SBRT for Oligoprogressive NSCLC After First Line Treatment With Immune Checkpoint Inhibitors

Inclusion Criteria:

* Age at least 18 years;
* ECOG PS 0-1;
* Patients with pathologically confirmed stage IV NSCLC by tumor biopsy and/or fine-needle aspiration （AJCC the 8th Edition）;
* Stable Disease for at least 6 months after first line immunotherapy;
* Oligoprogressive disease in 5 or fewer lesions and 3 or fewer organs;
* All oligopreogressive lesion ≤ 5cm, and intracranial lesion ≤3cm or 30cc;
* Progressive disease would be amenable to SBRT and without indications for palliative radiotherapy in the opinion of the investigator;
* Patients with a history of radiotherapy are eligible if radiotherapy administered more than 4 weeks before study entry;
* Adequate organ function prior to enrollment:

Adequate bone marrow function: white blood cell (WBC) count ≥ 3.0 \* 10 \^ 9/L or neutrophil count ≥ 1.5 \* 10 \^ 9/L, platelet count ≥ 100 \* 10 \^ 9/L and hemoglobin ≥90g/L,; Adequate hepatic function: total bilirubin, urea nitrogen and serum creatinine≤ 1.5 x upper limit of normal (ULN). Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.0 ULN;

* Life expectancy of more than 3 months;
* Ability to understand and willingness to provide the informed consent and signed informed consent for the use of fresh tumor biopsies before and during the treatment;
* Women of childbearing age and men must agree to use effective contraception during the trial.

Exclusion Criteria:

* History of another malignancy or concurrent malignancy (except for cured non-melanoma skin cancer, low-risk prostate cancer, T1/T2 glottic cancer, stage 0 or I breast cancer, non-invasive bladder cancer, cervical cancer in situ);
* Positive for driver genes including EGFR, ALK, and ROS-1;
* Mixed small cell with non-small cell lung cancer histology;
* Malignant pleural or ascites;
* Patients with brain metastasis require intracranial decompression;
* Symptoms of spinal cord compression;
* Severe autoimmune disease: inflammatory bowel disease (including Crohn's disease and ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Wegener's granulomatosis and related vasculitides;
* Symptomatic interstitial lung disease or clinically active infectious/non-infectious pneumonitis.
* History of another malignancy or concurrent malignancy;
* Active infection, congestive heart failure, or any evidence of myocardial infarction, unstable angina pectoris or cardiac arrhythmia within 6 months prior to enrollment;
* The patient is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding;
* Mental disorders, drug abuse, and social condition that may negatively impact compliance in the investigator's opinion.