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

• 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.