Vocal Cord vs Whole Laryngeal Radiotherapy for T1aN0 Glottic Cancer

Study Overview
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Brief Summary
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The primary objective of this prospective randomized clinical trial is to assess non inferiority in terms of local control achieved with single vocal cord hypofractionated radiotherapy compared to standard of care whole laryngeal radiotherapy in patients with T1aN0 glottic cancer . Secondary objectives include overall survival rate and to compare the Voice Handicap Index score between the 2 arms as well as acute and late toxicities. Patients are randomized in 1:1 ratio.

Detailed Description
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Most laryngeal cancers present in early stage and more than two thirds of it occur in the glottic region(T1-T2). Early glottic carcinoma is historically treated with conventional radiotherapy using large box fields (from lower border of hyoid to lower border of cricoid), using wedged parallel opposed photon beams. In spite of good local control rate of more than 90% for T1a glottic cases, the tumor-free contralateral vocal cord, arytenoids, thyroid cartilage, and all muscles responsible for opening and closing the vocal cords, the swallowing muscles, carotid arteries and thyroid gland are exposed to high radiation doses (fully or partially) which could lead to an increased probability of complications that negatively influence the quality of life of these patients. Typical complications have involved voice/ speech impairment, diet problems (swallowing, trismus), arytenoids edema, an increased risk of strokes, and reduced treatment options for previously irradiated patients. Many studies showed that increasing fraction size and shortening the overall treatment time (hypofractionated radiotherapy) could result in better local control of T1 glottic cancer The use of 63Gy/28 Fractions(Fx) showed superior local control compared with conventional use of 66Gy/33Fx with shorter overall treatment time. Based on this study this dose is the standard in our institute. In contrast to the traditional radiotherapy principle to treat the whole larynx, surgical laser excision of T1a glottic cancer involves removal of gross tumor with minimal, often sub-millimeter, excisional margins with good oncological outcome and good quality of voice. Similar to this surgical concept and with modern radiotherapy IMRT/VMAT technique, the approach of single vocal cord irradiation (SVCI) was introduced. A study of 30 patients with T1a glottis cancer treated by image guided vocal cord radiotherapy was published in 2015 and it showed 100% local control at 2 years and with no grade 3 toxicities reported and better quality of voice when compared to historical cohorts Dosimetric analysis showed that IMRT resulted in markedly reducing the dose to contralateral cord, arytenoids, thyroid cartilage, inferior constrictor muscle and carotid arteries. To date no prospective phase 3 trial was done to compare treatment outcome and toxicity profile of vocal cord only hypofractionated radiotherapy vs traditional whole laryngeal radiotherapy.

Official Title
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Vocal Cord Only Hypofractionated Radiotherapy vs Whole Laryngeal Radiotherapy for T1aN0 Glottic Cancer

Conditions
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Larynx Cancer Stage I, Glottic Carcinoma

Intervention / Treatment
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* Radiation: Hypofractionated single vocal cord irradiation
* Radiation: Whole laryngeal radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T10N0 glottic squamous cell carcinoma Ability to provide written informed consent Eastern Cooperative Oncology Group performance status 0-2 Exclusion Criteria: Previous head and neck irradiation. WHO performance status above 2.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single vocal cord hypofractionated radiotherapy<br>Hypofractionated radiotherapy 58.08Gy/16 fractions to affected vocal cord plus margins to account for motion and setup errors using IMRT/VMAT technique | Radiation: Hypofractionated single vocal cord irradiation<br>* Only the affected vocal cord with additional margin to account for motion and setup errors will receive 58.08Gy/16 fractions using IMRT/VMAT technique<br>|
| Active Comparator: Whole laryngeal radiotherapy<br>Radiotherapy 63Gy/28 fractions to whole larynx from lower border of hyoid bone to lower border of cricoid cartilage using IMRT/VMAT technique | Radiation: Whole laryngeal radiotherapy<br>* The whole larynx from lower border of hyoid bone to lower border of cricoid cartilage will receive 63Gy/28 fractions using IMRT/VMAT technique<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control | Rate of local control | at 1 year follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Voice Handicap index | Voice Handicap index score Scores are rated on a 0-4 scale to indicate the presence and severity of the symptoms. Lower scores represent better functioning and quality of life. | Pretreatment- 2 months 6 months 1 year and 1 year follow upn | 
| Rates of acute toxicity | Rates of acute toxicity as per CTCAE v5.0 | Week 0 post-treatment and at 2-month follow-up | 
| Rates of chronic toxicity | Rates of chronic toxicity as per CTCAE v5.0 | at 6 months - 1 year and 2 years follow up | 
| Overall survival | Overall survival | at 2 year follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Larynx, Glottic, T1, hypofractionated radiotherapy, Vocal cord, Laryngeal carcinoma