Manual Therapy for Fibrosis-Related Late Effect Dysphagia in Head and Neck Cancer Survivors: The MANTLE Nonrandomized Clinical Trial.

Abstract

Importance: Late radiation-associated dysphagia (RAD) after head and neck cancer (HNC) treatment is challenging and commonly treatment refractory, with fibrosis stiffening connective tissues and compressing peripheral nerve tracts, contributing to diminished strength and possibly denervation of swallowing muscles. Manual therapy (MT), while common for cancer-related pain and other indications, remains largely unstudied for fibrosis-related late RAD.

Objective: To determine the feasibility and safety of MT, estimate effect size and durability of MT for associated improvements in cervical range of motion (CROM), and examine functional outcomes after MT in survivors of HNC with fibrosis-related late RAD.

Design, setting, and participants: This nonrandomized clinical trial, Manual Therapy for Fibrosis-Related Late Effect (MANTLE) Dysphagia in Head and Neck Cancer Survivors, is a prospective, single-institution, pilot, single-arm supportive care trial conducted at a National Comprehensive Cancer Network-designated academic comprehensive cancer center. Participants were adult survivors of HNC who were disease free at 2 or more years after curative-intent radiotherapy with grade 2 or higher fibrosis (per Common Terminology Criteria for Adverse Events version 4.0) and grade 2 or higher dysphagia (per video fluoroscopy Dynamic Imaging Grade of Swallowing Toxicity [DIGEST]). Data were collected June 2018 to July 2021 and analyzed November 2022 to November 2024.

Intervention: MANTLE included 10 hourly MT sessions by lymphedema-certified speech-language pathologists over 6 weeks with a home exercise program. During the subsequent 6-week washout period, participants implemented only the home exercise program, without clinician MT.

Outcomes and measures: Primary end points were feasibility (per therapy completion rate, with a 75% target) and safety. Secondary end points included functional outcomes per CROM, dysphagia severity (per DIGEST), maximum interincisal opening (MIO), and validated participant-reported outcomes (PROs).

Results: Among 24 survivors of HNC (20 male [83.3%]; median [range] age, 68 [53-80] years), there was a median (range) of 8.9 (2.4-30.2) years after curative-intent radiotherapy. A total of 22 participants (91.7%) completed the 10 prescribed therapy sessions, and 1 participant experienced a severe adverse event. Secondary end points improved among participants who completed the therapy: MIO (r = 0.76; 95% CI, 0.66 to 0.94) and all 6 planes of CROM (eg, cervical extension: r = 0.86; 95% CI, 0.83 to 0.93) improved, with large effect sizes from baseline to after MT. Large to moderate effect sizes were achieved in symptom measures per PROs (eg, lymphedema-fibrosis symptom severity after MT: r = 0.74; 95% CI, 0.63 to 0.99). However, effect sizes were small to moderate or null in uncompensated swallowing outcome measures (eg, MD Anderson Dysphagia Inventory composite score from baseline to after MT: r = 0.38; 95% CI, 0.07 to 0.73).

Conclusions: This study found that MT was safe and feasible in long-term survivors of HNC with late RAD and was associated with several functional, physical, and psychosocial gains. This trial may offer insight into next directions to optimize swallowing outcomes by integrating MT into a comprehensive rehabilitation program.

Trial registration: ClinicalTrials.gov Identifier: NCT03612531.