The 3-Year Outcome of 3D High-Dose-Rate Brachytherapy in Combination With Regional Metastatic Lymph Nodes Intensity-Modulated Radiotherapy in Peripheral Locally Advanced Non-Small Cell Lung Cancer: A Phase I/II Clinical Trial.

Abstract

PURPOSE/OBJECTIVE(S)\nTo determine the safety, late toxicities and locoregional control of three-dimensional(3D) high-dose-rate (HDR) brachytherapy in combination with regional metastatic lymph nodes intensity-modulated radiotherapy (IMRT) in patients with peripheral locally advanced non-small cell lung cancer (LA-NSCLC).\n\n\nMATERIALS/METHODS\nEligible patients with LA-NSCLC were recruited to this prospective, phase I/II clinical study. The primary lung tumors were treated with the CT-guided interstitial HDR brachytherapy, DT:30Gy/F. The IMRT was applied to the regional positive lymph nodes, DT: 60-70Gy/30-33F/ 6-7W. The concurrent chemotherapy regimens include used Etoposide and cisplatin, the sequential chemotherapy consisted of paclitaxel/pemetrexed\u202f+\u202fcisplatin/carboplatin. The safety analysis included operational complications and toxicity related to radiotherapy and chemotherapy. Clinical evaluation includes short-term efficacy, survival, and quality of life scores.\n\n\nRESULTS\nA total of 83 patients were enrolled in this study. There were 56 males and 27 females, with a median age of 65 years (45-80 years). The median follow-up time was 55 months (32-114 months) up to November 2020. The operational complications included mild pneumothorax (16.8%) and minor hemorrhage around the needle (19.3%). The major toxicity was myelosuppression and gastrointestinal reaction during the concurrent chemoradiotherapy and sequential chemotherapy. The clinical symptoms alleviated after symptomatic supportive treatment. The radiotherapy was completed successfully without grade 4 or more serious acute toxicity. Grade 1 late radiation pneumonitis was found by in 5 patients (6.1%), and only showed imaging changes after radiotherapy. There were 61 patients achieved complete remission, 20 patients achieved partial remission, and 2 patients were in stable disease in the primary tumor, the total response rate was 97.6%. There were 55 patients achieved complete remission, 22 patients achieved partial remission, 5 patients were in stable disease and 1 patient with progressive disease in the positive lymph nodes, the total response rate was 92.8%. The 1-,2-,3-year overall survival rates were 90.6%, 70.6% and 62.4%. The 1-,2-,3-year local control rates were 90.0%,81.0% and 54.5%. The 1-,2-,3-year disease-free survival rates were 68.3%,42.2% and 23.9%. The 1-,2-,3-year metastasis-free survival rates were 73.3%, 50.9% and 39.5%. The patient who treated with 3D interstitial high dose rate brachytherapy has a higher life quality score than the baseline level.\n\n\nCONCLUSION\n3D interstitial high dose rate brachytherapy combined with regional positive lymph node intensity-modulated radiotherapy is safe and feasible for the locally advanced peripheral non-small cell lung cancer, with low adverse reactions, increased the survival, and improved the life quality. But it still needs a phase III randomized controlled trial to investigate its clinical utility and promotion, compared to IMRT.