The TAME adverse event summary and risk classification system: Analysis of the RTOG H&N Database

Abstract

6026 Background: There is currently no method for concisely summarizing and comparing aggregate adverse event (AE) data among treatment options. We propose a new concept (“toxicity burden”) and new metrics to reflect treatment-related risk. Analogous to the T-N-M tumor staging system, the “T-A-M End-results system” (TAME) consolidates adverse effects data into a concise index: short-term (acute) toxicity [T], adverse long-term effects [A] and mortality risk from treatment [M]. Methods: We estimated T-scores and A-scores from published adverse event data in 13 treatment arms from 5 RTOG H&N trials (90–03, 91–11, 95–01, 97–03, 99–14) conducted between 1990–2000 (>2200 patients). Estimation of T and A scores are calculated by dividing total number of RTOG grade 3–4 events for 13 pre-specified toxic categories by the number of patients in a cohort. We also calculated scores using individual patient data (IPD) from 2 arms of the RTOG 91–11 larynx preservation trial (314 patients). Results: Estimated T-scores demonstrate more than a 500% difference in acute toxicity burden when comparing aggressive chemoradiotherapy to conventional radiotherapy (range: 0.47–3.14). Less variation was seen in estimated late effects burden (range: 0.17–0.59). Putative T-risk burden classes were designated: ≤0.6 (low), 0.7–1.0 (mod), 1.0–2.5 (high), ≥2.5 (extreme). T-values from RTOG 91–11 (see table) suggest up to 250% more toxicity burden from the use of chemotherapy. Distribution of T-scores among the concurrent PLAT-RT group revealed 22% of patients experienced 3 high-grade events, and 23% experienced 4 or more (p=<0.0001). Correlations of T-scores with KPS and selected QOL domains at 3 months were modest as expected. Conclusions: TAME scores support the feasibility of quantifying toxicity burden and may have wide applications including safety monitoring and identification of patient groups at high risk for injury in multiple oncologic disorders. No significant financial relationships to disclose.