This is a prospective, single-arm, multicenter phase II clinical study evaluating the efficacy and safety of spatially fractionated radiotherapy (SFRT) combined with tislelizumab and platinum-based doublet chemotherapy as induction/conversion therapy for patients with potentially resectable stage III non-small cell lung cancer (NSCLC) with bulky disease (primary tumor \>5 cm).
SFRT, also known as lattice radiation therapy, is a novel radiotherapy technique that creates alternating high-dose and low-dose regions within the tumor. This approach not only reduces tumor burden but also may enhance anti-tumor immune responses, potentially working synergistically with immunotherapy.
Study participants will receive SFRT to the primary lung tumor (GTV 20 Gy/5 fractions, GTV-Lattice 60 Gy/5 fractions), followed by 2-4 cycles of tislelizumab (200 mg, Q3W) combined with platinum-based doublet chemotherapy. Surgery will be performed 4-6 weeks after the last cycle of neoadjuvant therapy. The first 6 enrolled patients will undergo dose-limiting toxicity (DLT) assessment within 21 days after the first dose of study drug.
The primary endpoint is major pathological response (MPR) rate, defined as the proportion of patients with ≤10% viable tumor cells in the resected specimen. Secondary endpoints include 1-year event-free survival (EFS), pathological complete response (pCR) rate, objective response rate (ORR), disease control rate (DCR), R0 resection rate, 1-year overall survival (OS), time to distant metastasis (TTDM), and safety.
A total of 44 patients will be enrolled across multiple centers in China. An interim analysis will be conducted after 50% of patients are enrolled.
Voluntary agreement to participate and signed written informed consent.
Cytologically or histologically confirmed (via percutaneous lung biopsy, bronchoscopy, mediastinoscopy, etc.) bulky stage III non-small cell lung cancer (NSCLC) per AJCC 9th edition staging, with primary tumor >5 cm (T3-T4), N0-N2, and no prior chemotherapy, radiotherapy, surgery, or immunotherapy.
Pulmonary lesion considered potentially resectable by a multidisciplinary team (MDT) including a thoracic surgeon.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
Has or is suspected of having an autoimmune disease. Note: patients with vitiligo, type I diabetes mellitus, or hypothyroidism (Hashimoto's thyroiditis) requiring only hormone replacement therapy may be enrolled if no significant signs of recurrence are present.
Requires systemic corticosteroid therapy (>10 mg prednisone or equivalent per day) or other immunosuppressive agents within 14 days after enrollment. Note: inhaled or topical corticosteroids, or adrenal hormone replacement therapy (>10 mg prednisone or equivalent per day) for patients without active autoimmune disease, are permitted.
Prior history of thoracic radiotherapy.
Active bleeding prior to treatment.