Jacques Guyotat

Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas: a series of 1097 cases: clinical article.

OBJECT The spontaneous prognostic factors and optimal therapeutic strategy for WHO Grade II gliomas (GIIGs) have yet to be unanimously defined. Specifically, the role of resection is still debated, most notably because the actual amount of resection has seldom been assessed. METHODS Cases of GIIGs treated before December 2007 were extracted from a multicenter database retrospectively collected since January 1985 and prospectively collected since 1996. Inclusion criteria were a patient age ≥ 18 years at diagnosis, histological diagnosis of WHO GIIG, and MRI evaluation of tumor volume at diagnosis and after initial surgery. One thousand ninety-seven lesions were included in the analysis. The mean follow-up was 7.4 years since radiological diagnosis. Factors significant in a univariate analysis (with a p value ≤ 0.1) were included in the multivariate Cox proportional hazard regression model analysis. RESULTS At the time of radiological diagnosis, independent spontaneous factors of a poor prognosis were an age ≥ 55 years, an impaired functional status, a tumor location in a nonfrontal area, and, most of all, a larger tumor size. When the study starting point was set at the time of first treatment, independent favorable prognostic factors were limited to a smaller tumor size, an epileptic symptomatology, and a greater extent of resection. CONCLUSIONS This large series with its volumetric assessment refines the prognostic value of previously stressed clinical and radiological parameters and highlights the importance of tumor size and location. The results support additional arguments in favor of the predominant role of resection, in accordance with recently reported experiences.

Syringomyelia Associated with Type I Chiari Malformation A 21-Year Retrospective Study on 75 Cases Treated by Foramen Magnum Decompression with a Special Emphasis on the Value of Tonsils Resection

Summary The purpose of the present study is to evaluate retrospectively the effects of several intra-operative manipulations on the results of foramen magnum decompression (FMD) in patients having syringomyelia associated with type I Chiari malformation. Seventy-five patients having syringomyelia associated with Chiari I malformation were operated on between 1975 and 1996. This population was grouped into 4 subgroups according to the surgical protocol: group I=42 patients with FMD alone; group II=16 patients with FMD and third ventricle shunting; group III=9 patients with FMD and syringosubarachnoid shunting (SSS); group IV=8 patients with FMD and cerebellar tonsils resection. Pre- and postsurgical magnetic resonance imaging (MRI) studies were analyzed (and compared). Nine patients were lost to follow-up. The results were evaluated in the 66 remaining patients (mean follow-up: 52 months), using the Bidzinskis outcome scale (ref). Two patients (3%) died postoperatively, 31 (47%) had very good results (after additional surgery in 7), 16 (24,2%) had good results (after additional surgery in 7) and 17 (25,7%) had poor results despite further surgery in 9. A total of 27 reoperations were undertaken after primary FMD in 23 patients (35%). Thirty-nine patients (59%) had both pre- and postsurgical MRI evaluation. In 28 (72%) the syrinx had markedly decreased whereas it had remained stable in 11 (28%). Clinical results were not significantly different between the patients of groups I, II and III. Very good or good results were obtained in 24 patients (64,8%) of group I (after additional surgery in 10), in 8 (61,5%) of group II (after additional surgery in 1) and in 7 (87,5%) of group III (after additional surgery in 3). Results in group IV were as follows: 7 patients (87%) had very good results and one had a good result. With a mean follow-up of 28 months, no patient required additional surgery. Postsurgical MRI syrinx reduction was observed in all 8 patients either in the early postoperative course or on delayed follow-up. It is suggested that tonsils resection might enhance the results of FMD in individuals having Chiari I-related syringomyelia.

Microarray analysis reveals differential gene expression patterns in tumors of the pineal region.

Several types of tumors are known to originate from the pineal region, among them pineal parenchymal tumors (PPTs) and papillary tumors of the pineal region (PTPRs), probably derived from the subcommissural organ. As a result of their rarity, their histologic diagnosis remains difficult. To identify molecular markers, using CodeLink oligonucleotide arrays, gene expression was studied in 3 PPTs (2 pineocytomas and one pineoblastoma), 2 PTPRs, and one chordoid glioma, another rare tumor of the third ventricle. Because PTPR and chordoid glioma may present ependymal differentiation, gene expression was also analyzed in 4 ependymomas. The gene patterns of the 3 PPTs fell in the same cluster. The pineocytomas showed high expression of TPH, HIOMT, and genes related to phototransduction in the retina (OPN4, RGS16, and CRB3), whereas the pineoblastoma showed high expression of UBEC2, SOX4, TERT, TEP1, PRAME, CD24, POU4F2, and HOXD13. Using reverse transcriptase-polymerase chain reaction on 13 PPTs, we demonstrated that PRAME, CD24, POU4F2, and HOXD13 might be candidates for grading PPT with intermediate differentiation. PTPRs, classified with chordoid glioma and separately from ependymomas, showed high expression of SPEDF, KRT18, and genes encoding proteins reported to be expressed in the subcommissural organ, namely ZFH4, RFX3, TTR, and CGRP. Our results highlight the usefulness of gene expression profiling for classify tumors of the pineal region and identify genes with potential use as diagnostic markers.

Intracranial ependymomas in adult patients: analyses of prognostic factors

AbstractObjective: The goal of our study is to identify significant prognostic factors for a series of intracranial ependymomas in an adult population. Age, location, histology, preoperative clinical status, extent of resection and radiotherapy were examined. Methods: Our series includes 34 patients. Ten tumors were located in the brain parenchyma, 5 in the lateral ventricle, 8 in the third and 11 in the fourth ventricle. Seventeen ependymomas were grades 2 and 17 were anaplastic. Surgical resection was gross-total in 27 patients and partial in 7. Results: At a mean follow-up of 9 years (±1 year) 16 patients died and, among the 18 survivors 14 are in complete remission and 4 present a local recurrence. The 5- and 10-year overall survival rates were respectively 62% and 43%. The 5- and 10-year progression-free survivals were 47% and 43%. Univariate analysis revealed that location in the brain parenchyma and anaplasia are the only statistically significant predictors of poor outcome. Conclusion: We can make out three groups of patients from our series: the first encompasses patients operated on for an intraparenchymal tumor, in all our cases an anaplastic ependymoma, with a 5-year rate of tumor-related deaths of 100%. The second group includes fourth ventricle ependymomas, which are mostly grade 2 tumors. They display a 10-year survival rate of 90%. Last group entails lateral and third ventricle ependymomas, of both low and high grade, with a 10-year survival rate of 60% for lateral ventricle and 35% for third ventricle tumors.

Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8-7.7) after PCV onset and 2.7 years (range, 0-7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonalds criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated.

Velocity of tumor spontaneous expansion predicts long-term outcomes for diffuse low-grade gliomas

BACKGROUND Supratentorial diffuse low-grade gliomas present a slow macroscopic tumor growth that can be quantified through the measurement of their velocity of diametric expansion. We assessed whether spontaneous velocity of diametric expansion can predict long-term outcomes as a categorical variable and as a continuous predictor. METHODS A total of 407 adult patients with newly diagnosed supratentorial diffuse low-grade gliomas in adults were studied. RESULTS The mean spontaneous velocity of diametric expansion before first-line treatment was 5.8 ± 6.3 mm/year. During the follow-up (mean, 86.5 ± 59.4 months), 209 patients presented a malignant transformation, and 87 died. The malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (median, 103 and 249 months, respectively) than in cases of fast velocity of diametric expansion (median, 35 and 91 months, respectively; P < .001). In multivariate analyses, spontaneous velocity of diametric expansion as a categorical variable (<4, ≥4 and <8, ≥8 and <12, ≥12 mm/year) was an independent prognostic factor for malignant progression-free survival (P < .001; hazard ratio, 3.87; 95% confidence interval [CI], 2.67-5.52) and for overall survival (P < .001; hazard ratio, 4.62; 95% CI, 2.58-7.97). Velocity of diametric expansion was also an independent prognostic factor for overall survival as a continuous predictor, showing a linear relationship between overall survival and spontaneous velocity of diametric expansion (hazard ratio, 1.09 per one unit increase; 95% CI, 1.06-1.12; P < .001). CONCLUSIONS Independent of the molecular status, the spontaneous velocity of diametric expansion allows the identification of rapidly growing diffuse low-grade gliomas (at higher risk of worsened evolution) during the pretherapeutic period and without delaying treatment.

Solitary fibrous tumors of the central nervous system: Clinicopathological and therapeutic considerations of 18 cases - Commentary

OBJECTIVEThis is a retrospective study of 18 patients harboring a solitary fibrous tumor of the central nervous system. Therapeutic management and outcome were analyzed. METHODSBetween 1999 and 2004, 18 patients harboring central nervous system solitary fibrous tumors were surgically treated at our two institutions. There were nine men and nine women. The patient ages ranged from 33 to 75 years, with a median age of 56.1 years. The locations were spinal in six cases (33.3%), the posterior fossa in six cases (33.3%), supratentorial in four cases (22.2%), and orbital in two cases (11.2%). RESULTSThe median follow-up period was 45.3 months. Gross total resection was achieved in 10 cases (55.6%); tumor recurrence or progression occurred in nine cases (50%). Incomplete surgical resection was significantly associated with recurrence (P = 0.018). On univariate analysis, extent of surgery was also associated with a longer progression-free survival (P = 0.05). No statistically significant correlation can be found between histological features and recurrence. CONCLUSIONPrognosis of solitary fibrous tumors of the central nervous system remains unclear; consequently, careful and close monitoring of patients and long-term follow-up are mandatory. Radical surgical excision seems to be a significant and reliable prognosis factor, although pathological prognostic features must be defined. In other respects, the role of postoperative radiotherapy in atypical or incompletely resected solitary fibrous tumors of the central nervous system remains to be determined and, therefore, warrants larger series with longer follow-up periods.

Solitary Fibrous Tumors and Hemangiopericytomas of the Meninges: Overlapping Pathological Features and Common Prognostic Factors Suggest the Same Spectrum of Tumors

Meningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) are distinct entities in the World Health Organization (WHO) classification of central nervous system (CNS) tumors while they belong to the same spectrum of tumors in other locations. Well‐defined histological prognostic factors are also lacking for these tumors. In order to clarify the relationship between SFT and HPC and to find histological and immunohistochemical prognostic factors, we carried out a retrospective study in 89 patients. The following histological parameters were recorded: hypercellularity, collagenic areas, cytonuclear atypias, necrosis, mitotic count per 10 high‐power fields, vasculo‐nervous adherences defined by engulfment of vessel or nerve by the tumor, brain infiltration. We found overlapping histological and immunohistochemical features between SFT and HPC. The most relevant histological prognostic factors in the whole cohort for both progression‐free survival (PFS) and overall survival (OS) in univariate analysis were hypercellularity, high mitotic count (>5 per 10 high‐power fields) and necrosis. On the basis of these results, we propose a new grading scheme for these tumors which was of pronostic value for both PFS and OS in uni‐ and multivariate analysis. As extent of surgery was also a prognostic factor for both PFS and OS in univariate analysis, we propose that management of SFT/HPC might be based both on quality of removal and histological grade.

Adult intracranial WHO grade II ependymomas: long-term outcome and prognostic factor analysis in a series of 114 patients

Ependymomas account for 2% of all intracranial tumors in adults. Considerable controversy continues to exist with regard to their prognostic factors and therapeutic management due to the rarity and the heterogeneity of series reported so far. The authors report a retrospective study of a homogenous population of 114 adult patients harboring WHO grade II intracranial ependymomas from 32 French Neurosurgical Centers between 1990 and 2004. All clinico-radiological and follow-up data were analyzed, and a central pathologic review was performed by two confirmed neuropathologists. The 5- and 10-year overall survival (OS) rates were 86.1% and 81.0%, respectively; the 5- and 10-year progression-free survival (PFS) rates were 74.6% and 58.9%, respectively. On multivariate analysis, the OS rates were associated with preoperative KPS score (P = .027), extent of surgery (P = .008), and tumor location (supratentorial vs infratentorial, P = .012). The multivariate analysis also revealed that the risk of recurrence was associated with incomplete resection (P = .001) and supratentotrial location (P = .038). Moreover, adjuvant radiotherapy (RT) for patients with incompletely resected tumors is responsible for a significant improvement of both overall (P = .005) and progression-free (P = .002) survival. This study clearly supports the major prognostic impact of the extent of surgery in WHO grade II. Interestingly, tumor location also seems to have an actual impact on both OS and PFS. Finally, the prognostic impact of RT was found to be beneficial for incompletely resected tumors.

High and Low Grade Oligodendrogliomas (ODG): Correlation of Amino-Acid and Glucose Uptakes Using PET and Histological Classifications

Classification and treatment strategy of Oligodendrogliomas (ODG) remain controversial. Imaging relies essentially on contrast enhancement using CT or MRI. The aim of our study was to use positron emission tomography (PET) using [18F]-flurodeoxyglucose (FDG) and [11C]-L-methyl-methionine (MET) to evaluate metabolic characteristics of (ODG). We studied 19 patients with proven ODG, comparing standardised uptake values (SUV) and maximal tumor/contralateral normal tissues ratios (T/N). Imaging findings were compared with WHO, Smith and Daumas—Duport classifications. Uptake of FDG was decreased only in 8 patients, independently of grading, while MET uptake was always increased. MET uptake was significantly higher for high grade tumors grouped according to Smith or Daumas—Duport classifications, while no significant difference in MET uptake was found when using WHO classification. A different correlation was found between FDG and MET uptakes in normal tissues and high grade tumors. A trend for improved progression free survival was found for tumors that lacked contrast enhancement on MRI or those showing low FDG or MET uptake.In conclusion, MET appeared more sensitive than FDG to detect proliferation in ODG. The preferential protein metabolism, already noticeable for low-grade tumor, correlated with glucose metabolism and helped to separate, in vivo, high and low grade tumors.