An Attempt to Reduce Lung Dose-Volume in the Era of Radiotherapy Combined Immunotherapy

Abstract

In immunotherapy era, the safety of thoracic radiotherapy, especially pneumonia is a concern of clinical and patients. The incidence of pneumonia in KEYNOTE 799 is higher than that in PACIFIC and GEMSTONE301, and the incidence of pneumonia is related to V20 Gy. This study aims to explore how to reduce the lung dose of immunotherapy plus concurrent chemoradiation therapy (cCRT). We prospectively selected 32 patients treat with IMRT for untreated, locally advanced, stage III NSCLC. They all received immunochemotherapy in the first cycle treatment and completed the first CT-based simulation. In the second cycle treatment, all patients received cCRT plus ICIs and each patient received the second radiotherapy location after 10 or 20 fractions of radiotherapy. The initial and second treatment plan based on CT image are Plan1 and Plan2. The volume changes of gross tumor volume (GTV) between primary and secondary CT scans were compared, and the dose-volume parameters such as lung volume (V5 Gy, V20 Gy, V30 Gy) and heart volume (V30 Gy) in Plan2 were compared with those of Plan1. Compared with the first and second CT scan, the mean volume of GTV is decreased by 34%. The dose-volume parameters of total lung and heart were significantly lower than those in Plan1.Among them the V20 Gy, V30 Gy of total lung have statistical difference (Z = -2.068, P = 0.039; Z = -3.008, P = 0.003; respectively) and decreased by 31%, 33%, respectively. Additionally, the V20 resected after the 10-fraction radiotherapy is less than the 20th (V20 Gy = 25.1%, 26.3%; respectively). Meanwhile, for treatment-related pneumonitis, there is only one case (5%) in grade 3 or higher pneumonitis, and most of pneumonitis can be relieved after symptomatic treatment. In the mode of immunotherapy plus cCRT, timely reduction measures in the process of radiotherapy will effectively reduce lung dose-volume (V20 Gy), so as to decrease pulmonary toxicity. Two-cycle induction therapy were followed by radiotherapy may be a potent treatment candidate.