Individualized Elective Neck Irradiation Based on MRI in NPC Patients (NPC-CTVn)

The Multicenter Randomized Phase 3 Trial of Individualized Elective Neck Irradiation Based on MRI in Patients With Nasopharyngeal Carcinoma

Currently, most protocols of nasopharyngeal carcinoma (NPC) of various research bodies such as the Radiation Therapy Oncology Group require routine elective irradiation to the retropharyngeal area and to levels II-V lymph nodal areas regardless of the status of nodal metastasis. Previous studies had confirmed that the pattern of cervical lymph node (LN) metastasis in NPC followed an orderly manner. Retropharyngeal LNs were the most commonly involved, followed by upper neck levels II, III, or VA nodes, and finally to the lower neck nodes including level IV and VB nodes; and the incidence of LN skip metastasis is rare, ranging from 0.5% to 7.9%. It was rare for NPC patients without neck LN metastases to experience neck failure after elective irradiation to levels II, III and VA. It was also confirmed that with unilateral LN metastases of higher-level LNs usually spread down ipsilateral LNs. Thus, the investigators conduct the non-inferior randomized trial to determine the value of elective neck irradiation in NPC patients with unilateral or bilateral uninvolved neck.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Radiation: Elective neck irradiation; Radiation: Whole neck irradiation

Detailed Description

Currently, most protocols of nasopharyngeal carcinoma (NPC) of various research bodies such as the Radiation Therapy Oncology Group require routine elective irradiation to the retropharyngeal area and to levels II-V lymph nodal areas regardless of the status of nodal metastasis. Previous studies had confirmed that the pattern of cervical lymph node (LN) metastasis in NPC followed an orderly manner. Retropharyngeal LNs were the most commonly involved, followed by upper neck levels II, III, or VA nodes, and finally to the lower neck nodes including level IV and VB nodes; and the incidence of LN skip metastasis is rare, ranging from 0.5% to 7.9%. It was rare for NPC patients without neck LN metastases to experience neck failure after elective irradiation to levels II, III and VA. It was also confirmed that with unilateral LN metastases of higher-level LNs usually spread down ipsilateral LNs. Thus, the investigators conduct the non-inferior randomized trial to determine the value of elective neck irradiation in NPC patients with unilateral or bilateral uninvolved neck.

• Study Type: Interventional
• Enrollment (Actual): 446
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

The eligibility criteria are: newly diagnosed, untreated, non-distant metastatic, and non-keratinizing NPC; with unilateral or bilateral uninvolved neck; aged between 18 and 65 years; Karnofsky performance-status score > 70; adequate haematological function, with a leucocyte count > 4 × 109/L, haemoglobin > 90 g/L, and a thrombocyte count > 100×109/L.

The exclusion criteria include: previous chemotherapy treatment, surgery (except diagnostic) or radiotherapy to the neck or nasopharyngeal regions; previous malignancy; lactation or pregnancy; or severe coexisting illness.

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: Elective neck irradiation; Whole neck irradiation is given in the involved neck. Elective neck irradiation of Level II,III and Va lymph node area is given in the uninvolved neck, and Level IV and Vb lymph node area were not irradiated in the uninvolved neck.	Radiation: Elective neck irradiation; Whole neck irradiation is given in the involved neck. Elective neck irradiation of Level II,III and Va lymph node area is given in the uninvolved neck, and Level IV and Vb lymph node area were not irradiated in the uninvolved neck.
Active Comparator: Whole neck irradiation; Whole neck irradiation is given regardless of the involved or uninvolved neck.	Radiation: Whole neck irradiation; Whole neck irradiation is given regardless of the involved or uninvolved neck.

What is the study measuring?

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiation-related toxicity	Acute and late toxicity will be documented according to RTOG/EORTC System and the CTCAE(Common Terminology Criteria for Adverse Events). Toxicity will be summarized using descriptive statistics.	Within 1 month after radiotherapy for acute toxicity; long term for late toxicity
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
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
Patient's quality-of-life: global health status	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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 global health status suggest better health.	3 year
Patient's quality-of-life: physical functioning	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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 functioning scales suggest better function.	3 year
Patient's quality-of-life: role functioning	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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 functioning scales suggest better function.	3 year
Patient's quality-of-life: emotional functioning	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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 functioning scales suggest better function.	3 year
Patient's quality-of-life: cognitive functioning	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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 functioning scales suggest better function.	3 year
Patient's quality-of-life: social functioning	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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 functioning scales suggest better function.	3 year
Patient's quality-of-life: fatigue	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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: nausea and vomiting	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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: pain	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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: dyspnoea	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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: insomnia	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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: appetite loss	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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: constipation	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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: diarrhoea	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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: financial difficulties	European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 items (QLQ-C30) 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: pain	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: swallowing	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: sense problems	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: speech problems	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: trouble social eating	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: trouble social contact	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: less sexuality	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: teeth	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: open 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: 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
Patient's quality-of-life: coughing	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: felt ill	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: pain killers	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: nutrition supplement	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: feeding tube	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: weight loss	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: weight gain	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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Guilin Medical College; First People's Hoapital of Foshan
• Investigators: Principal Investigator: Linglong Tang, M.D.,PhD, Sun sat-sen University Cancer Center

Publications and helpful links

General Publications

• Tang LL, Huang CL, Zhang N, Jiang W, Wu YS, Huang SH, Mao YP, Liu Q, Li JB, Liang SQ, Qin GJ, Hu WH, Sun Y, Xie FY, Chen L, Zhou GQ, Ma J. Elective upper-neck versus whole-neck irradiation of the uninvolved neck in patients with nasopharyngeal carcinoma: an open-label, non-inferiority, multicentre, randomised phase 3 trial. Lancet Oncol. 2022 Apr;23(4):479-490. doi: 10.1016/S1470-2045(22)00058-4. Epub 2022 Feb 28.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: December 16, 2015
• First Submitted That Met QC Criteria: December 25, 2015
• First Posted (Estimate): December 30, 2015

Study Record Updates

• Last Update Posted (Actual): November 5, 2021
• Last Update Submitted That Met QC Criteria: November 4, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: nasopharyngeal carcinoma; elective neck irradiation; upper neck irradiation; whole neck irradiation
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: 5010-2015-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No