To evaluate the association between smoking status, genetic alterations in primary glial neoplasms, and impact on survival. 

A retrospective analysis was performed on adult patients (>18 years) diagnosed with a malignant glioma (i.e., astrocytoma, oligodendroglioma, glioblastoma; WHO Grade 2-4) between 2000-2020 and receiving primary oncologic care at Wake Forest Baptist Comprehensive Cancer Center. Data was queried for demographic, clinical, molecular, and treatment characteristics. Smoking status was defined as active/former vs never smoker.

291 patients were identified; mean age 59+15 years; 54% male; 158 GBM, 64 astrocytoma (28 LGA, 36 AA), 48 oligodendroglioma (39 LGO, 10 AO), 20 other glioma. Of these, 58% were never smokers and 42% were current/former smokers with 7.1+12 years mean smoking duration. There was no difference in age (p=0.38), diagnosis (0.07), extent of resection (0.75), prior radiation (0.08), or chemotherapy (0.75) by smoking status. The most frequently altered genes were pTERT (69%), CDKN2A (41%), TP53 (45%), CDKN2B (38%), EGFR (33%), IDH (31.0%); mutational profiles did not differ by smoking status for all gliomas. In patients with astrocytoma, 73% of smokers and 42% non-smokers had TP53 mutation (p = 0.10); 7% smokers and 42% non-smokers had EGFR amplification (p = 0.06). Median OS was shorter for smokers (46 vs 141 months, p=0.045) with 42% greater risk of death (HR 1.42, 95%CI 1.01-1.99, p=0.045). This remained when controlling for histologic diagnosis (adjusted HR 1.45, 1.02-2.04, p=0.034) but not for age and diagnosis (adjusted HR 1.25, 0.88-1.78, p=0.20).

Smokers have shorter survival from malignant glioma. While differences in age may contribute, smoking-related genomic alterations are not a mechanism for survival differences.