Purpose/Objective(s): The purpose of JCOG0403 was to evaluate the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with both operable and inoperable T1N0M0 non-small cell lung cancer (NSCLC) (UICC 6th ed., 2002). The patient accrual started in 2004, and the three and five year follow-up results were published in 2015. This is the updated report with a 10-year follow-up period for the operable population.

Materials/Methods: The eligibility criteria included clinical T1N0M0 NSCLC, operable patients assessed by thoracic surgeons. Operability was recategorized by the study coordinator after registration and before the primary analysis. The prescription was 48 Gy at the isocenter in 4 fractions over 4-8 days. The primary endpoint was the three-year survival and the secondary endpoints included overall survival (OS), progression-free survival (PFS), local-progression free survival (LPFS), event-free survival (EFS), toxicity, and patterns of failure.

Results: Between July 2004 and May 2007, 65 operable patients were registered in this study from 15 institutions and 64 eligible patients were included in efficacy analysis. The patient characteristics were: male 45, female 20; median age 79 (range 50-91); and adenocarcinomas 40, squamous cell carcinomas 21, others 4. All patients completed the protocol treatment. At the last follow-up in February 2017 (median follow-up is 5.2 years), 20 patients died with disease, 24 patients died with other disease, 1 patient with treatment-related death, 2 died with unknown reason and 17patients still alive. Follow-up images of all patients were centrally reviewed by September 2017. The median survival was 5.6 year (95% CI: 4.1 – 7.1 year).The 3, 5, 10-year survival were 76.5% (95% CI: 64.0% - 85.1%), 54.0% (95% CI: 41.0% - 65.4%) and 23.8% (95% CI: 13.7% - 35.5%), respectively. The 10-year PFS, LPFS, and EFS were 19.1% (95% CI: 9.8% - 3.7%), 20.9% (95% CI: 11.1% -32.8%), 13.7% (95% CI: 6.0% - 24.6%), respectively. The 3, 5, 10-year local control rates were 85.4% (95% CI: 73.8% - 92.1%), 85.4% (95% CI: 73.8% - 92.1%) and 85.4% (95% CI: 73.8% - 92.1%), respectively. To date, a total of 27 failures were observed including 9 with local failure, 11 with regional nodal failure and 11 with distant metastases. Grade 3 toxicity was observed in 6 patients: chest pain in 1 (1.5%), dyspnea in 4 (6.2%), hypoxia in 1 (1.5%), and pneumonitis in 2 (3.1%). No grade 4 or 5 toxicity was observed.

Conclusion: Long term results confirmed the efficacy and safety of the previous result. SBRT has a potential to be an alternative to surgery for operable T1N0M0 NSCLC and deserves a further evaluation. To further improve the tumor control, a randomized phase III study investigating higher dose prescribed to the 80% isodose line is underway (JCOG1408).