Masaoki Ito1, Yoshihiro Miyata2, Yasuhiro Tsutani3, Hiroyuki Ito4, Haruhiko Nakayama5, Kentaro Imai6, Norihiko Ikeda7, Morihito Okada8. 1. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. Electronic address: itooo_m@yahoo.co.jp. 2. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. Electronic address: ymiyata@hiroshima-u.ac.jp. 3. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. Electronic address: yatsutani@gmail.com. 4. Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan. Electronic address: h-ito@kcch.jp. 5. Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan. Electronic address: nakayama-h@kcch.jp. 6. Department of Thoracic Surgery, Tokyo Medical School, Shinjuku-ku, Tokyo, Japan. Electronic address: kentaro-imai@tea.ocn.ne.jp. 7. Department of Thoracic Surgery, Tokyo Medical School, Shinjuku-ku, Tokyo, Japan. Electronic address: ikeda-n@tokyo-med.ac.jp. 8. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. Electronic address: morihito1217@gmail.com.
Abstract
OBJECTIVES: Recurrence risk of resected lung adenocarcinoma is represented by pathological stage (pStage), histological subtype, and potentially by EGFR mutation. However, the relationship among these factors and their combined impact on prognosis are unclear. MATERIALS AND METHODS: Using a multicenter database, we retrospectively investigated the prognostic impact of EGFR mutation status in relation to pStage and histological subtype in resected pN0-1M0 lung adenocarcinoma. RESULTS: Among 1155 pN0-1M0 adenocarcinoma cases, pStage 0 and IA1-IB were confirmed predominantly in EGFR-positive cases. AIS, MIA, and lepidic predominant adenocarcinoma were also more frequently found in EGFR-positive cases and showed no/little recurrence regardless of EGFR mutation status. The 5-year recurrence-free survival (RFS) of papillary, acinar, solid, and micropapillary predominant adenocarcinoma was stratified by pStage (IA1-IB, IIA-IIIA) or histological malignant subtype (intermediate or high malignant subtype), and more finely subdivided by EGFR mutation status. Positive EGFR mutation cases showed worse RFS in both classifications. Low malignant subtype and pStage IA1-IB intermediate malignant subtype showed low frequency of recurrence. Whereas, in pStage IA1-IB high malignant subtype and pStage IIA-IIIA cases, EGFR-positive cases showed poorer 5-year RFS than EGFR-negative (49.6% and 75.6%, respectively, hazard ratio [HR] = 1.84, 95% CI = 1.38-7.42, p < 0.01) and multivariate analysis indicated positive EGFR mutation status was significantly related to poorer PRF (HR = 2.005, 95% CI = 1.029-3.906, p = 0.041). CONCLUSION: EGFR mutation harbored primarily in early-stage or low-malignant histological subtypes with no/little recurrence. In pN0-1M0 adenocarcinoma with higher risk of recurrence, positive EGFR mutation cases showed worse RFS. EGFR mutation status enables better stratification of recurrence risk when considering pStage and histological malignant subtype.
OBJECTIVES: Recurrence risk of resected lung adenocarcinoma is represented by pathological stage (pStage), histological subtype, and potentially by EGFR mutation. However, the relationship among these factors and their combined impact on prognosis are unclear. MATERIALS AND METHODS: Using a multicenter database, we retrospectively investigated the prognostic impact of EGFR mutation status in relation to pStage and histological subtype in resected pN0-1M0 lung adenocarcinoma. RESULTS: Among 1155 pN0-1M0 adenocarcinoma cases, pStage 0 and IA1-IB were confirmed predominantly in EGFR-positive cases. AIS, MIA, and lepidic predominant adenocarcinoma were also more frequently found in EGFR-positive cases and showed no/little recurrence regardless of EGFR mutation status. The 5-year recurrence-free survival (RFS) of papillary, acinar, solid, and micropapillary predominant adenocarcinoma was stratified by pStage (IA1-IB, IIA-IIIA) or histological malignant subtype (intermediate or high malignant subtype), and more finely subdivided by EGFR mutation status. Positive EGFR mutation cases showed worse RFS in both classifications. Low malignant subtype and pStage IA1-IB intermediate malignant subtype showed low frequency of recurrence. Whereas, in pStage IA1-IB high malignant subtype and pStage IIA-IIIA cases, EGFR-positive cases showed poorer 5-year RFS than EGFR-negative (49.6% and 75.6%, respectively, hazard ratio [HR] = 1.84, 95% CI = 1.38-7.42, p < 0.01) and multivariate analysis indicated positive EGFR mutation status was significantly related to poorer PRF (HR = 2.005, 95% CI = 1.029-3.906, p = 0.041). CONCLUSION:EGFR mutation harbored primarily in early-stage or low-malignant histological subtypes with no/little recurrence. In pN0-1M0 adenocarcinoma with higher risk of recurrence, positive EGFR mutation cases showed worse RFS. EGFR mutation status enables better stratification of recurrence risk when considering pStage and histological malignant subtype.
Authors: Stephanie P L Saw; Siqin Zhou; Jianbin Chen; Gillianne Lai; Mei-Kim Ang; Kevin Chua; Ravindran Kanesvaran; Quan Sing Ng; Amit Jain; Wan Ling Tan; Tanujaa Rajasekaran; Darren W T Lim; Aaron Tan; Kam Weng Fong; Angela Takano; Xin Ming Cheng; Kiat Hon Lim; Tina Koh; Boon-Hean Ong; Eng Huat Tan; Chee Keong Toh; Anders J Skanderup; Sze Huey Tan; Daniel S W Tan Journal: JAMA Netw Open Date: 2021-11-01