IMRT and Timing in Combination With EGFRTKI for Stage IV Non-small-cell Lung Cancer

This study is for patients with EFGR gene sensitive mutations diagnosed by pathology or cytology, having a course of chest radiotherapy treatment and molecular Target Therapy for the treatment of stage IV non-small cell lung cancer. Patients with non-small cell lung cancer have a risk of the tumour in the lung recurring or progressing after treatment.

In this study, the investigators aim to verify the following hypothesis:

* whether in combination with concurrent or concomitant EGFR-TKI regimen chemotherapy, Intensity Modulated Radiation Therapy can reduce the risk of the tumour in the lung recurring or progressing similarily.
* Intensity Modulated Radiation Therapy concomitant with EGFR-TKI has a better normal tissue dose/volume tolerance than concurrent regimen.
* the survival can be improved by using this new molecular Target-radiotherapy method.


Eligibility Criteria:
Inclusion Criteria:

* Histologically or cytologically confirmed stage IV NSCLC\[UICC 2017 8th edition\] with known sensitive EGFR mutations(confirmed by tissue or blood).
* Have not received one or more prior treatments
* 18 to 80 years of age.ECOG performance status 0～2 or KPS≥60
* Have distant metastatic lesions≤5；and have clear consciousness when the metastatic sites were brain; and have no influence on pulmonary function when the metastatic sites were lung.
* Have no contraindications in radiotherapy, EGFR-TKI and chemotherapy
* Normal bone marrow and organ function as defined below:

Absolute neutrophil count ≥ 1,500/mcl Platelets ≥ 100,000/mcl Hemoglobin ≥ 9.0 g/dL Total bilirubin ≤ 2.0 x IULN AST (SGOT) / ALT (SGPT) ≤ 3.0 x IULN; if liver metastases, ≤ 5.0 x IULN Serum creatinine ≤ 1.5 x ULN LVEF ≥ 50% performed no more than 4 weeks prior to enrollment. FEV1\>50%，mild-moderate pulmonary function dysfunction.

* Able to understand and willing to sign a Human Research Protection Office (HRPO) approved written informed consent document (or that of legally authorized representative, if applicable).
* With good compliance to the treatment and Follow-up

Exclusion Criteria:

* Evidence of small cell, large cell neuroendocrine or carcinoid histology.
* Non-stage IV NSCLC and ECOG performance status 3～5 or KPS\<60
* Have a serious or uncontrolled medical condition that could compromise the patients' ability to adhere to the protocol.
* Malignant pleural effusion and pericardial effusion
* Uncontrolled intercurrent illness including, but not limited to, hypertension , diabetes mellitus ,ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant and/or breastfeeding: Patient must have a negative pregnancy test within 14 days of study entry.
* Have a secondary malignancy (except adequately treated non-melanomatous skin cancer, or other cancer such as in situ of the cervix. considered cured by surgical resection or radiation). Patients who have had another malignancy in the past but have been disease free for more than 5 years are eligible.
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to EGFR-TKI or other agents used in the study.
* With poor compliance
* The researchers consider it inappropriate to participate in the study