Hypoglossal neuropathy in the pathogenesis of radiation associated dysphagia (hRAD)

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ABSTRACT/SUMMARY Radiation-associated dysphagia (RAD) is a leading driver of QOL and a potentially life-threatening survivorship issue, afflicting more than half of patients treated with curative radiotherapy (RT) for oropharyngeal cancers (OPC). Aspirators are almost 5-times more likely to develop pneumonia than non-aspirators, and pneumonia confers a 42% increased risk of mortality among cancer survivors. Radiation fibrosis has long been considered the primary driver of RAD, but the investigators’ preliminary work points to late cranial neuropathy as a major contributor to truly severe forms of delayed or late-RAD. Cranial neuropathy (denervation) 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 profound functional injury is typically present at the time of diagnosis, limiting therapeutic potential. The long-term goal of this work is to reduce dysphagia burden through mechanistically and technically nimble surveillance algorithms as a major step toward personalized management. Our central hypothesis is that subclinical hypoglossal neuropathy is prevalent and associates with severity of RAD early in HNC survivorship and novel non-invasive lingual high density surface electromyography (HDSEMG) is feasible for quantitative functional surveillance. The objective of the proposed study is to analyze gold-standard needle EMG and experimental HDSEMG of the tongue as an optional procedure in an existing large-scale OPC cohort and two clinical trial datasets that capture robust longitudinal swallowing outcomes data to: 1) estimate prevalence of hypoglossal neuropathy along continuum of survivorship (diagnosis, early, and late) after oropharyngeal radiation (Aim 1); 2) correlate EMG-detected hypoglossal neuropathy and swallowing function over time before and after oropharyngeal radiation (Aim 2); and 3) examine feasibility of HDSEMG as a rapid, non-invasive quantitative screening method for hypoglossal neuropathy (Aim 3). Building upon the highly curated functional data from the MD Anderson OPC Patient-Reported Outcomes/Function (PROF) Core and investigators’ track record of non-invasive signal measurement in the tongue, we are uniquely positioned to accomplish these complementary aims. This high risk/high reward work could lead to practice- change. We expect the outcomes to provide proof of concept that subclinical hypoglossal neuropathy is a mechanism underlying RAD that can be measured with a novel, non-invasive device. Thus, providing data to support a novel and measurable target (subclinical hypoglossal neuropathy) underlying a hugely impactful and potentially deadly common toxicity –RAD– in a fast growing, young OPC survivor population.