Clinical Outcomes of Stereotactic Body Radiation Therapy Using Flattening Filter Free (FFF) in Early Non–Small Cell Lung Cancers and Metastatic Lung Cancers

SBRT with FFF is the new advanced radiation technology that promises delivery of high dose radiation in a short treatment time. However, its justification for use in the setting of early non–small cell lung cancer (NSCLC) and/or metastatic lung cancers, as well as its clinical data, is still limited regarding efficacy and toxicity profiles. Thus, we conducted a review in patients who received lung SBRT using FFF to assess 1-year local control (LC), overall survival (OS), progression-free survival (PFS), and treatment-related toxicities. From May 2013 to June 2016, 60 patients with early NSCLC or lung metastases treated with SBRT using FFF were reviewed. All patients received unflattened 6 or 10 MV photon beams. 4D-CT simulation or active breath-hold technique was used to account for internal organ motion. OS, PFS, and LC were assessed using the Kaplan Meier method. LC was defined as no tumor progression within irradiated areas. PFS was defined as time from date of SBRT to any disease progression. All target lesions were accounted for LC assessment. Fifty-seven patients and 80 lesions with follow-up period more than 3 months were included in the analysis. Median age at time of SBRT was 64 years old (IQR 55.5-78). Median follow-up time was 11.4 months (IQR 6.7-18.2). Of all 80 lesions, 16.2% were early NSCLC and 83.8% were lung metastases in which 38% were from primary lung cancers and 32.7% from colorectal cancers. Tumors were 3.8% at central, 20% at extremely central (attach mediastinum), 27.5% at peripheral and 48.8% at extremely peripheral (within 1 cm of chest wall) locations. Mean tumor volume was 31.7 cc and mean PTV volume was 68.6 cc. Doses of 48-60 Gy in 3-5 fractions (10-18 Gy/fraction, BED 100-151 Gy10) and 21-70 Gy in 1-10 fractions (5-25 Gy/fraction, BED 36-180 Gy10) were given to early NSCLC and metastatic lung cancers, respectively. Median dose fractionation was 10-12 Gy x 5 fractions. All patients completed treatment without any interruption. At 3 months, 35% of lesions showed partial response (PR) while 55% were stable (SD). At 6 months, 27.5% showed PR and 48.8% showed SD. One-year LC and OS were 100% and 83.3% for early NSCLC, and 93.5% and 80.0% for metastatic lung cancers. BED > 70 Gy10 was associated with better 1-yr LC (HR 0.09, 95%CI=0.01-0.87). Early NSCLC showed significant longer 1-year PFS than lung metastases (91.7% vs 58.1%, P=.03 by log-rank test). Four patients (7%) developed grade 2 pneumonitis. One patient developed grade 1 esophagitis. No grade 3-5 toxicity was observed. BED, dose fractionation, tumor volume and locations, prior lung irradiation, and ipsilateral lung dose of V5, V10, V20, and V30 showed no significant correlation to grade 2 or more pneumonitis. SBRT using FFF gives promising tumor control and minimal toxicities in both early NSCLC and metastatic lung cancers. Because of the radiobiology of FFF and the complexity of its beam profile, late effects need to be warranted.