Hyperfractionated Intensity-modulated Radiotherapy (IMRT) Versus Conventional Fraction IMRT for Patients With Loco-regionally Recurrent Nasopharyngeal Carcinoma.

Study Overview
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Brief Summary
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This study evaluates the hyperfractionated IMRT in the treatment of patients with locally recurrent nasopharyngeal carcinoma. Half of participants will receive hyperfractionated IMRT, while the other half will receive conventional fraction IMRT.

Detailed Description
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Local recurrence is one of the most challenging issues faced with nasopharyngeal carcinoma (NPC) patients. 8.4% to 10.9% of the patients developed recurrent diseases at the primary or/and regional site after definitive radiotherapy. Although some patients with limited recurrent lesions underwent surgery, the main treatment for these recurrent NPC patients was still re-irradiation. Multiple retrospective and prospective studies have reported: under the condition of conventional fraction IMRT with the total dose of 60 gray (Gy) (division 27 times, once a day, every 2.2Gy), you can get a better local tumor control rate and survival outcome. However, the patients still underwent some severe late complications including nasopharyngeal necrosis, nasopharyngeal bleeding, temporal lobe necrosis, with the incidence rates of 28.8%, 18.6%, 20.3%, respectively. Approximately 50% of recurrent NPC patients died of these severe late complications, significantly compromising the overall survival rate of the patients. Previous studies showed that hyperfractionated radiotherapy could reduce severe late complication rates significantly, without affecting the local control rate. Indeed, we found that under the condition of equal irradiation time and tumor equivalent dosage between hyperfractionated IMRT (total dose of 65Gy, division 54 times, twice a day, once 1.2Gy, irradiation interval of 6-8 hours) and conventional fraction IMRT (total dose of 60Gy, division 27 times, once a day, every 2.2Gy), the normal late responding tissues equivalent dosage( EQD2) significantly decreased compared with conventional fraction IMRT. Therefore, the use of hyperfractionated IMRT is expected to decrease severe late complications rates, thereby improving the quality of life and overall survival of patients.

Official Title
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Multiple Centre, Randomised, Controlled Trial of Hyperfractionated IMRT and Conventional Fraction IMRT for Patients With Loco-regionally Recurrent Nasopharyngeal Carcinoma.

Conditions
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Mortality, Nasopharyngeal Neoplasms, Quality of Life, Complications

Intervention / Treatment
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* Radiation: Hyperfractionated IMRT
* Radiation: Conventional Fraction IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically approved WHO III patients received radical radiotherapy initially before recurrence (irradiation dosage > 66 Gy). the interval time between initial treatment and relapse more than 1 year. recurrent Tumor stage2-4(rT2-4) Node stage0-2(rN0-2) Metastasis stage0(rM0) (rT2-4N0-2M0), overall stage II-IVa according to 2009 American Joint Committee on Cancer (AJCC/UICC) Tumor, Node, and Metastasis (TNM) staging system. a Karnofsky performance status (KPS) score more than 70. Exclusion Criteria: a history of previous or synchronous malignant tumors. recurrent Node stage3(rN3), recurrent Metastasis stage1(rM1) according to 2009 AJCC/UICC TNM staging system. positive surgical margin after neck dissection. patients suffered with severe mental illness. severe diseases of the lung and cardiovascular system. severe hepatic and renal dysfunction.

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: Hyperfractionated IMRT Group<br>IMRT (total dose of 65Gy, division 54 times, twice a day, once 1.2Gy, irradiation interval of 6-8 hours) | Radiation: Hyperfractionated IMRT<br> <br> |
| Active Comparator: Conventional Fraction IMRT Group<br>IMRT (total dose of 60Gy, division 27 times, once a day, every 2.2Gy) | Radiation: Conventional Fraction IMRT<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival rate |  | 3 year | 
| Severe late complications rate |  | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life questionnaire |  | 2 year | 
| Loco-regional relapse free survival rate |  | 3 year | 
| Distant metastasis free survival rate |  | 3 year |