marseille), Berger C. (Saint Etienne), Bernard C. (Toulon), Bernard M.H. (Reims), Berthelot J.L. (Clichy), Besson G. (Brest), Billant (Toulon), Billon‐Grand R. (Besancon), Bitar A. (Paris), Bizette C. (Colmar), Blanc J.L. (Poitiers), Blanquet A. (Montpellier), Blond S. (Lille), Blondet (Clamart), Boch A‐L. (Paris), Boetto S. (Toulouse), Boissonnet H. (Paris), Bord E. (Nantes), Borha A. (Caen), Bouali I. (Colmar), Bouazza S. (Paris), Bougeard R. (Villeurbanne), Bouillot P. (Nimes), Bourgeois P. (Lille), Bousigue J.Y. (Cornebarrieu), Bousquet C. (Perpignan), Bousquet O. (Dijon), Bousquet P. (Toulouse), Boyer P. (Strasbourg), Brassier G. (Rennes), Bresson D. (Paris), Bret P. (Lyon), Bruneau M. (Paris), Brunon J. (Saint Etienne), Buffenoir K. (Poitiers), Cabal P. (Pau), Caille J. (M. (Bordeaux), Caire F. (Limoges), Capelle L. (Paris), Cardoso M. (Colmar), Carpentier A. (Paris), Cesari J.B. (Montpellier), Chabane A. (Clermont‐Ferrand), Champeaux K. (Bordeaux), Chaynes P. (Toulouse), Chays A. (Reims), Chazal J. (Clermont‐Ferrand), Chibbaro S. (Paris), Chinot O. (Marseille), Chobaut J.C. (Besancon), Choplain J. (Brest), Choukri M. (Le Kremlin‐Bicetre), Cioloca C. (Paris), Civit T. (Nancy), Clemenceau S. (Paris), Colnat S. (Nancy), Comoy J. (Saint Pierre), Cornelius J. (Paris), Cornu P. (Paris), Coubes P. (Montpellier), Coulbois S. (Nancy), Crampette L. (Montpellier), Cristini A. (Lyon), Cuny E. (Bordeaux), Cuttaree H. (Paris), Czorny A. (Besancon), Dagain A. (Paris), Dahman (Rennes), Dam Hieu P. (Brest), Dandine J.B. (Toulouse), Darrouzet V. (Bordeaux), Dautheribes M. (Bordeaux), David P. (Le Kremlin‐Bicetre), De Germay B. (Saint Jean), De Soultrait F. (Clamart), Debono B. (Rouen), Debono B. (Cornebarrieu), Decq P. (Creteil), Delaretti (Lille), Delhaye M. (Angers), Delion (Angers), Delmas J.M. (Paris), Delsanti C. (Marseille), Derlon J.M. (Caen), Derrey S. (Rouen), Deruty R. (Lyon), Desenclos C. (Amiens), Desgeorges M. (Paris), Desplat A. (Pau), Destandau J. (Bordeaux), Destrieux C. (Tours), Devaux B. (Paris), Dezamis E. (Paris), Dhellemmes P. (Lille), Di Rocco F. (Paris), Di Tommaso L. (Besancon), Diabira S. (Rennes), Diaz A. (Saint Pierre), Dimitriu C. (Strasbourg), Djindjian M. (Creteil), Do L. (Pointe A Pitre), Doe K. (Saint Pierre), Dorfmuller G. (Paris), Dorwling‐Carter D. (Orleans), Dran G. (Montpellier), Dubois G. (Saint Jean), Ducolombier A. (Trappes), Duffau H. (Montpellier), Dufour T. (Orleans), Duhem R. (Lille), Dulou R. (Paris), Dumas B. (Saint Etienne), Duntze (Reims), Dupard T. (Lille), Duplessis (Cornebarrieu), Durand A. (Lyon), Durandeau A. (Bordeaux), Dutertre G. (Paris), Duthel R. (Saint Etienne), El Fertit H. (Montpellier), Emery E. (Caen), Espagno C. (Cornebarrieu), Esposito P. (Strasbourg), Fabre T. (Bordeaux), Faillot T. (Clichy), Farah W. (Dijon), Farizon F. (Saint Etienne), Faure A. (Nantes), Faure P. (Limoges), Fesselet J. (Toulon), Fichten A. (Amiens), Fischer D. (Strasbourg), Fono S. (Toulouse), Fontaine D. (Nice), Fotso M.J. (Saint Etienne), Fournier D. (Angers), Francois P. (Tours), Frank B. (Argonay), Freger P. (Rouen), Freppel S. (Nancy), Froelich S. (Strasbourg), Fuentes J.M. (Montpellier), Fuentes S. (Marseille), Gadan R. (Caen), Garrel R. (Montpellier), George B. (Paris), Giacomelli R. (Colmar), Gigaud M. (Toulouse), Gil Robles S. (Montpellier), Gimbert E. (Bordeaux), Goasguen O. (Paris), Godard J. (Besancon), Gomez A. (Marseille), Gosset (Amiens), Goutagny S. (Clichy), Gras R. (Marseille), Grayeli B. (Clichy), Graziani N. (Marseille), Grellier P. (Nice), Grisoli F. (Marseille), Guarnieri J. (Caen), Guegan Y. (Rennes), Guenot M. (Lyon), Guerrier B. (Montpellier), Gueye E. (Limoges), Guinguene C. (Lyon), Guy G. (Angers), Guyotat J. (Lyon), Haddad E. (Lille), Haegelen C. (Rennes), Hallacq M. (Lyon), Hallacq P. (Limoges), Hamcha (Poitiers), Hamdi S. (Paris), Hamlat A. (Rennes), Hansen F. (Caen), Hatem O. (Saint Etienne), Hattou M. (Creteil), Hayek G. (Angers), Henry (Brest), Heyman D. (Pau), Hladky J.P. (Nimes), Huot J.C. (Pau), Iakovlev G. (Clichy), Ibrahim R. (Angers), Irthum B. (Clermont‐Ferrand), Ischac R. (Fort De France), Jacquet G. (Besancon), Jan M. (Tours), Jarraya B. (Creteil), Jouanneau E. (Lyon), Joud A. (Nancy), Joulin (Brest), Kaczmarek D. (Saint Etienne), Kaddoum H. (Pointe A Pitre), Kalamarides M. (Clichy), Karachi C. (Paris), Katrangi H. (Besancon), Kaya J.M. (Marseille), Kehrli P. (Strasbourg), Keravel Y. (Creteil), Khalil T. (Marseille), Khouri K. (Montpellier), Khouri S. (Caen), Klein O. (Nancy), Koubaïssi W. (Angers), Kuzeawu A. (Colmar), Lacerda P. (Caen), Lagarrigue J. (Toulouse), Langlois O. (Rouen), Lapierre F. (Poitiers), Lapras C. (Argonay), Le Fay (Amiens), Le Franc (Amiens), Le Guerinel C. (Creteil), Le Nen (Brest), Legars D. (Amiens), Lejeune J.P. (Lille), Lemaire J.J. (Clermont‐Ferrand), Lena G. (Marseille), Lepeintre (Le Kremlin‐Bicetre), Leriche B. (Saint Pierre), Lescure J.P. (Cornebarrieu), Leston J.M. (Creteil), Leveque (Marseille), Liguoro D. (Bordeaux), Linne M. (Lyon), Lioret E. (Tours), Lisii D. (Lille), Listrat A. (Paris), Litre F. (Reims), Litrico S. (Nice), Loiseau H. (Bordeaux), Lonjon M. (Nice), Lonjon N. (Montpellier), Lopes M. (Saint Pierre), Lot G. (Paris), Louis E. (Lille), Louveau A. (Aix Les Bains), Lubrano V. (Toulouse), Lungu G. (Colmar), Madonnet E. (Paris), Maghreu (Caen), Magro E. (Brest), Mahla K. (Villeurbanne), Maillard A. (Perpignan), Maitrot D. (Strasbourg), Malca S. (Marseille), Mandat (Creteil), Manisor M. (Limoges), Mansour (Angers), Manzo N. (Fort De France), Marchal J.C. (Nancy), Marchal T. (Creteil), Marie J.P. (Rouen), Marnet D. (Reims), Martin S. (Nantes), Mascott (Toulouse), Mazon A. (Rennes), Memia Zolo D. (Fort De France), Menegalli D. (Nantes), Menei P. (Angers), Mercier P. (Angers), Merlet Chicoine I. (Poitiers), Merlot I. (Nancy), Mertens P. (Lyon), Metellus P. (Marseille), Mineo F. (Lille), Mireau E. (Paris), Monteil P. (Bordeaux), Morandi. (Rennes), Morar S. (Le Kremlin‐Bicetre), Moreau (Caen), Moreau J.J. (Limoges), Morel C. (Villeurbanne), Mortada J. (Colmar), Mostofi K. (Fort De France), Mottolese C. (Lyon), Moubarak K. (Creteil), Mourier L. (Dijon), Muckensturm B. (Orleans), Nader E. (Angers), Nahas F. (Pointe A Pitre), Namaki H. (Perpignan), Nataf F. (Paris), Navarro S. (Paris), Nguyen J.P. (Nantes), Njee Bugha T. (Marseille), Njee T. (Pointe A Pitre), Nogues L. (Saint Pierre), Noudel R. (Reims), Nouet A. (Paris), Nseir (Nancy), Nseir R. (Creteil), Nuti C. (Saint Etienne), Orabi M. (Paris), Orenstein D. (Colmar), Page P. (Paris), Palfi S. (Creteil), Pallud J. (Paris), Pampin S. (Rennes), Paquis P. (Nice), Paradot G. (Le Kremlin‐Bicetre), Parker F. (Le Kremlin‐Bicetre), Pasqualini E. (Rennes), Pech Gourg G. (Marseille), Pejeredou (Paris), Pelissou‐Guyotat I. (Lyon), Pellet W.J. (Marseille), Peltier J. (Amiens), Pencalet P. (Paris), Penchet G. (Bordeaux), Peragut J.C. (Marseille), Perie (Paris), Pernot P (Clamart), Perrin G. (Lyon), Person H. (Brest), Peruzzi P. (Reims), Pierre‐Kahn A. (Paris), Pinaudeau M. (Perpignan), Pinelli C. (Nancy), Plas J.Y. (Cornebarrieu), Polo G. (Lyon), Poncet J.L. (Paris), Porhiel V. (Perpignan), Postelnicu A. (Caen), Pouit B. (Paris), Prades (Saint Etienne), Privat J.M. (Montpellier), Proust F. (Rouen), Puget S. (Paris), Rabehenoina C. (Rouen), Rabhi M. (Clermont‐Ferrand), Ragragui O. (Lille), Raoul S. (Nantes), Rasendrarijao D. (Nice), Redondo A. (Clichy), Regis J. (Marseille), Remond J. (Villeurbanne), Reynier Y. (Marseille), Reyns N. (Lille), Ricci Franchi A.C. (Lyon), Richet A. (Fort De France), Riem T. (Bordeaux), Riem T. (Nantes), Riffaud L. (Rennes), Rigoard P. (Poitiers), Robert G. (Paris), Roche P.H. (Marseille), Rodriguez M.A. (Montpellier), Rodriguez V. (Brest), Roualdes G. (Poitiers), Roualdes V. (Nantes), Rougier A. (Bordeaux), Roujeau (Paris), Roujeau T. (Paris), Rousseau P. (Reims), Roux F. (Toulouse), Roux F.X. (Paris), Sabatier J. (Toulouse), Sabatier P. (Montpellier), Sabbah M. (Montpellier), Sacko O. (Toulouse), Sainte‐Rose C. (Paris), Sakka L. (Clermont‐Ferrand), Salmon B. (Saint Jean), San Galli F. (Bordeaux), Sautreaux J.L. (Dijon), Scarone P. (Paris), Scavarda D. (Marseille), Scherpereel B. (Reims), Schmidt E. (Toulouse), Segnarbieux F. (Montpellier), Seguin (Saint Etienne), Seigneuret E. (Rennes), Seizeur R. (Brest), Sichez J.P. (Paris), Sid Hamed S. (Brest), Silhouette B. (Paris), Simbert (Dijon), Simon A. (Brest), Simon E. (Lyon), Sinardet D. (Clermont‐Ferrand), Sindou M. (Lyon), Sleiman M. (Lille), Sol J.C. (Toulouse), Sorin A. (Paris), Soumare O. (Marseille), Srour A. (Paris), Stecken J. (Orleans), Sterkers O. (Clichy), Stilhart B. (Colmar), Szathmari A. (Lyon), Tadie M. (Le Kremlin‐Bicetre), Taha S. (Saint Pierre), Tarek A. (Marseille), Ternier J. (Marseille), Thines L. (Lille), Thomassin J.M. (Marseille), Tobenas Dujardin A.C. (Rouen), Tonnelle Duhem V. (Lille), Tourneux (Clermont‐Ferrand), Tourneux H. (Saint Etienne), Toussaint P. (Amiens), Touta A. (Marseille), Touzet G. (Lille), Travers N. (Tours), Travers N. (Lille), Tremoulet M. (Toulouse), Turak B. (Paris), Turner F. (Marseille), Valery C. (Paris), Vallee B. (Lyon), Van Effenterre R. (Paris), Vassal F. (Saint Etienne), Velut S. (Tours), Vidal (Bordeaux), Vidal J. (Limoges), Vignes J.R. (Bordeaux), Vincentelli F. (Marseille), Vinchon M. (Lille), Voirin J. (Nancy), Voirin J. (Strasbourg), Von Langsdorf D. (Nice), Vongsouthi (Montpellier), Wager M. (Poitiers), Zaïri F. (Lille), Zanaret M. (Marseille), Zemmoura I. (Tours), Zerah M. (Paris).

This work was conducted with the financial support of grants from the Ligue Nationale Contre le Cancer (France), INCa, Schering‐Plough Laboratory, Roche Laboratory, ANOCEF, SFNC, Associations pour la Recherche sur les Tumeurs Cérébrales (ARTC and ARTC Sud) (France), Département de l'Hérault (France), Rotary Club (AGLY), Archimedes Pharma Laboratory, Sophysa Laboratory and Groupe de Neuro‐Oncologie du Languedoc Roussillon (France).

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