TORS De-Intensification Protocol Version 2.0: Dose and Volume Reduction in the Neck

Study Overview
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Brief Summary
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This is a single-arm Phase II study of adjuvant radiation for locally advanced p16+ oropharyngeal squamous cell carcinoma. The main purpose of this research is to determine the likelihood of cancer growing back in the throat or in the neck two years after completion of radiation if lower doses of radiation are used to a smaller area of the head and neck region than is currently used in standard of care.

Detailed Description
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This is a single arm Phase II study of adjuvant radiation for locally-advanced p16+ oropharyngeal squamous cell carcinoma. Patients with pT0-T3, N0-N2b, M0 disease (per AJCC 7th ed) with <5 positive lymph nodes, will be eligible. Patients will have undergone TORS primary site resection and ipsilateral neck dissection. Patients will undergo radiation dose reduction and target volume reduction.

Official Title
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A Phase II Study of Volume and Dose De-Intensification Following Transoral Robotic Surgery (TORS) and Neck Dissection for p16+ Oropharyngeal Squamous Cell Carcinoma

Conditions
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Oropharyngeal Cancer, Squamous Cell Carcinoma, Human Papilloma Virus

Intervention / Treatment
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* Radiation: Radiation Therapy (IMRT or IMPT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients >= 18 years old Histologically confirmed diagnosis of squamous cell carcinoma of the oropharynx, p16-positive on immunohistochemistry Pathologic T0 (unknown primary), T1, T2, or T3 disease (per AJCC 7th Ed) Pathologic N0, N1, N2a, or N2b disease (per AJCC 7th Ed), with < 5 positive lymph nodes ECOG Performance Status 0-1 Exclusion Criteria: Prior radiation therapy to the head and neck Presence of T4 disease Presence of N2c or N3 neck disease (per AJCC 7th Ed) >= 5 lymph nodes Presence of distant metastatic disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>All patients will have the volume treated and radiation dose delivered to the regional lymphatics decreased according to the characteristics of the primary site and involved lymph nodes. The high risk neck will receive 50 Gy instead of 60 Gy, and the treated volume of the contralateral low risk neck will be reduced and receive only 45 Gy. | Radiation: Radiation Therapy (IMRT or IMPT)<br>* Treatment of the primary tumor bed will be omitted in appropriate patients, as per the initial TORS de-intensification protocol. In those patients requiring treatment of the primary site, reduced dose (50 Gy) will be delivered. Receipt of concurrent chemotherapy per current guidelines. Chemotherapy may be omitted in patients with focal or microscopic ENE (defined as ≤ 1 mm ENE), at the discretion of the treating Medical Oncologist. Blood samples will be obtained at time of enrollment, and at two time points during RT, to quantify circulating HPV DNA and perform immune profiling.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year locoregional control | Number of patients with 2-year locoregional control, defined as control at the primary site and in the neck, in patients undergoing de-intensified radiation to the primary site and regional lymphatics after Transoral Robotic Surgery (TORS) and neck dissection for p16+ oropharyngeal squamous cell carcinoma (OPSCC) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related toxicity | Number of participants with treatment-related toxicity as gauged by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. the CTCAE v.5 utilizes a five point scale to report Adverse Events (AEs), defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of medical treatment or procedure that may or may not be considered related to the medical treatment or procedure (cancer.gov) | 2 years | 
| 2-year progression-free survival | Number of participants with 2-year progression-free survival, defined as the length of time during and after treatment that a patient lives with the disease but it does not get worse (nih.gov) | 3 years | 
| Differences in toxicity between Intensity-modulated radiation therapy (IMRT) and Intensity Modulated Proton Therapy (IMPT) | Differences in toxicity outcomes in patients treated with IMRT versus proton therapy | 1 year | 
| Number of participants with change in circulating human papillomavirus(HPV) DNA over the course of treatment | Number of patients with a change in circulating HPV cells during the course of treatment, determined using a next generation sequencing (NGS) assay developed to detect HPV DNA in HPV+ oropharyngeal squamous cell carcinoma patients. | 2 years | 
| Metastasis-free survival | Number of participants with metastasis-free survival | 3 years | 
| Patient reported quality of life outcomes | Patient reported quality of life (QOL) outcomes using MD Anderson Symptom Inventory (MDASI) Head and Neck survey between patients treated with IMRT and IMPT. The MDASI-HN assesses the severity of symptoms in the last 24 hours using a 0-10 scale, with 0 being not present and 10 being as bad as you can imagine. The interference of symptoms in the last 24 hours is assessed using a 0-10 scale, with 0 being did not interfere and 10 being interfered completely. The mean of symptom severity and interference can be used to represent overall symptom distress and can be analyzed for changes over treatment and during follow-up. | 2.5 years | 
| Overall survival | Number of patients with overall survival, as defined by the length of time from the date of diagnosis or start of treatment for a disease that patients diagnosed with the disease are still alive (cancer.gov) | 5 years |