Shortened Course Adjuvant Radiotherapy Following TORS

A Phase II Study of Shortened Course, Dose De-Intensified Adjuvant Radiotherapy Following Transoral Robotic Surgery (TORS) and Neck Dissection for HPV-Associated Oropharyngeal Squamous Cell Carcinoma

This is a single-arm, phase II study to establish the safety of reducing radiation dose in selected HPV-Associated OPSCC patients receiving adjuvant radiation after TORS and neck dissection. This protocol also allows for sparing of the primary resection bed, in appropriate patients, as previously published by our group and found to be safe and effective.

Study Overview

• Status: Active, not recruiting
• Conditions: HPV-Associated Oropharyngeal Squamous Cell Carcinoma
• Intervention / Treatment: Radiation: Shortened Course Adjuvant Radiotherapy Following TORS

Detailed Description

This is a single-arm Phase II non-inferiority study of adjuvant radiation for locally-advanced HPV-Associated oropharyngeal squamous cell carcinoma. Patients with pT0-T3, N0-N1, M0 disease (per AJCC 8th Edition), detectable pre-operative and undetectable postoperative ctHPVDNA will be eligible. Patients will have undergone TORS primary site resection and neck dissection. Patients will undergo adjuvant RT +/- guideline-indicated chemotherapy. The neck and the primary site will be considered separately.

The primary objective of the study will be to determine the 2-year locoregional control (LRC) rate. Secondary objectives include measures of toxicity (as measured by CTCAE, version 5.0), patient-reported QOL (as measured by the MDASI and MDADI questionnaire), progression-free survival, metastasis-free survival, and overall survival. Differences between patients treated with IMRT and proton therapy in terms of toxicity and QOL will serve as another secondary objective.

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster General Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients ≥ 18 years old
• Histologically confirmed diagnosis of squamous cell carcinoma of the oropharynx, p16-positive on immunohistochemistry or HPV-positive by In-Situ Hybridization
• Pathologic T0 (unknown primary), T1, T2, or T3 disease (per AJCC 8th Ed)
• Pathologic N0-N1 disease (per AJCC 8th Ed)
• Preoperative plasma ctHPVDNA of ≥ 50 copies/mL
• Undetectable postoperative plasma ctHPVDNA
• ECOG Performance Status 0-1

Exclusion Criteria:

• Prior external beam radiation therapy to the head and neck
• Presence of T4 disease
• ≥ 5 positive lymph nodes (which is pathologic N2 disease, per AJCC 8th edition)
• Presence of distant metastatic disease
• Uncontrolled inter-current illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, connective tissue disease or psychiatric illness/social situations that would limit compliance with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Shortened Course Adjuvant Radiotherapy; The volume treated to the regional lymphatics will be according to the characteristics of the primary site and involved lymph nodes. The dose of radiotherapy delivered will be 30 Gy, over the course of 10 treatments (5 daily treatments/week). Treatment of the primary tumor bed will be omitted in appropriate patients, as per the initial TORS de-intensification protocol. In patients requiring treatment of the primary site, reduced dose (30 Gy) will be delivered.

Radiation: Shortened Course Adjuvant Radiotherapy Following TORS; Shortened Course Adjuvant Radiotherapy Following TORS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional control	To determine whether disease recurs locally (at primary site) or in regionally in the nodes of the neck	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	To determine overall survival (alive or not)	2 years
Progression-free survival	To determine progression-free survival (any progression)	2 Years
Metastasis-free survival	To determine metastasis-free survival (any distant metastasis)	2 years
Differences in toxicity between patients receiving IMRT and patients receiving PBT	To assess toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.	2 years
Patient-Reported Quality of Life using MDASI-HN	The MD Anderson Symptom Inventory - Head & Neck (MDASI-HN); Minimum Value: 0; Maximum Value: 280; Higher scores mean worse outcome	2 years
Patient-Reported Quality of Life using MDADI	The MD Anderson Dysphagia Inventory (MDADI); Minimum Value: 20; Maximum Value: 100; Higher scores mean better outcome	2 years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Alexander Lin, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2023
• Primary Completion (Estimated): October 10, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: August 3, 2022
• First Submitted That Met QC Criteria: February 2, 2023
• First Posted (Actual): February 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Squamous Cell
• Other Study ID Numbers: UPCC 06322; 852738 (Other Identifier: University of Pennsylvania Institutional Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No