Abstract
Current guidelines for adjuvant temozolomide (TMZ) treatment of glioma patients advocates 6 to 12 monthly cycles. Is that best? Will patients who receive > 12 cycles live longer? To find out, we conducted a 10-year (2006–2016) chart review of 1300 glioma patients treated at NorCal Kaiser Permanente facilities to determine the impact of dose-week (AUC) quartiles and duration of TMZ therapy quartiles on median overall survival (mOS) in new low- and mid-grade gliomas (Group A) and glioblastoma (Group B) patients. Group A had 357 patients with WHO grade II and III astrocytic and oligodendroglial tumors; Group B had 943 patients with glioblastoma. The median AUC in Group A was 337 mg/m2 (IQR 129, 1095) and the median weeks of TMZ 15 (IQR 1, 42). In Group B, median AUC was 210 mg/m2 (IQR 79,581) and median weeks of TMZ 24 (IQR 9. 45). Based on quartile ranking of AUC, a higher AUC was found to be associated with longer mOS in Group A and B. In Group A, for increasing AUC quartiles, mOS was 134, 146, 369, and 397 weeks (p=0.0014); for Group B, mOs were 30, 48, 74, and 117 weeks (p< 0.0001). Based on increasing quartiles for TMZ treatment duration for quartiles 2–4, Group A patient mOS increased from 122 weeks to 431 weeks (p = ns) and Group B patients, increased mOS from 51 to 143 weeks (p< 0.0001). This retrospective analysis of 10-years of neuro-oncology practice brings into question limiting TMZ dose in WHO grade 2–3 glioma and WHO grade 4 glioblastoma patients as higher dose toleration and longer duration of treatment appears to be associated with longer mOS in both groups. Or does it show that patients who do well elect to take TMZ longer and maybe these findings reflect reverse causality?