J Cancer 2020; 11(20):6114-6121. doi:10.7150/jca.47119 This issue

Research Paper

Risk Prediction for Locoregional Recurrence in Epidermal Growth Factor Receptor-Mutant Stage III-pN2 Lung Adenocarcinoma after Complete Resection: A Multi-center Retrospective Study

Qi-Wen Li1,2*, Bo Qiu1,2*, Wen-Hua Liang3*, Jun-Ye Wang2,4*, Wan-Ming Hu2,5, Tian Zhang6, Shuang-Bing Xu7, José López8, Nai-Bin Chen1,2, Min-Zhang Guo3, Yi Zhao3, Ling-Juan Chen7, Song-Ran Liu2,5, Jing-Ping Yun2,5, Jin-Yu Guo1,2, Si-Yu Wang2,4, Xin Wang2,4, Li Zhang2,9, Dong-Sheng Yue10, Zhong-Xing Liao11, Steven H. Lin11, Hao Long2,4✉, Qing-Song Pang6✉, Hui Liu1,2✉

1. Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
2. Lung Cancer Research Center, Sun Yat-sen University, Guangzhou, China
3. Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University/State Key Laboratory of Respiratory Disease/National Clinical Research Center of Respiratory Disease, Guangzhou, China
4. Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
5. Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
6. Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
7. Union Hospital Cancer Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
8. Group of Technological Innovation, Radiation Oncology, University Hospital Virgen del Rocio, Sevilla, Spain
9. Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
10. Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
11. Department of Radiation Oncology, M.D. Anderson Cancer Center, Houston, Texas, USA
*Qi-Wen Li, Bo Qiu, Wen-Hua Liang and Jun-Ye Wang contributed equally to this work.

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Citation:
Li QW, Qiu B, Liang WH, Wang JY, Hu WM, Zhang T, Xu SB, López J, Chen NB, Guo MZ, Zhao Y, Chen LJ, Liu SR, Yun JP, Guo JY, Wang SY, Wang X, Zhang L, Yue DS, Liao ZX, Lin SH, Long H, Pang QS, Liu H. Risk Prediction for Locoregional Recurrence in Epidermal Growth Factor Receptor-Mutant Stage III-pN2 Lung Adenocarcinoma after Complete Resection: A Multi-center Retrospective Study. J Cancer 2020; 11(20):6114-6121. doi:10.7150/jca.47119. Available from https://www.jcancer.org/v11p6114.htm

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Abstract

Background: This study aimed to develop a predictive model based on the risk of locoregional recurrence (LRR) in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma after complete resection.

Methods: A total of 11,020 patients with lung surgery were screened to determine completely resected EGFR-mutant stage III-pN2 lung adenocarcinoma. Patients were excluded if they received preoperative therapy or postoperative radiation therapy (PORT). The time from surgery to LRR was recorded. Clinicopathological variables with statistical significance predicting LRR in the multivariate Cox regression were incorporated into the competing risk nomogram. Patients were then sub-grouped based on different recurrence risk as a result of the nomogram.

Results: Two hundred and eighty-eight patients were enrolled, including 191 (66.3%) with unforeseen N2 (IIIA1-2), 75 (26.0%) with minimal/single station N2 (IIIA3), and 22 (7.6%) with bulky and/or multilevel N2 (IIIA4). The 2-year overall cumulative incidence of LRR was 27.2% (confidence interval [CI], 16.3%-38.0%). IIIA4 disease (hazard ratio, 2.65; CI, 1.15-6.07; P=0.022) and extranodal extension (hazard ratio, 3.33; CI, 1.76-6.30; P<0.001) were independent risk factors for LRR and were incorporated into the nomogram. Based on the nomogram, patients who did not have any risk factor (low-risk) had a significantly lower predicted 2-year incidence of LRR than those with any of the risk factors (high-risk; 4.6% vs 21.9%, P<0.001).

Conclusions: Pre-treatment bulky/multilevel N2 and pathological extranodal extension are risk factors for locoregional recurrence in EGFR-mutant stage III-pN2 lung adenocarcinoma. Intensive adjuvant therapies and active follow-up should be considered in patients with any of the risk factors.

Keywords: Locoregional recurrence, postoperative radiotherapy, lymph node metastasis, extranodal extension, Robinson classification