A Phase II Prospective, Open-Label, Single-Arm Study Evaluating the Efficacy and Safety of Spatially Fractionated Radiotherapy Combined With Immunotherapy in Patients With Advanced Solid Tumors
Lattice radiation therapy (LRT) is a spatially fractionated radiotherapy technique that creates alternating high - and low - dose areas within a tumor to enhance local control and reduce toxicity to surrounding tissues. This study aims to evaluate the effectiveness and safety of combining LRT with immunotherapy in patients with advanced or metastatic solid tumors, through a Phase II clinical trial. Patients will receive specific - dose irradiation using a medical linear accelerator. Within the GTV of the largest tumor, spheres (0.5 - 3 cm in diameter) will be created as high - dose targets (LRT targets), spaced 2.0 - 5.0 cm apart. The LRT targets must be drawn within the GTV, avoiding blood vessels, with a margin of at least 1 cm from the GTV margin, and a volume ratio of 1% - 10% of the GTV. For a single lesion, the D95 of the GTV will be ≥1 Gy/fraction, and the D95 of the LRT target will be 8 - 12 Gy/fraction, with minimal possible single - fraction doses to organs at risk. All other irradiated metastases will receive low - dose radiotherapy (100 - 300 cGy × 5 fractions), except for brain and bone metastases, which will be treated with palliative radiotherapy as per clinical routine. Immunotherapy will be administered during or within one week after radiotherapy.
• 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.