Comparison of Recurrence With High Retropharyngeal Nodal-Sparing Intensity-Modulated Radiation Therapy in HPV-Related and HPV-Unrelated Oropharyngeal Cancer

Purpose/Objective(s) Patients with HPV-related oropharyngeal cancers (HPV+OPC) are known to have a superior locoregional control when compared to HPV-unrelated oropharyngeal cancers (HPV-OPC). The introduction of intensity-modulated radiation therapy (IMRT) has allowed dose painting and sparing of bilateral uninvolved high retropharyngeal nodes (RP). We reviewed outcomes and patterns of recurrence in patients with oropharyngeal cancer (OPC) treated with IMRT in patients with HPV+OPC and those with HPV–OPC. We hypothesize that high-RP sparing RT can reduce morbidity in HPV+OPC without sacrificing disease control. Materials/Methods We retrospectively reviewed all adults with OPCs treated with curative intent IMRT ± chemotherapy from 2012-2017 at a single institution. HPV status was tested by p16 staining for all OPCs and patients were staged per the TNM 8th edition. All patients were treated with high-RP sparing, meaning omission of the nodal basin from the caudal limit of C2 to the base of skull bilaterally. Patients who did not complete prescribed treatments, with multiple primaries or with less than 3 months of follow up were excluded. Patients, disease, treatment and outcome data were retrieved. Date and location of local, regional, retropharyngeal and distant recurrences were recorded. Time to events, including RP recurrence-free survival (RP-RFS), regional recurrence-free survival (R-RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and log-rank test were performed, for HPV+OPC vs HPV-OPC. Results The final analysis included 240 patients. Median follow-up was 4.18 years (0.25- 8.46). HPV+OPC patients accounted for 81% while HPV-OPC 19%. Median age was of 60 years (40 – 94.6) and 85.2% of patients were male. The most common primary subsites were tonsil (66.5%), and base of tongue (32.8%). Patients had stage I disease in 43%, stage II in 29%, stage III in 18% and stage IV in 10%; 84.6% of patients had nodal disease. Concurrent systemic treatments were delivered in 74% of patients. Overall, there were 3 patients (1.5%) with RP recurrences in HPV+OPC vs 2 patients (4.4%) in HPV-OPC. The 2-year RP and 5-year RP-RFS was 98% for HPV+OPC and 94% for HPV–OPC (P = 0.169). The 2-year and 5-year R-RFS was 92%/89% for HPV+OPC vs 80%/74% for HPV–OPC (P = 0.015) and 2-year and 5-year overall survival was 92%/78% for HPV+OPC vs 81%/59% for HPV–OPC (P = 0.009). Conclusion High-RP sparing IMRT technique is associated with less than 5% of isolated recurrence in the high RP nodal region, despite most patients presenting with involved nodal disease. Our data showed no statistically significantly difference in the HPV+OPC vs HPV–OPC patients. As a result, these data suggest that continuing this practice is associated reasonable disease control and further studies are needed to evaluate patients’ long-term quality of life and morbidity.