283 - Measuring the Integration of Stereotactic Ablative Radiotherapy plus Surgery for Early-Stage Non-Small Cell Lung Cancer (MISSILE): Long-Term Clinical Outcomes

V. S. Tan¹, R. J. M. Correa¹, T. Nguyen¹, A. V. Louie², R. Malthaner³, D. Fortin³, G. Rodrigues¹, B. P. Yaremko¹, J. M. Laba¹, K. Kwan⁴, S. Gaede⁵, T. Lee⁶, A. Ward⁶, A. Warner¹, R. Inculet³, and D. A. Palma¹; ¹Department of Radiation Oncology, Western University, London, ON, Canada, ²Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, ³Department of Surgery, Division of Thoracic Surgery, Western University, London, ON, Canada, ⁴Department of Pathology, Western University, London, ON, Canada, ⁵London Health Sciences Centre, London, ON, Canada, ⁶Department of Medical Biophysics, Western University, London, ON, Canada

Purpose/Objective(s): For early-stage non-small cell lung cancer (NSCLC), surgery is the preferred approach in operable patients, whereas stereotactic ablative radiotherapy (SABR) is preferred for medically inoperable patients. The combination of neoadjuvant SABR followed by surgery was explored in the MISSILE phase II trial and was hypothesized to improve outcomes by cytoreducing tumors before surgery and/or inducing antitumor immune activity. Herein, we report long-term clinical outcomes, beyond 5 years of follow-up. Materials/

Methods: Patients diagnosed with T1-2N0M0 NSCLC with ECOG 0-2 and postoperative predicted FEV1 = 30% were enrolled. Patients underwent neoadjuvant SABR using a risk-adapted fractionation schema (with all dose fractionations exceeding a biological effective dose of at least 100 Gy₁₀) followed by lobectomy/wedge resection. The primary endpoint was pathological complete response (pCR). Other endpoints included major pathologic response (MPR), overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), local control (LC), regional control (RC), distant control (DC), toxicity (based on CTCAE) and quality of life (based on FACT-G).
Results: Forty patients received SABR, and 90% of these (n=36) proceeded with surgery. The pCR rate, as previously reported, was 60% and the MPR rate was 63%. For patients who received SABR and surgery, median follow-up was 6.6 years. Five-year OS was 66.7% (95% CI: 48.8-79.5), PFS was 58.3% (95% CI: 40.7-72.4) and CSS was 76.4% (95% CI: 58.2-87.4). Five-year LC, RC and DC were 93.5% (95% CI: 76.3-98.4), 80.1% (95% CI: 62.7-90.0) and 82.4% (95% CI: 64.9-91.7) respectively. After SABR and surgery, 16.7% (n=6) of patients experienced related grade = 3 adverse events. Observed grade 4 adverse events were atelectasis, atrial fibrillation, bronchopleural fistula and respiratory failure. There were no grade 5 adverse events. FACT-G total showed significant declines in the post-surgery period that were worst at 12-months post-surgery (mean ± SD: 84.1 ± 16.1 vs. 92.9 ± 10.5, p=0.006) but recovered thereafter. Predictors of improved OS on univariable analysis were T1 vs. T2 tumor size (hazard ratio [HR]: 0.33, 95% CI: 0.12-0.93, p=0.036), increasing post-treatment FEV₁ (HR per 10%: 0.60, 95% CI: 0.38-0.97, p=0.035), and VATS vs. open surgical approach (HR: 0.19, 95% CI: 0.04-0.90, p=0.037).
Conclusion: The combination of SABR and surgery was safe, but outcomes were similar to either modality alone. A combined may be considered when surgery is desired but operating room availability is restricted, or temporary medical factors preclude immediate surgery.