Stellenwert der Verlaufsbeobachtung, operativen Tumorresektion und Monochemotherapie bei Oligodendrogliomen WHO Grad II

Weller, Jonathan (2022): Stellenwert der Verlaufsbeobachtung, operativen Tumorresektion und Monochemotherapie bei Oligodendrogliomen WHO Grad II. Dissertation, LMU München: Medizinische Fakultät

Abstract

INTRODUCTION Gliomas of histological WHO grades 2 and 3 show a heterogenous prognosis that largely depends on molecular tumor characteristics. Presence of 1p/19q codeletions distinguishes oligodendroglioma from astrocytoma among IDHmut gliomas. Both entities are associated with favourable outcome when compared to IDHwt WHO grade 2 and 3 astrocytomas with molecular features of glioblastomas, e.g., pTERTmut (which are now referred as glioblastoma). We here investigated different therapies in WHO grade 2 oligodendrogliomas (Publication I) and assessed clinical and epigenetic similarities between IDHwt pTERTmut WHO grade 2 and 3 astrocytomas and glioblastoma (Publication II). METHODS In this single-centre, retrospective study, 420 patients were included, including 142 patients with oligodendroglioma, 54 patients with IDHwt astrocytoma WHO grade 2 or 3 with pTERTmut and 224 patients with histopathological glioblastoma. In Publication I, different therapeutic approaches in the treatment of oligodendroglioma WHO grade 2 were investigated, including surveillance strategies after biopsy (wait-and-scan; n=59) or tumor resection (n=27), temozolomide chemotherapy after biopsy (n=26) or the combination therapy of procarbazine, CCNU/lomustine and vincristine (PCV; n=30) after biopsy. In Publication II, extent and pattern of MGMT promoter methylation in IDHwt pTERTmut astrocytomas WHO grade 2 and 3 and in histological glioblastoma were investigated through PCR and Sanger sequencing. RESULTS The retrospective outcome analysis of WHO grade 2 oligodendrogliomas showed superior progression-free survival in patients receiving PCV therapy after biopsy when compared to wait-and-scan or resection only or temozolomide. (in years, 9.1 (PCV) vs 5.1 (wait-and-scan) vs 4.4 (resection) vs 3.6 (temozolomide); p=0.05). Longer progression-free survival in patients treated with PCV when compared to temozolomide was also seen in a matched-pair analysis (p=0.03) and in patients that were treated with PCV or temozolomide at first progression (p=0.04). Histological progression occurred at significantly lower rate in the PCV cohort when compared to all other cohorts (p=0.01). Epigenetic analyses of the MGMT promoter showed similar pattern and extent of methylation in IDHwt pTERTmut astrocytomas and glioblastomas. Overall survival and progression-free survival were similar in both groups irrespective of lower initial histological grade. CONCLUSION PCV chemotherapy prolongs progression-free survival and potentially delays malignant transformation in oligodendroglioma WHO grade 2. Extent and pattern of MGMT promoter methylation in IDHwt pTERTmut astrocytomas and glioblastomas are similar.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Deutsch
• Datum der mündlichen Prüfung: 6. Oktober 2022
• 1. Bericht­erstatter:in: Tonn, Jörg-Christian