Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: Implications for risk-based therapeutic intensity trials. Cancer Fakhry, C., Zhang, Q., Gillison, M. L., Nguyen-Tan, P. F., Rosenthal, D. I., Weber, R. S., Lambert, L., Trotti, A. M., Barrett, W. L., Thorstad, W. L., Yom, S. S., Wong, S. J., Ridge, J. A., Rao, S. S., Spencer, S., Fortin, A., Raben, D., Harris, J., Le, Q. 2019


BACKGROUND: Radiation Therapy Oncology Group (RTOG)-0129 recursive partitioning analysis was the basis for risk-based therapeutic intensification trials for oropharyngeal cancer (OPC). To the authors' knowledge, the question of whether RTOG-0129 overall survival (OS) estimates for low-risk, intermediate-risk, and high-risk groups are similar in other data sets or applicable to progression-free survival (PFS) is unknown. Therefore, the authors evaluated whether survival differences between RTOG-0129 risk groups persist at 5years, are reproducible in an independent clinical trial, and are applicable to PFS, and whether toxicities differ across risk groups.METHODS: Prospective randomized clinical trials were analyzed retrospectively. RTOG-0129 evaluated standard versus accelerated fractionation radiotherapy concurrent with cisplatin. RTOG-0522 compared the combination of cisplatin and accelerated fractionation with or without cetuximab. Patients with OPC with available p16 status and tobacco history were eligible.RESULTS: There was a total of 260 patients and 287 patients, respectively, from RTOG-0129 and RTOG-0522, with median follow-ups for surviving patients of 7.9years (range, 1.7-9.9years) and 4.7years (range, 0.1-7.0years), respectively. Previous OS differences in RTOG-0129 persisted at 5years. In RTOG-0522, the 5-year OS rates for the low-risk, intermediate-risk, and high-risk groups were 88.1%, 69.9%, and 45.1%, respectively (P for trend, <.001). The 5-year PFS rates for the same 3 groups were 72.9%, 56.1%, and 42.2%, respectively. In RTOG-0522 among a subgroup of patients considered to be at very good risk (p16-positive disease, smoking history of =10 pack-years, and classified with T1-T2 disease with ipsilateral lymph nodes measuring =6cm or T3 disease without contralateral or >6cm lymph nodes), the 5-year OS and PFS rates were 93.8% and 82.2%, respectively. Overall rates of acute and late toxicities were similar by risk group.CONCLUSIONS: RTOG-0129 risk groups persisted at 5years and were reproducible in RTOG-0522. However, there was variability in the estimates. These data underscore the importance of long-term follow-up and appropriate patient selection in therapeutic deintensification trials.

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