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

Abstract

Aims

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.

Materials and methods

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.

Results

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.

Conclusion

Modern diagnostic and therapeutic techniques affected a near-doubling of survival and acceptable late toxicity, as compared to historical data.