SBRT Combined With PD-1 Inhibitor and Thoracic Hyperthermia for Advanced NSCLC

Inclusion Criteria: * 1.Age≥18. * 2.ECOG PS 0-1. * 3.Histopathologically confirmed stage IV non-small-cell lung cancer. * 4.EGFR/ALK/ROS-1 negetive. * 5.Disease progression after first-line therapy including platinum chemotherapy, but not include PD-1/L1 inhibitors. * 6.Subjects with brain metastases were eligible, but only if they had no neurologic symptoms or disease stable without systemic glucocorticoid. * 7.At least one lesion with a diameter of 1-5cm which could be treated with SBRT at a dose of 32Gy/4Fx, and at least one lesion which could be measured other than SBRT (RECIST1.1); Lymph nodes can be used as independent measurable lesions or receive SBRT. Brain lesions should not be used as separate SBRT lesions or as measurable lesions. * 8.The subjects did not had radiotherapy before. * 9.The subjects did not currently need palliative radiotherapy at any part according to the researchers. * 10.It was necessary for the subjects who underwent surgery to fully recover from the toxicity and complications caused by surgical intervention prior to treatment. * 11.Subjects should provide appropriate biopsy specimens before and during treatment according to the clinical trial protocol. * 12.Male or female subjects agree to contraception during the trial (surgical ligation or oral contraceptive/IUD + condom). * 13.Life expectancy ≥ 3 months. * 14.The organ function level meet the following standards one week before enrollment: ①Bone marrow: hemoglobin ≥80g/L, white blood cell count ≥4.0\*10\^9/L or neutrophil count ≥1.5\*10\^9/L, platelet count ≥100\*10\^9/L. ②Liver: Serum total bilirubin level ≤1.5 upper limit of normal (ULN), when serum total bilirubin level \> 1.5 ULN, direct bilirubin level must be ≤ ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ULN. ③ Kidney: serum creatinine level \< 1.5 ULN or creatinine clearance rate ≥ 50ml/min, urea nitrogen ≤ 200mg/L; Serum albumin ≥ 30g/L. * 15\. Subjects must be able to understand and voluntarily sign informed consent. Exclusion Criteria: * 1.Prior treatment with anti-PD-1 /L1 drugs or other investigational immunotherapy agent. * 2.Subjects had prior radiotherapy. * 3.Subjects had severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease and ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granuloma), etc. * 4.Symptomatic interstitial lung disease or active infectious/noninfectious pneumonia. * 5.Subjects had risk factors for bowel perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer, or other risk factors for bowel perforation. * 6.History of other malignant tumors. * 7.Subjects who have current infection, heart failure, heart attack, unstable angina, or unstable arrhythmia in the last 6 months. * 8.Subjects with physical examination or clinical trial findings, or other uncontrolled conditions that the investigator believes may interfere with the outcome or increase the risk of treatment complications. * 9.Subjects without platinum-based combination chemotherapy included as first-line treatment. * 10.The pathology reports showed a mixture of small cell lung cancer components. * 11.Lactating or pregnant women. * 12.Congenital or acquired immunodeficiency diseases including human immunodeficiency virus (HIV), or a history of organ transplantation, allogeneic stem cell transplantation. * 13.Known hepatitis B virus (HBV), hepatitis C virus (HCV), active pulmonary tuberculosis infections. * 14.Subjects had cancer vaccines other vaccines within 4 weeks before treatment initiation. (Seasonal influenza vaccines are usually inactivated and are permitted, whereas intranasal preparations are usually live attenuated vaccines and therefore are not permitted) * 15.Subjects who currently use other immune agents, chemotherapy agents, other investigational drugs or long-term cortisol therapy. * 16.Subjects with mental illness, substance abuse, and social problems that affected compliance were not included in the study according to doctor's evaluation. * 17.Allergic or contraindicated to PD-1 inhibitors.