Spatially Fractionated Radiotherapy Combined With Immunotherapy for Advanced Solid Tumors

\*\*Inclusion Criteria:\*\*

1. Signed informed consent.
2. Histologically or cytologically confirmed malignant solid tumor.
3. Advanced solid tumor unsuitable for surgery as determined by a multidisciplinary tumor board or consulting physicians.
4. No available standard therapy or inability to tolerate it, with imaging and clinical assessment showing stable disease (SD) or progressive disease (PD).
5. Age ≥18 years on the day of signing informed consent.
6. No prior radiotherapy to the proposed site, or last radiotherapy ≥6 months ago.
7. KPS score ≥70.
8. At least one measurable lesion per RECIST 1.1. Previously irradiated lesions qualify only if significant progression post - radiotherapy.
9. Life expectancy \>3 months.
10. 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.
11. Recovery from prior therapy - related adverse events (≤Grade 1 or baseline).
12. Willingness to use appropriate contraception.
13. No radiotherapy contraindications as judged by the radiation oncologist.
14. Agreement to receive both immunotherapy and radiotherapy.

\*\*Exclusion Criteria:\*\*

1. Active central nervous system (CNS) metastases, carcinomatous meningitis, or spinal cord compression.
2. 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.
3. Evidence of interstitial lung disease or active/non - infectious pneumonia (e.g., drug - induced, radiation - induced) requiring steroid treatment.
4. History of pulmonary fibrosis, pulmonary artery hypertension, or severe irreversible airway obstruction.
5. Presence of peripheral neuropathy.
6. Severe organ dysfunction (e.g., hepatic, cardiopulmonary failure) that is likely to make radiotherapy intolerable.
7. Known allergy to study drugs or excipients, or a history of severe allergic reaction to any PD - 1 monoclonal antibody.
8. 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.
9. 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.
10. History of allogeneic organ transplant (except corneal) or allogeneic hematopoietic stem cell transplant.
11. Pregnant or breastfeeding women.
12. Any other condition that the investigator deems a valid reason for disqualification based on the protocol.