284 - A Phase II Randomized Trial of Radical Resection vs. Stereotactic Body Radiation Therapy (SBRT) in Patients with Operable Stage I Non-Small Cell Lung Cancer (NSCLC): Final Report Of RTOG-F3502

F. M. Kong¹, J. Yu², J. J. Dignam³, L. Xing⁴, C. Hu⁵, Y. Xiao⁶, Y. Yin⁷, A. Chang⁸, M. Orringer⁹, T. DAmico¹⁰, F. F. Yin¹¹, N. J. Yue¹², W. Mao¹³, K. L. Zhao¹⁴, L. H. Wang¹⁵, W. J. Curran Jr¹⁶, and M. Machtay¹⁷; ¹The University of Hong Kong, Hong Kong, China, ²Shandong Cancer Hospital and Institute, Jinan, China, ³University of Chicago, Department of Public Health Sciences, Chicago, IL, ⁴Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, ⁵Division of Quantitative Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, ⁶Department of Radiation Oncology, Division of Physics, University of Pennsylvania, Philadelphia, PA, ⁷Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China, ⁸University of Michigan, Ann Arbor, MI, ⁹University of Michigan Cancer Center, Ann Arbor, MI, ¹⁰Duke University Medical Center, Durham, NC, ¹¹Department of Radiation Oncology, Duke University Medical Center, Durham, NC, ¹²Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, ¹³Zhejiang Key Laboratory of the Diagnosis & Treatment Technology on Thoracic Oncology, Hangzhou, China, ¹⁴Fudan University Cancer Center, Shanghai, China, ¹⁵Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China, Shenzhen, China, ¹⁶Piedmont Oncology Institute, Atlanta, GA, ¹⁷Penn State University -Penn State Cancer Institute, Hershey, PA

Purpose/Objective(s): We hypothesized that for early stage, operable NSCLC, local-regional control (LRC) would not be more than 15% lower in patients treated with SBRT compared with radical surgical resection with nodal sampling/dissection (RODS). Materials/

Methods: Patients with T1-2N0M0 NSCLC were randomized to: 1) RODS or 2) SBRT of 55 Gy in 5 fractions (BED 118 Gy). The primary endpoint was 2-year LRC, defined as freedom from recurrence in the primary tumor site, involved-lobe, and/or regional-nodal sites. A secondary objective was to assess the logistical feasibility of an RTOG-Foundation SBRT trial at academic centers in China. SBRT credentialing processes, including a dry-run planning case, were required by RTOG before allowing patient registration. Other secondary endpoints included overall survival (OS), patterns of failure, and toxicity. Original sample size goal was 76 patients.
Results: The study opened in 02-2013, and closed to accrual 01-2020, following the recommendations of the RTOG Foundation DMC. Five centers in China were selected for participation; all received IRB approval and satisfied credentials for SBRT and participating surgeons. A total of 47 patients enrolled from 4 centers; 44 patients were randomized, with 22 in each arm. One from each arm withdrew consent after randomization. The median follow-up of surviving patients is 5.0 years. The median patient age was 65 years (range 49-82) and all patients had Zubrod performance status 0-1. Most (59.1%) patients had adenocarcinoma. Median FEV1 was 2.29 L/sec and median DLCO was 90% of predicted. The 2-year LRC rates were 95.2% (95% CI: 70.7-99.3) for RODS and 66.7% (95% CI: 42.5-82.5) for SBRT; this does not satisfy the target criterion of no more than 15% decreased LR control. The HR for local-regional control was 5.11 (95% CI: 1.10-23.7), in favor of surgery. Of 9 patients with local-regional failure in SBRT arm, 3 had major deviations on target delineation and 2 did not have RT data submitted. Regional nodal failure occurred in 6 patients (3 nodal-only failure). Two patients had LR in RODS arm, both at resection margin. There was no significant difference between arms in OS (HR=0.96, 95% CI:0.28-3.31). The 2-year/5-year OS rates were 85.7%/74.7% and 90.5%/73.0% for RODS and SBRT, respectively. Among 35 patients who received any protocol treatment (16 RODS; 19 SBRT), 6 patients (37.5%) on RODS and 1 patient (5.3%) on SBRT had grade 2 treatment-related toxicities; there were no reported Grade 3-5 toxicities.
Conclusion: SBRT was feasible and well-tolerated, with survival similar to surgery, but did not achieve the protocol target local-regional tumor-control compared with radical surgery, which should remain the standard of care for operable patients. Review of available RT imaging and patterns of failure in this study are reminders of the importance of nodal staging and rigorous RT quality assurance.

Funding: This project was supported in part by Varian Med Inc. ClinicalTrials.gov ID: NCT01753414