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Marc Sanson

Publications and source records attributed to Marc Sanson.

At least 19 recordsLinked to original sources
PubMed2007

MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities.

MGMT promoter methylation, which has been correlated with the response to alkylating agents, was investigated in a retrospective series of 219 glioblastomas (GBMs) treated with various modalities. MGMT methylation had no impact on survival for the whole group, but showed a significant advantage (17.1 months vs. 13.1) for patients treated with RT+ adjuvant chemotherapy (relative risk of death (RR) = 0.53; P = 0.041), particularly when patients received CT during the course of RT (MS = 19.9 months vs. 12.5 months; RR = 0.227, P = 0.001). This suggests that the prognostic impact of MGMT methylation is dependent on therapeutic modalities and schedules. MGMT methylation was not correlated with the main molecular alterations, such as 10q loss and p53 expression.

Adult↗
PubMed2007

The 61 A/G EGF polymorphism is functional but is neither a prognostic marker nor a risk factor for glioblastoma.

The A/G61 polymorphism located in the 5'UTR of the EGF gene has been found to be both a risk factor and a prognostic factor in glioblastoma (GBM), but the functional consequences have not been investigated. Here we show, in vitro, that this polymorphism is functional, in that the G allele promoter is 40% more active than the A variant (P < 0.001). However, analysis of a large series of 209 GBM patients and 214 control subjects did not confirm that A/G61 polymorphism is a significant risk factor for GBM, despite a trend for higher GG frequency in these patients. Furthermore, A/G61 polymorphism was not a prognostic factor for survival in GBM patients, although it does appear to affect progression-free survival.

5' Untranslated Regions↗
PubMed2006

Progressive multifocal leukoencephalopathy mimicking cerebral vasculitis in systemic granulomatosis.

We describe the case of a 69-year-old man with systemic granulomatosis who presented with left-sided hemiplegia. Initial diagnosis concerning the neurological troubles was cerebral vasculitis. Corticosteroids associated with antituberculosis therapy showed a rapid but transient amelioration followed by neurological aggravation. Two weeks later, JC virus was detected in cerebrospinal fluid by PCR and the diagnosis of progressive multifocal leukoencephalopathy (PML) was made. Treatment with cytarabine and cidofovir was initiated but the patient died three months after the first neurological signs. In the presence of central neurological symptoms occurring during systemic granulomatosis before specific therapy, PML should be evoked.

Adrenal Cortex Hormones↗
PubMed2006

Prognostic stratification of patients with anaplastic gliomas according to genetic profile.

BACKGROUND: There is a need to improve the current, controversial, and poorly reproducible classification of anaplastic gliomas, which represent a highly heterogeneous entity in terms of survival. METHODS: The impact of the most common genetic alterations on survival was investigated based on 156 anaplastic gliomas: Among the patients who were included, the gender ratio was 1.32, the median age was 45.5 years (range, 20-83 years), and the median Karnofsky performance status was 70 (range, 40-100). Genetic analysis included a search for loss of heterozygosity (LOH) on chromosomes 1p and 19q; amplification of chromosomes 9p and 10q and of the epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4) and mouse double-minute (MDM2) genes; and p53 expression. RESULTS: The median survival was 33.5 months, and the median progression-free survival was 15.8 months. In a univariate analysis, LOH on 1p and 19q was correlated with longer survival, whereas p53 expression, LOH on 9p, LOH on 10q, amplified EGFR, and deleted CDKN2A were correlated with shorter survival. LOH on 1p and 19q were associated with oligodendrogliomas, LOH on 10q was related to EGFR amplification, and LOH on 1p and 19q was mutually exclusive with EGFR amplification and LOH on 10q. In a multivariate analysis, the significant prognostic factors were age, histology, LOH on 1p and 19q, and P16/CDKN2A deletion. Recursive partitioning analysis (RPA) divided the whole group hierarchically into 3 distinct prognostic subgroups: Group A with 1p19q codeletion (median survival, 98 months), Group B with EGFR amplification (median survival, 17 months), and Group CC (median survival, 31 months), providing a basis for a genetically based prognostic subclassification for patients with Grade III gliomas. CONCLUSIONS: The search for 1p19q codeletion and EGFR receptor amplification provides a simple, clinically relevant prognostic subclassification of grade III gliomas.

Adult↗
PubMed2006

Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial.

PURPOSE: Anaplastic oligodendrogliomas are more responsive to chemotherapy than high-grade astrocytomas. We investigated, in a multicenter randomized controlled trial, whether adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy improves overall survival (OS) in newly diagnosed patients with anaplastic oligodendrogliomas or anaplastic oligoastrocytomas. PATIENTS AND METHODS: The primary end point of the study was OS; secondary end points were progression-free survival (PFS) and toxicity. Patients were randomly assigned to either 59.4 Gy of radiotherapy (RT) in 33 fractions only or to the same RT followed by six cycles of standard PCV chemotherapy (RT/PCV). 1p and 19q deletions were assessed with fluorescent in situ hybridization. RESULTS: A total of 368 patients were included. The median follow-up time was 60 months, and 59% of patients have died. In the RT arm, 82% of patients with tumor progression received chemotherapy. In 38% of patients in the RT/PCV arm, adjuvant PCV was discontinued for toxicity. OS time after RT/PCV was 40.3 months compared with 30.6 months after RT only (P = .23). RT/PCV increased PFS time compared with RT only (23 v 13.2 months, respectively; P = .0018). Twenty-five percent of patients were diagnosed with combined 1p/19q loss; 74% of this subgroup was still alive after 60 months. RT/PCV did not improve survival in the subgroup of patients with 1p/19q loss. CONCLUSION: Adjuvant PCV chemotherapy does not prolong OS but does increase PFS in anaplastic oligodendroglioma. Combined loss of 1p/19q identifies a favorable subgroup of oligodendroglial tumors. No genetic subgroup could be identified that benefited with respect to OS from adjuvant PCV.

Adult↗
PubMed2006

Prognostic impact of molecular markers in a series of 220 primary glioblastomas.

BACKGROUND: In contrast to oligodendrogliomas, molecular predictors of prognosis have not been consistently found in glioblastomas. However, genetic studies show that glioblastomas consist of several genetic subtypes and raise the possibility that molecular alterations could be predictive of survival. METHODS: A search for loss of heterozygosity (LOH) on chromosome 1p, 9p, 10q, 19q, EGFR (epidermal growth factor receptor), CDK4, and MDM2 (mouse double minute) amplifications, CDKN2A (INK4A/ARF) homozygous deletions, p53 expression, was performed in a series of 220 primary glioblastomas. The molecular alterations were then correlated with each other to identify distinct molecular pathways and with clinical parameters and the course of the disease to identify prognostic markers. RESULTS: Nonrandom associations were found between EGFR amplification and LOH10q, LOH9p, and INK4A/ARF deletion, LOH1p and LOH19q, and MDM2 and CDK4 amplification, whereas mutual exclusions were found between p53 expression and EGFR amplification, LOH 9p/INK4A/ARF homozygous deletion, and MDM2 and CDK4 amplification. Age (P = 4.10(-5)) and performance status (P = .003) were the main predictors of outcome. In contrast, molecular markers were of limited impact: MDM2 amplification correlated with poor outcome on both univariate and multivariate analysis (P = .01) and EGFR amplification with good prognosis on multivariate analysis (P = .02). CONCLUSION: Despite their limited prognostic impact, the genetic markers investigated here outline distinct molecular pathways involved in glioblastoma tumorigenesis and warrant broader molecular screening.

Adolescent↗
PubMed2006

MGMT methylation: a marker of response to temozolomide in low-grade gliomas.

The methylation status of the O6-methylguanine-methyltransferase promoter (MGMTP) was evaluated in 68 low-grade gliomas treated by neoadjuvant temozolomide. Methylated MGMTP was detected in 63 of 68 (92.6 %) patients and was a favorable predictor of progression-free survival as compared with unmethylated MGMTP tumors (p < 0.0001). Assessment of MGMTP status could help identifying low-grade gliomas patients more likely to respond to chemotherapy or to benefit from MGMT depletion strategies.

Adult↗
PubMed2006

Gliomatosis cerebri: a review of 296 cases from the ANOCEF database and the literature.

Gliomatosis cerebri (GC) is a rare disease, defined as a diffuse neoplastic glial cell infiltration of the brain. Diagnosis and management of GC are difficult. This study analyzed 296 individual cases (90 patients followed through the ANOCEF network, and 206 cases from the literature), aged 1 month to 85 years (median 42), sex ratio=1.31. Median survival was 14.5 months. It was higher for patients younger than 42 years (17 months vs. 13 months), with performance status>or=80 (27 months vs. 9 months), low grade gliomatosis (grade 2=20 months, grade 3=11.5 months, grade 4=8.5 months), oligodendroglial subtype (36 months compared to 14 months for mixed GC and 11 months for astrocytic GC). Male population was younger (median 39 years vs. 45), had a higher incidence of oligodendroglial GC (22% vs. 13%), which may explain their better prognosis (median survival 17 months vs. 11.5 months) than female population. Despite a high rate of stabilization, the impact on survival of whole brain radiotherapy, which carries the risk of severe toxicity, is still unclear. Up-front chemotherapy benefit to some patients and may be preferred to whole brain radiotherapy. However, the many bias of such retrospective heterogeneous data claim for multicentric clinical trials in this rare disease.

Adolescent↗
PubMed2006

Loss of 22q chromosome is related to glioma progression and loss of 10q.

Loss of heterozygosity (LOH) of chromosome 22q has been investigated in 160 gliomas. LOH at one or more microsatellite increased with increasing grade of the tumor (P < 0.01). LOH22q was more frequent in astrocytic tumors (37%) compared to mixed or oligodendroglial tumors (21%) (P = 0.02). LOH22q was correlated to 10q loss but not to 1p or 9p loss. Taken together, these data suggest that LOH22q is an alteration associated with malignant progression of gliomas.

Brain Neoplasms↗
PubMed2006

Molecular changes in brain tumors: prognostic and therapeutic impact.

PURPOSE OF REVIEW: This review focuses on recent advances in the molecular biology of the main primary brain tumors (gliomas, medulloblastomas, and ependymomas), with particular emphasis on prognostic markers and potential therapeutic targets. RECENT FINDINGS: Current biologic markers are useful for predicting prognosis (e.g. 1p/19q codeletion in grade 2 and 3 gliomas, nuclear beta-catenin expression in medulloblastoma) or response to the treatment (e.g. the methyl guanyl methyl transferase promoter methylation status). Recent gene profiling studies have identified specific molecular signatures that permit a molecular classification and that also provide new, potentially useful prognostic markers. The studies have also shown a striking parallel between central nervous system ontogenesis and the oncogenesis of brain tumors. By elucidating the underlying activated molecular pathways, these approaches provide the basis for a biologic therapy to target the critically activated pathways. SUMMARY: Important advances have been made in the biologic understanding, molecular subclassification, and identification of prognostic markers in brain tumors, thereby improving the current classifications. Such data provide a rational basis for current and future targeted biologically based strategies.

Antineoplastic Agents↗
PubMed2006

Genetic alterations associated with acquired temozolomide resistance in SNB-19, a human glioma cell line.

Gliomas are highly lethal neoplasms that cannot be cured by currently available therapies. Temozolomide is a recently introduced alkylating agent that has yielded a significant benefit in the treatment of high-grade gliomas. However, either de novo or acquired chemoresistance occurs frequently and has been attributed to increased levels of O6-methylguanine-DNA methyltransferase or to the loss of mismatch repair capacity. However, very few gliomas overexpress O6-methylguanine-DNA methyltransferase or are mismatch repair-deficient, suggesting that other mechanisms may be involved in the resistance to temozolomide. The purpose of the present study was to generate temozolomide-resistant variants from a human glioma cell line (SNB-19) and to use large-scale genomic and transcriptional analyses to study the molecular basis of acquired temozolomide resistance. Two independently obtained temozolomide-resistant variants exhibited no cross-resistance to other alkylating agents [1,3-bis(2-chloroethyl)-1-nitrosourea and carboplatin] and shared genetic alterations, such as loss of a 2p region and loss of amplification of chromosome 4 and 16q regions. The karyotypic alterations were compatible with clonal selection of preexistent resistant cells in the parental SNB-19 cell line. Microarray analysis showed that 78 out of 17,000 genes were differentially expressed between parental cells and both temozolomide-resistant variants. None are implicated in known resistance mechanisms, such as DNA repair, whereas interestingly, several genes involved in differentiation were down-regulated. The data suggest that the acquisition of resistance to temozolomide in this model resulted from the selection of less differentiated preexistent resistant cells in the parental tumor.

Antineoplastic Agents, Alkylating↗
PubMed2006

Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma.

Oligodeoxynucleotides containing CpG motifs (CpG ODNs) display a strong immunostimulating activity and drive the immune response toward the Th1 (T helper type 1) phenotype. These ODNs have shown promising efficacy in preclinical studies when injected locally in several cancer models. We conducted a phase 1 trial to define the safety profile of CpG-28, a phosphorothioate CpG ODN, administered intratumorally by convection-enhanced delivery in patients with recurrent glioblastoma. Cohorts of three to six patients were treated with escalating doses of CpG-28 (0.5-20 mg), and patients were observed for at least four months. Twenty-four patients entered the trial. All patients had previously been treated with radiotherapy, and most patients had received one or several types of chemotherapy. Median age was 58 years (range, 25-73) and median KPS was 80% (range, 60%-100%). Adverse effects possibly or probably related to the studied drug were moderate and consisted mainly in worsening of neurological conditions (four patients), fever above 38 degrees C that disappeared within a few days (five patients), and reversible grade 3 lymphopenia (seven patients). Only one patient experienced a dose-limiting toxicity. Preliminary evidence of activity was suggested by a minor response observed in two patients and an overall median survival of 7.2 months. In conclusion, CpG-28 was well tolerated at doses up to 20 mg per injection in patients with recurrent glioblastoma. Main side effects were limited to transient worsening of neurological condition and fever.

Adjuvants, Immunologic↗
PubMed2005

Chromosome 1p loss: a favorable prognostic factor in low-grade gliomas.

Search for loss of heterozygosity on chromosomes 1p, 9p, 10q, and 19q, epidermal growth factor receptor (EGFR) gene amplification, and p53 expression was performed in a series of 131 low-grade gliomas. The profile of molecular changes, clinical findings, and histology were subsequently correlated with the course of the disease, mainly progression-free survival. When these parameters were considered as candidate variables in a multivariate analysis, only loss of heterozygosity on chromosome 1p was associated with increased progression-free survival (hazard ratio, 0.521), indicating a major favorable prognostic role of this genetic alteration in low-grade gliomas.

Adolescent↗
PubMed2005

Two types of chromosome 1p losses with opposite significance in gliomas.

Deletion of the short arm of chromosome 1 (1p) is considered a favorable prognostic factor in glial tumors. High-density array-comparative genomic hybridization analysis of 108 gliomas shows two distinct types of 1p deletions. Complete hemizygous losses of 1p, which are tightly associated with 19q loss and oligodendroglial phenotype, and partial 1p deletions mainly observed in astrocytic tumors and not associated with 19q loss. Whereas the first type predicts longer overall and progression-free survival (p < 0.0001), the second type has a pejorative prognostic value. Complete 1p-arm evaluation therefore is required to appreciate the real clinical significance of 1p loss in gliomas.

Adult↗
PubMed2005

Leptomeningeal metastases from solid malignancy: a review.

Leptomeningeal metastases (LMM) consist of diffuse involvement of the leptomeninges by infiltrating cancer cells. In solid tumors, the most frequent primary sites are lung and breast cancers, two tumors where the incidence of LMM is apparently increasing. Careful neurological examination is required to demonstrate multifocal involvement of the central nervous system (CNS), cranial nerves, and spinal roots, which constitute the clinical hallmark of the disease. Cerebro-spinal fluid (CSF) analysis is almost always abnormal but only a positive cytology or demonstration of intrathecal synthesis of tumor markers is diagnostic. T1-weighted gadolinium-enhanced sequence of the entire neuraxis (brain and spine) plays an important role in supporting the diagnosis, demonstrating the involved sites and guiding treatment. Radionuclide CSF flow studies detect CSF compartmentalization and are useful for treatment planning. Standard therapy relies mainly on focal irradiation and intrathecal or systemic chemotherapy. Studies using other therapeutic approaches such as new biological or cytotoxic compounds are ongoing. The overall prognosis remains grim and quality of life should remain the priority when deciding which treatment option to apply. However, a sub-group of patients, tentatively defined here, may benefit from an aggressive treatment.

Breast Neoplasms↗
PubMed2005

[Towards a molecular classification of gliomas].

Several molecular genetic alterations have been characterized in gliomas in the past years. Molecular profiles have been associated with specific histologic and prognostic tumor subgroups, contributing to improve the classification of gliomas. At least two alternative molecular pathways have been suggested in the astrocytoma progression involving TP53 inactivation (secondary glioblastomas) and EGFR amplification (de novo glioblastomas) respectively. Oligodendroglial tumors have demonstrated recurrent combined loss of chromosome 1p/19q, which represent a favorable prognosis marker and probably a predictor of a good chemosensitivity of the tumor. This review discusses recent molecular advances and clinical implications with special focus on oligodendroglial tumors.

Astrocytoma↗
PubMed2004

[The genetics of glioma: molecular classification].

Gliomas result from specific genetic alterations--such as activation of specific oncogenes and/or inactivation of specific tumor suppressor genes. These alterations affect specific pathways involved in either signal transduction or cell cycle control, leading to phenotypic changes such as uncontrolled proliferation, inhibition of apoptosis, genetic instability, invasive properties. Tumoral progression includes multiple molecular pathways of clinical relevance: early alterations (p53 mutations for astrocytomas, 1p and 19q loss for oligodendrogliomas) and late alterations (EGF-R amplification, PTEN and P16/CDKN2A inactivation). Genetic profile is not only of diagnostic--but also prognostic relevance, as shown by 1p associated to 19q loss in oligodendrogliomas which is predictive of better prognosis and higher response rate.

Brain Neoplasms↗