Safety and Efficacy of Radiotherapy Combined with Immunotherapy for Advanced Malignant Tumors.

More effective treatment regimens remain to be explored for advanced malignancies with multiple metastatic after standard treatment failure/drug resistance. The combination of radiotherapy and immunotherapy is considered to be a promising therapeutic strategy. Studies showed the efficacy of PRaG (PD-1 inhibitor, Radiotherapy and GM-CSF) treatment and stereotactic radiotherapy (SBRT) combined with low-dose radiotherapy (LDRT) for advanced tumors. Therefore, the investigators designed a new radioimmunotherapy regimen, including SBRT, LDRT , PD-1/PD-L1 inhibitor, and GM-CSF. This study aimed to evaluate the safety and efficacy of the new regimen for advanced multiple metastatic solid tumors standard treatment failure/drug resistance, and explore the impact on immune function.

Inclusion criteria

• advanced malignant solid tumors with multiple metastases or relapses, with pathological diagnosis or medical record;
• disease progression or recurrence after standard treatment, or unsuitable/intolerable for standard treatment, or rejection of standard treatment due to personal willingness;
• patients with disease progression or drug resistance after previous immunotherapy are allowed to be included; a history of radiotherapy in the LDRT area or other sites is allowed to be included, provided that there are no residual toxic effects;
• at least ≥1 lesion suitable for SBRT, and ≥1 lesion suitable for LDRT, and the above lesions must be measured;
• no contraindications to radiotherapy;
• Eastern Cooperative Oncology Group (ECOG) score: 0-2 points, and life expectancy >3 months;
• important organ function is acceptable, defined as: white blood cells ≥3.0×10^9/L, platelets ≥75×10^9/L, hemoglobin ≥90g/L, glutamic pyruvic transaminase and glutamic oxalacetic transaminase ≤2.5 times the upper limit of normal value, serum creatinine < 178μmol/L;
• voluntary participation and sign the informed consent.

Exclusion criteria

• no suitable lesions for radiotherapy, or the limit of important organs at risk could not be met;
• permanent discontinuation of PD-1/L1 inhibitors due to ≥ grade 3 immune-related toxic reactions;
• serious cardiovascular or cerebrovascular diseases, severe liver or kidney dysfunction, serious and uncontrolled systemic infections or other contraindications, or any contraindications to radiotherapy, and some comorbidities should be re-evaluated after symptomatic treatment;
• any active immune system disease or related history;
• systemic immunosuppressive drugs are expected to be used during the study;
• a history of severe uncontrollable central nervous system diseases or mental disorders, which may hinder the signing of informed consent or treatment compliance;
• other important medical or physiological conditions (such as pregnancy or breastfeeding status);
• patients who are known to be allergic to the drugs used in this study;
• patients refuse or are unable to sign the informed consent.