Fig 3.

Personalized survival effects of extent of resection (EOR) of gadolinium enhancing (T1) tumor and adjuvant therapy as simultaneous covariates and how to use an integrated EOR and adjuvant therapy survival curve (Fig 1D) to estimate the personalized survival effects of simultaneous changes in these modifiable covariates. (A) The combined effects of EOR and adjuvant therapy on estimated survival in a hypothetical young (age 40 years), high-functioning (Karnofsky performance score [KPS], 100) patient is examined. When 95% resection is achieved (blue intervals), cranial radiotherapy (XRT) alone adds an estimated 120 days of survival (Δ₂) and concomitant temozolomide-based chemotherapy (TMZ) adds an additional 260 days (Δ₁) for a total of 380 days of estimated survival advantage versus no adjuvant therapy (680 days v 300 days total, Δ₃). When EOR is decreased from 95% to 75%, the absolute values of the intervals decrease, and the absolute survival advantage is reduced (relative to the estimated survival for 95% EOR) from 680 to 540 days. (B) The combined effects of EOR and adjuvant therapy on estimated survival in a hypothetical patient who is elderly (age 84 years) and debilitated (KPS, 60) is examined. When 95% resection is achieved (blue intervals), XRT alone adds an estimated 50 days of survival (Δ₂) and concomitant TMZ adds an additional 100 days (Δ₁) for a total of 150 days of estimated survival advantage versus no adjuvant therapy (270 days v 120 days total, Δ₃). When EOR is reduced from 95% to 75%, the absolute values of the intervals decrease and the absolute survival advantage is reduced (relative to the estimated survival for 95% EOR) from 270 to 220 days. Together, these observations may have implications for the interpretation of the incremental advantages of adjuvant therapy as well as for the design, analysis, and interpretation of future trials that incorporate surgery, TMZ, or XRT.