Establishment and evaluation of a predictive model for clinical remission of advanced esophageal squamous cell carcinoma after neoadjuvant chemotherapy_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YANG Hao , YANG Linqi , WANG Zhi , XIE Fei ,  FU Maoyong

Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, P. R. China;

Corresponding?author：

FU Maoyong, Email: fumaoyong@163.com

Keywords：

Neoadjuvant chemotherapy; esophageal squamous cell carcinoma; clinical remission; influencing factors; clinical prediction model

DOI：

10.7507/1007-4848.202103132

Video：

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Objective To investigate the influencing factors for the clinical remission of advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemotherapy, establish an individualized nomogram model to predict the clinical remission of advanced ESCC with neoadjuvant chemotherapy and evaluate its efficacy, providing serve for the preoperative adjuvant treatment of ESCC.Methods The clinical data of patients with esophageal cancer who underwent neoadjuvant chemotherapy (nedaplatin 80 mg/m², day 3+docetaxel 75 mg/m², day 1, 2 cycles, 21 days per cycle interval) in the Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College from February 2016 to August 2020 were analyzed retrospectively. According to the WHO criteria for efficacy assessment of solid tumors, tumors were divided into complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD). CR and PR were defined as effective neoadjuvant chemotherapy, and SD and PD were defined as ineffective neoadjuvant chemotherapy. Univariate and multivariate analyses were used to analyze the influencing factors for the short-term efficacy of neoadjuvant chemotherapy. The R software was used to establish a nomogram model for predicting the clinical remission of advanced ESCC with neoadjuvant chemotherapy, and Bootstrap method for internal verification of the model. C-index, calibration curve and receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the nomogram.Results Finally 115 patients were enrolled, including 93 males and 22 females, aged 40-75 (64.0±8.0) years. After receiving docetaxel+nedaplatin neoadjuvant chemotherapy for 2 cycles, there were 9 patients with CR, 56 patients with PR, 43 patients with SD and 7 patients with PD. Among them, chemotherapy was effective (CR+PR) in 65 patients and ineffective (SD+PD) in 50 patients, with the clinical effective rate of about 56.5% (65/115). Univariate analysis showed that there were statistical differences in smoking history, alcoholism history, tumor location, tumor differentiation degree, and cN stage before chemotherapy between the effective neoadjuvant chemotherapy group and the ineffective neoadjuvant chemotherapy group (P<0.05). Logistic regression analysis showed that low-differentiation advanced ESCC had the worst clinical response to neoadjuvant chemotherapy, moderately-highly differentiated ESCC responded better (P<0.05). Stage cN0 advanced ESCC responded better to neoadjuvant chemotherapy than stage cN1 and cN2 (P<0.05). The C-index and the area under the ROC curve of the nomogram were both 0.763 (95%CI 0.676-0.850), the calibration curve fit well, the best critical value of the nomogram calculated by the Youden index was 70.04 points, and the sensitivity and specificity of the critical value were 80.0% and 58.0%, respectively.Conclusion The established clinical prediction model has good discrimination and accuracy, and can provide a reference for individualized analysis of the clinical remission of advanced ESCC with neoadjuvant chemotherapy and the screening of new adjuvant treatment subjects.

Citation： YANG Hao, YANG Linqi, WANG Zhi, XIE Fei, FU Maoyong. Establishment and evaluation of a predictive model for clinical remission of advanced esophageal squamous cell carcinoma after neoadjuvant chemotherapy. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(5): 690-698. doi: 10.7507/1007-4848.202103132 Copy

1.	Feng RM, Zong YN, Cao SM, et al. Current cancer situation in China: Good or bad news from the 2018 Global Cancer Statistics? Cancer Commun (Lond), 2019, 39(1): 22.
2.	Chen MF, Yang YH, Lai CH, et al. Outcome of patients with esophageal cancer: A nationwide analysis. Ann Surg Oncol, 2013, 20(9): 3023-3030.
3.	黃楚堅, 蔡松華, 杜隆德, 等. 食管鱗癌以手術治療為主的多學科治療新研究進展. 中國癌癥防治雜志, 2020, 12(4): 463-468.
4.	Ando N, Kato H, Igaki H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol, 2012, 19(1): 68-74.
5.	Yang H, Liu H, Chen Y, et al. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010): A phase Ⅲ multicenter, randomized, open-label clinical trial. J Clin Oncol, 2018, 36(27): 2796-2803.
6.	Allum WH, Stenning SP, Bancewicz J, et al. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol, 2009, 27(30): 5062-5067.
7.	Fujita Y, Hiramatsu M, Kawai M, et al. Evaluation of combined docetaxel and nedaplatin chemotherapy for recurrent esophageal cancer compared with conventional chemotherapy using cisplatin and 5-fluorouracil: A retrospective study. Dis Esophagus, 2008, 21(6): 496-501.
8.	程良, 高薇, 楊毫, 等. 新輔助化療對進展期食管鱗癌的近期療效觀察. 中國腫瘤外科雜志, 2020, 12(3): 223-227.
9.	Rice TW, Ishwaran H, Ferguson MK, et al. Cancer of the esophagus and esophagogastric junction: An eighth edition staging primer. J Thorac Oncol, 2017, 12(1): 36-42.
10.	desai RK, Tagliabue JR, Wegryn SA, et al. CT evaluation of wall thickening in the alimentary tract. Radiographics, 1991, 11(5): 771-783.
11.	Swisher SG, Maish M, Erasmus JJ, et al. Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer. Ann Thorac Surg, 2004, 78(4): 1152-1160.
12.	Tio TL, Cohen P, Coene PP, et al. Endosonography and computed tomography of esophageal carcinoma. Preoperative classification compared to the new (1987) TNM system. Gastroenterology, 1989, 96(6): 1478-1486.
13.	Hong SJ, Kim TJ, Nam KB, et al. New TNM staging system for esophageal cancer: What chest radiologists need to know. Radiographics, 2014, 34(6): 1722-1740.
14.	劉東紅, 呂明德, 謝曉燕, 等. 頸部淋巴結轉移的超聲診斷. 中國超聲醫學雜志, 2001, 17(12): 921-923.
15.	Therasse P. New guideline to evaluate the response to treatment in solid tumors. J Natl Cancer Inst, 2005, 12(1): S16-S27.
16.	Gay JA, Dyk P, Deasy JO, et al. Common terminology criteria for adverse events (CTCAE) v4.0 based hybrid patient and physician questionnaire for head and neck (HN) radiotherapy symptom reporting. Intern J Radia Oncol Biol Phys, 2011, 81(2): S673.
17.	赫捷, 李進程, 吳一龍, 等. 中國臨床腫瘤學會(CSCO)食管癌診療指南. 北京: 人民衛生出版社, 2020.
18.	郭睿, 楊勇偉, 金澄宇, 等. 食管癌淋巴結轉移的危險因素分析. 中華胃食管反流病電子雜志, 2018, 5(1): 7-9.
19.	van Hootegem SJM, Smithers BM, Gotley DC, et al. The impact of signet ring cell differentiation on outcome in patients with esophageal and gastroesophageal junction adenocarcinoma. Ann Surg Oncol, 2019, 26(8): 2375-2384.
20.	Shimodaira Y, Slack RS, Harada K, et al. Influence of induction chemotherapy in trimodality therapy-eligible oesophageal cancer patients: secondary analysis of a randomised trial. Br J Cancer, 2018, 118(3): 331-337.
21.	杜海磊, 施敏敏, 車嘉銘, 等. 食管鱗癌腫瘤分化程度對早期食管癌患者預后的影響. 杭州: 中國醫師協會胸外科醫師分會2015年會、第六屆全國胸外科學術大會暨第八屆浙江省胸部腫瘤論壇, 2015.
22.	Korst RJ, Kansler AL, Port JL, et al. Downstaging of T or N predicts long-term survival after preoperative chemotherapy and radical resection for esophageal carcinoma. Ann Thorac Surg, 2006, 82(2): 480-484.
23.	葉凱, 許建華, 鄭正榮, 等. 胸段食管癌孤立性淋巴結轉移規律及其臨床價值. 中國腫瘤臨床, 2011, 38(17): 1035-1038.
24.	Konishi H, Fujiwara H, Shiozaki A, et al. Effects of neoadjuvant 5-fluorouracil and cisplatin therapy in patients with clinical stage Ⅱ/Ⅲ esophageal squamous cell carcinoma. Anticancer Res, 2018, 38(2): 1017-1023.
25.	Tanabe S, Shirakawa Y, Maeda N, et al. Current status of neoadjuvant chemotherapy for advanced esophageal cancer. Gan To Kagaku Ryoho, 2013, 40(12): 1612-1614.
26.	Konieczny A, Meyer P, Schnider A, et al. Accuracy of multidetector-row CT for restaging after neoadjuvant treatment in patients with oesophageal cancer. Eur Radiol, 2013, 23(9): 2492-2502.
27.	Borggreve AS, Goense L, van Rossum PSN, et al. Preoperative prediction of pathologic response to neoadjuvant chemoradiotherapy in patients with esophageal cancer using 18 F-FDG PET/CT and DW-MRI: A prospective multicenter study. Int J Radiat Oncol Biol Phys, 2020, 106(5): 998-1009.
28.	Peng Q, Chen H, Huo JR. Alcohol consumption and corresponding factors: A novel perspective on the risk factors of esophageal cancer. Oncol Lett, 2016, 11(5): 3231-3239.
29.	Sundel?f M, Lagergren J, Ye W. Patient demographics and lifestyle factors influencing long-term survival of oesophageal cancer and gastric cardia cancer in a nationwide study in Sweden. Eur J Cancer, 2008, 44(11): 1566-1571.
30.	陳潔, 袁志平. 吸煙對中晚期食管癌患者放化療后相關并發癥和相關指標及預后的影響. 東南大學學報(醫學版), 2019, 38(1): 47-50.
31.	孫小莉, 曹曉俠. 伴有長期吸煙史食管癌患者中 VEGF和 Ki-67水平的臨床意義. 實用癌癥雜志, 2015, 30(12): 1793-1796.
32.	Shitara K, Matsuo K, Hatooka S, et al. Heavy smoking history interacts with chemoradiotherapy for esophageal cancer prognosis: A retrospective study. Cancer Sci, 2010, 101(4): 1001-1006.
33.	趙蓉蓉, 李文強, 王傳升, 等. 酒精依賴甲基化敏感基因篩選. 中華精神科雜志, 2011, 44(4): 223-225.
34.	卞保祥, 洪義東, 胡楠, 等. TFAP2E基因CpG島甲基化狀態與食管癌患者化療療效的關系研究. 中國現代應用藥學, 2017, 34(12): 1756-1758.
35.	Ebert MP, T?nzer M, Balluff B, et al. TFAP2E-DKK4 and chemoresistance in colorectal cancer. N Engl J Med, 2012, 366(1): 44-53.
36.	Sun J, Du N, Li J, et al. Transcription factor AP2ε: A potential predictor of chemoresistance in patients with gastric cancer. Technol Cancer Res Treat, 2016, 15(2): 285-295.

1. Feng RM, Zong YN, Cao SM, et al. Current cancer situation in China: Good or bad news from the 2018 Global Cancer Statistics? Cancer Commun (Lond), 2019, 39(1): 22.
2. Chen MF, Yang YH, Lai CH, et al. Outcome of patients with esophageal cancer: A nationwide analysis. Ann Surg Oncol, 2013, 20(9): 3023-3030.
3. 黃楚堅, 蔡松華, 杜隆德, 等. 食管鱗癌以手術治療為主的多學科治療新研究進展. 中國癌癥防治雜志, 2020, 12(4): 463-468.
4. Ando N, Kato H, Igaki H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol, 2012, 19(1): 68-74.
5. Yang H, Liu H, Chen Y, et al. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010): A phase Ⅲ multicenter, randomized, open-label clinical trial. J Clin Oncol, 2018, 36(27): 2796-2803.
6. Allum WH, Stenning SP, Bancewicz J, et al. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol, 2009, 27(30): 5062-5067.
7. Fujita Y, Hiramatsu M, Kawai M, et al. Evaluation of combined docetaxel and nedaplatin chemotherapy for recurrent esophageal cancer compared with conventional chemotherapy using cisplatin and 5-fluorouracil: A retrospective study. Dis Esophagus, 2008, 21(6): 496-501.
8. 程良, 高薇, 楊毫, 等. 新輔助化療對進展期食管鱗癌的近期療效觀察. 中國腫瘤外科雜志, 2020, 12(3): 223-227.
9. Rice TW, Ishwaran H, Ferguson MK, et al. Cancer of the esophagus and esophagogastric junction: An eighth edition staging primer. J Thorac Oncol, 2017, 12(1): 36-42.
10. desai RK, Tagliabue JR, Wegryn SA, et al. CT evaluation of wall thickening in the alimentary tract. Radiographics, 1991, 11(5): 771-783.
11. Swisher SG, Maish M, Erasmus JJ, et al. Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer. Ann Thorac Surg, 2004, 78(4): 1152-1160.
12. Tio TL, Cohen P, Coene PP, et al. Endosonography and computed tomography of esophageal carcinoma. Preoperative classification compared to the new (1987) TNM system. Gastroenterology, 1989, 96(6): 1478-1486.
13. Hong SJ, Kim TJ, Nam KB, et al. New TNM staging system for esophageal cancer: What chest radiologists need to know. Radiographics, 2014, 34(6): 1722-1740.
14. 劉東紅, 呂明德, 謝曉燕, 等. 頸部淋巴結轉移的超聲診斷. 中國超聲醫學雜志, 2001, 17(12): 921-923.
15. Therasse P. New guideline to evaluate the response to treatment in solid tumors. J Natl Cancer Inst, 2005, 12(1): S16-S27.
16. Gay JA, Dyk P, Deasy JO, et al. Common terminology criteria for adverse events (CTCAE) v4.0 based hybrid patient and physician questionnaire for head and neck (HN) radiotherapy symptom reporting. Intern J Radia Oncol Biol Phys, 2011, 81(2): S673.
17. 赫捷, 李進程, 吳一龍, 等. 中國臨床腫瘤學會(CSCO)食管癌診療指南. 北京: 人民衛生出版社, 2020.
18. 郭睿, 楊勇偉, 金澄宇, 等. 食管癌淋巴結轉移的危險因素分析. 中華胃食管反流病電子雜志, 2018, 5(1): 7-9.
19. van Hootegem SJM, Smithers BM, Gotley DC, et al. The impact of signet ring cell differentiation on outcome in patients with esophageal and gastroesophageal junction adenocarcinoma. Ann Surg Oncol, 2019, 26(8): 2375-2384.
20. Shimodaira Y, Slack RS, Harada K, et al. Influence of induction chemotherapy in trimodality therapy-eligible oesophageal cancer patients: secondary analysis of a randomised trial. Br J Cancer, 2018, 118(3): 331-337.
21. 杜海磊, 施敏敏, 車嘉銘, 等. 食管鱗癌腫瘤分化程度對早期食管癌患者預后的影響. 杭州: 中國醫師協會胸外科醫師分會2015年會、第六屆全國胸外科學術大會暨第八屆浙江省胸部腫瘤論壇, 2015.
22. Korst RJ, Kansler AL, Port JL, et al. Downstaging of T or N predicts long-term survival after preoperative chemotherapy and radical resection for esophageal carcinoma. Ann Thorac Surg, 2006, 82(2): 480-484.
23. 葉凱, 許建華, 鄭正榮, 等. 胸段食管癌孤立性淋巴結轉移規律及其臨床價值. 中國腫瘤臨床, 2011, 38(17): 1035-1038.
24. Konishi H, Fujiwara H, Shiozaki A, et al. Effects of neoadjuvant 5-fluorouracil and cisplatin therapy in patients with clinical stage Ⅱ/Ⅲ esophageal squamous cell carcinoma. Anticancer Res, 2018, 38(2): 1017-1023.
25. Tanabe S, Shirakawa Y, Maeda N, et al. Current status of neoadjuvant chemotherapy for advanced esophageal cancer. Gan To Kagaku Ryoho, 2013, 40(12): 1612-1614.
26. Konieczny A, Meyer P, Schnider A, et al. Accuracy of multidetector-row CT for restaging after neoadjuvant treatment in patients with oesophageal cancer. Eur Radiol, 2013, 23(9): 2492-2502.
27. Borggreve AS, Goense L, van Rossum PSN, et al. Preoperative prediction of pathologic response to neoadjuvant chemoradiotherapy in patients with esophageal cancer using 18 F-FDG PET/CT and DW-MRI: A prospective multicenter study. Int J Radiat Oncol Biol Phys, 2020, 106(5): 998-1009.
28. Peng Q, Chen H, Huo JR. Alcohol consumption and corresponding factors: A novel perspective on the risk factors of esophageal cancer. Oncol Lett, 2016, 11(5): 3231-3239.
29. Sundel?f M, Lagergren J, Ye W. Patient demographics and lifestyle factors influencing long-term survival of oesophageal cancer and gastric cardia cancer in a nationwide study in Sweden. Eur J Cancer, 2008, 44(11): 1566-1571.
30. 陳潔, 袁志平. 吸煙對中晚期食管癌患者放化療后相關并發癥和相關指標及預后的影響. 東南大學學報(醫學版), 2019, 38(1): 47-50.
31. 孫小莉, 曹曉俠. 伴有長期吸煙史食管癌患者中 VEGF和 Ki-67水平的臨床意義. 實用癌癥雜志, 2015, 30(12): 1793-1796.
32. Shitara K, Matsuo K, Hatooka S, et al. Heavy smoking history interacts with chemoradiotherapy for esophageal cancer prognosis: A retrospective study. Cancer Sci, 2010, 101(4): 1001-1006.
33. 趙蓉蓉, 李文強, 王傳升, 等. 酒精依賴甲基化敏感基因篩選. 中華精神科雜志, 2011, 44(4): 223-225.
34. 卞保祥, 洪義東, 胡楠, 等. TFAP2E基因CpG島甲基化狀態與食管癌患者化療療效的關系研究. 中國現代應用藥學, 2017, 34(12): 1756-1758.
35. Ebert MP, T?nzer M, Balluff B, et al. TFAP2E-DKK4 and chemoresistance in colorectal cancer. N Engl J Med, 2012, 366(1): 44-53.
36. Sun J, Du N, Li J, et al. Transcription factor AP2ε: A potential predictor of chemoresistance in patients with gastric cancer. Technol Cancer Res Treat, 2016, 15(2): 285-295.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Establishment and evaluation of a predictive model for clinical remission of advanced esophageal squamous cell carcinoma after neoadjuvant chemotherapy

Abstract Full text Figures/Tables Video References Cited by

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