Prophylactic Limbo: How Low Can We Go on HPV+OPSCC Prophylactic Nodal Coverage?

Abstract

The last 2 decades has seen an increase in HPV-associated oropharyngeal cancers. As they are notable for their radiosensitivity and younger population, efforts to de-intensify therapy to minimize long-term morbidity from treatment are under investigation. We hypothesize reducing the dose and volume of elective nodal coverage in these patients can maintain disease control with an improvement in QOL. Herein we characterize the recurrence patterns and salvage options for patients treated in a dose- and volume-reduced approach. We retrospectively characterized a cohort of patients with HPV-associated oropharyngeal cancer irradiated at our institution from 2013-2018. After IRB approval, we collected patient demographics, definitive vs. adjuvant approach, radiation doses and volumes, chemotherapy, QOL factors, and recurrence and survival outcomes. Survival and recurrence were measured from the final day of radiotherapy until death or last follow-up. A total of 270 patients were identified at our institution with an ICD9/10 code that suggested a neoplasm of the oropharynx. A preliminary assessment of the first 104 patients identified 44 with HPV+ confirmed OPSCC. By AJCC7 criteria, a majority of tumors were T1 or T2 (34/44) and most patients demonstrated clinical N2 disease (35/44). 9 patients were treated in a post-operative setting, almost all (42/44) received concurrent chemotherapy with 15 receiving induction as well. With the exception of 3 post-operative patients, all received >60 Gy to the primary tumor volume in 200-220 cGy per fraction. 4 patients did not receive any radiation to low-risk nodal levels and 34 received a dose of 44-48.4 Gy to these echelons, the remaining six received doses 50-50.6 Gy. 11 out of 44 patients received unilateral hemineck irradiation due to well-lateralized tumors. Of these 44 patients assessed at this time, 4 demonstrated recurrence or persistent disease by biopsy or PET scan. Three were in the primary site (2) or high-dose involved nodal level (1) whereas the last developed an HPV-associated squamous cell carcinoma of the glottic larynx with extension to the untreated neck. No recurrences were identified in the reduced-dose prophylactic nodal levels or in the volume-reduced non-irradiated neck. This suggests that prophylactic doses of 44-50.6 Gy with concurrent chemotherapy may be sufficient to control low-risk nodal echelons. In well-selected patients, further reduction in the treatment volumes may confer additional morbidity benefit without sacrificing disease control. Subsequent analysis will characterize treatment-related morbidity and QOL.