title: Late radiation-associated dysphagia (late-RAD) with lower cranial neuropathy after oropharyngeal radiotherapy: a preliminary dosimetric comparison.
abstract: OBJECTIVE
  Late radiation-associated dysphagia (late-RAD) is a rare delayed toxicity, in oropharyngeal cancer (OPC) survivors. Prevention of late-RAD is paramount because the functional impairment can be profound and refractory to standard therapies. The objective of this analysis is to identify candidate dosimetric predictors of late-RAD and associated lower cranial neuropathies after radiotherapy (RT) or chemo-RT (CRT) for OPC.
  
  
  METHODS
  An unmatched retrospective case-control analysis was conducted. Late-RAD cases were identified among OPC patients treated with definitive RT or CRT. Controls were selected with minimum of 6 years without symptoms of late-RAD. Dysphagia-aspiration related structures (DARS) and regions of interest containing cranial nerve paths (RCCNPs) were retrospectively contoured. Dose volume histograms were calculated. Non-parametric bivariate associations were analyzed with Bonferroni correction and multiple logistic regression models were fit.
  
  
  RESULTS
  Thirty-eight patients were included (12 late-RAD cases, 26 controls). Median latency to late-RAD was 5.8 years (range: 4.5-11.3 years). Lower cranial neuropathies were present in 10 of 12 late-RAD cases. Mean superior pharyngeal constrictor (SPC) dose was higher in cases relative to controls (median: 70.5 vs. 61.6 Gy). Mean SPC dose significantly predicted late-RAD (p = 0.036) and related cranial neuropathies (p = 0.019). RCCNPs did not significantly predict late-RAD or cranial neuropathies.
  
  
  CONCLUSIONS
  SPC dose may predict for late-RAD and related lower cranial neuropathies. These data, and those of previous studies that have associated SPC dose with classical dysphagia endpoints, suggest impetus to constrain dose to the SPCs when possible.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77082, United States; Department of Radiation Oncology, Case Western Reserve University Hospitals, Cleveland, OH 44106, United States. Electronic address: muawan@gmail.com.
authors.forename: Musaddiq J
authors.initials: MJ
authors.lastname: Awan
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77082, United States; Department of Clinical Oncology, Faculty of Medicine, The University of Alexandria, Alexandria, Egypt. Electronic address: abdallah.sherif@alexmed.edu.eg.
authors.forename: Abdallah S R
authors.initials: AS
authors.lastname: Mohamed
authors.affiliation: Department of Head & Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, United States. Electronic address: jlewin@mdanderson.org.
authors.forename: Jan S
authors.initials: JS
authors.lastname: Lewin
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77082, United States. Electronic address: cbaron@wesleyan.edu.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Baron
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77082, United States. Electronic address: gbgunn@mdanderson.org.
authors.forename: G Brandon
authors.initials: GB
authors.lastname: Gunn
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77082, United States. Electronic address: dirosenthal@mdanderson.org.
authors.forename: David I
authors.initials: DI
authors.lastname: Rosenthal
authors.affiliation: Department of Head and Neck Surgery, Department of Otolaryngology, Stanford University, Stanford, CA 94305, United States. Electronic address: holsinger@stanford.edu.
authors.forename: F Christopher
authors.initials: FC
authors.lastname: Holsinger
authors.affiliation: Department of Radiation Oncology, The University of Texas Southwestern, Dallas, TX, United States. Electronic address: dschwartz516@gmail.com.
authors.forename: David L
authors.initials: DL
authors.lastname: Schwartz
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77082, United States. Electronic address: cdfuller@mdanderson.org.
authors.forename: Clifton D
authors.initials: CD
authors.lastname: Fuller
authors.affiliation: Department of Head & Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, United States. Electronic address: karnold@mdanderson.org.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hutcheson
mesh_terms: D016022:Case-Control Studies; D003389:Cranial Nerve Diseases / Q000209:etiology*; D003680:Deglutition Disorders / Q000209:etiology*; D006801:Humans; D009959:Oropharyngeal Neoplasms / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012189:Retrospective Studies
keywords: Dysphagia; Oropharyngeal cancer; Pharyngeal constrictors; Quality-of-life; Radiotherapy