Final Results Of A Phase 1/2 Study Of Stereotactic Body Radiation Therapy With Real-Time Tumor Tracking Using A Robotic Radiosurgery System Based On The Monte Carlo Algorithm For Lung Tumors

Previous studies of stereotactic body radiation therapy (SBRT) for lung tumors have shown that more precious dose calculation algorithms such as Monte Carlo algorithm are desirable for evaluation of local tumor control and prediction of adverse events, and reduction of internal margins using tracking technology may lead to decrease of the risk of high-grade radiation pneumonitis. Therefore, we conducted a phase I/II study of SBRT for lung tumors with real-time tumor tracking using a robotic radiosurgery system based on the Monte Carlo algorithm. The eligibility criteria were as follows: (1) histologically confirmed primary non-small-cell lung cancer staged as T1a-T2aN0M0 (UICC TNM 7th ed.) or pulmonary oligometastasis ≤ 5 cm; (2) dose constraints of the organs at risk achievable; (3) no previous radiation therapy around the lesion; (4) age > 20 years; (5) ECOG-PS ≤ 2; (6) treatment with the tracking system applicable; (7) FEV1.0 ≥ 700 ml and PaO2 ≥ 60 torr in room air; and (8) written informed consent. Primary endpoint was the incidence of Grade 3 or higher radiation pneumonitis (RP) within 180 days after the start of SBRT. Secondary endpoint was the local control rate. Five patients were first enrolled at level-1 (50 Gy/4 fr); during the observation period, level-0 (45 Gy/4 fr) was tested. After confirming the safety of level-1, level-2 (55 Gy/4 fr) was investigated. When grade 3 or higher RP was observed in one patient, additional 5 patients were enrolled at the same level. The dose was escalated to the next level when grade 3 or higher RP was observed in none of 5 or 1 of 10 patients. If it was observed in 2 or more of 10 patients, the preceding lower level was considered to be a recommended dose (RD). For the dose of 60 Gy in 4 Fr, virtual QA planning was performed, but dose constraints of the organs at risk did not seem to be within acceptable ranges. So, level-2 (55 Gy/4 fr) was considered as an upper limit. Patients could be enrolled at a preceding lower level during the observation period for RP at each level, and were included in this analysis. After RD was determined, additional 15 patients were enrolled at RD. A prescribed dose was normalized at PTVD95 (95% volume border of the PTV) based on the Monte Carlo algorithm. Adverse events were scored with CTCAE version 4.0. The UMIN Clinical Trials Registry number was UMIN 000005061519. From September 2011 through September 2015, 40 patients (primary, 30; metastasis, 10) were enrolled. Maximum tumor diameter ranged from 15 to 42 mm (median, 23). Five patients were enrolled at level 0, 15 at level 1, and 20 at level 2. Only 1 grade 3 RP was observed at level 1. The 2-year local control and overall survival rates were 97% and 74%, respectively. The RD was 55 Gy in 4 fr. SBRT with real-time tumor tracking using a robotic radiosurgery system based on the Monte Carlo algorithm was well tolerated and appeared to be effective for solitary lung tumors.