EVOLVE: Evaluating the Safety of De-escalated Head and Neck Irradiation in HPV Positive Oropharynx Cancer in Non/Minimal Smokers.

Abstract

<h3>Purpose/Objective(s)</h3> HPV mediated oropharynx cancer in minimal smokers is a favorable disease entity but with high treatment related quality of life burden. Single institutional studies in large academic centers have favorable results with aggressive radiotherapy de-escalation after surgery or after complete response to induction chemotherapy. We hypothesize that radiotherapy can be safely de-escalated in the community cancer center setting. <h3>Materials/Methods</h3> Adults with HPV mediated squamous cell carcinoma of the oropharynx with ≤ 10 pack year smoking history T0-T3N0-N2M0 (AJCC8, including unknown primary p16+ minimal smokers) and with negative margins (if surgical arm) were enrolled on this prospective observational study. Initial surgical resection was performed if an R0 resection was anticipated AND if the surgeon would anticipate a good functional outcome post-operatively. Adjuvant radiotherapy was as per Ma <i>et al</i> JCO 2019. Induction chemotherapy with de-escalated radiotherapy to complete responders was undertaken when surgical resection was not deemed optimal. Platinum eligible induction chemotherapy was as per Marur <i>et al</i> JCO 2017. Platinum ineligible induction chemotherapy was as per Chen <i>et al</i> Lancet Oncology 2017. The primary endpoint was cumulative incidence of local/regional recurrence. Secondary endpoints included quality of life as determined by Head and Neck PRO (FACT-H&N, EORTC QLQ-C30 and H&N35), distant metastasis free survival and overall survival. Preliminary report includes 39 patients with at least 3 months follow-up. Planned accrual is 60 patients. <h3>Results</h3> Median follow-up was 18 months (3-45 months). 31/39 (80%) received initial surgery. 8/39 (20%) received initial induction chemotherapy. 1 withdrew during induction. 100% of patients receiving induction therapy had adequate response to qualify for de-escalation. Cumulative incidence of local/regional recurrence was 3% (1/39). Cumulative incidence of distant metastases was 3% (1/39). Both recurrences occurred in the surgical arm. Overall survival is 100%. No patient in the induction arm required salvage neck dissection or recurred. 1/11 (9%) of patients with extranodal extension (ENE) recurred locally/regionally. 1/11 (9%) patients with ENE recurred distantly. ENE status is unknown in the non-surgical arm. There were no recurrences in the 7 patients with N2 disease. No de-escalated patient required treatment related feeding tube placement. Patient reported quality of life was stable to improved at 12 month follow-up. <h3>Conclusion</h3> In a rural community setting, early results of aggressive de-escalation of radiotherapy demonstrate this approach to be both safe and effective with minimal change in patient reported quality of life. In this favorable disease entity, reported de-escalation results from large academic centers are readily translatable to daily community practice.