Vocal Cord vs Whole Laryngeal Radiotherapy for T1aN0 Glottic Cancer (VC-Larynx)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Larynx Cancer Stage I; Glottic Carcinoma
• Intervention / Treatment: Radiation: Hypofractionated single vocal cord irradiation; Radiation: Whole laryngeal radiotherapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mohamed Mortada Elsharief; Phone Number: +0201128512966; Email: drmohamedelcherif@gmail.com

Study Locations

• Egypt
  • Cairo, Egypt, 11796
    • Recruiting
    • National Cancer Institute, Cairo University
    • Contact: Mohamed Mortada Elsharief; Phone Number: +0201128512966; Email: drmohamedelcherif@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single vocal cord hypofractionated radiotherapy; 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; 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
Active Comparator: Whole laryngeal radiotherapy; 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; The whole larynx from lower border of hyoid bone to lower border of cricoid cartilage will receive 63Gy/28 fractions using IMRT/VMAT technique

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute, Egypt
• Collaborators: Cairo University
• Investigators: Principal Investigator: Mohamed Mortada Elsharief, NCI, Cairo University, Egypt; Study Chair: Tarek Shouman, NCI, Cairo University, Egypt

Publications and helpful links

General Publications

• Yamazaki H, Nishiyama K, Tanaka E, Koizumi M, Chatani M. Radiotherapy for early glottic carcinoma (T1N0M0): results of prospective randomized study of radiation fraction size and overall treatment time. Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):77-82. doi: 10.1016/j.ijrobp.2005.06.014. Epub 2005 Sep 19.
• Gowda RV, Henk JM, Mais KL, Sykes AJ, Swindell R, Slevin NJ. Three weeks radiotherapy for T1 glottic cancer: the Christie and Royal Marsden Hospital Experience. Radiother Oncol. 2003 Aug;68(2):105-11. doi: 10.1016/s0167-8140(03)00059-8.
• Al-Mamgani A, Kwa SL, Tans L, Moring M, Fransen D, Mehilal R, Verduijn GM, Baatenburg de Jong RJ, Heijmen BJ, Levendag PC. Single Vocal Cord Irradiation: Image Guided Intensity Modulated Hypofractionated Radiation Therapy for T1a Glottic Cancer: Early Clinical Results. Int J Radiat Oncol Biol Phys. 2015 Oct 1;93(2):337-43. doi: 10.1016/j.ijrobp.2015.06.016. Epub 2015 Jun 14.
• Osman SO, Astreinidou E, de Boer HC, Keskin-Cambay F, Breedveld S, Voet P, Al-Mamgani A, Heijmen BJ, Levendag PC. IMRT for image-guided single vocal cord irradiation. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):989-97. doi: 10.1016/j.ijrobp.2010.12.022. Epub 2011 Feb 6.
• Dornfeld K, Simmons JR, Karnell L, Karnell M, Funk G, Yao M, Wacha J, Zimmerman B, Buatti JM. Radiation doses to structures within and adjacent to the larynx are correlated with long-term diet- and speech-related quality of life. Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):750-7. doi: 10.1016/j.ijrobp.2007.01.047. Epub 2007 Apr 6.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: January 10, 2023
• First Posted (Estimate): January 11, 2023

Study Record Updates

• Last Update Posted (Estimate): January 11, 2023
• Last Update Submitted That Met QC Criteria: January 10, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Larynx; hypofractionated radiotherapy; T1; Glottic; Vocal cord; Laryngeal carcinoma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Respiratory Tract Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Laryngeal Diseases; Laryngeal Neoplasms
• Other Study ID Numbers: R02002-30908

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: Yes
• product manufactured in and exported from the U.S.: Yes