Three-dimensional lattice radiotherapy with PD-1/PD-L1 inhibitors for advanced solid tumors

Inclusion Criteria:

* 1.1 age 18-80 years old, male or female; 1.2 the enrolled patients are advanced solid tumors with recurrence or metastasis (no limit to tumor species), tumor location is not limited (except for brain metastasis), with clear pathological diagnosis or clinical history, and at least one large tumor lesion that can be measured by imaging (single tumor diameter ≥ 5cm, volume 50cc\~3000cc); 1.3 PD (progression) after using the first-line and above system treatment scheme (including chemotherapy, targeted or immunotherapy, etc.) recommended by the guidelines, or the patient cannot tolerate the first-line treatment scheme (chemotherapy, etc.); 1.4 biochemical indicators of important organs meet the following requirements: absolute neutrophil count (ANC) ≥ 1.5 × 109/L; platelet ≥ 80 × 109/L; hemoglobin ≥ 80g/L; Serum albumin ≥ 28g/L; Total bilirubin ≤ 1.5 × Upper limit of normal value (ULN) , Alanine aminotransferase (ALT), Aspartate Aminotransferase (AST) and/or Alkaline Phosphatase (AKP) ≤ 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60ml/min (calculated according to Cockcroft Gault formula); International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (for anticoagulant therapy using a stable dose, such as low molecular weight heparin or warfarin, and INR can be screened within the expected treatment range of anticoagulants); 1.5 no congestive heart failure, unstable angina pectoris or unstable arrhythmia occurred in recent 6 months; 1.6 patients' activity status score was 0-2 points in the Eastern Cooperative Oncology Group (ECOG) score method or ≥ 70 points in the Karnofsky (KPS) score method, and ≥ 6 months in the life expectancy assessment; 1.7 no previous history of immune diseases; 1.8 patients voluntarily participate in the study, sign the informed consent, have the conditions for follow-up and are willing to adhere to the follow-up.

Exclusion Criteria:

* 2.1 patients with cavity organ metastasis; There are important nerves or blood vessels passing through the large tumor, which can not be avoided when placing lattice ball; 2.2 brain metastases; 2.3 for those who have a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the clinical severity may hinder the signing of informed consent or affect the patient's compliance with drug treatment according to the judgment of the investigator; 2.4 have any active autoimmune disease or history of autoimmune disease (such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism); Except for patients with vitiligo or cured asthma/allergy of the same age, who do not need any intervention after adulthood; Patients with autoimmune hypothyroidism treated with stable dose of thyroid hormone replacement therapy and type I diabetes treated with stable dose of insulin can be included; Adverse reactions of previous immunotherapy ≥ grade 2; 2.5 have a history of immune deficiency, including HIV test positive, or suffer from other acquired and congenital immune deficiency diseases, or have a history of organ transplantation and allogeneic bone marrow transplantation; 2.6 have uncontrollable cardiac clinical symptoms or diseases, such as (1) heart failure of NYHA II and above; (2) Unstable angina pectoris; (3) Myocardial infarction occurred within 1 year; (4) Subjects with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention; 2.7 severe infection (CTCAE\>grade 2) occurred within 4 weeks before the first use of the study drug, such as severe pneumonia, bacteremia, and infection complications requiring hospitalization; The symptoms and signs of active pulmonary inflammation and infection within 2 weeks before the first use of the study drug in the baseline chest imaging examination require oral or intravenous antibiotic treatment, except for the use of prophylactic antibiotics; 2.8 patients with active pulmonary tuberculosis infection found by medical history or CT examination, or patients with active pulmonary tuberculosis infection history within 1 year before enrollment, or patients with active pulmonary tuberculosis infection history more than 1 year ago but without formal treatment; 2.9 the subjects had active hepatitis B (HBV DNA ≥ 2000 iu/ml or 104 copies/ml), hepatitis C (HCV antibody was positive, and HCV-RNA was higher than the detection limit of the analysis method); 2.10 there were abnormal laboratory test values of sodium, potassium and calcium greater than grade 1 within 2 weeks before enrollment, which could not be improved after treatment; 2.11 have been diagnosed as any other malignant tumor, except the malignant tumor with low risk of metastasis and death (5-year survival rate\>90%), including but not limited to fully treated basal cell carcinoma or squamous cell skin carcinoma, cervical carcinoma in situ, breast carcinoma in situ and papillary thyroid carcinoma; 2.12 patients with KPS ≤ 60, extensive systemic metastasis, too large tumor load, or life expectancy ≤ 6 months. 2.13 according to the judgment of the investigator, the patient has other factors that may cause him to be forced to terminate the study halfway, such as suffering from other serious diseases (including mental diseases) and requiring combined treatment, recently having other serious diseases (such as myocardial infarction and cerebrovascular accident) and considering the high risk of recurrence, serious abnormal laboratory test values, family or social factors, which may affect the patient safety or the collection of test data.