A CASE OF EXCEPTIONALLY LONG PROGRESSION-FREE SURVIVAL (MORE THAN 10 YEARS) IN THE PATIENT WITH PRIMARY GLIOBLASTOMA AFTER RADIATION AND CHEMOTHERAPY WITH MUTATION IDH1(R132H) WITHOUT SURGICAL RESECTION

BACKGROUND: Overall survival (OS) of untreated patients with glioblastoma (GB) typically does not exceed 2–4 months. Radiation without surgery prolongs OS up to 5 months and chemotherapy enables further prolongation up to 5–26 months (depending on MGMT status). In particular cases both modalities exert very long-lasting responses leading to survival times of the patients far beyond average values. These cases are thought to be at least in part characterized by very high sensitivity of the tumor to cytostatics which is due to certain individual molecular features of malignant cells.

METHOD AND CASE REPORT: 39 years old male patient was diagnosed with glioblastoma with mutation IDH1(R132H) on the basis of stereotaxic core biopsy specimen histologic (microscopic appearance, endothelium proliferation, necrosis) and IHC (GFAP+, Ki-67 18–20%) features. Mutations in IDH1 (exon 4) and IDH2 (exon 4) were tested by High Resolution Melting Analysis (HRMA) with subsequent sequencing. MGMT mRNA expression was assessed by RT-PCR in formalin fixed paraffin embedded tumor tissue. The expression level of the gene in this case appeared to be one of the lowest among series of more than 250 brain tumors which were evaluated in our laboratory (∆Ct=7,7).

RESULTS: The patient undergone 70Gy radiation (proton therapy) and 15 cycles of temozolomide monotherapy with a complete response to therapy. Until now the patient is still alive and response is ongoing. Progression-free survival is 9 years 2 months up to date and OS — 10 years 2 months.

CONCLUSIONS: We propose that in this case remarkably low expression of MGMT (which is when highly expressed considered to be the powerful tool for tumor cell recovery after temozolomide treatment) caused unprecedented suxcess of radiochemotherapy without surgery with 10+ years ОS.

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