Precision Radiotherapy for Refractory Brain Metastases: A Multicenter Study

Inclusion criteria

• Pathologically diagnosed non-small cell lung cancer or small cell lung cancer;
• Brain metastases diagnosed by contrast-enhanced MRI;
• KPS ≥ 60, or KPS ≥ 40 if caused solely by intracranial tumors;
• Brain metastases with a diameter ≥ 2 cm or volume ≥ 6 cm³, with 1-3 lesions;
• No prior brain radiotherapy;
• Able to undergo MRI examination;
• Good compliance and ability to lie flat for more than 45 minutes;
• No major organ dysfunction, etc.;
• Signed informed consent and agreement to receive post-treatment follow-up;
• All patients must be willing to provide tumor tissue samples before randomization;
• At least one measurable tumor lesion according to RECIST v1.1 or iRECIST criteria.

Exclusion criteria

• Other serious illnesses;
• Presence of implants in the patient's body, such as cardiac pacemakers, prostheses, or surgical stents, particularly cerebrovascular stents;
• Presence of shrapnel, bullets, or other foreign objects anywhere in the body;
• Severe back pain when lying supine;
• Severe claustrophobia;
• Inability to complete treatment or estimated survival < 3 months;
• Currently participating in other clinical trials for the treatment of brain metastases;
• Prior history of intracranial radiotherapy;
• Unstable angina, myocardial infarction, coronary artery bypass grafting, congestive heart failure, cerebrovascular accident (including transient ischemic attack, pulmonary embolism) within 3 months prior to enrollment;
• Persistent arrhythmia (CTCAE grade ≥ 2), atrial fibrillation of any degree, prolonged QTc interval ( > 450 ms in males, > 470 ms in females);
• Refractory hypertension (blood pressure still > 150/100 mm Hg despite optimal medical therapy);
• Known history of human immunodeficiency virus (HIV) infection;
• Pregnant or breastfeeding women;
• Receipt of a live vaccine within 30 days prior to the first dose of study drug. Live vaccines include, but are not limited to: measles, mumps, rubella, varicella/zoster (chickenpox), yellow fever, rabies, bacillus Calmette-Guérin (BCG), and typhoid vaccines. Seasonal influenza vaccines for injection are typically inactivated virus vaccines and are permitted; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not permitted;
• Active autoimmune disease requiring systemic treatment (i.e., immunomodulatory drugs, corticosteroids, or immunosuppressive drugs) within the past 2 years (autoimmune diseases include, for example: autoimmune hepatitis, interstitial pneumonia, uveitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome-associated vascular thrombosis, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, glomerulonephritis, hyperthyroidism or hypothyroidism, asthma requiring bronchodilators, etc., i.e., immunomodulatory drugs, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment and is permitted;
• Concomitant medical contraindications to receiving any contrast-enhanced imaging examination (CT or MRI);
• Severe hypersensitivity (grade ≥ 3) to the study intervention and/or any of its excipients;
• Uncontrolled metabolic disorders or other non-malignant organ or systemic diseases, or secondary responses to cancer that may lead to increased medical risk and/or uncertainty in survival assessment;
• Major surgery (as determined by the investigator) or significant trauma within 4 weeks prior to randomization; or elective major surgery planned during the study period. Biopsy for diagnostic purposes is permitted.