Spatially Fractionated Radiotherapy Combined With Immunotherapy for Advanced Solid Tumors

Inclusion criteria

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• Signed informed consent.
• Histologically or cytologically confirmed malignant solid tumor.
• Advanced solid tumor unsuitable for surgery as determined by a multidisciplinary tumor board or consulting physicians.
• No available standard therapy or inability to tolerate it, with imaging and clinical assessment showing stable disease (SD) or progressive disease (PD).
• Age ≥18 years on the day of signing informed consent.
• No prior radiotherapy to the proposed site, or last radiotherapy ≥6 months ago.
• KPS score ≥70.
• At least one measurable lesion per RECIST 1.1. Previously irradiated lesions qualify only if significant progression post - radiotherapy.
• Life expectancy \>3 months.
• Adequate organ and bone marrow function:
• Marrow: ANC ≥1.5×10⁹/L, platelets ≥80×10⁹/L, hemoglobin ≥9 g/dL;
• Liver: Total bilirubin ≤1.5× upper limit of normal (ULN), ALT/AST ≤1.5× ULN;
• Kidney: Serum creatinine ≤1.5× ULN or creatinine clearance ≥50 ml/min, blood urea nitrogen ≤200 mg/L;
• Coagulation: INR ≤1.5× ULN, PTT ≤1.5× ULN.
• Recovery from prior therapy - related adverse events (≤Grade 1 or baseline).
• Willingness to use appropriate contraception.
• No radiotherapy contraindications as judged by the radiation oncologist.
• Agreement to receive both immunotherapy and radiotherapy.
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Exclusion criteria

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• Active central nervous system (CNS) metastases, carcinomatous meningitis, or spinal cord compression.
• Severe comorbidities such as myocardial infarction within 6 months, severe arrhythmias, or psychosis that may affect treatment completion or result in a life expectancy of \<3 months.
• Evidence of interstitial lung disease or active/non - infectious pneumonia (e.g., drug - induced, radiation - induced) requiring steroid treatment.
• History of pulmonary fibrosis, pulmonary artery hypertension, or severe irreversible airway obstruction.
• Presence of peripheral neuropathy.
• Severe organ dysfunction (e.g., hepatic, cardiopulmonary failure) that is likely to make radiotherapy intolerable.
• Known allergy to study drugs or excipients, or a history of severe allergic reaction to any PD - 1 monoclonal antibody.
• Serious infection within 4 weeks prior to the start of study treatment, including but not limited to hospitalization for infection, bacteremia, or severe pneumonia; or receipt of oral or intravenous antibiotics within 2 weeks prior to study treatment. Patients receiving prophylactic antibiotics (e.g., for urinary tract infections or chronic obstructive pulmonary disease exacerbations) are eligible.
• Known or suspected active autoimmune disease (e.g., uveitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, thyroiditis). Exceptions: patients with vitiligo, cured childhood asthma; patients with well - controlled type 1 diabetes on insulin.
• History of allogeneic organ transplant (except corneal) or allogeneic hematopoietic stem cell transplant.
• Pregnant or breastfeeding women.
• Any other condition that the investigator deems a valid reason for disqualification based on the protocol.