Neoplasms

All Conditions

Digestive System Diseases

Ear, Nose, and Throat Diseases

Mouth and Tooth Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Deglutition Disorders

Esophageal Diseases

Gastrointestinal Diseases

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Participants will be trained to initiate swallowing during expiration.

Participants will practice swallowing, but will not learn the key therapeutic element (i.e., initiating swallowing during expiration).

Participants will complete 6 respiratory-swallow phase training sessions that will last approximately one hour.

Respiratory-Swallow Phase Training

Participants will complete 6 "swallow practice" sessions that will last approximately one hour.

Swallow Practice

Bonnie Martin-Harris, PhD

Head and neck cancers have escalated to epidemic levels in the United States, and survivors are suffering from life-long, devastating swallowing disorders with limited therapeutic options. This clinical trial investigates a novel swallowing treatment that trains initiation of swallowing during the expiratory phase of respiration to improve swallowing safety and efficiency.

Head and neck cancers (HNC) have increased to epidemic levels in the United States. Despite good response to cancer treatment, survivors are suffering life-long toxicities that result in swallowing problems (dysphagia). Treatment options for dysphagia after HNC are extremely limited, focus on swallowing movements alone, and do not consider the importance of respiratory-swallow phase patterning. Prior evidence has demonstrated that when aberrant respiratory-swallow phase patterning is present (initiation of swallowing during inspiration) in patients with HNC, there is a higher occurrence of swallowing impairments, increased residue, and airway invasion. Further, it has been well established that the expiratory limb of the respiratory cycle provides a biomechanically advantageous set point in which to initiate safe and efficient swallowing. This randomized, controlled, Phase II clinical trial examines if respiratory-swallow phase training improves airway protection and swallowing efficiency in HNC survivors who are three or more months post-completion of first-line cancer treatment. The primary goal (Aim 1) is to determine if respiratory-swallow phase training results in increased frequency (%) of swallows initiated during expiration and improved swallowing safety. The secondary goal (Aim 2) is to examine the impact of respiratory-swallow phase training on the frequency of swallows initiated during expiration in wakeful, naturalistic swallowing environments, including eating and drinking. The investigators will recruit 88 HNC survivors with dysphagia, impaired respiratory-swallow phase patterning, and airway compromise. The investigators will deliver therapy remotely using a telehealth platform and an innovative wearable sensor that provides real-time visual feedback of respiratory-swallow movements. Endpoints will be measured from synchronized videofluoroscopic and respiratory-swallow sensor recordings at baseline, within 1-week post-treatment, and 1-month and 3-months post-treatment.

Participants and outcome assessors will be naive to experimental condition.

Training Swallowing Initiation During Expiration

Training Swallowing Initiation During Expiration: Impact on Safety and Efficiency Following Treatment for Oropharyngeal Head and Neck Cancer

Evaluates the impact of dysphagia on the quality of life of patients with head and neck cancer

Determines percent (frequency) of the target (expiratory phase) for each swallow.

Measures presence, depth and reaction to penetration and aspiration.

Quantifies pharyngeal space residue obtained in the lateral view during Modified Barium Swallow Study (MBSS)

Measures physiologic swallowing impairment from observations of MBSS recordings

Northwestern Memorial Hospital

Northwestern University

Professor

Oropharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Stomatognathic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Pembrolizumab

Antibodies

Antibodies, Monoclonal

Cetuximab

Cisplatin

Immunomodulating Agents

Durvalumab

Immunoglobulins

Mitogens

Antibodies, Blocking

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients treated with definitive RT and chemotherapy (cisplatin) or targeted therapy (cetuximab)

Patients treated with definitive RT and immunotherapy (pembrolizumab, nivolumab, or durvalumab)

Routine radiation dosing (approximately 70 Gy in 35 fractions over 6.5 weeks) to the head and neck for the treatment of head and neck cancer

Radiation Therapy

Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor used for the treatment of head and neck cancer

Cisplatin is a chemotherapy medication used to treat a number of cancers, including head and neck cancer

Chemotherapy

Keytruda or Pembrolizumab is a highly selective humanized monoclonal IgG4 antibody directed against the PD-1 receptor on the cell surface.

Opdivo or Nivolumab is a targeted therapy. It is a human programmed death receptor-1 (PD-1) blocking antibody.

Imfinzi or Durvalumab is an anti-cancer ("antineoplastic") drug. This medication is classified as an Anti-PD-L1 monoclonal antibody.

Immunotherapy

Khusbu Singh, MBBS, CCRP

Gerald Henderson

Khushbu Singh, MBBS, CCRP

Loren Mell, MD

Gerald Henderson, BA

Loren K Mell, MD

To use novel methods for quantitative analysis of VFSS (videofluoroscopic swallow study, also known as modified barium swallow) to study and compare dysphagia in patients treated for head and neck carcinoma with concurrent radiation therapy and chemotherapy (cisplatin) or targeted therapy (cetuximab) vs. immunotherapy (pembrolizumab, nivolumab, or durvalumab).

Our hypothesis is that pharyngeal constriction will be greater (lower ratio) with concurrent immunotherapy compared to chemotherapy, as measured by the pharyngeal constriction ratio (PCR).

The QUASAR study will use a prospective, observational, cross sectional design (See Schema). HNC patients treated with definitive RT and immunotherapy or chemotherapy (cetuximab or cisplatin) will undergo VFSS at 4-6 and 12-24 months post-treatment. Patients enrolled prior to 6 months after finishing therapy will undergo a swallow study during the 4-6 month period AND the 12-24 month period. Patients enrolled after 6 months after finishing therapy will undergo a single swallow study in the 12-24 month period. The primary endpoint of PCR at 12-24 months will be compared between patients treated with immunotherapy versus chemotherapy.

All patients with HNC treated with definitive RT and systemic therapy at our institution will be eligible. In particular, we will recruit patients for this study from participants in two ongoing trials investigating the use of concurrent immunotherapy. The KEYCHAIN trial (ClinicalTrials.gov Identifier: NCT03383094) randomizes patients with locally advanced p16+ HNC undergoing definitive RT to concurrent q3 week cisplatin versus concurrent and adjuvant pembrolizumab. NRG-HN004 (ClinicalTrials.gov Identifier: NCT03258554) is a cooperative group trial that compares HNC patients that are not eligible for cisplatin undergoing definitive radiation therapy to concurrent cetuximab versus durvalumab.

QUantitative Assessment of Swallowing After Radiation (QUASAR)

QUantitative Assessment of Swallowing After Radiation (QUASAR): A Longitudinal Comparison of Swallowing Function by Systemic Therapy in Head and Neck Cancer Patients

will use a two-sample t-test at 0.05 level to compare Pharyngeal Constriction Ratio (PCR) between groups

To compare swallowing function between systemic therapies with additional quantitative metrics of swallowing dysfunction from the VFSS including TPT, PRR and PPWT.

The presence of aspiration or strictures on VFSS will be compared as binary variables between groups using Pearson's Chi squared test.

To compare patient reported assessments of swallowing function with the EAT-10 tool between systemic therapies.

To test if there is correlation between the quantitative VFSS metrics and patient reported outcomes on the EAT-10 index, we will calculate Pearson's correlation coefficient and plot the results on a correlation matrix. The Holm step down procedure will be used to adjust for multiple testing to control the family-wise error rate at 0.05 level.

The purpose of this aim is to evaluate the effect of radiation dose on swallowing structures, applying a previously developed space-preserving NTCP approach based on principal component analysis (PCA).

Using this approach, dose distributions to the global swallowing apparatus (i.e. pharynx, larynx and esophagus) will be standardized for patients from both arms of Aim 1, using deformable registration to standardize organs and 3-D dose distributions to a common template. Dose distributions will be converted into a dose array and PCA will be applied to the dose array, as previously described. We will then use PC linear regression to identify eigenvectors significantly associated with long term dysphagia (as measured by PCR).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Training Swallowing Initiation During Expiration	NCT05278039	Head and Neck C... Dysphagia Oropharyngeal D... Oropharynx Squa...	Respiratory-Swa... Swallow Practic...	18 Years -	Northwestern University
QUantitative Assessment of Swallowing After Radiation (QUASAR)	NCT04359199	Head and Neck C... Dysphagia Oropharyngeal D... Oropharynx Canc... Oropharynx Squa...	Radiation Thera... Cetuximab Chemotherapy Immunotherapy	18 Years -	University of California, San Diego
Training Swallowing Initiation During Expiration	NCT05278039	Head and Neck C... Dysphagia Oropharyngeal D... Oropharynx Squa...	Respiratory-Swa... Swallow Practic...	18 Years -	Northwestern University
Training Swallowing Initiation During Expiration	NCT05278039	Head and Neck C... Dysphagia Oropharyngeal D... Oropharynx Squa...	Respiratory-Swa... Swallow Practic...	18 Years -	Northwestern University

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