Comparison Of Adjuvant Versus Salvage Therapy Among IDH Mutant Low-Grade Glioma

Abstract

Timing of postoperative management in low grade glioma (LGG) is controversial. We sought to evaluate the clinical outcomes among molecularly classified LGG patients (pts) treated with adjuvant (adj) versus (v) salvage treatment (salv). We included pts ≥ 18 yrs old at diagnosis of LGG (WHO grade II) from 1980-2018 with an IDH mutation (mut) and 1p19q data allowing for molecular classification. Pts in the adj group received immediate postoperative treatment (temozolomide [TMZ] and/or radiotherapy [RT]) prior to progression. Salv pts were initially observed then received TMZ and/or RT at disease progression. Endpoints were calculated from date of first surgical resection or biopsy, and included overall survival (OS) and next intervention free survival (NIFS), defined as the date of either surgery or treatment subsequent to adj or salv, or death. 296 IDH mut pts were included. Among the 168 pts with 1p19q codel, median follow up was 8.3 yrs (range, .03 – 26), median age was 43 yrs (range, 20-78), 57% were male, and 29% had GTR (gross total resection). 100 pts (60%) received adj (TMZ, 22%; RT, 65%; TMZ+RT, 13%), which was more likely in pts who were older, had larger tumors, or underwent biopsy alone (p<.05 for each). On univariable analysis (UVA), 5 yr NIFS for adj v salv was 70% (95% CI, 61-80%) v 83% (74-93%; p = 0.06), and 5 yr OS was 90% (84-97%) v 97% (93-100%; p<0.01), respectively. However, when adjusting for high risk factors associated with selection bias on multivariable analysis (MVA, Table), adj was not associated with either NIFS or OS as compared to salv. Among the 128 pts with 1p19q intact, median follow up was 6 yrs (range, 0.04 – 19), median age was 35 yrs (range, 19-66), 52% were male, and 41% had GTR. 49 pts (38%) received adj (TMZ, 29%; RT, 26%; TMZ+RT, 45%), which was more likely in pts who were older, had larger tumors, or underwent biopsy alone (p<.05 for each). On UVA, 5-year NIFS for adj v salv was 69% (95% CI, 56-85%) v 41% (31-56%; p<0.01), and 5-year OS was 85% (75-97%) v 91% (84-98%; p = 0.7), respectively. On MVA (Table), adj remained associated with improved NIFS compared to salv, but had no association with OS. Among IDH mut 1p19q codel pts, adj was not associated with improved NIFS or OS, suggesting initial observation followed by salv at progression is appropriate for this population. In contrast, among IDH mut 1p19q intact pts, adj was associated with improved NIFS, but not OS, supporting a more individualized postoperative management approach.Abstract 3689; TableMVAIDH mut 1p19q codelIDH mut 1p19q intactNIFSOSNIFSOSHR (95% CI)pHR (95% CI)pHR (95% CI)pHR (95% CI)pAdj v salv1.2 (0.8-1.9).421.3 (0.7-2.4).380.4 (0.2-0.7)<.010.9 (0.5-1.6).69Age ≥40 v <401.5 (1.0-2.3).072.1 (1.2-3.8).011.1 (0.7-1.9).631.3 (0.7-2.5).37Biopsy.16.02.09.18GTR0.7 (0.4-1.1).130.4 (0.2-0.8).011.0 (0.5-2.3).910.6 (0.2-1.6).34STR0.7 (0.4-1.1).090.6 (0.3-1.0).051.7 (0.8-3.6).131.3 (0.6-2.7).57Female v male0.8 (0.5-1.2).340.7 (0.4-1.2).230.5 (0.3-0.9).010.5 (0.3-0.9).04 Open table in a new tab