A Multi-institutional Phase II Study of Dynamic Tumor Tracking SBRT for the Lung

Abstract

The purpose of the present study was to evaluate safety and efficacy of dynamic tumor tracking stereotactic radiotherapy (DTT-SBRT) for lung cancer. The main eligibility criteria for the study were as follows: (1) primary or metastatic lung cancer with a diameter of 5 cm or less, and up to 3 lesions without any extra-pulmonary lesions; (2) ineligibility to standard surgery, or patient's refusal of surgery; (3) ECOG-PS of 0 to 2; and (4) respiratory motion of 10 mm or more. Spherical gold markers were inserted near the tumor using a bronchofiberscope. CTV was defined as the GTV, which was delineated on exhale CT images, plus 3-mm margins. PTV was determined CTV plus margins compensating errors related to positional variations between CTV and the fiducials, correlation models, and mechanical errors for tracking. The prescribed dose was 50 Gy in 4 fractions to PTV D95. A gimbal-mounted Linac was used for delivery of DTT-SBRT. Primary endpoint was 2-year local control rate. The sample size was determined as 48 to test the expected value of 90% with the threshold value of 80%, one-sided alpha of 0.15 and power of 80%. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Forty-eight patients from 4 institutions were enrolled into the study between July 2015 and Jan 2018. The patient cohort consisted of 38 males and 10 females with a median age of 80 years (range, 49-90 years). Forty-two patients had primary non-small cell lung cancer, and 6 patients had metastatic lung tumors. The tumor diameter was 23.5 mm in median (range, 5-47 mm). DTT-SBRT was successfully delivered to 47 lesions in 47 patients. A median treatment time per fraction in DTT-SBRT was 28 min (range, 14-77 min). Amplitude of respiratory motion during the treatment was 13.7 mm in median (range, 4.5-28.1 mm). Abdominal wall motion in the remaining one patient was not well correlated with the tumor movement, to which the ITV method was applied. The median follow-up period was 32.3 months (range, 3.0-53.8 months) at the time of data cut-off. Local control rate at 2 years was 95.2% (lower limit of the one-sided 85% confidence interval, 90.3%). Overall survival and progression-free survival at 2 years were 79.2% and 75.0%, respectively. There was no Grade 4 or 5 toxicity. Grade 3 toxicity was observed in one patient (2%) with radiation pneumonitis. Regarding Grade 2 toxicities, radiation pneumonitis, dermatitis, rib fracture, and pleural effusion were observed in 3, 1, 2, and 1 patient, respectively. DTT-SBRT achieved excellent local control and low incidence of severe toxicities for lung tumors with substantial respiratory motion. To the best of our knowledge, the present study is the first phase 2 trial evaluating DTT-SBRT for the lung in a multi-institutional setting. (Funded by the Japan Agency for Medical Research and Development; and UMIN Clinical Trials Registry number, UMIN000016547).