Project 2: OPC-NERVE

ABSTRACT: PROJECT 2 (OPC-NERVE) While most patients with oropharyngeal cancer (OPC) present with near normal functioning at the time of diagnosis, a growing number of survivors suffer profound disability from delayed onset of lower cranial neuropathy (LCNP) as a latent sequela of curative radiotherapy (RT). By 5 years’ survival, our group published that at least 5% of patients cured of OPC develop LCNP with cumulative lifetime risk exceeding 10%. LCNP is associated with excess symptom burden, disrupting critical functions of eating, breathing, and speaking. Crippling swallowing dysfunction manifest by LCNP results in refractory aspiration of food and liquids into the lungs. The investigators published that delayed, typically lifelong feeding tube insertion, tracheostomy, and pneumonia years after cure of OPC occur almost exclusively in survivors who develop LCNP. Our publications report functional loss over time after LCNP despite standard therapies. New therapy strategies are badly needed. LCNP is clinically detected a median of 5 to 8 years after RT after a “quiet period” of functional recovery. There is currently no early indicator for this injury. Delayed identification means that muscle atrophy and symptomatic functional injury is typically present at the time of diagnosis, limiting therapeutic potential. Our long- term goal is to improve lifelong function and health after OPC through mechanistically targeted and technically nimble surveillance and mitigation of LCNP. Our central hypothesis is that subclinical cranial neuropathy is prevalent early and increases over time after OPC RT as an untapped target for proactive mitigation strategies, and novel patient reported outcome (PRO) and non-invasive objective measures with remote monitoring potential are sensitive clinical markers of LCNP. The objective of the proposed study is to analyze gold-standard needle EMG and non-invasive nerve function measures as correlative procedures in an ongoing large-scale OPC cohort that captures robust longitudinal PRO and functional data to: Aim 1: estimate rates of hypoglossal neuropathy (per gold standard EMG) over first 12 years post-RT; Aim 2: provide clinic ready symptom-based and non-invasive objective clinical markers of LCNP by examining: a) a candidate multi-symptom nerve score from the MD Anderson Symptom Inventory – Head and Neck Module (MDASI-HN), b) high-density surface EMG (HDSEMG) as a rapid, non-invasive neurophysiologic measure of hypoglossal neuropathy, and c) mobile app- based speech acoustic measures; Aim 3: conduct a 3-arm feasibility RCT for go/no go decision on high-dose steroid and behavioral therapies for subclinical EMG detected XII neuropathy. Building upon the infrastructure of the MD Anderson OPC cohort and investigators’ track record of non-invasive signal measurement in the tongue and supportive care trials in OPC, we are uniquely positioned to accomplish these complementary aims. We expect this Project integrated within the OPC-SURVIVOR P01 has potential for practice changing insights regarding time to nerve injury, non-invasive measurement, and earlier evidence-based mitigation.