Manual Therapy for Fibrosis-Related Late Effect Dysphagia in head and neck cancer survivors: the pilot MANTLE trial.
Ontology highlight
ABSTRACT: Introduction
Late dysphagia that develops or persists years after head and neck cancer (HNC) is a disabling survivorship issue. Fibrosis is thought to stiffen connective tissues and compress peripheral nerve tracts, thereby contributing to diminished strength, flexibility, and in some cases denervation of swallowing muscles. Manual therapy (MT) is used in cancer survivors for pain and other indications, but it is unknown if increasing blood flow, flexibility and cervical range of motion (CROM) in the head and neck may improve late dysphagia.Methods and analysis
Manual Therapy for Fibrosis-Related Late Effect Dysphagia (MANTLE) is a National Cancer Institute-funded prospective single-arm pilot trial evaluating the feasibility, safety and therapeutic potential of MT in patients with late dysphagia after radiotherapy (RT) for HNC. Disease-free survivors ≥2 years after curative-intent RT for HNC with at least moderate dysphagia and grade ≥2 Common Terminology Criteria for Adverse Events version 4.0 fibrosis are eligible. The target sample size is 24 participants who begin the MANTLE programme. MANTLE is delivered in 10 MT sessions over 6 weeks with an accompanying home exercise programme (HEP). Patients then transition to a 6-week post-washout period during which they complete the HEP and then return for a final post-washout evaluation. Feasibility (primary endpoint) and safety will be examined. Serial assessments include CROM, modified barium swallow studies, quantitative MRI, electromyography (optional) and patient-reported outcomes as secondary, tertiary and exploratory endpoints.Ethics and dissemination
The research protocol and informed consent document was approved by the Institutional Review Board at the University of Texas MD Anderson Cancer Center. Findings will be disseminated through peer-reviewed publication that will be made publicly available on PubMed Central on acceptance for publication, in compliance with NIH public access policy.Trial registration number
NCT03612531.
SUBMITTER: Hutcheson K
PROVIDER: S-EPMC8340274 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Dysphagia is a significant late morbidity following treatment with radiotherapy (RT) for head and neck squamous cell carcinomas (HNSCC). The purpose of this feasibility study was to test a gel-based saliva substitute to reduce the subjective assessment of dysphagia while eating food items varying in size and texture. Eligible study subjects treated with curative intended RT and suffering from dysphagia and xerostomia were recruited from the outpatient clinic during a two-month period. Nineteen subjects consented to participation and completed the EORTC QLQ-H&N35 questionnaire and three test meals. A Numeric Rating Scale (NRS) was used for subjective assessment of dysphagia during all test meals. All data on patient, tumor, and treatment characteristics were obtained from the Danish Head and Neck Cancer (DAHANCA) database. NRS data suggested reduction of dysphagia after application of the oral gel. The swallowing dysfunctions, discomfort while swallowing (p = 0.008), stuck food items (p = 0.02), and multiple attempts of clearing the throat (p = 0.05), improved significantly for soft and regular items. Both small- and large-sized food items were tested. EORTC QLQ-H&N35 showed improvement regarding eating problems (p = 0.03) and social eating (p = 0.02). No episodes of food aspiration were recorded during the test meals. Late dysphagia reduces QOL and is an important morbidity following RT. In this feasibility study, the oral gel was able to reduce dysphagia while eating soft and selected regular food items. Eating-related EORTC QLQ-H&N35 items also improved, indicating a beneficial reduction in dysphagia after application of the oral gel.
| S-EPMC7136308 | biostudies-literature
Project description:Dysphagia is common in head and neck cancer patients after concurrent chemoradiation therapy (CRT). This study evaluated the feasibility of conducting a randomized sham-controlled trial and collected preliminary data on safety and efficacy of acupuncture.Head and neck cancer (HNC) patients with stage III-IV squamous cell carcinoma were randomized to 12 sessions of either active acupuncture (AA) or sham acupuncture (SA) during and following CRT. Patients were blinded to treatment assignment. Swallowing-related quality of life (QOL) was assessed using the MD Anderson Dysphagia Inventory (MDADI) total and subscale scores.Multiple aspects of trial feasibility were confirmed. Forty-two of 196 patients screened (21%) were enrolled and randomized to receive AA (n = 21) or SA (n = 21); 79% completed at least 10 of 12 planned acupuncture sessions; 81% completed the study follow-ups. The majority of patients reported uncertainty regarding their treatment assignment, with no difference between the AA and SA groups. Audits confirmed both AA and SA treatments were delivered with high fidelity. No serious acupuncture-related side effects were observed. MDADI total scores significantly improved from baseline to 12 months post-CRT in both groups (AA: +7.9; SA +13.9; p = .044, p < .001). Similar patterns were observed for the MDADI global subscale (AA: +25.0; SA +22.7; p = .001, p = .002). Intent-to-treat analyses suggested no difference between the treatment groups (p = .17, p = .76 for MDADI total and global scores, respectively).A sham-controlled randomized trial evaluating acupuncture in dysphagia-related QOL in HNC found the procedure to be feasible and safe. Further investigation is required to evaluate efficacy.Dysphagia or swallowing difficulty is an important and common condition after concurrent chemoradiation therapy in head and neck cancer patients. In addition to current available supportive care, acupuncture may offer potential for treating dysphagia. This study demonstrated that both active acupuncture and sham acupuncture are safe and were associated with improved dysphagia-related quality of life from baseline to 12 months after concurrent chemoradiation therapy. This study was not designed to inform underlying specific versus nonspecific effects. Future larger-scale pragmatic clinical trials evaluating the effectiveness of acupuncture versus standard of care are warranted, and further mechanistic research is needed to understand how active versus purportedly sham acupuncture procedures affect dysphagia-related symptoms.
| S-EPMC5153334 | biostudies-literature
Project description:BackgroundRadiation-associated dysphagia is a common and debilitating consequence of treatment for head and neck cancer (HNC). Since commonly employed dysphagia therapy programs for HNC patients still lack authoritative efficacy, some speech-language pathologists (SLPs) have started employing manual therapy (MT) techniques in an attempt to prevent or rehabilitate dysphagia in this patient population. However, exceptionally little is known about the use of MT in this patient population.ObjectivesThe purpose of this study was to describe practice patterns as well as the rate, type, and severity of adverse events associated with SLP provision of MT to HNC patients.MethodsAn Internet-based questionnaire geared toward SLPs who practice MT was developed and sent to SLPs practicing in the United States, 3 times, through 3 national listservs (American Speech Language Hearing Association [ASHA] Special Interest Division 13, ASHA Special Interest Division 3, and University of Iowa Voiceserv), over the course of 4 weeks.ResultsOf the 255 respondents, 116 (45.5%) performed MT on HNC patients. Of these 116 SLPs, 27.6% provided proactive MT during radiation, 62.1% provided 1 to 2 sessions per week, and 94.8% prescribed a MT home program. The rate, type, and severity of reported adverse events were similar between HNC and non-HNC patients.ConclusionThis preliminary survey demonstrated that SLPs provide MT to HNC patients during and after cancer treatment, and that reported adverse events paralleled those experienced by noncancer patients. However, these results should be taken with caution, and a well-designed prospective study is needed to formally establish the safety and the preliminary efficacy of this novel clinical intervention.
| S-EPMC6482656 | biostudies-literature
Project description:Background and purpose:Dysphagia is a common, severe and dose-limiting toxicity after oncological treatment of head and neck cancer (HNC). This study aims to investigate relationships between radiation doses to structures involved in normal swallowing and patient-reported as well as clinically measured swallowing function in HNC patients after curative (chemo-) radiation therapy (RT) with focus on late effects. Materials and methods:Patients (n?=?90) with HNC curatively treated with RT?±?chemotherapy in 2007-2015 were assessed for dysphagia post-treatment by telephone interview and videofluoroscopy (VFS). A study-specific symptom score was used to determine patient-reported dysphagia. The Penetration-Aspiration Scale (PAS) was applied to determine swallowing function by VFS (PAS???4/???6?=?moderate/severe dysphagia). Thirteen anatomical structures involved in normal swallowing were individually delineated on the patients' original planning CT scans and associated dose-volume histograms (DVHs) retrieved. Relationships between structure doses and late toxicity were investigated through univariable and multivariable logistic regression analysis (UVA/MVA) accounting for effects by relevant clinical factors. Results:Median assessment time was 7?months post-RT (range: 5-34?months). Mean dose to the contralateral parotid gland and supraglottic larynx as well as maximum dose to the contralateral anterior digastric muscle predicted patient-reported dysphagia (AUC?=?0.64-0.67). Mean dose to the pharyngeal constrictor muscle, the larynx, the supraglottic larynx and the epiglottis, as well as maximum dose to the contralateral submandibular gland predicted moderate and severe dysphagia by VFS (AUC?=?0.71-0.80). Conclusion:The patients in this cohort were consecutively identified pre-treatment, and were structurally approached and assessed for dysphagia after treatment at a specific time point. In addition to established dysphagia organs-at-risk (OARs), our data suggest that epiglottic and submandibular gland doses are important for swallowing function post-RT. Keeping DVH thresholds below V60?=?60% and V60?=?17%, respectively, may increase chances to reduce occurrence of severe late dysphagia. The results need to be externally validated in future studies.
| S-EPMC6804434 | biostudies-literature
Project description:BackgroundSurvivors of head and neck cancer (HNC) have increased risk of opioid misuse.MethodsUsing Surveillance, Epidemiology and End-Results-Medicare data, we matched adults ≥66 years diagnosed with HNC 2008-2015 with cancer-free controls. We computed odds ratios (OR) for receipt of chronic opioid therapy (COT, claims for ≥90 consecutive days) for HNC survivors compared to controls each year after matching through 2016.ResultsThe cohort of HNC survivors declined from 5107 in the first year after diagnosis to 604 in the sixth year after diagnosis. For 5 years, rates of COT among HNC survivors exceeded that of controls. Differences between survivors and controls declined each year (ORs: year 1, 4.36; year 2, 2.60; year 3, 2.18; year 4, 1.85; and year 5, 1.35; all P-values <.05).ConclusionsAmong older HNC survivors, cancer-associated opioid use in the first years after diagnosis suggests that the benefit of opioids must balance the risk of opioid misuse.
| S-EPMC8405132 | biostudies-literature
Project description:PURPOSE:Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue-sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. METHODS AND MATERIALS:FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares-logistic regression [FPLS-LR] and functional principal component-logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate-response associations, assessed using bootstrapping. RESULTS:The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/-0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/-0.96, 0.79/-0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than approximately 1.0 Gy/fraction were most strongly associated with severe acute mucositis and dysphagia in the FDA models. CONCLUSIONS:FPLS and functional principal component analysis marginally improved predictive performance compared with PLR and provided robust dose-response associations. FDA is recommended for use in normal tissue complication probability modeling.
| S-EPMC5653218 | biostudies-literature
Project description:PurposeLymphedema is a common debilitating late effect among patients post-head and neck cancer (HNC) treatment. Head and neck lymphedema was associated with symptom burden, functional impairment, and decreased quality of life. The objective of this study was to determine the feasibility and potential efficacy of the use of photobiomodulation (PBM) therapy for head and neck lymphedema, symptom burden, and neck range of motion among HNC survivors.MethodsThis was a single-arm, pre- and post-design clinical trial. Eligible patients included those with lymphedema after completion of complete decongestive therapy (CDT) and 3 to 18 months after completion of cancer therapy. The intervention included PBM therapy 2 times a week for 6 weeks for a total of 12 treatments. Lymphedema, symptom burden, and neck range of motion were measured at baseline, end-of-intervention, and 4-week post-intervention.ResultsOf the 12 patients enrolled in the study, 91.7% (n = 11) completed the study intervention and assessment visits, and no adverse events were reported. When comparing the baseline to 4-week post-intervention, we found statistically significant improvements in the severity of external lymphedema, symptom burden, and neck range of motion (all P < .05).ConclusionPBM therapy was feasible and potentially effective for the treatment of head and neck lymphedema. Future randomized controlled trials are warranted to examine the efficacy of PBM therapy for HNC-related lymphedema.Trial registration number and date of registrationClinicalTrials.gov Identifier: NCT03738332; date of registration: November 13, 2018.
| S-EPMC8366198 | biostudies-literature
Project description:ObjectivesTo characterize the late cranial neuropathy among 10-year survivors of head and neck cancer treatment.Materials and methodsWe retrospectively evaluated patients treated with curative-intent radiation for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up ≥ 10 years. New findings of CNP were considered radiation-induced when examination, imaging and/or biopsy did not demonstrate a structural or malignant cause. Cox proportional hazards modeling was used for univariable analysis (UVA) and multivariable analysis (MVA) for time to CNP after completion of radiation.ResultsWe identified 112 patients with no evidence of disease and follow-up ≥ 10 years (median 12.2). Sixteen (14%) patients developed at least one CNP. The median time to CNP was 7.7 years (range 0.6-10.6 years). Most common was CN XII deficit in eight patients (7%), followed by CN X deficit in seven patients (6%). Others included CN V deficit in three, and CN XI deficit in two. Eight of the thirteen patients with a CN X and/or CN XII deficit required a permanent gastrostomy tube. On UVA, site of primary disease, post-radiation neck dissection, chemotherapy, and radiation dose were significantly associated with increased risk of CNP.ConclusionIatrogenic CNP may develop years after head and neck cancer treatment and often leads to swallowing dysfunction. Long-term follow up is essential for these patients receiving head and neck radiation.
| S-EPMC7747216 | biostudies-literature
Project description:ImportanceSurvivors of head and neck cancers (HNC) have increased risk of stroke. A comprehensive report using standardized methods is warranted to characterize the risk and to inform on survivorship strategy.ObjectiveTo determine the stroke risk in subpopulations of survivors of HNC in Singapore.Design, setting, and participantsThis national, registry-based, cross-sectional study aimed to estimate stroke risk in subgroups of the HNC population between January 2005 and December 2020. Participants were identified from the Singapore Cancer Registry, the Singapore Stroke Registry, and the Registry of Birth and Deaths using relevant International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes. HNC subgroups were defined based on patient demographic, disease, and treatment factors. Data were analyzed from September 2022 to September 2023.ExposureDiagnosis of HNC.Main outcomes and measuresBoth ischemic and hemorrhagic stroke were studied. The age-standardized incidence rate ratio (SIRR) and age-standardized incidence rate difference (SIRD) were reported. The Singapore general population (approximately 4 million) served as the reference group for these estimations.ResultsA total of 9803 survivors of HNC (median [IQR] age at diagnosis, 58 [49-68] years; 7166 [73.1%] male) were identified. The most common HNC subsites were nasopharynx (4680 individuals [47.7%]), larynx (1228 individuals [12.5%]), and tongue (1059 individuals [10.8%]). A total of 337 individuals (3.4%) developed stroke over a median (IQR) follow-up of 42.5 (15.0-94.5) months. The overall SIRR was 2.46 (95% CI, 2.21-2.74), and the overall SIRD was 4.11 (95% CI, 3.37-4.85) strokes per 1000 person-years (PY). The cumulative incidence of stroke was 3% at 5 years and 7% at 10 years after HNC diagnosis. The SIRR was highest among individuals diagnosed at younger than 40 years (SIRR, 30.55 [95% CI, 16.24-52.35]). All population subsets defined by age, sex, race and ethnicity, HNC subsites (except tongue), stage, histology, and treatment modalities had increased risk of stroke compared with the general population. The SIRR and SIRD were significantly higher among individuals who had a primary radiation treatment approach (SIRR, 3.01 [95% CI, 2.64-3.43]; SIRD, 5.12 [95% CI, 4.18-6.29] strokes per 1000 PY) compared with a primary surgery approach (SIRR, 1.64 [95% CI, 1.31-2.05]; SIRD, 1.84 [95% CI, 0.923.67] strokes per 1000 PY).Conclusions and relevanceIn this cross-sectional study of survivors of HNC, elevated stroke risks were observed across different age, subsites, and treatment modalities, underscoring the importance of early screening and intervention.
| S-EPMC10865145 | biostudies-literature
Project description:BACKGROUND:Head and neck cancer (HNC) patients are at high risk for developing lymphedema and fibrosis (LEF) following cancer treatment. Once HNC patients develop LEF, they need to conduct life-long self-care to slow LEF progression and reduce associated symptom burden and functional deficits. Data demonstrate that inadequate LEF self-care may be a potentially remediable issue. The objective of this study is to explore the feasibility and preliminary efficacy of an Information-Motivation-Behavioral (IMB) Skills model-driven self-care program (SCP) to improve LEF management and reduce LEF-related symptom burden and functional impairments. METHODS/DESIGN:This is a three-arm, prospective, randomized controlled clinical trial to compare: Group 1 - Usual Care, Group 2 - Usual Care Plus LEF-SCP, and Group 3 - Usual Care Plus LEF-SCP Plus Follow-Up. Participants will be HNC survivors aged >?18?years of age, who meet predefined inclusion and exclusion criteria. A sample size of 75 participants is targeted. Interventions will be provided by trained staff. The study assessments for all groups will take place at five points: study entry then 3, 6, 9, and 12 months post enrollment. Outcome measures include: (1) feasibility (barriers to implementation, safety, and satisfaction) of the proposed intervention; (2) self-efficacy and adherence to self-care; and (3) preliminary efficacy (LEF progression, symptom burden, and functional status) of the proposed intervention. DISCUSSION:This will be the first study to evaluate the feasibility of a LEF-SCP in the HNC population and its impact on self-efficacy and adherence. Furthermore, it will evaluate the potential benefit of routine follow-up on adherence and fidelity to the self-care protocol. We expect that the trial will provide evidence supporting the feasibility of a LEF self-care program. In addition, we anticipate that preliminary data will support improved outcomes including increased adherence and fidelity, and decreased LEF-associated symptoms. TRIAL REGISTRATION:ClinicalTrials.gov, a service of the US National Institute of Health (NCT03030859). Registered on 22 January 2017.
| S-EPMC6935145 | biostudies-literature