The effect of age on outcome in prospective, phase III NRG Oncology/RTOG trials of radiotherapy (XRT) +/- chemotherapy in locally advanced (LA) head and neck cancer (HNC).

Abstract

6003 Background: The effect of advanced age on outcome for single agent XRT and combined modality therapy in LA-HNC is not well defined. Methods: The effect of age (< 70 vs ≥ 70 years) on survival and toxicity was examined in LA-HNC patients (pts) on RTOG 9003 testing 3 altered fractionation (fx) XRT schedules versus standard daily XRT (SFX); RTOG 0129 comparing concurrent SFX + cisplatin (DDP) to accelerated fx with concomitant boost XRT (AFX-C) + DDP; and RTOG 0522, testing AFX-C + concurrent DDP +/- cetuximab. Results: Secondary analysis included 2,688 pts. Median followup for surviving pts was 5.2 years (range 0.01 to 20.3) overall, 14.1 yrs in RTOG 9003, 7.9 years in RTOG 0129, and 4.6 years in RTOG 0522. Pts age ≥ 70 were more likely to be female with poorer PS, heavier smoking history and p16 (-) status (p < 0.001 each). Adjusting for covariates, patients age ≥ 70 had worse survival regardless of smoking or p16 status. Adverse effect of patients age ≥ 70 may have been worse in p16 (+) pts (HR 2.07 vs. 1.30; interaction p = 0.09), (n = 34). Maximum grade stomatitis and other toxicities were similar by age cohort and tx arms on RTOG 9003. In the DDP-based studies, the elderly experienced more grade 3-5 thrombocytopenia (p = 0.02), anemia (p = 0.03), nephrotoxcity (p = 0.01) and possibly ototoxicity (p = 0.06) but less mucositis (p = 0.04). Conclusions: Pts age ≥ 70 were under-represented in RTOG trials evaluating tx for LA-HNC relative to their population overall. Their survival was inferior compared to pts age < 70; this was more apparent in combined modality, DDP-based trials, which featured heightened nephrotoxicity, myelosuppression, and ototoxicity. Delineation of causes of death and tx compliance will provide insight into future trial design. NCI grants U10CA21661, U10CA180868, U10CA180822, U10CA37422 and UG1CA189867. Funded in part under grant with PA Dept of Health which disclaims responsibility for any analyses, interpretations or conclusions and BMS. Trial Total accrual N(%) ≥ 70 yrs Hazard Ratio(HR) for death(95% CI) P Value 9003 1076 207(19.2) 1.34(1.15-1.57) < 0.001 0129 721 48(6.7) 2.34(1.68-3.26) < 0.001 0522 891 54(6.1) 2.45(1.69-3.53) < 0.001 Combined 2688 309(11.5) 1.55(1.35-1.77) < 0.001