313 - Re-Examining Post-Operative Chemoradiotherapy in Head and Neck Cancer: An Updated Long-Term Combined Analysis of RTOG 9501/EORTC 22931
Presenter(s)
Z. S. Zumsteg1, M. Luu1, C. Fortpied2, J. K. Jang1, M. M. Chen3, J. Mallen-St. Clair1, E. Walgama1, Q. T. Le4, M. Machtay5, S. Tribius6, S. Wong7, E. M. Ozsahin Jr8, V. G. Gregoire9, J. Vermorken10, A. S. Ho1, and S. S. Yom11; 1Cedars-Sinai Medical Center, Los Angeles, CA, 2EORTC Headquarters, Brussels, Belgium, 3Department of Otolaryngology, University of Michigan, Ann Arbor, MI, 4Stanford University, Stanford, CA, 5Penn State Cancer Institute and College of Medicine, Hershey, PA, 6University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany, 7Department of Medical Oncology, Medical College of Wisconsin, Milwaukee, WI, 8Radiation Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, 9Université Catholique de Louvain, Bruxelles, Belgium, 10Antwerp University Hospital, Edegem, Belgium, 11University of California San Francisco, San Francisco, CA
Purpose/Objective(s): Two decades ago, a combined post-hoc analysis of RTOG 9501 and EORTC 22931 showed improved survival with post-operative chemoradiation (CRT) versus radiotherapy (RT) alone in head and neck cancer (HNC) patients with extranodal extension (ENE) and/or positive margins, but not in those without these features. However, this analysis lacked formal interaction testing necessary to identify a predictive biomarker. In addition, updated data is now available to provide longer-term outcomes.
Materials/Methods: This study assessed 744 HNC patients enrolled on the RTOG 9501 and EORTC 22931 randomized trials that compared cisplatin-based CRT to RT following surgery. Overall survival (OS) was analyzed with Cox regression. Cancer-specific mortality (CSM), other-cause mortality (OCM), locoregional recurrence (LRR), and distant metastasis (DM) rates were analyzed with competing risk methodology. Tests of interaction were performed to assess for differential benefits of CRT in various subgroups, and a Bonferroni adjustment was applied to account for multiple hypothesis testing.
Results: Median follow-up was 6.9 years. 91% of patients met eligibility criteria for both trials. Median age was 55, with 3.5% of patients older than 70. Among all patients, CRT improved OS (HR=0.81, 95% CI: 0.68-0.97, P=0.026), with 7-year OS of 41% vs 33%. Although CRT improved OS in the subgroup with ENE and/or positive margins (HR=0.71, 95% CI: 0.57-0.89, P=0.003) and not in those without these features (HR=0.94, 95% CI: 0.68-1.30, P=0.7), tests of interaction showed no evidence of a differential effect of CRT in these subgroups (P-interaction=0.17). There was also no evidence of interaction when analyzing CSM, LRR, or DM, or when assessing ENE and margin status individually. While CRT reduced CSM (HR=0.68, 95% CI: 0.55-0.83, P<0.001), it also increased OCM (HR=1.51, 95% CI: 1.07-2.12, P =0.018). The 7-year incidence of CSM was 37% vs 53% for patients receiving post-operative CRT vs RT alone, respectively, compared to 7-year OCM of 21% vs. 14%. There was a trend towards CRT being associated with higher OCM in patients aged 60 or older vs. younger patients (P-interaction = 0.02), but this was not significant when adjusting for multiple hypothesis testing. CRT improved LRR (HR=0.64, 95% CI: 0.48-0.85, P=0.002), but not DM (HR=0.83, 95% CI=0.64-1.08, P=0.17).
Conclusion: Post-operative CRT improved OS in HNC patients compared to RT alone in the combined populations of EORTC 22931 and RTOG 9501 by reducing LRR. However, while the subset of patients having ENE and/or positive margins had a statistically significant OS benefit from CRT, ENE and margin status are not predictive biomarkers, and patients without these features may still benefit from CRT. Although CRT improved CSM, this was partly offset by significantly increased OCM. Refining the population most likely to benefit from post-operative CRT, taking into consideration both oncologic and patient-related factors, still needs further exploration.