OPC SURVIVOR: Optimizing OroPharyngeal Cancer SURVIVORship

ABSTRACT: OVERALL Oropharyngeal cancer (OPC) is rising in epidemic proportions, largely owing to rise in highly curable oncogenic human papillomavirus (HPV) attributable disease. HPV-associated OPC is often diagnosed in young individuals presenting with near normal functional status and high quality of life (QOL) at diagnosis. Standard therapy offers

excellent two- and five-year survival probability of 95% and 79%, respectively, yet at a high cost in QOL lost. Long-term survivors risk a host of debilitating delayed adverse sequelae of therapy. Randomized trials seeking to mitigate toxicity by reducing the intensity of systemic therapy or decrease radiotherapy dose in HPV-

associated OPC surprisingly resulted in inferior survival (e.g., RTOG-1016, HN005). Other noteworthy efforts to optimize the therapeutic ratio (e.g., transoral robotic surgery [TORS] and highly conformal radiotherapy) still yield significant early toxicities published extensively by the investigators, as well as numerous late symptoms

that persist or develop many years into survivorship as independent drivers of unemployment in young survivors (under age 60) and decisional regret about cancer therapy long after cure (median 7-years survival). The investigators have further published extensively on three distinct, but inter-related highly morbid delayed

adverse sequelae that threaten QOL and health: 1) mandibular osteoradionecrosis (ORN), 2) late radiation- associated dysphagia (late-RAD), and 3) late lower cranial neuropathy (LCNP). To advance precision health of OPC survivors, we must integrate these individual lines of inquiry to better describe the intersection of actionable

phenotypic presentations, trajectories, and clusters of adverse events and novel therapies to mitigate chronic disability as adverse events evolve from early to late survivorship. The absence of well curated long-term survivor cohorts was the stimulus for the development of the MD Anderson Oropharynx (MDA-OPC) cohort,

an active, single institution, prospective longitudinal cancer cohort. Since 2015, 1,750 OPC patients have enrolled with interdisciplinary characterization of exposures, diagnostic/staging, treatment, disease control, and validated clinician- and patient-reported survivorship outcomes. Survivors are in longitudinal follow-up by the

Patient-Reported Outcomes/Function (PROF) Core which has to date acquired 31,370 PRO questionnaires and 3,687 toxicity imaging studies. The MDA-OPC cohort is an unparalleled resource for integrated OPC specific Projects focusing on delayed treatment sequelae in this rapidly growing cancer survivor population. The OPC-

SURVIVOR P01 Program Project aims to maintain and enrich MDA-OPC infrastructure, extending outcomes data collection beyond 5-years into long-term survivorship to support three integrated Projects focused on: 1) osteoradionecrosis (OPC-ORN), 2) cranial neuropathy (OPC-NERVE), and 3) late radiation-associated

dysphagia (late-RAD). Our central hypothesis is that clinically feasible PRO and objective measures uncover phenotypes and trajectories of delayed cancer therapy induced adverse events for earlier detection and mechanistically targeted mitigation strategies.