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ABSTRACT: L’intérêt pour les lymphomes primitifs du système nerveux central (LPSNC) est lié à l’augmentation importante de son incidence
observée aussi bien chez l’immunocompétent que chez l’immunodéprimé et aux progrès réalisés ces dernières années dans le pronostic
de ces tumeurs. Le traitement de référence repose sur l’adjonction d’une chimiothérapie (CT) à base de méthotrexate (MTX)
intraveineux à forte dose à la radiothérapie (RT) encéphalique, autorisant une médiane de survie de trois à quatre ans et
un taux de longs survivants de 30 %. Chez les patients âgés (> 60 ans) qui constituent la moitié des patients, la RT de consolidation
n’est plus recommandée en cas d’obtention d’une rémission complète avec la CT seule en raison d’un haut risque de leucoencéphalopathie.
L’intensification de la CT avec greffe de cellule souche périphérique constitue une perspective thérapeutique très prometteuse
dans les récidives ou, éventuellement, en alternative à la RT dans le traitement initial.
Interest in primary CNS lymphoma (PCNSL) is growing because of its increasing incidence in both the immunocompetent and immunodeficient
populations. The addition of high-dose methotrexate (MTX) based chemotherapy (CT) before whole brain radiotherapy (WBRT) has
significantly improved the prognosis for PCNSL with a median survival rate of 3–4 years and about 30% of the patients having
the possibility of lengthy survival and cure. In the elderly (age > 60 years) CT alone (without RT) as initial treatment is
recommended. This approach seems a good way of avoiding RT and thereby reducing the risk of delayed neurotoxicity. Intensive
CT followed by hematopoietic stem cell rescue (ICH) seems a promising approach for recurrent tumours and a potential alternative
option to RT as consolidation treatment in newly diagnosed patients.
Oncologie 04/2012; 11(2):78-82. · 0.17 Impact Factor
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G Kaloshi,
A Benouaich-Amiel,
F Diakite,
S Taillibert,
J Lejeune,
F Laigle-Donadey,
M-A Renard,
W Iraqi,
A Idbaih,
S Paris, [......],
H Duffau,
P Cornu,
J M Simon,
K Mokhtari,
M Polivka,
A Omuro,
A Carpentier,
M Sanson,
J Y Delattre,
K Hoang-Xuan
Neurology 07/2011; 77(3):263. · 8.31 Impact Factor
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Clinical Oncology 04/2011; 23(7):495. · 2.07 Impact Factor
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C Houillier,
X Wang, G Kaloshi,
K Mokhtari,
R Guillevin,
J Laffaire,
S Paris,
B Boisselier,
A Idbaih,
F Laigle-Donadey,
K Hoang-Xuan,
M Sanson,
J-Y Delattre
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ABSTRACT: Recent studies have shown that IDH1 and IDH2 mutations occur frequently in gliomas, including low-grade gliomas. However, their impact on the prognosis and chemosensitivity of low-grade gliomas remains unclear.
Search for IDH1 and IDH2 mutations, loss of heterozygosity on chromosomes 1p and 19q, MGMT promoter methylation, and p53 expression was performed in a series of 271 low-grade gliomas and correlated with overall survival. A subgroup of 84 patients treated up-front with temozolomide was individualized. Response to temozolomide was evaluated by progression-free survival, as well as by tumor size on successive MRI scans, and then correlated with molecular alterations.
IDH (IDH1 or IDH2) mutations were found in 132/189 patients (70%). IDH mutation and 1p-19q codeletion were associated with prolonged overall survival in univariate (p = 0.002 and p = 0.0001) and multivariate analysis (p = 0.003 and p = 0.004). 1p-19q codeletion, MGMT promoter methylation, and IDH mutation (p = 0.01) were correlated with a higher rate of response to temozolomide. Further analysis of the course of the disease prior to any treatment except for surgery (untreated subgroup) showed that 1p-19q codeletion was associated with prolonged progression-free survival in univariate analysis, whereas IDH mutation was not.
IDH mutation appears to be a significant marker of positive prognosis and chemosensitivity in low-grade gliomas, independently of 1p-19q codeletion, whereas its impact on the course of untreated tumors seems to be limited.
Neurology 10/2010; 75(17):1560-6. · 8.31 Impact Factor
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G Kaloshi,
D Psimaras,
K Mokhtari,
C Dehais,
C Houillier,
Y Marie,
F Laigle-Donadey,
S Taillibert,
R Guillevin,
N Martin-Duverneuil,
M Sanson,
K Hoang-Xuan,
J-Y Delattre
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ABSTRACT: Low-grade gliomas (LGG) are thought to be very rare in elderly patients (>60 years) and have not been thoroughly studied.
A series of 62 elderly (>or=60 years of age) LGG patients were identified in a department database collecting information on pathologically identified adult supratentorial LGG. The clinical, radiologic, pathologic, and therapeutic data of these patients were analyzed and compared to those of 704 younger LGG patients (<60 years).
Comparisons between older and younger groups showed that elderly patients more often presented with a clinical deficit (p < 0.0001), a lower Karnofsky performance status (p = 0.0002), a larger tumor on MRI (p = 0.03), and a lower rate of tumor resection (p < 0.0001). Chemotherapy was more often used as first line treatment (p = 0.001). Among the patients who died of progressive disease, 55% of the elderly patients had not received radiotherapy compared to 11% in the younger group (p < 0.0001). Survival was shorter in older patients (p < 0.0001), with a 5-year survival rate of 40%. An astrocytic phenotype (p = 0.0097), increasing age (p = 0.0049), and a tumor crossing the midline (p = 0.028) were negative prognostic factors in the older group.
We found that 8% of low-grade gliomas (LGG) occur in older patients (>or=60 years of age). The clinical-radiologic picture of LGG in the elderly population differs from younger patients. Although long-term survival occurs, the course is generally more severe because elderly patients accumulate negative prognostic factors and because they are probably undertreated.
Neurology 11/2009; 73(24):2093-8. · 8.31 Impact Factor
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ABSTRACT: In gliomatosis cerebri (GC), defined as a diffuse neoplastic glial cell infiltration of the brain, upfront chemotherapy is often proposed as an alternative to radiotherapy. GC invades both white matter and gray matter in varying proportions, as reflected by the gray matter index (GMI), i.e., the estimated percentage of gray matter involvement.
The GMI was estimated in 71 patients with GC (42 men and 29 women; median age, 47 years) treated with upfront chemotherapy (7 PCV, 64 temozolomide).
Median GMI was 30%. Patients were separated into 2 groups according to this median GMI. Compared to the 33 patients with GMI >30% (group B), the 38 patients from group A (defined as GMI <or=30%) had better performance status (p = 0.03), higher response rate to chemotherapy (30/38 vs only 5/33; p < 0.0001), longer progression-free survival (21.2 vs 11.7 months, p = 0.005), and longer overall survival (56.1 vs 26.4 months; p = 0.003). There was no significant correlation with histologic subtype (oligodendroglial vs astrocytic or mixed GC), grading, tumor localization (particularly basal nuclei involvement), or laterality. The deletion of chromosomes 1p and 19q tended to be more frequent in group A (8/17 [47%] vs 1/9 [11%] in group B [p = 0.057]).
These data suggest that gray matter index is a prognostic and predictive marker in gliomatosis cerebri that may in part depend on the 1p/19q status.
Neurology 09/2009; 73(6):445-9. · 8.31 Impact Factor
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G Kaloshi,
S Everhard,
F Laigle-Donadey,
Y Marie,
S Navarro,
K Mokhtari,
A Idbaih,
F Ducray,
J Thillet,
K Hoang-Xuan,
J-Y Delattre,
M Sanson
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ABSTRACT: Up-front temozolomide (TMZ) has been recently proposed as a treatment for gliomatosis cerebri (GC), but no predictive or prognostic markers have been identified so far. Because 1p19q codeletion and methylguanine methyl transferase promoter (MGMTP) methylation have been correlated with chemosensitivity of gliomas, their value was investigated in a cohort of patients with GC treated with TMZ.
A cohort of 25 GC patients who were treated with TMZ was investigated for 1p19q codeletion and O6-methylguanine DNA.
Patients with a 1p/19q codeletion had a higher response rate (88% [8/9] vs 25% [4/16], p = 0.002), higher progression-free survival (24.5 vs 13.7 months, p = 0.017), and higher overall survival (66.8 vs 15.2 months, p = 0.011) than patients without 1p/19q codeletion. Fourteen of 19 evaluable tumors for MGMTP status were methylated. MGMTP methylation was associated with 1p/19q codeletion (p = 0.045). Patients with unmethylated MGMTP tended to have a shorter progression-free survival and a higher rate of progressive disease.
Response rate to temozolomide and prognosis seem tightly correlated to 1p19q loss. The impact of methylguanine methyl transferase promoter methylation status on gliomatosis cerebri is still unsettled in this population.
Neurology 03/2008; 70(8):590-5. · 8.31 Impact Factor
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G Kaloshi,
A Benouaich-Amiel,
F Diakite,
S Taillibert,
J Lejeune,
F Laigle-Donadey,
M-A Renard,
W Iraqi,
A Idbaih,
S Paris, [......],
H Duffau,
P Cornu,
J-M Simon,
K Mokhtari,
M Polivka,
A Omuro,
A Carpentier,
M Sanson,
J-Y Delattre,
K Hoang-Xuan
[show abstract]
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ABSTRACT: To evaluate the predictive impact of chromosome 1p/19q deletions on the response and outcome of progressive low-grade gliomas (LGG) treated with up-front temozolomide (TMZ) chemotherapy.
Adult patients with measurable, progressive LGG (WHO grade II) treated with TMZ delivered at the conventional schedule (200 mg/m(2)/day for 5 consecutive days, repeated every 28 days) were retrospectively evaluated for response by central review of MRI-s. Chromosome 1p and 19q deletions were detected by the loss of the heterozygosity technique (LOH).
A total of 149 consecutive patients were included in this retrospective, single center observational study. The median number of TMZ cycles delivered was 14 (range 2 to 30). Seventy-seven patients (53%) experienced an objective response (including 22 [15%] cases of partial response and 55 [38%] cases of minor response), 55 (37%) patients had stable disease, and 14 (10%) had a progressive disease. The median time to maximum tumor response was 12 months (range 3 to 30 months). The median progression-free survival (PFS) was 28 months (95% CI: 23.4 to 32.6). Material for genotyping was available for 86 patients. Combined 1p/19q LOH was present in 42% of the cases and was significantly associated with a higher rate (p = 0.02) and longer objective response to chemotherapy (p = 0.017), and both longer PFS (p = 4.10(-5)) and overall survival (p = 0.04).
Low-grade gliomas respond to temozolomide and loss of chromosome 1p/19q predicts both a durable chemosensitivity and a favorable outcome.
Neurology 06/2007; 68(21):1831-6. · 8.31 Impact Factor
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ABSTRACT: We investigated two polymorphisms of the epidermal growth factor receptor promoter as potential risk factors and prognostic markers for glioblastoma. The -216T allele (which results in a 30% higher activity) was more frequent in the patients compared with the control population (224/376 = 59.6% vs 165/352 = 46.8%; p = 0.0006) corresponding to an odd ratio of 1.67 (1.24; 2.25). A modest difference in median survival was also associated with the TT genotype.
Neurology 10/2006; 67(5):872-4. · 8.31 Impact Factor
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ABSTRACT: Although a rare entity, multiple gliomas must be recognized and distinguished from other causes of multiple brain lesions.
Clinical and radiological features of 33 multiple gliomas were reviewed, including 20 synchronous cases and 13 metachronous cases.
In 17 patients, radiological features were highly suggestive of spread from a primary site (multifocal gliomas). No apparent dissemination route was identified in the other cases which were presumed to be multicentric gliomas. For nine patients (27 percent), a second neoplasia or cancer was found in first degree relatives suggesting a genetic predisposition. Overall median survival was 79 weeks (64 weeks for glioblastomas). The age at onset was the main prognostic factor.
Multiple gliomas represent a heterogeneous entity, probably corresponding to different mechanisms. In our group, survival was comparable to unique glioma.
Revue Neurologique 10/2006; 162(8-9):845-51. · 0.49 Impact Factor
