Individualized Elective Neck Irradiation Based on MRI in NPC Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Radiation: Elective neck irradiation
* Radiation: Whole neck irradiation


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Elective neck irradiation<br>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<br>* 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.<br>|
| Active Comparator: Whole neck irradiation<br>Whole neck irradiation is given regardless of the involved or uninvolved neck. | Radiation: Whole neck irradiation<br>* Whole neck irradiation is given regardless of the involved or uninvolved neck.<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 | 

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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nasopharyngeal carcinoma, elective neck irradiation, upper neck irradiation, whole neck irradiation