Preservation of swallowing in resected oral cavity squamous cell carcinoma: examining radiation volume effects (PRESERVE): study protocol for a randomized phase II trial

Pencilla Lang, Jessika Contreras, Noah Kalman, Claire Paterson, Houda Bahig, Astrid Billfalk-Kelly, Sinead Brennan, Kathy Rock, Nancy Read, Varagur Venkatesan, Jinka Sathya, Lucas C Mendez, S Danielle MacNeil, Anthony C Nichols, Kevin Fung, Adrian Mendez, Eric Winquist, Sara Kuruvilla, Paul Stewart, Andrew Warner, Sylvia Mitchell, Julie A Theurer, David A Palma, Pencilla Lang, Jessika Contreras, Noah Kalman, Claire Paterson, Houda Bahig, Astrid Billfalk-Kelly, Sinead Brennan, Kathy Rock, Nancy Read, Varagur Venkatesan, Jinka Sathya, Lucas C Mendez, S Danielle MacNeil, Anthony C Nichols, Kevin Fung, Adrian Mendez, Eric Winquist, Sara Kuruvilla, Paul Stewart, Andrew Warner, Sylvia Mitchell, Julie A Theurer, David A Palma

Abstract

Background: Patients with resected oral cavity squamous cell carcinoma (OCSCC) are often treated with adjuvant radiation (RT) ± concomitant chemotherapy based on pathological findings. Standard RT volumes include all surgically dissected areas, including the tumour bed and dissected neck. RT has significant acute and long-term toxicities including odynophagia, dysphagia, dermatitis and fibrosis. The goal of this study is to assess the rate of regional failure with omission of radiation to the surgically dissected pathologically node negative (pN0) hemi-neck(s) compared to historical control, and to compare oncologic outcomes, toxicity, and quality of life (QoL) profiles between standard RT volumes and omission of RT to the pN0 neck.

Methods: This is a multicentre phase II study randomizing 90 patients with T1-4 N0-2 OCSCC with at least one pN0 hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). Patients will be stratified based on overall nodal status (nodal involvement vs. no nodal involvement) and use of concurrent chemotherapy. The primary endpoint is regional failure in the pN0 hemi-neck(s); we hypothesize that a 2-year regional recurrence of 20% or less will be achieved. Secondary endpoints include overall and progression-free survival, local recurrence, rate of salvage therapy, toxicity and QoL.

Discussion: This study will provide an assessment of omission of RT to the dissected pN0 hemi-neck(s) on oncologic outcomes, QoL and toxicity. Results will inform the design of future definitive phase III trials.

Trial registration: Clinicaltrials.gov identifier: NCT03997643 . Date of registration: June 25, 2019, Current version: 2.0 on July 11 2020.

Keywords: De-escalation; Head and neck cancer; Oral cavity; Quality of life; Radiotherapy; Randomized controlled trial; Recurrence; Survival.

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Study schema
Fig. 2
Fig. 2
The “Randomization Volume” corresponds to the pN0 hemi-neck(s). The neck volumes included in the “Randomization Volume” depend on whether the patient had an ipsilateral vs. bilateral neck dissection, and the pathological findings in each hemi-neck(s). Patients with bilaterally involved neck nodes are ineligible. Patients with an ipsilateral neck dissection with positive lymph nodes are ineligible unless they undergo a contralateral neck dissection that is pN0. If randomized to standard treatment volumes (Arm 1), all contoured volumes, including the “Randomization Volume” will be treated. If randomized to omission of the pN0 neck (Arm 2), the “Randomization Volume” will be omitted from treatment planning
Fig. 3
Fig. 3
Flowchart showing timing of randomization with respect to peer review and treatment planning. Contours must be finalized before randomization and may not be changed after randomization

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