A Study Evaluating the Contribution of Non-Coplanar Beam Arrangement in Reducing Toxicity in Radiotherapy for Upper Aerodigestive Tract Cancers

Official title

A Randomized Pilot Study Evaluating the Contribution of Non-Coplanar Beam Arrangement in Reducing Toxicity in Radiotherapy for Upper Aerodigestive Tract Cancers

Overview

Cancers of the upper aerodigestive tract (UADT) are frequently treated with external beam radiotherapy, either alone or in combination with chemotherapy. Despite major advances achieved with intensity-modulated radiotherapy (IMRT/VMAT), irradiation of organs at risk (OARs) remains unavoidable and may lead to acute and late toxicities such as xerostomia, hyposalivation, swallowing disorders, and impaired quality of life. These toxicities are closely related to the dose delivered to salivary glands and other critical structures, and recommended OAR dose constraints are often exceeded to ensure adequate tumor coverage. Non-coplanar beam arrangements (NCBA) represent a potential strategy to further reduce radiation dose to OARs while maintaining equivalent target coverage. However, their clinical implementation has been limited due to technical complexity and the risk of collisions between the linear accelerator and the patient. The recent implementation of the opto-numerical solution MapRT® (VisionRT), based on three-dimensional modeling of the patient and the linear accelerator, allows safe and reliable identification of feasible non-coplanar beam trajectories. Retrospective dosimetric analyses conducted at our institution have demonstrated significant dose reductions to several OARs in UADT cancer patients treated with NCBA compared with conventional coplanar beam arrangements, without compromising tumor dose coverage. BaReTox is a prospective, open-label, randomized, single-center pilot trial designed to evaluate the clinical impact of non-coplanar beam radiotherapy on treatment-related toxicities and quality of life in patients with non-operated, non-metastatic squamous cell carcinoma of the oral cavity or oropharynx. Adult patients eligible for curative-intent bilateral radiotherapy, with known HPV (p16) status, are randomized to receive either standard coplanar radiotherapy (control arm) or non-coplanar radiotherapy (experimental arm), with or without concomitant chemotherapy. All patients receive a standard photobiomodulation protocol during radiotherapy. The primary objective is to compare the change in head and neck cancer-specific quality of life between baseline and three months after completion of radiotherapy, assessed using the EORTC QLQ-H\&N35 questionnaire, focusing on swallowing, social eating, and dry mouth domains. Secondary objectives include comparison of acute and late toxicities graded according to CTCAE version 5.0, assessment of salivary function by sialometry, evaluation of global and disease-specific quality of life over time, progression-free survival, feasibility of delivering non-coplanar radiotherapy, dosimetric impact on organs at risk, and evaluation of radiation-induced lymphopenia. This pilot study aims to provide clinical proof of concept for the benefit of non-coplanar beam radiotherapy in reducing toxicity and improving quality of life in patients with UADT cancers

Interventions

• Radiation Coplanar External Beam Radiotherapy
  Patients receive external beam radiotherapy using a coplanar beam arrangement (standard approach) to treat squamous cell carcinoma of the oral cavity or oropharynx. Treatment is delivered according to routine clinical protocols with curative intent.
• Radiation Non-Coplanar External Beam Radiotherapy
  Patients receive external beam radiotherapy using a non-coplanar beam arrangement, planned with 3D modeling (MapRT®) to reduce dose to organs at risk while maintaining tumor coverage. Treatment is delivered according to routine clinical protocols with curative intent.

Primary outcome measures

• Change in Quality of Life (QOL) after Radiotherapy with Coplanar vs Non-Coplanar Beam Arrangement [Time frame: From baseline (before radiotherapy) to 3 months after the completion of radiotherapy.]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Patient diagnosed with non-operated, non-metastatic squamous cell carcinoma of the oral cavity or oropharynx, histologically confirmed, with p16 status determined by immunohistochemistry, and indicated for curative bilateral radiotherapy, with or without concomitant chemotherapy
• Patient scheduled to receive standard photobiomodulation treatment protocol during radiotherapy
• ECOG performance status ≤ 2
• Presence of xerostomia < 1 according to CTCAE v6.0 at pre-inclusion
• Patient able to provide informed consent and capable of complying with study follow-up, including visits for completion of quality of life questionnaires and salivary tests
• Patient affiliated with a social security system or equivalent

Inclusion Criteria (RECOARD 2.0 recommendations) to be confirmed with the information provided by the simulation/plan treatment CT scan :

\- Exceedance of a dose constraint for at least one Organ at Risk (OAR) as defined below with a coplanar beam arrangement :

• The average dose delivered to at least one parotid gland must be greater than 26 Grays, and/or => 65% of the oral cavity receives a dose greater than 30 Grays, and/or
• The average dose delivered to at least one submandibular gland must be greater than 32 Grays, and/or
• The average dose delivered to the larynx exceeds 43.5 Grays.

Exclusion criteria

• Other head and neck locations than the oral cavity and oropharynx, and/or a surgically treated UADT cancer, and/or radiotherapy treatment already started.
• Histologies other than squamous cell carcinoma
• Tumors requiring only unilateral irradiation.
• Non-curative irradiation and/or metastatic patient
• Double tumor localization
• Previous history of head and neck radiotherapy.
• Inability to comply with study follow-up visits and medical assessments due to geographical, social, or psychological reasons.
• Individuals under legal custody or guardianship (including curatorship).
• Pregnant or breastfeeding women (pregnancy test required at inclusion).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• Centre Georges-François Leclerc — Dijon

Identifiers

NCT: NCT07413627 · 2025-A02764-45

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗