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

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.

SUBMITTER: Li QW

PROVIDER: S-EPMC7477429 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Li Qi-Wen QW Qiu Bo B Liang Wen-Hua WH Wang Jun-Ye JY Hu Wan-Ming WM Zhang Tian T Xu Shuang-Bing SB López José J Chen Nai-Bin NB Guo Min-Zhang MZ Zhao Yi Y Chen Ling-Juan LJ Liu Song-Ran SR Yun Jing-Ping JP Guo Jin-Yu JY Wang Si-Yu SY Wang Xin X Zhang Li L Yue Dong-Sheng DS Liao Zhong-Xing ZX Lin Steven H SH Long Hao H Pang Qing-Song QS Liu Hui H

Journal of Cancer 20200825 20

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). ...[more]

PMID: 32922551

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Project description:BackgroundRecent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma.MethodsTwo hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated.ResultsThere were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p < 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p < 0.001) for DFS, and EGFR mutation type (p < 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40; p = 0.036; TKIs vs. chemotherapy, HR = 0.38; p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22; p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42; p = 0.034; TKIs vs. chemotherapy, HR = 0.33; p < 0.001) for DFS. No significant difference was found in the incidence of Grade 3-4 toxicities between groups (p = 0.445).ConclusionsAdjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.

Project description:Background: The lymph node ratio (LNR), involved nodes/ lymph nodes examined, is associated with survival in colon cancer. Previous studies investigated the prognostic role of LNR regardless of TNM N staging or compared LNR and TNM N stages for prognostic strength. However, LNR may be utilized to obtain additional prognostic information rather than replacing TNM staging in daily practice. This study aimed to evaluate the role of LNR in TNM N stages to provide further prognostic information in daily practice. Methods: Patients with stage-III colon cancer who underwent surgery and adjuvant chemotherapy were included. pN1c tumors (tumor deposits without node involvement) and rectal cancers were excluded. Clinicopathological parameters and LNR in pN1a-b and pN2 groups were evaluated for recurrence-free survival (RFS). Results: A total of 97 patients were included [pN1a-b: n=69 (71.1%) and pN2: n=28 (28.9%)]. Median LNR in the entire population was 0.09 (0.01-0.84) with a median lymph node examined of 22 (8-89) and involved of 2 (1-17). Median RFS was not reached in the pN1a-b and pN2 groups during a median follow-up of 20.8 months (1.13-101.03), with significantly better survival of the pN1a-b group (p=0.003). Among the pN1a-b group, the LNR cut-off was set as 0.10. LNR significantly discriminated RFS (Median not-reached, p=0.001). Among the pN2 group, the LNR cut-off was set as 0.25 and LNR significantly discriminated RFS [Not reached vs. 11.40 months (95%CI: 3.57-16.83), p=0.004]. Combined pN-LNR groups revealed significant discrimination in RFS (p<0.001). RFS was not statistically different between pN2-LNR≤0.25 and pN1-LNR>0.10 groups (p=0.282). In multivariable analysis with clinicopathological parameters, only LNR was significant (p=0.023), whereas the pN stage did not remain significant (p=0.637). Conclusion: LNR adds further prognostication in pN1a-b and N2 groups. LNR may be utilized to detect patient subgroups in different TNM N sages (pN1a-b and pN2) but with similar prognoses. This further prognostic information may assist clinical decisions in practice. The results of this study emphasize an adequate and higher number of lymph node samples in surgery.

Dataset Information

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

Publications

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

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