IDH-mutant grade 4 astrocytoma: a comparison integrating the clinical, pathological, and survival features between primary and secondary patients

OBJECTIVE IDH -mutant grade 4 astrocytomas (A IDHmut/G4 ) are divided into primary de novo (pA IDHmut/G4 ) and secondary with a history of prior lower-grade gliomas (LGGs; sA IDHmut/G4 ). The mutational spectrum and DNA methylation patterns are homogeneous within de novo pA IDHmut/G4 and evolved sA IDHmut/G4 , but the two groups have different diagnoses, management, and outcomes. This study sought to systematically compare the clinical, pathological, and survival characteristics between them. METHODS Of the 871 grade 4 astrocytomas with data for IDH mutation, 698 (80.1%) were primary and 173 (19.9%) were secondary. Of the 698 primary tumors, 103 (14.8%) were pA IDHmut/G4 , and of the 173 secondary tumors, 108 (62.4%) were sA IDHmut/G4 . Clinical, pathological, and survival features were compared between pA IDHmut/G4 and sA IDHmut/G4 . Multivariate analyses were performed to identify prognostic factors. RESULTS Patients with sA IDHmut/G4 had significantly shorter median overall survival (OS; 11.8 vs 34.2 months, hazard ratio [HR] 2.69, 95% confidence interval [CI] 1.367–5.306, p = 0.004) and progression-free survival (PFS; 8.5 vs 24.3 months, HR 2.83, 95% CI 1.532–5.235, p = 0.001) than patients with pA IDHmut/G4 . In patients with sA IDHmut/G4 , resection status and chemotherapy were independent prognostic factors for OS and PFS; in patients with pA IDHmut/G4 , LGG component, resection status, and O 6 -methylguanine DNA methyltransferase promoter methylation were independent prognostic factors. The therapeutic strategies of LGGs did not influence survival of patients with sA IDHmut/G4 , but patients who had not received radiotherapy or chemotherapy when they were diagnosed with LGGs were found to benefit from radiotherapy or chemotherapy when they progressed to sA IDHmut/G4 . CONCLUSIONS The different clinical characteristics, survival, and risk factors between sA IDHmut/G4 and pA IDHmut/G4 provide a reference to guide treatment decisions in A IDHmut/G4 .