Association of CDKN2A /B Homozygous Deletion and Extent of Resection With Survival of Patients With WHO CNS5 Grade 4 Astrocytoma

OBJECTIVES: WHO grade 4 astrocytomas are associated with poor prognosis, and their prognostic factors remain controversial. This study aimed to identify the prognostic factors and develop a management algorithm for these patients. METHODS: This study retrospectively included 151 CNS5 adult grade 4 astrocytomas from two medical centers. The tumors were classified as histologic grade 2/3 astrocytomas with CDKN2A/B homozygous deletion (molecular grade 4 astrocytoma, MA4), histologic grade 4 astrocytomas with CDKN2A/B homozygous deletion (molecular and histologic grade 4 astrocytoma, MHA4), and histologic grade 4 astrocytomas without CDKN2A/B homozygous deletion (histologic grade 4 astrocytoma, HA4). Prognostic factors were identified and incorporated into recursive partitioning analysis (RPA) for survival risk stratification. RESULTS: Histologic grade 4 astrocytomas with CDKN2A/B homozygous deletion, postoperative tumor volume (TV), and chemoradiotherapy were associated with patient survival. RPA identified three groups with distinct prognoses (p = 0.001). Group 1 had a median overall survival (OS) of 77.8 months, consisting of MA4 and HA4 with postoperative TV on FLAIR ≤ 28.5 mL. Group 2 had a median OS of 32.2 months, including MA4 and HA4 with postoperative TV on FLAIR > 28.5 mL receiving chemoradiotherapy, or MHA4 with postoperative TV on FLAIR ≤ 28.5 mL. Group 3 had a median OS of 14.9 months, including MA4 and HA4 with postoperative TV on FLAIR > 28.5 mL without chemoradiotherapy, or MHA4 with postoperative TV on FLAIR > 28.5 mL receiving chemoradiotherapy. CONCLUSION: Histologic grade 4 astrocytomas with CDKN2A/B homozygous deletion confer the worst survival. Maximal or complete resection, as assessed on FLAIR images, is critical to improving outcomes.