3702 - NCDB Analysis of Low-Risk HPV-Related H&N SCC of the Oropharynx Treated with Surgery: Can Adjuvant RT be Safely Omitted in Node Positive Patients?

C. Morrison¹, R. P. McDougall¹, Y. Shi¹, C. C. Hsu¹, L. Wang Jr¹, and J. R. Robbins²; ¹University of Arizona - Department of Radiation Oncology, Tucson, AZ, ²University of Arizona, College of Medicine-Tucson, Department of Radiation Oncology, Tucson, AZ

Purpose/Objective(s): Given the toxicity associated with radiation to the head and neck, it is critical to identify patients who can safely omit adjuvant radiation therapy (aRT) after surgical management for HPV-related oropharyngeal squamous cell carcinoma (OPSCC). Various trials have taken steps in this direction but typically based inclusion on the AJCC 7^th edition. For example, in the phase II ECOG 3311 study, patients with <=1 positive lymph node (LN), less than 3cm, were observed after surgery. Our hypothesis is that sub-groups of patients with >1 positive LN may be at low enough risk to safely omit aRT. Materials/

Methods: The latest NCDB database version was used to identify patients with low-risk HPV-related OPSCC that were primarily treated with surgery to the primary and neck, with or without aRT. Low-risk patients were defined as those with T0 or T1-T2 primaries that were resected with negative margins, lymph nodes <= 3 cm, and no pathological evidence for extra-nodal extension. Comparisons of Kaplan-Meier projections of overall survival (OS) were analyzed using the log-rank test, and hazard ratios (HR) with a multivariate Cox Proportional Hazards (CPH).
Results: There were 32,089 cases of non-metastatic OPSCC who were treated with surgery between 2009-2021. 4,316 patients fit our criteria for low-risk, HPV-related tumors (2056 with aRT and 2260 without). Patients were grouped by the number of positive LNs: zero (n=1011), one (n= 1814), two (n=810), and three or more (n = 681), and their OS compared. Without aRT, the median OS of patients was 74.6, 43.7, 44.7, and 40.0 months in patients with 0,1,2,3+ LNs respectively. The group with 0 LNs was statistically significantly different from the other groups, while there was no statistically significant difference between the groups with any positive nodes. With aRT, OS was 83.6, 51.8, 49.1, and 49.2 months in patients with 0,1,2,3+ LNs respectively, and again, only the patients with 0 LNs had statistically different OS from the other groups. In the 1,814 patients with 1 LN, the addition of aRT improved OS (51.8 vs 43.7 months, p < 0.001) and even in the 1,011 patients with no LNs, the addition of aRT improved OS (83.6 vs 74.6 months; p < 0.001). When a CPH model including age, Charlson-Deyo comorbidity score, T stage, LN group, and receipt of aRT was analyzed, the number of LNs and receipt of aRT remained significantly associated with OS. The HR for omission of aRT was 1.4, while having 1, 2, and 3+ LNs resulted in HRs of 1.8, 2.1, and 1.9 respectively (all p < 0.001).
Conclusion: Based on this NCDB analysis, with all the usual caveats associated with such studies, our hypothesis was disproven. Even patients with 1 LN, where omission of aRT is thought to be safe, benefitted from aRT. This study also corroborates the current AJCC nodal staging system by showing no difference in OS between patients with 1 or more positive LNs. Future studies looking to omit aRT in low-risk HPV-related OPSCC should give careful consideration when including patients with any positive LNs after surgery.