Mid-treatment MRI Perfusion Changes in Constrictor Muscles Correlate with Dysphagia

Abstract

Individualized radiation therapy requires assessment of an individual patient’s susceptibility to dysphagia beyond population-based clinical and dosimetric factors. We have previously shown that radiation effects on the pharyngeal constrictors are dose-dependent and that mid-treatment DCE-MRI blood volume (BV) in the constrictors correlate with RT dose. In this study, we aim to evaluate pre- and mid-treatment DCE-MRI imaging parameters in the pharyngeal constrictor muscles and their correlation with dysphagia. Patients with “poor prognosis” head and neck (HN) cancer including human papilloma virus negative (HPV-) loco-regionally advanced HN cancer or stage III AJCC 8 p16+ OPSCC (oropharyngeal squamous cell carcinoma) were enrolled in a randomized phase II trial where high risk tumor subvolumes received 70 vs 86Gy EQD2 with concurrent cisplatin or carboplatin. Multiparametric MRI were acquired at baseline and between fraction (fx) 8-12 of radiation. Analysis were performed on the first 23 patients free of loco-regional recurrence with minimum 12 months of follow-up. Superior, middle and inferior pharyngeal constrictor muscles (SPCM, MPCM and IPCM) were contoured on post contrast T1 MR images and transferred onto BV maps derived from DCE-MRI. Sternocleidomastoid muscle (SCM) was contoured as control. BV changes in the swallowing structures were correlated with RT dose and the following parameters at 3 and 12 months post-RT: IMRT swallow score of videofluoroscopy, EORTC HN35 PRO and any feeding tube use using Spearman rank coefficient. Mean doses to the SPCM, MPCM and IPCM were 59Gy (+/- 6), 56Gy (+/- 9), 33Gy (+/- 17) and respectively. Average BV values were 6.8 (SPCM), 5.8 (MPCM), 5.7 (IPCM) and 2.9 ml/100g (SCM) pretreatment, and changed to 10.4 (SPCM), 9.5 (MPCM), 7.4 (IPCM) and 2.6 (SCM) at 2wk. The increases in BV between pre-treatment and 2wk were significant in SPCM (p=0.01), MPCM (p<0.01), and IPCM (p=0.03), but not in SCM control (p=0.4). There was a significant correlation between the increased BV value at 2wk vs pretreatment and the mean dose in the total constrictor musculature (TPCM) (p=0.03, Spearmen rank correlation). Any feeding tube use was present in 16% of patients at 3 months and 0% at 12 months post-RT. The increased mid-treatment BV values in SPCM and MPCM were significantly correlated with the use of feeding tube at 3 months post-RT (p=0.02 and 0.05, respectively). These findings suggest that MRI BV is a sensitive early indicator of pharyngeal constrictor inflammation and edema. We have also seen significant dispersion of BV estimates between patients, suggesting substantial individual differences in dose-effect relationships. These findings provide a rationale for individualizing swallowing structures doses based on early toxicity prediction. The lack of any feeding tube use at 12mo in this population receiving 70-86Gy to PTVhigh is encouraging.