Late dysphagia years after head and neck cancer (HNC) presents a challenging, often treatment-refractory condition. Fibrosis stiffens connective tissues and compresses peripheral nerve tracts, thereby contributing to diminished strength and possibly denervation of swallowing muscles. Manual therapy (MT) is commonly used in cancer survivors for pain and other indications. However few studies examine how increasing blood flow and cervical range of motion (CROM) might influence late dysphagia.
1) Determine the feasibility and safety of MT to treat fibrosis-related late dysphagia in HNC survivors; and 2) examine preliminary efficacy and functional outcomes after MT for this indication.
MANTLE is an ongoing NCI-funded single institution phase I/II, single-arm supportive care trial.
Comprehensive cancer center
Disease-free, adult HNC survivors ≥2 years post-curative-intent radiotherapy for HNC with grade ≥2 fibrosis (per CTCAE v4.0) and grade ≥2 dysphagia (per videofluoroscopy DIGEST) willing and able to return for therapy were eligible. Exclusion criteria included active recurrent/second primary cancers, active radionecrosis or wounds in the MT treatment field, total laryngectomy or total glossectomy, or functionally limiting cardiopulmonary or neuromuscular disease. In the ongoing MANTLE trial, 23 of 24 patients have completed therapy at the time of this preliminary analysis, with projected enrollment completion (n=24) by February 2021.
MANTLE included 10 hourly sessions of MT by a lymphedema certified speech-language pathologist conducted over 6 weeks. During the subsequent 6 week washout period, the patient independently implemented a clinician prescribed home exercise program.
Outcomes and Measures:
Trial completion rate was the primary feasibility endpoint (80% target). Secondary endpoints included CROM, dysphagia severity (per DIGEST), maximum interincisal opening (MIO), swallowing-related QOL (per MDADI), symptom burden (per MDASI-HN), lymphedema/fibrosis symptoms (per L-SIDS), and diet (per PSS-HN). Paired t-tests and Wilcoxon signed-rank tests compared normally and non-normally distributed endpoints pre- and post-MT, respectively.
23 participants began MT a median of 11.2 years after RT. The majority (16/23,70%) were oropharyngeal cancer survivors. Most (19/23, 82.6%) had a history of primary RT ± chemotherapy, and 4/15 (26.7%) had a history of surgery and adjuvant RT/CRT. MT completion rate was 91% (21/23). All 21 completed the full 10 prescribed sessions. Two participants experienced adverse events (2/23, 9% AE rate, grade 3 dyspnea with a history of longstanding bilateral vocal fold paresis and grade 2 hypotension prior to MT that day). The following secondary endpoints significantly improved among the 21 who completed MANTLE: CROM (6/6 tested planes improved p<0.05); total LSIDS (pre: 29.3±11.2 post: 27.6±10.4,, p=0.047); symptom severity (L-SIDS severity mean pre: 82.6±38.6, post: 65.7±30.8, p=0.001); symptom bother (L-SIDS pre: 80.9±42.6 post: 63.6±33.2, p=0.003); MDASI-HN severity (mean pre: 2.7±1.4, post: 1.8±1.00, p=0.001); MDASI-HN interference (mean pre: 2.44±2.1, post: 1.9±2.05, p=0.015) and oral opening (MIO pre: 29.4±10.8, post: 32.8±9.7, p<0.001). MDADI, DIGEST, and PSS-HN did not significantly improve.
Manual therapy is feasible and safe in long-term survivors. Preliminary evidence suggests that 6 weeks of manual therapy is associated with improved CROM and lymphedema/fibrosis and cancer symptom burden. The durability of these outcomes is under investigation.