Yoichi Ohtaki1, Kimihiro Shimizu2, Hiroyuki Suzuki3, Kenji Suzuki4, Masahiro Tsuboi5, Tetsuya Mitsudomi6, Motoshi Takao7, Tomohiro Murakawa8, Hiroyuki Ito9, Kenichi Yoshimura10, Morihito Okada11, Masayuki Chida12. 1. Department of General Surgical Science, Gunma University Graduate School of Medicine, Division of General Thoracic Surgery, Integrative Center of General Surgery, Gunma University Hospital, Gunma, Japan. 2. Department of General Surgical Science, Gunma University Graduate School of Medicine, Division of General Thoracic Surgery, Integrative Center of General Surgery, Gunma University Hospital, Gunma, Japan; Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan. Electronic address: kmshimizu@shinshu-u.ac.jp. 3. Department of Chest Surgery, Fukushima Medical University, Fukushima, Japan. 4. Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan. 5. Division of General Thoracic Surgery, National Cancer Center Hospital East, Chiba, Japan. 6. Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan. 7. Department of General Thoracic and Cardiovascular Surgery, Mie University School of Medicine, Mie, Japan. 8. Department of Thoracic Surgery, Kansai Medical University, Osaka, Japan. 9. Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan. 10. Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan. 11. Department of Surgical Oncology, Hiroshima University, Hiroshima, Hiroshima, Japan. 12. Department of General Thoracic Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan.
Abstract
OBJECTIVES: The prognostic impact of surgical intervention for recurrent or residual non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement after tyrosine-kinase inhibitor (TKI) treatment remains unclear. We aimed to describe the characteristics and outcomes of patients undergoing salvage surgery in this setting. METHODS: We retrospectively collected and analyzed nationwide Japanese data on perioperative and postoperative outcomes of patients who underwent salvage surgery after EGFR or ALK-TKI during 2010-2015. The primary endpoint was a 3-year overall survival (OS) rate and secondary endpoints were the rate of adverse events, perioperative mortality rate, 3-year recurrence-free survival (RFS) rate, and median survival time after salvage lung resection. Univariate and multivariate analyses were performed to identify independent prognostic factors of OS and RFS. RESULTS: Thirty-six patients were included (EGFR-TKI: 33, ALK-TKI: 3). The 3-year OS and RFS after the surgery were 75.1 % (95 % confidence interval [CI] 55.9-86.9 %) and 22.2 % (95 % CI 8.6-39.7 %), respectively. Of clinicopathological factors, the progression of disease while on TKI and preoperative carcinoembryonic antigen (CEA) levels (≥5 ng/mL) were shown to be worse independent prognosticators of OS (hazard ratio [HR] 9.38, 95 % CI 1.57-55.88, P = .014; HR 4.84, 95 % CI 1.62-14.46, P = .005, respectively). Older age at initial treatment (≥70 years) and advanced pathological T stage (T2-T4) were the worse prognosticators for RFS (HR 12.58, 95 % CI 2.51-62.97, P = .002; HR 3.06, 95 % CI 1.04-9.03, P = .043, respectively). Grade 3 adverse events occurred in 5.6 % (2/36) patients, but no deaths were reported within 90 days after surgery. CONCLUSION: Our study showed that salvage surgery after TKI treatment was safe and feasible and may contribute to prolonged OS time by reducing the local tumor burden.
OBJECTIVES: The prognostic impact of surgical intervention for recurrent or residual non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement after tyrosine-kinase inhibitor (TKI) treatment remains unclear. We aimed to describe the characteristics and outcomes of patients undergoing salvage surgery in this setting. METHODS: We retrospectively collected and analyzed nationwide Japanese data on perioperative and postoperative outcomes of patients who underwent salvage surgery after EGFR or ALK-TKI during 2010-2015. The primary endpoint was a 3-year overall survival (OS) rate and secondary endpoints were the rate of adverse events, perioperative mortality rate, 3-year recurrence-free survival (RFS) rate, and median survival time after salvage lung resection. Univariate and multivariate analyses were performed to identify independent prognostic factors of OS and RFS. RESULTS: Thirty-six patients were included (EGFR-TKI: 33, ALK-TKI: 3). The 3-year OS and RFS after the surgery were 75.1 % (95 % confidence interval [CI] 55.9-86.9 %) and 22.2 % (95 % CI 8.6-39.7 %), respectively. Of clinicopathological factors, the progression of disease while on TKI and preoperative carcinoembryonic antigen (CEA) levels (≥5 ng/mL) were shown to be worse independent prognosticators of OS (hazard ratio [HR] 9.38, 95 % CI 1.57-55.88, P = .014; HR 4.84, 95 % CI 1.62-14.46, P = .005, respectively). Older age at initial treatment (≥70 years) and advanced pathological T stage (T2-T4) were the worse prognosticators for RFS (HR 12.58, 95 % CI 2.51-62.97, P = .002; HR 3.06, 95 % CI 1.04-9.03, P = .043, respectively). Grade 3 adverse events occurred in 5.6 % (2/36) patients, but no deaths were reported within 90 days after surgery. CONCLUSION: Our study showed that salvage surgery after TKI treatment was safe and feasible and may contribute to prolonged OS time by reducing the local tumor burden.