Elective Level Ib Irradiation in Nasopharyngeal Carcinoma Patients Based on the International Guidelines

Study Overview
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Brief Summary
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Currently, nasopharyngeal carcinoma (NPC) patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II will be recommended to receive level Ib-covering IMRT according to the International Guidelines. Our previous study, which retrospectively analyzed a cohort of 390 patients, indicated that it should be safe and feasible for patients who only had at least one of the above two radiological features. Thus, the investigators conduct this non-inferior phase 3, randomized trial to further determine the feasibility of sparing level Ib in patients who had level II involvement with ECE, and/or had a MAD of greater than 2cm in level II.

Detailed Description
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Currently, nasopharyngeal carcinoma (NPC) patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II will be recommended to receive level Ib-covering IMRT according to the International Guidelines. Our previous study, which retrospectively analyzed a cohort of 390 patients, indicated that it should be safe and feasible for patients who only had at least one of the above two radiological features. Thus, the investigators conduct this non-inferior phase 3, randomized trial to further determine the feasibility of sparing level Ib in patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II.

Official Title
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Elective Level Ib Irradiation in Nasopharyngeal Carcinoma Patients Based on the International Guidelines: an Open-label, Non-inferiority, Multicentre, Randomised Phase 3 Trial

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Radiation: level Ib-covering IMRT
* Radiation: level Ib-sparing IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed, non-metastatic nasopharyngeal carcinoma histologically confirmed by biopsy; the following conditions: ① involvement of level II LNs with extracapsular extension(ECE); ② level II LNs involvement with maximum nodal axial diameter (MAD) greater than 2 cm; Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. Exclusion Criteria: level Ib involvement with positive pathological results; submandibular glands (SMGs) involvement; involvement of structures that drain to level Ib as the first echelon site (the oral cavity, anterior half of nasal cavity involvement); previous malignancy or other concomitant malignant disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: level Ib-covering IMRT<br>Patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II. | Radiation: level Ib-covering IMRT<br>* Patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II.<br>|
| Experimental: level Ib-sparing IMRT<br>Patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II | Radiation: level Ib-sparing IMRT<br>* Patients who had level II involvement with extracapsular extension (ECE), and/or had a maximum nodal axial diameter (MAD) of greater than 2cm in level II.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional relapse-free survival | The regional relapse-free survival rate will be estimated using Kaplan-Meier method for each arm from the date of randomization to the date of nodal relapse or death from any cause, whichever occurred first. Their differences will be compared between treatment arms using the log-rank test. | 3 year | 
| level Ib recurrence rate | The level Ib recurrent rate will be calculated by the ratio of mumbers of patients relapsed in level Ib and the numbers of cases in the whole group. | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local relapse-free survival | The local relapse-free survival rate will be estimated using Kaplan-Meier method for each arm from the date of randomization to documented local relapse or death from any cause. Their differences will be compared between treatment arms using the log-rank test. | 3 year | 
| Distant metastasis-free survival | The distant metastasis-free survival rate will be estimated using Kaplan-Meier method for each arm from the date of randomization to documented distant metastasis or death from any cause. Their differences will be compared between treatment arms using the log-rank test. | 3 year | 
| Overall survival | The overall survival rate will be estimated using Kaplan-Meier method for each arm from the date of randomization to death from any cause. Their differences will be compared between treatment arms using the log-rank test. | 3 year | 
| Patient's quality-of-life: dry mouth | European Organization for Research and Treatment of Cancer Quality-of-Life Head and Neck 35 items (QLQ-H&N35) version 1.0 questionnaires will be used to assess quality-of-life. All items pointing to this domain are averaged and then transformed to a scale of 0-100 according to the EORTC scoring manual. Higher scores on the symptom scales indicate more severe symptoms. | 3 year | 
| Patient's quality-of-life: sticky saliva | European Organization for Research and Treatment of Cancer Quality-of-Life Head and Neck 35 items (QLQ-H&N35) version 1.0 questionnaires will be used to assess quality-of-life. All items pointing to this domain are averaged and then transformed to a scale of 0-100 according to the EORTC scoring manual. Higher scores on the symptom scales indicate more severe symptoms. | 3 year |