Contemporary Long-term Survival Outcomes and Prognostic Factors in Adult grade 4 Astrocytoma: An Institutional Analysis.

in Clinical oncology (Royal College of Radiologists (Great Britain)) by K Narang, T Kataria, S S Bisht, D Gupta, S Banerjee, M Mayank, S Shishak, V Kaliyaperumal, S Tamilselvan, D Kamaraj, S Abraham

TLDR

  • The study shows that modern treatment methods for astrocytoma grade 4 or glioblastoma improve survival rates and reduce late toxicity compared to historical methods.
  • MGMT-methylation testing is an important factor in predicting treatment outcomes and patient selection.

Abstract

Astrocytoma grade 4 without isocitrate dehydrogenase (IDH)-based characterisation has been called glioblastoma (GBM) in historical cohorts. There have been significant advancements in diagnostic radiology and pathology, and in the technical aspects of surgery, radiation therapy, and temozolomide (TMZ) used for treatment of this disease. We analysed the outcomes of 267 adult astrocytoma grade 4/GBM patients, consecutively treated between December 2010 and November 2018 using modern techniques at our institute. All patients underwent surgical resection, histopathology review, and O6-methylguanine-DNA methyltransferase (MGMT) methylation testing, volumetric modulated arc therapy (VMAT)-based radiation therapy using institute-specific target-delineation guidelines and image guidance, and TMZ according to Stupp protocol. Serial multiparametric magnetic resonance imaging-based follow-up ensured early detection of disease progression. Appropriate salvage therapy was determined based on clinicopathological attributes. Kaplan-Meier survival plots, log-rank test, and Cox regression analysis were performed on the prospectively recorded dataset to estimate survival and the factors affecting it. At a median follow-up of 72 months, the median progression-free survival (PFS), 1-year PFS, and 2-year PFS were 10 months, 37.8%, and 17.5%, respectively. MGMT-methylation, a radiation dose ≥54 Gy, and ≥4 adjuvant TMZ cycles were associated with favourable PFS. Median overall survival (OS), 2-year OS and 5-year OS were 24 months, 48%, and 18%, respectively. MGMT-methylation and 1-year disease control were associated with favourable OS. Salvage treatment could be offered to 69.2% patients, with use of all the three treatment modalities in 12.4%. Salvage reirradiation could be used in 30.8% patients. Haematological toxicity ≥grade 2 was evident in 6% patients during concurrent radiation-TMZ phase and in 9% patients in adjuvant TMZ phase. Postradiation neurocognitive deficits were noted in 20.1% patients, with onset at a median duration of 10 months. Modern diagnostic and therapeutic techniques affected a near-doubling of survival and acceptable late toxicity, as compared to historical data.

Overview

  • The study analyzed the outcomes of 267 adult astrocytoma grade 4/GBM patients treated between 2010 and 2018 using modern techniques.
  • The patients underwent surgical resection, histopathology review, MGMT methylation testing, VMAT-based radiation therapy, and TMZ according to Stupp protocol.
  • The study aimed to investigate the factors affecting progression-free survival (PFS) and overall survival (OS) in adult astrocytoma grade 4/GBM patients.

Comparative Analysis & Findings

  • At a median follow-up of 72 months, the median PFS was 10 months, 1-year PFS was 37.8%, and 2-year PFS was 17.5%.
  • MGMT-methylation, radiation dose ≥54 Gy, and ≥4 adjuvant TMZ cycles were associated with favourable PFS.
  • The median OS was 24 months, 2-year OS was 48%, and 5-year OS was 18%, with MGMT-methylation and 1-year disease control being associated with favourable OS.

Implications and Future Directions

  • Modern diagnostic and therapeutic techniques affected a near-doubling of survival and acceptable late toxicity compared to historical data.
  • Future studies can explore the use of novel agents and combination therapies to improve PFS and OS in adult astrocytoma grade 4/GBM patients.
  • The study highlights the importance of MGMT-methylation testing in predicting treatment outcomes and patient selection.