Oropharyngeal Squamous Cell Carcinoma (OPSCC)

This single-arm Phase II trial evaluates whether omission of postoperative radiotherapy is feasible and oncologically safe in select patients with HPV-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC). Eligible patients undergo transoral robotic surgery (TORS) and are observed without adjuvant radiation if they demonstrate low or intermediate pathological risk features and have negative circulating tumor HPV DNA (ctHPVDNA) two weeks post-operatively. Patients are followed with standard clinical surveillance combined with serial ctHPVDNA testing (NavDx®) to facilitate early detection of recurrence and prompt salvage therapy as needed.

This study will evaluate whether adding rimegepant to standard neoadjuvant chemoimmunotherapy can improve treatment response in patients with primary or recurrent oral or oropharyngeal squamous cell carcinoma who are planned to undergo surgery. Rimegepant blocks the receptor for calcitonin gene-related peptide, also known as CGRP. CGRP signaling may affect the tumor immune environment and the response of tumors to anticancer treatment. The study includes an initial safety run-in stage involving 20 participants, followed by a randomized controlled stage involving 200 participants. During the randomized stage, participants will be assigned in a 1:1 ratio to receive standard neoadjuvant chemoimmunotherapy either with or without rimegepant. All participants will receive two cycles of neoadjuvant treatment followed by definitive or intended curative surgery. The main outcome is the major pathological response rate, defined as 10% or less residual viable tumor in the surgical specimen. Other outcomes include pathological complete response, objective response, event-free survival, overall survival, changes in pain and quality of life, and treatment safety.

The purpose of this research study is to investigate the relationship between vascular habitats and treatment response AND to investigate the potential utility of dynamic contrast enhanced (DCE)-MRI derived parameters in predicting treatment response. This data can be used to assist in the development of a clinical decision support (CDS) tool for risk categorization and individualized decision-making. While "low-risk" patients could benefit from de-escalated radiation therapy, "high-risk" patients could receive early initiation of targeted therapies, or immunotherapies.

Patients with human papillomavirus (HPV)-related oropharyngeal cancer generally have very good outcomes. Patients' treatment responses depend more on their individual cancer characteristics and personal risk factors than on the specific type of treatment they receive. However, the different treatments used for this cancer can cause significant side effects. Because outcomes are often favorable regardless of treatment type, reducing treatment-related side effects should be a priority when choosing care. Studies have reported that lowering radiation doses for some patients can reduce side effects while still effectively controlling the cancer. Patients with this type of head and neck cancer typically receive either surgery or radiation as their first treatment. For patients who receive surgery first, radiation to the surgical area and nearby neck lymph nodes is often recommended afterward. In these patients, the study will test whether lowering the radiation dose to low-risk lymph nodes on the side of the neck opposite the tumor can reduce side effects while still effectively controlling the cancer (Method A). For patients who receive radiation as their first treatment, the study will test one or both of two radiation approaches aimed at reducing both short-term and long-term side effects. These approaches include reduced lymph node radiation (Method A, described above) and a tumor dose reduction approach (Method B), which lowers the radiation dose delivered directly to the tumor. Information such as tumor size, the number of cancerous or suspicious lymph nodes, and risk factors like smoking history will be used to determine which patients may be eligible for reduced lymph node radiation (Method A), reduced tumor radiation (Method B), or both. Patients who may qualify for tumor dose reduction (Method B), either alone or combined with Method A, will need an additional blood test called a circulating tumor DNA (ctDNA) test to determine eligibility. The ctDNA test measures small amounts of tumor-related DNA in the blood, which are often elevated at the time of diagnosis. Studies have shown that cancer is more likely to return when ctDNA levels remain positive after treatment. This study will evaluate whether ctDNA levels measured before and during treatment can help identify patients who can safely receive lower radiation doses to the tumor (Method B). Overall, this study aims to safely evaluate two radiation de-escalation approaches in order to lessen short- and long-term side effects while maintaining excellent cancer control.