Tongue-out Radiation Therapy (TORT) for the Mitigation of Radiotherapy-related Toxicities in Patients With Head and Neck Cancer

Overview

Our institution recently began incorporating a novel "tongue-out" radiation therapy (TORT) technique for patients with head and neck tumors at particular subsites (oropharynx, larynx, hypopharynx). Protruding the tongue, i.e. "tongue-out" position, induces anatomical changes that facilitate decreased radiation dose to the oral tongue and PCM. The long-term goal is to determine whether TORT results in reduced severity and faster recovery from acute treatment-related toxicities (particularly mucositis, dysphagia, and dysgeusia) and improved long-term swallowing function and taste compared to traditional "tongue-in" RT for patients with HNC.

Detailed description

Despite good disease control and organ preservation outcomes after radiotherapy (RT) for head and neck cancers (HNC), particularly human papillomavirus (HPV)-related oropharyngeal cancer, treatment-related toxicities remain a challenging survivorship problem. Impaired calorie intake due to common RT-associated toxicities such as mucositis, dysphagia (difficulty swallowing), and dysgeusia (taste loss) can lead to treatment breaks that reduce treatment efficacy and prolong recovery, some of which persist long-term and negatively impact quality of life (QOL). Radiation doses to the pharyngeal constrictor muscles (PCM) and oral tongue correlate with incidence and severity of dysphagia and dysgeusia. Doses to the pharyngeal and oral tongue mucosa are associated with incidence and severity of mucositis. "Tongue-out" radiation therapy (TORT) is a treatment positioning technique for patients with head and neck tumors at particular subsites (e.g., oropharynx, larynx, hypopharynx). Protruding the tongue, i.e. "tongue-out" position, during pre-treatment simulation and subsequent treatment induces anatomical changes that facilitate decreased radiation dose to the oral tongue and PCM. TORT for oropharyngeal, laryngeal, and hypopharyngeal cancers may result in significantly lower radiation dose to the PCM and oral tongue compared to "tongue-in" RT, and that this reduced dose to organs at risk (OARs) will yield clinically meaningful improvements in severity and duration of dysphagia, dysgeusia, and mucositis.

Interventions

• Radiation Tongue-out radiation therapy (TORT)
  The high-risk PTV will contain the primary tumor and any lymph nodes confirmed or suspected to harbor metastatic disease based on imaging findings, pathology reports, and/or clinical exam. Dose to the high-risk PTV must be 70.0 Gy at 2.0 Gy per fraction. The intermediate-risk PTV will contain areas considered to contain potential microscopic disease in close proximity to the primary tumor (GTV + 10 mm with adjustments per above based on anatomic boundaries or air) and the entire cervical lymph

Primary outcome measures

• Eating Assessment Tool 10 (EAT-10) [Time frame: At Baseline]
• Eating Assessment Tool 10 (EAT-10) [Time frame: At 6 weeks post-treatment]

Secondary outcome measures (7)

• Eating Assessment Tool 10 (EAT-10) [Time frame: At 58 weeks post treatment]
• Change in Eating Assessment Tool 10 (EAT-10) Scores [Time frame: At Baseline and 6 weeks post-treatment]
• Change in Eating Assessment Tool 10 (EAT-10) Scores [Time frame: At Baseline and 58 weeks post treatment]
• University of Washington Quality of Life Questionnaire (UW-QOL) [Time frame: At 6 weeks post-treatment]
• Change in QoL per University of Washington Quality of Life Questionnaire (UW-QOL) [Time frame: At Baseline and 6 weeks post-treatment]
• Difference in radiation doses - oral tongue [Time frame: Up to 38 months]
• Difference in radiation doses - pharyngeal [Time frame: Up to 38 moonths]

Eligibility criteria

Inclusion criteria

• Must have histologically or cytologically confirmed squamous cell carcinoma of the oropharynx, larynx, or hypopharynx (cT0-4, N0-3, M0-1).
• Patients with metastatic disease will be included if the following criteria are met:

• Definitive RT dose is planned for the primary site
• The number of metastatic lesions is ≤5
• All metastatic lesions are confined to a single organ (e.g., lung)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
• Female subjects of childbearing potential must not be pregnant or breastfeeding at screening.

• Female subjects are considered to be of childbearing potential unless one of the following criteria is met:

o Permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes. Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.

• Female subjects of childbearing potential must utilize an appropriate method of birth control such as hormonal methods (oral, injectable, implant, skin patch, vaginal ring), intrauterine devices, barrier methods (consistent use of male/female condoms, diaphragms, cervical caps), surgical methods (vasectomy, tubal ligation), or true abstinence.
• Must be able to comfortably protrude tongue in the treatment position for at least 1 minute.
• Must have the ability to understand and the willingness to sign a written informed consent document.
• Must be willing to comply with all study procedures.
• Must be able to complete patient-reported outcome (PRO) questionnaires in English.

Exclusion criteria

• Patients with T1-T2 N0 glottic cancer (i.e., planned to undergo RT to the larynx only)
• Posterior pharyngeal wall primary tumor
• Widely metastatic disease
• Surgical resection of the primary tumor
• Induction chemotherapy or immunotherapy prior to planned radiotherapy
• Prior head and neck radiotherapy

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• UPMC Hillman Cancer Center — Pittsburgh

Identifiers

NCT: NCT07227792 · HCC 25-085

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗