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

Oropharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Esophageal Diseases

Gastrointestinal Diseases

Pharyngeal Diseases

Otorhinolaryngologic Diseases

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).

Spots Global Cancer Trial Database for videofluoroscopic swallow study