PURPOSE: Chemoradiotherapy is standard for unresectable stage III non-small cell lung cancer (NSCLC). This phase Ib study assessed the safety and surgical conversion of neoadjuvant low-dose stereotactic body radiotherapy (SBRT) -based radiotherapy followed by pembrolizumab and chemotherapy in patients with potentially resectable stage III NSCLC. METHODS: Patients deemed potentially resectable by the multidisciplinary team (MDT) received neoadjuvant low-dose SBRT-based radiotherapy to the primary tumor (24 Gy for peripheral lesions and 12 Gy for central lesions) delivered in three fractions. Selective planning target volume were applied to spare critical structures and optimize surgical safety. Two cycles of 100 mg pembrolizumab plus platinum-based chemotherapy followed. Surgical feasibility was evaluated by the second MDT 4-6 weeks after neoadjuvant therapy. Primary endpoint was safety; secondary endpoints included pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). RESULTS: Seventeen patients received neoadjuvant therapy, with no dose-limiting toxicities observed. Across the overall treatment course, grade 3-5 treatment-related adverse events were reported in 5 patients (29.4%), most commonly grade 3 leukopenia (2 patients, 11.8%), and included one grade 5 surgical event due to fatal pulmonary artery hemorrhage. Objective responses were noted in 16 patients (94.1%). Surgery was successfully conducted in 11 patients (64.7%), with 10 (90.9%) achieving R0 resection. 6 patients (54.5%) achieved pCR. At a median follow-up of 22.8 months (95%CI: 18.9-26.7), the median PFS was 29.0 months (95%CI: 18.1-39.9), and median OS was 37.9 months (95%CI: 21.9-53.9). CONCLUSION: Neoadjuvant low-dose SBRT-based radiotherapy followed by pembrolizumab and chemotherapy is tolerable and demonstrates promising rates of surgical conversion and pathological response in patients with potentially resectable stage III NSCLC.
Zhu et al. (Mon,) studied this question.