Radiotherapy Combined With PD-1 Inhibitors and Chemotherapy in the Treatment of NSCLC Patients With Symptomatic Brain Metastases

Inclusion Criteria:

1\. Age ≥ 18 years old; patients with metastatic NSCLC with at least one measurable brain metastases, the longest diameter of the brain metastases is 0.5 to 3 cm, and the brain metastases have not received radiotherapy; stable neurological symptoms and/or are receiving Corticosteroid therapy. In addition, the following conditions are raised:

1. Patients with negative driver-gene mutations who have not received systemic treatment before, and patients who have progressed after receiving neoadjuvant or adjuvant therapy, and the interval between disease progression or recurrence and the end of the last chemotherapy drug treatment is at least 6 months, and is allowed to enter this study;
2. Patients with known EGFR sensitive mutation, ALK rearrangement or ROS1 fusion must have received at least one EGFR or ALK, ROS1 fusion inhibitor treatment and had disease progression or drug intolerance.
3. Subjects with neurological symptoms can receive dexamethasone within 10 days before the first treatment, but the total daily dose is stable at no more than 4 mg or other Corticosteroids at the same dose. Subjects with neurologic symptoms but not receiving steroids should experience no seizures within 10 days prior to first treatment.

2\. For patients with non-brain oligometastases, according to Response Evaluation Criteria in Solid Tumors Version 1.1 (mRECIST v1.1), there is at least 1 measurable or evaluable lesion in addition to brain metastases.

3\. The Eastern Cooperative Oncology Group Physical Status Score (ECOG PS score) is 0-2 points.

4\. The patient has a clear mind, can answer correctly, and has basically normal vision, etc., and can cooperate with cognitive function assessment 5. Expected survival time ≥ 12 weeks. 6. The patient has adequate organ and bone marrow functions, as defined below:

1. Blood routine: absolute neutrophil count ≥1.5×109/L; platelet count ≥100×109/L; hemoglobin content ≥9.0 g/dL.
2. Liver function: serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); for patients with HCC, liver metastases, or a history/suspect of Gilbert syndrome (persistent or recurrent hyperbilirubinemia , mainly high unconjugated bilirubin, no evidence of hemolysis or liver disease), TBIL ≤ 3 × ULN; for patients without HCC and liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; for patients with HCC or with liver metastases, ALT or AST ≤ 5 × ULN.
3. Renal function: serum creatinine (Cr) ≤ 1.5×ULN or creatinine clearance (CCr) ≥ 50mL/min; urine test paper test results show urine protein \<2+.
4. Coagulation function: activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5×ULN.

Exclusion Criteria:

1. Receive live attenuated vaccine within 4 weeks before enrollment or plan to receive live attenuated vaccine during the study.
2. Active, known or suspected autoimmune disease.
3. Known history of primary immunodeficiency.
4. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
5. Female patients who are pregnant or breastfeeding.
6. Untreated acute or chronic active hepatitis B or hepatitis C infection. Patients who are receiving antiviral treatment will be judged by doctors according to the individual conditions of the patients under the condition of monitoring the virus copy number.
7. History of dementia, Alzheimer's disease, Parkinson's disease and other diseases that can cause cognitive dysfunction
8. History of schizophrenia, severe anxiety, depression, or other mental illnesses
9. Uncontrolled concurrent diseases, including but not limited to:

   1. HIV-infected persons (HIV antibody positive).
   2. Serious infection that is active or poorly controlled clinically.
   3. Serious or uncontrolled systemic disease (such as severe mental, neurological disease, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, hepatic or renal disease, uncontrolled hypertension \[i.e. Evidence of greater than or equal to CTCAE grade 2 hypertension after drug treatment\]).
   4. Active bleeding or new thrombotic disease is taking therapeutic dose of anticoagulant drugs or bleeding tendency