QUantitative Assessment of Swallowing After Radiation (QUASAR)

Loren Mell, MD42 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Head and Neck Cancer Dysphagia

Interventions

Radiation TherapyRADIATION

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

CetuximabDRUG

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

ChemotherapyDRUG

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

ImmunotherapyDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Biopsy-proven, un-resected invasive carcinoma of the head and neck. * Treated with definitive RT and concurrent systemic therapy or treated within the past 4-24 months * Concurrent systemic therapy with Cisplatin, Cetuximab or immunotherapy. * Age ≥ 18 * Able to understand and willing to sign a written informed consent. Exclusion Criteria: * Prior radiotherapy that would result in overlap of planned radiation therapy fields. * Prior systemic chemotherapy, unless as part of the coordinated plan of care for the treatment of the carcinoma (e.g., induction/neoadjuvant chemotherapy is allowed) * Planned adjuvant (i.e., following definitive chemoradiotherapy) chemotherapy or surgery

Outcomes

Primary Outcomes

Swallowing function 12-24 months after concurrent radiation and systemic therapy for HNC, as measured by the PCR

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

Time frame: 12-24 months

Secondary Outcomes

Quantitative swallowing function at 4-6 months and 12-24 months by PCR, TPT, PRR and PPWT

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.

Time frame: 4-6 months and 12-24 months

Correlation between quantitative swallowing function and patient reported symptoms using the EAT-10 tool

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.

Time frame: 12-24 months

Correlation between radiation dose and location of swallowing function and quantitative swallowing function

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).

Time frame: 24 months