A nomogram to predict lymph node metastasis risk for early esophageal squamous cell carcinoma

Xiaofeng Duan, Xiaobin Shang, Jie Yue, Zhao Ma, Chuangui Chen, Peng Tang, Hongjing Jiang, Zhentao Yu, Xiaofeng Duan, Xiaobin Shang, Jie Yue, Zhao Ma, Chuangui Chen, Peng Tang, Hongjing Jiang, Zhentao Yu

Abstract

Background: A nomogram was developed to predict lymph node metastasis (LNM) for patients with early-stage esophageal squamous cell carcinoma (ESCC).

Methods: We used the clinical data of ESCC patients with pathological T1 stage disease who underwent surgery from January 2011 to June 2018 to develop a nomogram model. Multivariable logistic regression was used to confirm the risk factors for variable selection. The risk of LNM was stratified based on the nomogram model. The nomogram was validated by an independent cohort which included early ESCC patients underwent esophagectomy between July 2018 and December 2019.

Results: Of the 223 patients, 36 (16.1%) patients had LNM. The following three variables were confirmed as LNM risk factors and were included in the nomogram model: tumor differentiation (odds ratio [OR] = 3.776, 95% confidence interval [CI] 1.515-9.360, p = 0.004), depth of tumor invasion (OR = 3.124, 95% CI 1.146-8.511, p = 0.026), and tumor size (OR = 2.420, 95% CI 1.070-5.473, p = 0.034). The C-index was 0.810 (95% CI 0.742-0.895) in the derivation cohort (223 patients) and 0.830 (95% CI 0.763-0.902) in the validation cohort (80 patients).

Conclusions: A validated nomogram can predict the risk of LNM via risk stratification. It could be used to assist in the decision-making process to determine which patients should undergo esophagectomy and for which patients with a low risk of LNM, curative endoscopic resection would be sufficient.

Keywords: Cancer; Esophagus; Lymph nodes; Metastasis; Nomogram model.

Conflict of interest statement

Not applicable.

Figures

Fig. 1
Fig. 1
Study flow chart
Fig. 2
Fig. 2
The prediction ability of each risk factor and the combined model. a. Derivation cohort. Tumor differentiation in blue line: AUC 0.617, 95% CI 0.509–0.724 (Sensitivity 0.356, Specificity 0.870); pT stage in green line: 0.623, 95% CI 0.532–0.714 (Sensitivity 0.812, Specificity 0.413); Tumor size in brown line: 0.596, 95% CI 0.494–0.697 (Sensitivity 0.552, Specificity 0.645); Combined full model in red line: 0.810 95% CI 0.742–0.895 (Sensitivity 0.821, Specificity 0.652). b. Validation cohort. Tumor differentiation in green line: AUC 0.765, 95% CI 0.596–0.933 (Sensitivity 0.650, Specificity 0.830); pT stage in brown line: 0.647, 95% CI 0.498–0.796 (Sensitivity 0.980, Specificity 0.312); Tumor size in blue line: 0.686, 95% CI 0.515–0.858 (Sensitivity 0.650, Specificity 0.682); Combined full model in red line: 0.830, 95% CI 0.763–0.902 (Sensitivity 0.820, Specificity 0.760)
Fig. 3
Fig. 3
Nomogram to predict the LNM risk for each patient. The patient’s nomogram calculated the risk of LNM as 59%. Nomogram calculations are as follows: size ≥2.5 cm, which corresponds to 61 points; low differentiation, which corresponds to 100 points; pT1b, which corresponds to 85 points; this equals 246 total points, corresponding to a LNM rate of 59%

References

    1. Chen W, Zheng R, Zuo T, et al. National cancer incidence and mortality in China, 2012. Chin J Cancer Res. 2016;28:1–11. doi: 10.21147/j.issn.1000-9604.2016.06.02.
    1. Merkow RP, Bilimoria KY, Keswani RN, Chung J, Sherman KL, Knab LM, et al. Treatment trends, risk of lymph node metastasis, and outcomes for localized esophageal cancer. J Natl Cancer Inst. 2014;106(7):dju133. 10.1093/jnci/dju133.
    1. Nentwich MF, von Loga K, Reeh M, Uzunoglu FG, Marx A, Izbicki JR, et al. Depth of submucosal tumor infiltration and its relevance in lymphatic metastasis formation for T1b squamous cell and adenocarcinomas of the esophagus. J Gastrointest Surg. 2014;18(2):242–9; discussion 249. 10.1007/s11605-013-2367-2.
    1. Akutsu Y, Uesato M, Shuto K, Kono T, Hoshino I, Horibe D, et al. The overall prevalence of metastasis in T1 esophageal squamous cell carcinoma: a retrospective analysis of 295 patients. Ann Surg. 2013;257(6):1032–8. 10.1097/SLA.0b013e31827017fc.
    1. Lee L, Ronellenfitsch U, Hofstetter WL, Darling G, Gaiser T, Lippert C, et al. Predicting lymph node metastases in early esophageal adenocarcinoma using a simple scoring system. J Am Coll Surg. 2013;217(2):191–9. 10.1016/j.jamcollsurg.2013.03.015.
    1. Gertler R, Stein HJ, Schuster T, Rondak IC, Höfler H, Feith M. Prevalence and topography of lymph node metastases in early esophageal and gastric cancer. Ann Surg. 2014;259(1):96–101. doi: 10.1097/SLA.0000000000000239.
    1. Tanaka T, Matono S, Mori N, Shirouzu K, Fujita H. T1 squamous cell carcinoma of the esophagus: long-term outcomes and prognostic factors after esophagectomy. Ann Surg Oncol. 2014;21(3):932–938. doi: 10.1245/s10434-013-3372-0.
    1. Dubecz A, Kern M, Solymosi N, Schweigert M, Stein HJ. Predictors of lymph node metastasis in surgically resected T1 Esophageal Cancer. Ann Thorac Surg. 2015;99(6):1879–1885. doi: 10.1016/j.athoracsur.2015.02.112.
    1. Holscher AH, Bollschweiler E, Schroder W, et al. Prognostic impact of upper, middle, and lower third mucosal or submucosal infiltration in early esophageal cancer. Ann Surg. 2011;254(5):802–807. doi: 10.1097/SLA.0b013e3182369128.
    1. Duan X, Tang P, Shang X, et al. The prevalence of lymph node metastasis for pathological T1 esophageal cancer: a retrospective study of 143 cases. Surg Oncol. 2018;27(1):1–6. doi: 10.1016/j.suronc.2017.11.002.
    1. Zheng H, Tang H, Wang H, Fang Y, Shen Y, Feng M, et al. Nomogram to predict lymph node metastasis in patients with early oesophageal squamous cell carcinoma. British J Surg. 2018;105(11):1464–70. 10.1002/bjs.10882.
    1. Thosani N, Singh H, Kapadia A, Ochi N, Lee JH, Ajani J, et al. Diagnostic accuracy of EUS in differentiating mucosal versus submucosal invasion of superficial esophageal cancers: a systematic review and meta-analysis. Gastrointest Endosc. 2012;75(2):242–53. 10.1016/j.gie.2011.09.016.
    1. Pouw RE, Heldoorn N, Alvarez Herrero L, et al. Do we still need EUS in the workup of patients with early esophageal neoplasia? A retrospective analysis of 131 cases. Gastrointest Endosc. 2011;73(4):662–668. doi: 10.1016/j.gie.2010.10.046.
    1. Aoyama J, Kawakubo H, Mayanagi S, et al. Discrepancy Between the Clinical and Final Pathological Findings of Lymph Node Metastasis in Superficial Esophageal Cancer. Ann Surg Oncol. 2019.
    1. Akutsu Y, Kato K, Igaki H, et al. The prevalence of overall and initial lymph node metastases in clinical T1N0 thoracic Esophageal Cancer: from the results of JCOG0502, a prospective Multicenter study. Ann Surg. 2015.
    1. Rice TW, Rusch VW, Ishwaran H, Blackstone EH. Cancer of the esophagus and esophagogastric junction: data-driven staging for the seventh edition of the American joint committee on Cancer/International Union against Cancer Cancer staging manuals. Cancer. 2010;116(16):3763–3773. doi: 10.1002/cncr.25146.
    1. Zhang H, Tang P, Miao X et al. Does tumor size improve the accuracy of prognostic prediction in patients with esophageal squamous cell carcinoma after surgical resection? Oncotarget. 2016.
    1. Ancona E, Rampado S, Cassaro M, Battaglia G, Ruol A, Castoro C, et al. Prediction of lymph node status in superficial esophageal carcinoma. Ann Surg Oncol. 2008;15(11):3278–88. 10.1245/s10434-008-0065-1.
    1. Leers JM, DeMeester SR, Oezcelik A, et al. The prevalence of lymph node metastases in patients with T1 esophageal adenocarcinoma a retrospective review of esophagectomy specimens. Ann Surg. 2011;253(2):271–278. doi: 10.1097/SLA.0b013e3181fbad42.
    1. Ma Z, Chen C, Duan X, et al. Characteristics and risk factors of lymph node metastasis in pN1 stage esophageal squamous cell carcinoma. Zhonghua Wai Ke Za Zhi. 2015;53:513–517.
    1. Zhu Z, Yu W, Li H, Zhao K, Zhao W, Zhang Y, et al. Nodal skip metastasis is not a predictor of survival in thoracic esophageal squamous cell carcinoma. Ann Surg Oncol. 2013;20(9):3052–8. 10.1245/s10434-013-2987-5.
    1. Bollschweiler E, Baldus SE, Schroder W, et al. High rate of lymph-node metastasis in submucosal esophageal squamous-cell carcinomas and adenocarcinomas. Endoscopy. 2006;38(2):149–156. doi: 10.1055/s-2006-924993.
    1. Endo M, Yoshino K, Kawano T, Nagai K, Inoue H. Clinicopathologic analysis of lymph node metastasis in surgically resected superficial cancer of the thoracic esophagus. Dis Esophagus. 2000;13(2):125–129. doi: 10.1046/j.1442-2050.2000.00100.x.
    1. Semenkovich T, Yan Y, Subramanian M, et al. A Clinical Nomogram for Predicting Node-positive Disease in Esophageal Cancer. Ann Surg. 2019.
    1. Newton A, Predina J, Xia L, et al. Surgical Management of Early-Stage Esophageal Adenocarcinoma Based on lymph node metastasis risk. Ann Surg Oncol. 2018;25(1):318–325. doi: 10.1245/s10434-017-6238-z.
    1. Weksler B, Kennedy K, Sullivan J. Using the National Cancer Database to create a scoring system that identifies patients with early-stage esophageal cancer at risk for nodal metastases. J Thorac Cardiovasc Surg. 2017;154(5):1787–1793. doi: 10.1016/j.jtcvs.2017.07.036.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit