Parotid sparing adaptive radiotherapy in head and neck cancer.

Phase 3

Recruiting

Conditions: Malignant neoplasms of lip, oral cavity and pharynx, (2) ICD-10 Condition: C32||Malignant neoplasm of larynx,

Registration Number: CTRI/2023/05/052216

Lead Sponsor: Tata Medical Center

Brief Summary: Radiation therapy (RT) is a key component of the treatment of head and neck cancers (HNC). RT is used as the primary treatment in most cancers of the pharynx and larynx and is used as a post-surgical adjuvant therapy in cancers of the oral cavity. Typical radiation therapy treatment schedules include 30-35 fractions of daily treatments delivered 5 days a week over 6-7 weeks. One of the main side-effects of RT for HNC is long-term xerostomia (mouth dryness) due to high doses of RT to the parotid glands, which adversely affects the quality of life. Modern RT techniques involve the use of intensity-modulated RT (IMRT) to spare the parotid glands by very conformally sculpting the radiation dose away from these glands while giving a high dose to the tumor. IMRT is now the preferred way of delivering RT for head and neck cancers.

As RT needs to be delivered with many treatments over several weeks, there are ongoing changes to the position and shape of the anatomy that results in changes to the dose delivered to the parotid gland and other structures. Studies have shown that weight loss and tumor shrinkage during the course of treatment may increase doses to the parotid gland as the treatments go on. To prevent higher doses to the parotid glands, patients can be replanned during the course of RT - a process called adaptive radiation therapy (ART). Parotid glands therefore receiving too little (mean parotid dose less than 25 Gy or more than 30 Gy) over the treatment course may not be optimally benefiting from the dosimetric advantages of ART. Rather parotid glands receiving between 25-30 Gy may be best suited to benefit from dosimetric replanning advantages.

In a prior published study, we demonstrated that ART is feasible and effective in reducing parotid gland doses. But it is a time-consuming process. It is not yet established if the dosimetric gains of ART translates to better clinical outcomes in terms of lower xerostomia or other side effects.

This study is a randomized controlled trial that tests whether ART performed mid-treatment leads to less xerostomia and better quality of life in patients who have increased doses to the parotid gland compared to the initially planned doses.

We plan to enrol consecutive patients aged between 18-80 who receive curative intent RT which involves treatment of both sides of the neck. They will be tested for parotid volume and dose changes between 15-18 fractions of the planned 30 fractions. Those patients who have a greater than 2% dose increase to the parotid glands will be randomized to continue with the initial plan (control arm) or ART (experimental arm). We plan to randomize 144 patients who meet the criteria for adaptation.

We will evaluate several patient-reported outcomes including xerostomia and head and neck quality of life at specified time points before, during, and after RT for a period of 1 year after treatment. We will evaluate if these scores are better in those receiving ART.

If ART improves xerostomia, it will be considered a standard approach for parotid sparing in the future and improve the quality of life of thousands of head and neck cancer patients who receive RT.

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: All

Target Recruitment: 300

Inclusion Criteria

Pathologically proven squamous cell carcinomas of head and neck including oral cavity, oropharynx, hypopharynx, larynx and nasopharynx.
Age between 18 â€“ 80 years Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Undergoing radical or adjuvant radiation/chemoradiation and requiring bilateral neck irradiation.
One or both parotids are intended to receive at least a dose between 25 â€“ 30 Gy in the initial plan.

Exclusion Criteria

Prior surgery of the parotid glands Prior radiation therapy to the head and neck region.
Prior cytotoxic chemotherapy Poor candidates for regular post-treatment surveillance.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Mean XeQoLS score changes with time between the arms	end of treatment, 3 months, 6 months, 9 months and 12 months

Secondary Outcome Measures

Name	Time	Method
Mean EORTC QLQ C30 and HN35 global quality of life, functioning and symptom burden scale changes with time between arms.
Mean XeQoLS domain scores for xerostomia related physical functioning, pain or discomfort, personal / psychological functioning and social functioning changes with time between arms
Disease free survival	Median and 2-year
Overall survival	Median and 2-year

Trial Locations

Locations (1): Tata Medical Center
🇮🇳
Kolkata, WEST BENGAL, India
Tata Medical Center
🇮🇳Kolkata, WEST BENGAL, India
Dr Indranil Mallick
Principal investigator
03366058065
indranil.mallick@tmckolkata.com