Hypofraction Radiotherapy Followed by Immune Checkpoint Inhibitors for Locally Advanced Non-Small Cell Lung Cancer: A Phase I/II Clinical Trial

Abstract

<h3>Purpose/Objective(s)</h3> To explore the safety and primary efficacy of hypofraction radiotherapy followed by immune checkpoint inhibitors (ICI) for stage III locally advanced non-small cell lung cancer patients. <h3>Materials/Methods</h3> We anticipated to enrolled 36 patients with stage III locally advanced non-small cell lung cancer, among which 18 patients were supposed to receive high-dose hypofraction radiotherapy (60-68Gy/15-17f) with ICI and another 18 patients for low-dose hypofraction radiotherapy (48Gy/12f) with ICI. The technique of esophagus-sparing simultaneous integrated boost was utilized. Chemotherapy could be given before or concurrent with hypofraction radiotherapy. The primary endpoints were the rate of radiation-induced pneumonitis (Grade III or more), esophagitis and myelosuppression. The second endpoints were 1-year local-regional control rate, 1-year progression-free survival rate, 1-year overall survival rate. <h3>Results</h3> From June 1^st, 2021 to December 31th 2021, we totally enrolled 13 male patients (51-82 years old) and at present reported the primary outcome of safety and efficacy. All of these 13 patients were squamous cell carcinoma, among which there were 4 patients with stage IIIA, 6 patients with stage IIIB and 3 patients with IIIC. 11 patients received 60Gy/15f, 1 patient received 64Gy/16f and 1 patient received 68Gy/17f. 7 patients received inductive chemotherapy before radiotherapy and 8 patients received concurrent chemotherapy. 6 patients are currently within ICI maintenance (Durvalumab for 3 patients and Tislelizumab for 2 patients). After hypofraction radiotherapy, 4 patients were evaluated as partial response and the remaining 9 patients were evaluated as complete response (ORR=100%). No patients developed Grade III or more radiation-induced pneumonitis. 1 and 3 patients developed Grade I and Grade II esophagitis respectively. 2 patients developed myelosuppression (1 for Grade II and 1 for Grade IV, both patients received concurrent chemotherapy). <h3>Conclusion</h3> Within short-term follow-up, hypofraction radiotherapy followed by immune checkpoint inhibitors is safe and efficacious.