A Phase Ii Study Of Radiation Therapy Deintensification For Hpv-Associated Oropharyngeal Carcinomas: Long-Term Oncologic And Toxicity Results

Human papilloma virus (HPV) – associated oropharyngeal squamous cell carcinomas (OPSCC) have a favorable prognosis. When treated with radiation therapy (RT), reducing the risk of late complications while maintaining oncologic efficacy are important goals. Our group hypothesized that our deintensification protocol would limit the 2-year grade ≥3 late CTCAE toxicities to <15% while maintaining local-regional tumor control >85%. We sought to report the mature results of our study. From 2010 to 2015, we prospectively enrolled patients on a phase II trial of AJCC (version VII) stage I-IV HPV-OPSCC treated with RT or concurrent chemoradiation (CRT) with weekly cisplatin, excluding T4 tumors. Patients with T1-2 N0-1 tumors were eligible for treatment with RT alone to 70 Gy to the primary and nodal gross tumor volume (GTV). All remaining patients received CRT with the primary GTV reduced to 63 Gy where it overlapped the pharyngeal constrictor muscles, larynx or the parotid glands and 70 Gy to the nodal GTV. Patients were prospectively evaluated for the primary composite endpoint of 2-year local-regional tumor control and late CTCAE toxicities. Fifty-nine patients were enrolled with a median follow up of 49.3 months (19.1-87 months). Median age was 59 years old (39 - 80). Seventeen (28.8%), 30 (50.9%), and 11 (18.6%) patients had T1, T2, and T3 tumors, respectively. The majority of patients had advanced nodal disease (N2a – 5, N2b – 29, N2c – 13, N3 – 4) and stage (IVA – 47, IVB – 4). At last follow up, one patient had local recurrence (at 8 months), two patients had regional recurrences (at 3.5 and 21.3 months), three patients developed distant metastasis, and one patient developed synchronous regional and distant failure. The cumulative 2-year incidence of local failure was 1.5%, region failure was 3.5% and local-regional failure 5.0%. Fifty-four (91.5%) patients had at least two-year follow-up toxicity data. At two years, 32 (59.3%) patients reported no dysphagia, 21 (38.9%) reported grade 1 dysphagia, and 1 (1.9%) reported grade 3 dysphagia; 33 (61%) and 15 (27.8%) reported grade 1 or 2 xerostomia and none reported grade 3 xerostomia. M. D. Anderson Dysphagia Inventory (MDADI) scores at 2 years were available for 45 (76.2%) patients. Median MDADI score for the population was 64 (range 41-76). Sydney swallow questionnaire scores were available for 54 patients at a median of 48.8 months with a median SSQ score of 118.8 (range 15.2-808.9) suggesting normal patient-reported physiologic swallow function (0-234). RT de-intensification was safely conducted in HPV+OPSCC with a favorable toxicity profile, limited to a single grade 3 toxicity. While successfully achieving the primary study endpoint, the MDADI evaluation suggests that further deintensification efforts are needed along with more sensitive toxicity measures beyond CTCAE grading for future study endpoints.