Functional Burden Associated with Late Lower Cranial Neuropathy in Long-Term Oropharyngeal Cancer Survivors Treated with Definitive Radiation Therapy

Abstract

Lower cranial neuropathy (LCNP) is a rare potentially disabling late toxicity induced by damage due to radiotherapy (RT) and other cancer therapies. The objective of this paper was to examine the impact of late LCNP on functional burden and swallowing related QOL. We hypothesized that OPC survivors with late LCNP would report significantly worse swallowing-related QOL scores. A total of 882 OPC survivors (median survival time: 7 years) who received definitive RT at an institution between January 2000 – December 2013 completed a cross-sectional survey (56% response rate) that included the MD Anderson Dysphagia Inventory (MDADI). The 19-item composite MDADI score representing overall swallowing-related QOL was the primary outcome and composite emotional, physical and functional subscale scores were secondary outcomes. Late LCNP events defined by onset >3-months after cancer therapy were abstracted from medical records. Multivariate models regressed MDADI scores on late LCNP status adjusting for clinical covariates. A total of 3.9% (n=34) of respondents (median survival time: 11.5 years) developed late LCNP. Among them, 50% were treated with RT and concurrent chemotherapy and 32%with RT only. They were treated with a higher total mean RT dose (LCNP: 69.5 vs. 68.2 Gy, p<0.001), 64% received IMRT-SF and 26% received 3D Conformal RT. Patients with late LCNP reported significantly worse mean composites scores (LCNP: 67.6 vs. no LCNP: 79.8, p<0.001). Late LCNP was independently associated with worse mean composite scores (β= -7.6, p=0.007, 95%CI: -13.1, -2.0) adjusting for age, survival time, sex, education, treatment modality, T-stage, subsite, RT type, solid food at baseline and smoking. Subscale scores that were most severe, in rank order of means, included physical (LCNP: 62.0 vs. no LCNP: 75.5, p<0.001), global (LCNP: 64.1 vs. no LCNP: 80.8, p<0.001), emotional (LCNP: 69.9 vs. no LCNP: 80.6, p<0.001) and functional scores (LCNP: 73.8 vs. no LCNP: 85.5, p<0.001). Late LCNP was independently associated with worse physical (β = - 8.8, p=0.008, 95%CI: - 15.23, -2.29), global (β = -10.6, p=0.01, 95%CI: -18.6, - 2.5), emotional (β = -6.1, p=0.035, 95%CI: -11.7, -4.2) and functional scores (β = -7.5, p=0.009, 95%CI: -13.0, -1.9) adjusting for age, survival time, sex, education, treatment modality, T-stage, subsite, RT type, solid food at baseline and smoking. In our large survey study, OPC survivors with late LCNP reported significantly poor swallowing related QOL and higher levels of functional impairment. Late LCNP may lead to profound deficits in swallowing, extended placement of feeding tubes, tracheostomy tubes, and refractory aspiration that can lead to pneumonia and diminished QOL. Further efforts are necessary to alleviate the functional burden associated with this disabling late effect of cancer treatment experienced by OPC survivors.