Tag: MGMT

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Molecular stereotactic biopsy technique improves diagnostic accuracy and enables personalized treatment strategies in glioma patients

Molecular stereotactic biopsy technique

Acta Neurochir (2014) 156:1427–1440

In gliomas molecular biomarkers are increasingly gaining diagnostic, prognostic and predictive significance. Determination of biomarker status after biopsy is important as not all patients are eligible for open tumor resection.We developed and validated prospectively (6/10–12/11) a protocol allowing for both reliable determination of multiple biomarkers and representative histological diagnoses from small-sized biopsies.

Methods All molecular stereotactic biopsies were performed according to a detailed workflow. The selection of specimens best suited for molecular analyses was intra-operatively guided by the attending neuropathologist. Postoperative screening was done by methylation specific PCR using two distinct cryopreserved specimens to test for reproducibility of the findings and to rule out contamination. The DNA of a single best-suited specimen (1 mm3) was subjected to detailed molecular analysis (MGMT promoter methylation, IDH1/2 mutational status, LOH 1p and/or 19q).

Results 159 consecutively enrolled untreated gliomas were analyzed (94 glioblastomas, 2 gliosarcomas, 24 anaplastic astrocytomas, 10 oligo-tumors grade II/III, 20 grade II astrocytomas and 9 pilocytic astrocytomas). Transient morbidity was 2 %. Overall, the drop-out rate due to tissue contamination was 0.4 %. Median time from biopsy to histological and molecular genetic analyses was 3 and 5 days, respectively. Distributions of the respective biomarker status for tumor subgroups were consistent with the literature. The final histological diagnosis was changed/modified in 5/159 patients according to molecular findings. Treatment after molecular biopsy was highly personalized.

Conclusions Molecular stereotactic biopsy is feasible and safe, can be implemented in daily clinical practice, improves diagnostic precision and enables personalized treatment. Keywords

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Long-term survivors of glioblastoma: clinical features and molecular analysis

Acta Neurochir (2009) 151:1349–1358. DOI 10.1007/s00701-009-0387-1

Glioblastoma is a highly lethal neoplasm with a median survival of 12–14 months; only 2–5% of patients survive >3 years.

Methods At our institute, patients with glioblastoma are initially treated with maximum tumor resection followed by radiation and the intravenous injection of nimustine hydrochloride (ACNU).

Results Using this strategy, 18 of 123 (14.6%) patients treated at our hospital survived >3 years; 7 manifested no recurrence, and the other 11 had early recurrence and received additional therapies. To identify factors associated with prolonged survival, we compared these patients with 21 short-term (<1.5 years) glioblastoma survivors. In the long-term survivors, the MGMT promoter methylation was significantly more frequent. The rate of p53 mutation was lower, and the rate of PTEN mutations and the proliferation index were slightly higher in short-term survivors.

Conclusion By multivariate analysis,  we found that a younger age and MGMT promoter methylation were significant favorable factors in patients with glioblastoma.

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Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status

J Neurooncol. DOI 10.1007/s11060-009-0032-0

This retrospective series explores temozolomide monotherapy in elderly patients with primary CNS lymphoma (PCNSL) and severe comorbidities. In 17 patients (62–90 years old), the complete response rate was 47%, median progression-free survival was 5 months, and median overall survival was 21 months. Five of 17 patients (29.4%) had prolonged responses for at least 12 months and survived for more than 24 months. Three of these patients had a methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, while the MGMT status was not assessable in the remaining two patients.

Temozolomide monotherapy appears to be effective in a subgroup of elderly PCNSL patients and deserves further evaluation.

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