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Published in: Annals of Surgical Oncology 5/2024

20-01-2024 | Esophagus Resection | Thoracic Oncology

Absence of Hypercoagulation Status after Neoadjuvant Treatment is Associated with Favorable Prognosis in Patients Undergoing Subtotal Esophagectomy for Esophageal Squamous Cell Carcinoma

Authors: Fumitake Sugiyama, MD, Mitsuro Kanda, MD, FACS, Dai Shimizu, MD, Shinichi Umeda, MD, Yoshikuni Inokawa, MD, Norifumi Hattori, MD, Masamichi Hayashi, MD, FACS, Chie Tanaka, MD, Goro Nakayama, MD, Yasuhiro Kodera, MD, FACS

Published in: Annals of Surgical Oncology | Issue 5/2024

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Abstract

Background

Abnormal activation of the coagulation system is associated with malignant tumor progression. Although neoadjuvant treatment (NAT) for resectable esophageal squamous cell carcinoma (ESCC) is the standard of care, the correlation between coagulation status and prognosis of patients undergoing preoperative treatment is insufficiently understood.

Methods

Patients (n = 200) who underwent radical subtotal esophagectomy after preoperative treatment for ESCC between January 2012 and December 2021were included in the analysis. Plasma D-dimer and fibrinogen levels and their combined indices (non-hypercoagulation; D-dimer and fibrinogen levels within the upper normal limit, or hypercoagulation; D-dimer or fibrinogen levels above the upper normal limit) were determined before and after NAT and correlated to clinicopathological factors and prognosis.

Results

The nonhypercoagulation group achieved superior overall survival (OS) than the hypercoagulation group (5-year OS rates = 89% vs. 55%; hazard ratio 3.62, P = 0.0008) when determined according to coagulation status after NAT. Multivariate analysis showed that hypercoagulation after NAT served as an independent factor for poor postoperative OS (hazard ratio 3.20; P = 0.0028). The nonhypercoagulation group achieved significantly better disease-free survival (76% vs. 54%; P = 0.0065) than the hypercoagulation group that experienced a significantly higher rate of hematogenous metastasis as an initial recurrence (P = 0.0337).

Conclusions

Hypercoagulation state after NAT served as a valid indicator correlating with postoperative outcomes of patients with ESCC who underwent NAT followed by radical subtotal esophagectomy.
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Literature
1.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
2.
go back to reference Watanabe M, Toh Y, Ishihara R, et al. Comprehensive registry of esophageal cancer in Japan, 2015. Esophagus. 2023;20(1):1–28.PubMedCrossRef Watanabe M, Toh Y, Ishihara R, et al. Comprehensive registry of esophageal cancer in Japan, 2015. Esophagus. 2023;20(1):1–28.PubMedCrossRef
3.
go back to reference Kanda M, Koike M, Shimizu D, et al. Characteristics associated with nodal and distant recurrence after radical esophagectomy for squamous cell carcinoma of the thoracic esophagus. Ann Surg Oncol. 2020;27(9):3195–205.PubMedCrossRef Kanda M, Koike M, Shimizu D, et al. Characteristics associated with nodal and distant recurrence after radical esophagectomy for squamous cell carcinoma of the thoracic esophagus. Ann Surg Oncol. 2020;27(9):3195–205.PubMedCrossRef
4.
go back to reference Zhang D, Zhou X, Bao W, et al. Plasma fibrinogen levels are correlated with postoperative distant metastasis and prognosis in esophageal squamous cell carcinoma. Oncotarget. 2015;6(35):38410–20.PubMedPubMedCentralCrossRef Zhang D, Zhou X, Bao W, et al. Plasma fibrinogen levels are correlated with postoperative distant metastasis and prognosis in esophageal squamous cell carcinoma. Oncotarget. 2015;6(35):38410–20.PubMedPubMedCentralCrossRef
5.
go back to reference Diao D, Zhu K, Wang Z, et al. Prognostic value of the D-dimer test in oesophageal cancer during the perioperative period. J Surg Oncol. 2013;108(1):34–41.PubMedCrossRef Diao D, Zhu K, Wang Z, et al. Prognostic value of the D-dimer test in oesophageal cancer during the perioperative period. J Surg Oncol. 2013;108(1):34–41.PubMedCrossRef
6.
go back to reference Zhang Han-Ze, Jin Guang-Fu, Shen Hong-Bing. Epidemiologic differences in esophageal cancer between Asian and Western populations. Chin J Cancer. 2012;31(6):281–6.PubMedPubMedCentralCrossRef Zhang Han-Ze, Jin Guang-Fu, Shen Hong-Bing. Epidemiologic differences in esophageal cancer between Asian and Western populations. Chin J Cancer. 2012;31(6):281–6.PubMedPubMedCentralCrossRef
7.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMedCrossRef Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMedCrossRef
8.
go back to reference Uhlenhopp DJ, Then EO, Sunkara T, Gaduputi V. Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol. 2020;13(6):1010–21.PubMedCrossRef Uhlenhopp DJ, Then EO, Sunkara T, Gaduputi V. Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol. 2020;13(6):1010–21.PubMedCrossRef
9.
go back to reference Matz M, Valkov M, Sekerija M, et al. Worldwide trends in esophageal cancer survival, by sub-site, morphology, and sex: an analysis of 696,974 adults diagnosed in 60 countries during 2000–2014(CONCORD-3). Cancer Commun (Lond). 2023;43(9):963–80.PubMedPubMedCentralCrossRef Matz M, Valkov M, Sekerija M, et al. Worldwide trends in esophageal cancer survival, by sub-site, morphology, and sex: an analysis of 696,974 adults diagnosed in 60 countries during 2000–2014(CONCORD-3). Cancer Commun (Lond). 2023;43(9):963–80.PubMedPubMedCentralCrossRef
11.
go back to reference Falanga A, Marchetti M, Vignoli A. Coagulation and cancer: biological and clinical aspects. J Thromb Haemost. 2013;11(2):223–33.PubMedCrossRef Falanga A, Marchetti M, Vignoli A. Coagulation and cancer: biological and clinical aspects. J Thromb Haemost. 2013;11(2):223–33.PubMedCrossRef
12.
go back to reference Yang Y, Xu H, Zhou L, et al. Platelet to lymphocyte ratio is a predictive marker of prognosis and therapeutic effect of postoperative chemotherapy in non-metastatic esophageal squamous cell carcinoma. Clin Chim Acta. 2018;479:160–5.PubMedCrossRef Yang Y, Xu H, Zhou L, et al. Platelet to lymphocyte ratio is a predictive marker of prognosis and therapeutic effect of postoperative chemotherapy in non-metastatic esophageal squamous cell carcinoma. Clin Chim Acta. 2018;479:160–5.PubMedCrossRef
13.
go back to reference Kato T, Oshikiri T, Goto H, et al. Impact of the platelet-to-lymphocyte ratio as a biomarker for esophageal squamous cell carcinoma. Anticancer Res. 2022;42(5):2775–82.PubMedCrossRef Kato T, Oshikiri T, Goto H, et al. Impact of the platelet-to-lymphocyte ratio as a biomarker for esophageal squamous cell carcinoma. Anticancer Res. 2022;42(5):2775–82.PubMedCrossRef
14.
go back to reference Li J, Zheng Z, Fang M. Impact of pretreatment plasma D-dimer levels and its perioperative change on prognosis in operable esophageal squamous cell carcinoma. Oncotarget. 2017;8(45):79537–45.PubMedPubMedCentralCrossRef Li J, Zheng Z, Fang M. Impact of pretreatment plasma D-dimer levels and its perioperative change on prognosis in operable esophageal squamous cell carcinoma. Oncotarget. 2017;8(45):79537–45.PubMedPubMedCentralCrossRef
15.
go back to reference Ma M, Cao R, Wang W, et al. The D-dimer level predicts the prognosis in patients with lung cancer: a systematic review and meta-analysis. J Cardiothorac Surg. 2021;16(1):243.PubMedPubMedCentralCrossRef Ma M, Cao R, Wang W, et al. The D-dimer level predicts the prognosis in patients with lung cancer: a systematic review and meta-analysis. J Cardiothorac Surg. 2021;16(1):243.PubMedPubMedCentralCrossRef
16.
go back to reference Zhao LY, Zhao YL, Wang JJ, et al. Is preoperative fibrinogen associated with the survival prognosis of gastric cancer patients? A multi-centered, propensity score-matched retrospective study. World J Surg. 2020;44(1):213–22.PubMedCrossRef Zhao LY, Zhao YL, Wang JJ, et al. Is preoperative fibrinogen associated with the survival prognosis of gastric cancer patients? A multi-centered, propensity score-matched retrospective study. World J Surg. 2020;44(1):213–22.PubMedCrossRef
17.
go back to reference Matsuda S, Takeuchi H, Fukuda K, et al. Clinical significance of plasma fibrinogen level as a predictive marker for postoperative recurrence of esophageal squamous cell carcinoma in patients receiving neoadjuvant treatment. Dis Esophagus. 2014;27(7):654–61.PubMedCrossRef Matsuda S, Takeuchi H, Fukuda K, et al. Clinical significance of plasma fibrinogen level as a predictive marker for postoperative recurrence of esophageal squamous cell carcinoma in patients receiving neoadjuvant treatment. Dis Esophagus. 2014;27(7):654–61.PubMedCrossRef
18.
go back to reference Liu DQ, Li FF, Jia WH. Cumulative scores based on plasma D-dimer and serum albumin levels predict survival in esophageal squamous cell carcinoma patients treated with transthoracic esophagectomy. Chin J Cancer. 2016;35:11.PubMedPubMedCentralCrossRef Liu DQ, Li FF, Jia WH. Cumulative scores based on plasma D-dimer and serum albumin levels predict survival in esophageal squamous cell carcinoma patients treated with transthoracic esophagectomy. Chin J Cancer. 2016;35:11.PubMedPubMedCentralCrossRef
19.
go back to reference Zhang F, Chen Z, Wang P, et al. Combination of platelet count and mean platelet volume (COP-MPV) predicts postoperative prognosis in both resectable early and advanced stage esophageal squamous cell cancer patients. Tumour Biol. 2016;37(7):9323–31.PubMedCrossRef Zhang F, Chen Z, Wang P, et al. Combination of platelet count and mean platelet volume (COP-MPV) predicts postoperative prognosis in both resectable early and advanced stage esophageal squamous cell cancer patients. Tumour Biol. 2016;37(7):9323–31.PubMedCrossRef
20.
go back to reference Feng JF, Huang Y, Chen QX. Preoperative platelet lymphocyte ratio (PLR) is superior to neutrophil lymphocyte ratio (NLR) as a predictive factor in patients with esophageal squamous cell carcinoma. World J Surg Oncol. 2014;12:58.PubMedPubMedCentralCrossRef Feng JF, Huang Y, Chen QX. Preoperative platelet lymphocyte ratio (PLR) is superior to neutrophil lymphocyte ratio (NLR) as a predictive factor in patients with esophageal squamous cell carcinoma. World J Surg Oncol. 2014;12:58.PubMedPubMedCentralCrossRef
21.
go back to reference Zhang D, Zheng Y, Wang Z, et al. Comparison of the 7th and proposed 8th editions of the AJCC/UICC TNM staging system for esophageal squamous cell carcinoma underwent radical surgery. Eur J Surg Oncol. 2017;43(10):1949–55.PubMedCrossRef Zhang D, Zheng Y, Wang Z, et al. Comparison of the 7th and proposed 8th editions of the AJCC/UICC TNM staging system for esophageal squamous cell carcinoma underwent radical surgery. Eur J Surg Oncol. 2017;43(10):1949–55.PubMedCrossRef
22.
go back to reference Kanda M, Koike M, Iwata N, et al. An open-label single-arm phase II study of treatment with neoadjuvant S-1 plus cisplatin for clinical stage III squamous cell carcinoma of the esophagus. Oncologist. 2020;25(11):e1650–4.PubMedPubMedCentralCrossRef Kanda M, Koike M, Iwata N, et al. An open-label single-arm phase II study of treatment with neoadjuvant S-1 plus cisplatin for clinical stage III squamous cell carcinoma of the esophagus. Oncologist. 2020;25(11):e1650–4.PubMedPubMedCentralCrossRef
23.
go back to reference Nakamura K, Kato K, Igaki H, et al. Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study). Jpn J Clin Oncol. 2013;43(7):752–5.PubMedCrossRef Nakamura K, Kato K, Igaki H, et al. Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study). Jpn J Clin Oncol. 2013;43(7):752–5.PubMedCrossRef
24.
go back to reference Ken K, Kei M, Nobutoshi A, et al. A phase II study of nedaplatin and 5-fluorouracil in metastatic squamous cell carcinoma of the esophagus: The Japan Clinical Oncology Group (JCOG) Trial (JCOG 9905-DI). Esophagus. 2014;11(3):183–8.CrossRef Ken K, Kei M, Nobutoshi A, et al. A phase II study of nedaplatin and 5-fluorouracil in metastatic squamous cell carcinoma of the esophagus: The Japan Clinical Oncology Group (JCOG) Trial (JCOG 9905-DI). Esophagus. 2014;11(3):183–8.CrossRef
25.
go back to reference Miyata H, Sugimura K, Motoori M, et al. Clinical Implications of Conversion Surgery After Induction Therapy for T4b Thoracic Esophageal Squamous Cell Carcinoma. Ann Surg Oncol. 2019;26(13):4737–43.PubMedCrossRef Miyata H, Sugimura K, Motoori M, et al. Clinical Implications of Conversion Surgery After Induction Therapy for T4b Thoracic Esophageal Squamous Cell Carcinoma. Ann Surg Oncol. 2019;26(13):4737–43.PubMedCrossRef
26.
go back to reference Kanda M, Shimizu D, Sawaki K, et al. Therapeutic monoclonal antibody targeting of neuronal pentraxin receptor to control metastasis in gastric cancer. Mol Cancer. 2020;19(1):131.PubMedPubMedCentralCrossRef Kanda M, Shimizu D, Sawaki K, et al. Therapeutic monoclonal antibody targeting of neuronal pentraxin receptor to control metastasis in gastric cancer. Mol Cancer. 2020;19(1):131.PubMedPubMedCentralCrossRef
27.
go back to reference Kanda M, Kasahara Y, Shimizu D, et al. Amido-bridged nucleic acid-modified antisense oligonucleotides targeting SYT13 to treat peritoneal metastasis of gastric cancer. Mol Ther Nucleic Acids. 2020;22:791–802.PubMedPubMedCentralCrossRef Kanda M, Kasahara Y, Shimizu D, et al. Amido-bridged nucleic acid-modified antisense oligonucleotides targeting SYT13 to treat peritoneal metastasis of gastric cancer. Mol Ther Nucleic Acids. 2020;22:791–802.PubMedPubMedCentralCrossRef
28.
go back to reference Licciardello JT, Moake JL, Rudy CK, Karp DD, Hong WK. Elevated plasma von Willebrand factor levels and arterial occlusive complications associated with cisplatin-based chemotherapy. Oncology. 1985;42(5):296–300.PubMedCrossRef Licciardello JT, Moake JL, Rudy CK, Karp DD, Hong WK. Elevated plasma von Willebrand factor levels and arterial occlusive complications associated with cisplatin-based chemotherapy. Oncology. 1985;42(5):296–300.PubMedCrossRef
29.
go back to reference Fernandes CJ, Morinaga LTK, Alves JLJ, et al. Cancer-associated thrombosis: the when, how and why. Eur Respir Rev. 2019; 28(151). Fernandes CJ, Morinaga LTK, Alves JLJ, et al. Cancer-associated thrombosis: the when, how and why. Eur Respir Rev. 2019; 28(151).
31.
go back to reference Mukai M, Oka T. Mechanism and management of cancer-associated thrombosis. J Cardiol. 2018;72(2):89–93.PubMedCrossRef Mukai M, Oka T. Mechanism and management of cancer-associated thrombosis. J Cardiol. 2018;72(2):89–93.PubMedCrossRef
32.
go back to reference Liu P, Zhu Y, Liu L. Elevated pretreatment plasma D-dimer levels and platelet counts predict poor prognosis in pancreatic adenocarcinoma. Oncol Targets Ther. 2015;8:1335–40.CrossRef Liu P, Zhu Y, Liu L. Elevated pretreatment plasma D-dimer levels and platelet counts predict poor prognosis in pancreatic adenocarcinoma. Oncol Targets Ther. 2015;8:1335–40.CrossRef
33.
go back to reference Palumbo JS, Talmage KE, Massari JV, et al. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood. 2005;105(1):178–85.PubMedCrossRef Palumbo JS, Talmage KE, Massari JV, et al. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood. 2005;105(1):178–85.PubMedCrossRef
35.
go back to reference Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021;384(13):1191–203.PubMedCrossRef Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021;384(13):1191–203.PubMedCrossRef
36.
go back to reference Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomized controlled trials. Lancet. 2012;379(9826):1591–601.PubMedCrossRef Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomized controlled trials. Lancet. 2012;379(9826):1591–601.PubMedCrossRef
37.
go back to reference Mahmud S, Franco E, Aprikian A. Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis. Br J Cancer. 2004;90(1):93–9.PubMedPubMedCentralCrossRef Mahmud S, Franco E, Aprikian A. Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis. Br J Cancer. 2004;90(1):93–9.PubMedPubMedCentralCrossRef
39.
go back to reference Jiang Y, Su Z, Li C, et al. Association between the use of aspirin and risk of lung cancer: results from pooled cohorts and Mendelian randomization analyses. J Cancer Res Clin Oncol. 2021;147(1):139–51.PubMedCrossRef Jiang Y, Su Z, Li C, et al. Association between the use of aspirin and risk of lung cancer: results from pooled cohorts and Mendelian randomization analyses. J Cancer Res Clin Oncol. 2021;147(1):139–51.PubMedCrossRef
40.
go back to reference Corley DA, Kerlikowske K, Verma R, Buffler P. Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology. 2003;124(1):47–56.PubMedCrossRef Corley DA, Kerlikowske K, Verma R, Buffler P. Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology. 2003;124(1):47–56.PubMedCrossRef
41.
go back to reference Thun MJ. Beyond willow bark: aspirin in the prevention of chronic disease. Epidemiology. 2000;11(4):371–4.PubMedCrossRef Thun MJ. Beyond willow bark: aspirin in the prevention of chronic disease. Epidemiology. 2000;11(4):371–4.PubMedCrossRef
42.
go back to reference Liu JF, Jamieson GG, Wu TC, Zhu GJ, Drew PA. A preliminary study on the postoperative survival of patients given aspirin after resection for squamous cell carcinoma of the esophagus or adenocarcinoma of the cardia. Ann Surg Oncol. 2009;16(5):1397–402.PubMedCrossRef Liu JF, Jamieson GG, Wu TC, Zhu GJ, Drew PA. A preliminary study on the postoperative survival of patients given aspirin after resection for squamous cell carcinoma of the esophagus or adenocarcinoma of the cardia. Ann Surg Oncol. 2009;16(5):1397–402.PubMedCrossRef
43.
go back to reference Coyle C, Cafferty FH, Rowley S, et al. ADD-ASPIRIN: A phase III, double blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours. Contemp Clin Trials. 2016;51:56–64.PubMedPubMedCentralCrossRef Coyle C, Cafferty FH, Rowley S, et al. ADD-ASPIRIN: A phase III, double blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours. Contemp Clin Trials. 2016;51:56–64.PubMedPubMedCentralCrossRef
44.
go back to reference van Hagen P, Hulshof MCCM, van Lanschot JJB, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. 2012;366(22):2074–84.PubMed van Hagen P, Hulshof MCCM, van Lanschot JJB, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. 2012;366(22):2074–84.PubMed
Metadata
Title
Absence of Hypercoagulation Status after Neoadjuvant Treatment is Associated with Favorable Prognosis in Patients Undergoing Subtotal Esophagectomy for Esophageal Squamous Cell Carcinoma
Authors
Fumitake Sugiyama, MD
Mitsuro Kanda, MD, FACS
Dai Shimizu, MD
Shinichi Umeda, MD
Yoshikuni Inokawa, MD
Norifumi Hattori, MD
Masamichi Hayashi, MD, FACS
Chie Tanaka, MD
Goro Nakayama, MD
Yasuhiro Kodera, MD, FACS
Publication date
20-01-2024
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 5/2024
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-024-14938-1

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