Plasma miRNAs Predict Radiosensitivity of Different Fractionation Regimes in Palliative Radiotherapy for Advanced Non-small Cell Lung Cancer：Multicenter Controlled Study.(RadimiR-01)

Study Overview
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Brief Summary
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Lung cancer is a malignant tumor that causes the highest morbidity and mortality, and the main pathological type is non-small cell lung cancer (NSCLC). Most of them present with advanced stage at diagnosis. Radiotherapy is an important treatment strategy for advanced non-small cell lung cancer. However patients have different responses to radiotherapy due to individual differences, thus there is still lacking of sensitive markers to predict treatment response at present. Using bioinformatics to process the data and small sample clinical trial, our previous study found 5 plasma miRNAs were related to radiosensitivity. The design is controlled clinical trial. According to the size of lung lesions, the investigators divided the patients into hyperfractionated radiotherapy group（50Gy/11F/2W) with lesion ≤5cm in diameter and conventional fractionated radiotherapy group（60Gy/30F/6W）with lesion >5cm in diameter.

Official Title
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Plasma miRNAs Predict Radiosensitivity of Different Fractionation Regimes in Palliative Radiotherapy for Advanced Non-small Cell Lung Cancer：Multicenter Controlled Study.

Conditions
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Advanced Nsclc

Intervention / Treatment
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* Radiation: radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological histology and/or cytology confirmed NSCLC; Based on AJCC Cancer Staging, IIIA, IIIB, IV lung cancer patients with NSCLC; PS 0-2; Expected survival > 3 months; Age 18 75 years old; The function of lung, liver, kidney, bone marrow was normal; The patients had not received radiotherapy for previous primary tumor and metastases; At least accept 2-4 cycles of chemotherapy,not disease progression after chemotherapy,start radiotherapy in two weeks after the last cycle of chemotherapy; Wild-type EGFR; Sensitive mutant EGFR, but refused to targeted therapy; In line with the indications of radiotherapy and accept it; Voluntarily enrolled to participate in,better compliance, cooperate with experimental observations, and sign informed consent. Exclusion Criteria: Vital organs (e.g., heart, liver, kidney) have serious dysfunction; Patients with other malignancies; Patients with a history of autoimmune disease; The patients are pregnant and lactating (Women of childbearing age need to check the pregnancy test); In the activity of acute or chronic infectious diseases; Patients with a clear history of drug allergy or allergic genus; Patients with participating in other clinical trials at the same time; Other cases that researchers believe that patients should not participate in the present trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hyperfractionated radiotherapy group<br>According to the size of lung lesions,we divided the patients with lesion ≤5cm in diameterand into hyperfractionated radiotherapy group（50Gy/11F/2W). | Radiation: radiotherapy<br>* The patient in supine position with hands catch the plate column by crossing the head, and body fixed by vacuum mould. An enhanced 4DCT scan is conducted with a layer thickness and a distance each of 5 mm. the imaging information is input into the Eclipse program system,the gross tumor volume of the primary tumor (GTVt) and pathological lymph nodes (GTVn) are delineated,GTV is expanded in all 3D direction to create PGTV by 5mm margin for squamous cell carcinoma, or an 8mm margin for adenocarcinoma.Radiaion therapy is delivered by 5F-IMRT.For conventional fractionated radiotherapy,the prescribed dose covering 95% of PGTV is 60Gy/30F/6W.For hyperfractionated radiotherapy,the prescribed dose covering 95% of PGTV is 50Gy/11F/2W.lung V20 <25%, lung V30 <18%, spinal cord <36 Gy.<br>|
| Experimental: conventional fractionated radiotherapy group<br>According to the size of lung lesions,we divided the patients with lesion >5cm in diameterand into conventional fractionated radiotherapy group（60Gy/30F/6W）. | Radiation: radiotherapy<br>* The patient in supine position with hands catch the plate column by crossing the head, and body fixed by vacuum mould. An enhanced 4DCT scan is conducted with a layer thickness and a distance each of 5 mm. the imaging information is input into the Eclipse program system,the gross tumor volume of the primary tumor (GTVt) and pathological lymph nodes (GTVn) are delineated,GTV is expanded in all 3D direction to create PGTV by 5mm margin for squamous cell carcinoma, or an 8mm margin for adenocarcinoma.Radiaion therapy is delivered by 5F-IMRT.For conventional fractionated radiotherapy,the prescribed dose covering 95% of PGTV is 60Gy/30F/6W.For hyperfractionated radiotherapy,the prescribed dose covering 95% of PGTV is 50Gy/11F/2W.lung V20 <25%, lung V30 <18%, spinal cord <36 Gy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate（ORR） | Based on the WHO evaluation criteria for the therapeutic effect of solid tumors, the evaluation of the therapeutic effect was divided into complete remission (CR),partial remission (PR), no change (NC) and progression of disease (PD). The CR + PR meant objective response rate (ORR). | up to two and a half years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between the expression level of miRNAs and the ORR. | Plasma samples were collected in patients with NSCLC before radiotherapy. qRT- PCR was used to detect miRNAs expression in these plasma samples. The correlation between expression of miRNAs and radiotherapy in patients was analyzed and the value of best cut-off miRNA was calculated though receiver operating characteristic (ROC). | up to two and a half years | 
| Progression free survival（PFS） | According to the follow-up data, whether there is difference in progression free survival (PFS) between miRNAs high expression and miRNAs low expression. | up to two and a half years | 
| side effects of radiation | According to the follow-up data, whether there is difference in side effects of radiation between hyperfractionated radiotherapy group and conventional fractionated radiotherapy group. | up to two and a half years | 
| quality of life | According to the follow-up data, whether there is difference in quality of life between hyperfractionated radiotherapy group and conventional fractionated radiotherapy group. | up to two and a half years |