Skip to main content

Advertisement

SpringerLink
Log in

Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

  • Original Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Purpose

Few studies have reported the impact of chemoradiotherapy (CRT) on the objective response of patients with locally advanced unresectable esophageal squamous cell carcinoma (ESCC). We evaluated the factors predicting therapeutic effectiveness and the short- and long-term outcomes in patients with T4b ESCC treated with CRT.

Methods

We included 155 patients with T4b ESCC who underwent CRT at the Department of Surgery, Gastroenterological Center, Yokohama City University, between January 2000 and December 2018. Responders were defined as patients who demonstrated a complete response (CR) or partial response (PR). Multivariate analysis for objective response was performed using a logistic regression model, and prognostic factors were evaluated by univariate and multivariate analyses.

Results

Among the 155 patients included, 20 and 84 patients demonstrated a CR and PR, respectively, resulting in a response rate of 67.1%. The median overall survival (OS) was 15.2 months, and the 3-year survival rate was 32.1%. High Glasgow prognostic score (GPS) and advanced N-category independently predicted the objective response to CRT. GPS and objective response were independent prognostic factors for OS. There was no significant difference in the long-term survival of responders who received subsequent chemotherapy or salvage surgery.

Conclusions

High GPS and advanced N-category predicted a poor objective response to CRT in patients with T4b ESCC. Therefore, chemotherapeutic regimens with a higher efficacy are required. The indications for salvage surgery for responders should be carefully considered, with care taken to avoid complications. To confirm this, prospective randomized controlled studies are necessary.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Availability of data and material

Data analysis available upon specific request.

References

  1. Thoen H, Ceelen W, Boterberg T, Van Daele E, Pattyn P (2015) Tumor recurrence and in-field control after multimodality treatment of locally advanced esophageal cancer. Radiother Oncol 115:16–21

    Article  PubMed  Google Scholar 

  2. Rice TW, Patil DT, Blackstone EH (2017) 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice. Ann Cardiothorac Surg 6:119–130

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tachimori Y, Ozawa S, Numasaki H, Ishihara R, Matsubara H, Muro K, Oyama T, Toh Y, Udagawa H, Uno T, Registration Committee for Esophageal Cancer of the Japan Esophageal S (2019) Comprehensive registry of esophageal cancer in Japan, 2012. Esophagus 16:221-245

  4. Booka E, Takeuchi H, Nishi T, Matsuda S, Kaburagi T, Fukuda K, Nakamura R, Takahashi T, Wada N, Kawakubo H, Omori T, Kitagawa Y (2015) The Impact of Postoperative Complications on Survivals After Esophagectomy for Esophageal Cancer. Medicine (Baltimore) 94:e1369

    Article  Google Scholar 

  5. Ishida K, Ando N, Yamamoto S, Ide H, Shinoda M (2004) Phase II study of cisplatin and 5-fluorouracil with concurrent radiotherapy in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group trial (JCOG9516). Jpn J Clin Oncol 34:615–619

    Article  PubMed  Google Scholar 

  6. Fujita H, Sueyoshi S, Tanaka T, Tanaka Y, Matono S, Mori N, Shirouzu K, Yamana H, Suzuki G, Hayabuchi N, Matsui M (2005) Esophagectomy: is it necessary after chemoradiotherapy for a locally advanced T4 esophageal cancer? Prospective nonrandomized trial comparing chemoradiotherapy with surgery versus without surgery. World J Surg 29:25–30; discussion 30–21

  7. Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA, Jr., Al-Sarraf M, Byhardt R, Russell AH, Beitler JJ, Spencer S, Asbell SO, Graham MV, Leichman LL (1999) Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA 281:1623-1627

  8. Watanabe M, Otake R, Kozuki R, Toihata T, Takahashi K, Okamura A, Imamura Y (2020) Recent progress in multidisciplinary treatment for patients with esophageal cancer. Surg Today 50:12–20

    Article  PubMed  Google Scholar 

  9. Makino T, Yamasaki M, Tanaka K, Miyazaki Y, Takahashi T, Kurokawa Y, Motoori M, Kimura Y, Nakajima K, Mori M, Doki Y (2019) Treatment and clinical outcome of clinical T4 esophageal cancer: A systematic review. Ann Gastroenterol Surg 3:169–180

    Article  PubMed  Google Scholar 

  10. Kaklamanos IG, Walker GR, Ferry K, Franceschi D, Livingstone AS (2003) Neoadjuvant treatment for resectable cancer of the esophagus and the gastroesophageal junction: a meta-analysis of randomized clinical trials. Ann Surg Oncol 10:754–761

    Article  PubMed  Google Scholar 

  11. Urba S (2004) Esophageal cancer: preoperative or definitive chemoradiation. Ann Oncol 15 Suppl 4:iv93–96

  12. Ku GY, Ilson DH (2008) Multimodality therapy for the curative treatment of cancer of the esophagus and gastroesophageal junction. Expert Rev Anticancer Ther 8:1953–1964

    Article  PubMed  Google Scholar 

  13. Ajani JA, D’Amico TA, Bentrem DJ, Chao J, Corvera C, Das P, Denlinger CS, Enzinger PC, Fanta P, Farjah F, Gerdes H, Gibson M, Glasgow RE, Hayman JA, Hochwald S, Hofstetter WL, Ilson DH, Jaroszewski D, Johung KL, Keswani RN, Kleinberg LR, Leong S, Ly QP, Matkowskyj KA, McNamara M, Mulcahy MF, Paluri RK, Park H, Perry KA, Pimiento J, Poultsides GA, Roses R, Strong VE, Wiesner G, Willett CG, Wright CD, McMillian NR, Pluchino LA (2019) Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 17:855–883

    Article  CAS  PubMed  Google Scholar 

  14. Chang Y, An H, Xu L, Zhu Y, Yang Y, Lin Z, Xu J (2015) Systemic inflammation score predicts postoperative prognosis of patients with clear-cell renal cell carcinoma. Br J Cancer 113:626–633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. McMillan DC (2013) The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. Cancer Treat Rev 39:534–540

    Article  PubMed  Google Scholar 

  16. Japan Esophageal S (2017) Japanese Classification of Esophageal Cancer, 11th Edition: part I. Esophagus 14:1–36

    Article  Google Scholar 

  17. Picus D, Balfe DM, Koehler RE, Roper CL, Owen JW (1983) Computed tomography in the staging of esophageal carcinoma. Radiology 146:433–438

    Article  CAS  PubMed  Google Scholar 

  18. Takagawa R, Kunisaki C, Makino H, Kosaka T, Ono HA, Akiyama H, Shimada H (2009) Efficacy of chemoradiotherapy with low-dose cisplatin and continuous infusion of 5-fluorouracil for unresectable squamous cell carcinoma of the esophagus. Dis Esophagus 22:482–489

    Article  PubMed  Google Scholar 

  19. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247

    Article  CAS  PubMed  Google Scholar 

  20. Iguchi K, Kunisaki C, Sato S, Tanaka Y, Miyamoto H, Kosaka T, Sato K, Akiyama H, Endo I, Yukawa N, Rino Y, Masuda M, Yamanaka T (2020) Efficacy of Video-assisted Thoracoscopic Esophagectomy for Stage II/III Esophageal Cancer: Analysis Using the Propensity Scoring System. Anticancer Res 40:1587–1595

    Article  PubMed  Google Scholar 

  21. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213

    Article  PubMed  PubMed Central  Google Scholar 

  22. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibanes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M (2009) The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 250:187–196

    Article  PubMed  Google Scholar 

  23. Berry MF (2014) Esophageal cancer: staging system and guidelines for staging and treatment. J Thorac Dis 6(Suppl 3):S289-297

    PubMed  PubMed Central  Google Scholar 

  24. Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, Klump B, Budach W, Teichmann R, Schmitt M, Schmitt G, Franke C, Wilke H (2005) Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 23:2310–2317

    Article  PubMed  Google Scholar 

  25. Bedenne L, Michel P, Bouche O, Milan C, Mariette C, Conroy T, Pezet D, Roullet B, Seitz JF, Herr JP, Paillot B, Arveux P, Bonnetain F, Binquet C (2007) Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 25:1160–1168

    Article  CAS  PubMed  Google Scholar 

  26. van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A, Group C (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366:2074-2084

  27. Adenis A, Tresch E, Dewas S, Romano O, Messager M, Amela E, Clisant S, Kramar A, Mariette C, Mirabel X (2013) Clinical complete responders to definite chemoradiation or radiation therapy for oesophageal cancer: predictors of outcome. BMC Cancer 13:413

    Article  PubMed  PubMed Central  Google Scholar 

  28. Zhao Z, Zhang Y, Wang X, Geng X, Zhu L, Li M (2020) Clinical response to chemoradiotherapy in esophageal carcinoma is associated with survival and benefit of consolidation chemotherapy. Cancer Med 9:5881–5888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Blum Murphy M, Xiao L, Patel VR, Maru DM, Correa AM, F GA, Liao Z, Komaki R, Lin SH, Skinner HD, Vaporciyan A, Walsh GL, Swisher SG, Sepesi B, Lee JH, Bhutani MS, Weston B, Hofstetter WL, Ajani JA (2017) Pathological complete response in patients with esophageal cancer after the trimodality approach: The association with baseline variables and survival-The University of Texas MD Anderson Cancer Center experience. Cancer 123:4106-4113

  30. Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ (2004) Comparison of an inflammation-based prognostic score (GPS) with performance status (ECOG) in patients receiving platinum-based chemotherapy for inoperable non-small-cell lung cancer. Br J Cancer 90:1704–1706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Al Murri AM, Bartlett JM, Canney PA, Doughty JC, Wilson C, McMillan DC (2006) Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer. Br J Cancer 94:227–230

    Article  CAS  PubMed  Google Scholar 

  32. Glen P, Jamieson NB, McMillan DC, Carter R, Imrie CW, McKay CJ (2006) Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer. Pancreatology 6:450–453

    Article  PubMed  Google Scholar 

  33. Ramsey S, Lamb GW, Aitchison M, Graham J, McMillan DC (2007) Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer. Cancer 109:205–212

    Article  PubMed  Google Scholar 

  34. McMillan DC, Crozier JE, Canna K, Angerson WJ, McArdle CS (2007) Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis 22:881–886

    Article  PubMed  Google Scholar 

  35. McMillan DC (2009) Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care 12:223–226

    Article  PubMed  Google Scholar 

  36. Okuno T, Wakabayashi M, Kato K, Shinoda M, Katayama H, Igaki H, Tsubosa Y, Kojima T, Okabe H, Kimura Y, Kawano T, Kosugi S, Toh Y, Kato H, Nakamura K, Fukuda H, Ishikura S, Ando N, Kitagawa Y, Japan Esophageal Oncology Group/Japan Clinical Oncology G (2017) Esophageal stenosis and the Glasgow Prognostic Score as independent factors of poor prognosis for patients with locally advanced unresectable esophageal cancer treated with chemoradiotherapy (exploratory analysis of JCOG0303). Int J Clin Oncol 22:1042-1049

  37. Nakamura M, Iwahashi M, Nakamori M, Ojima T, Katsuda M, Iida T, Hayata K, Kato T, Yamaue H (2014) New prognostic score for the survival of patients with esophageal squamous cell carcinoma. Surg Today 44:875–883

    Article  CAS  PubMed  Google Scholar 

  38. Feng JF, Zhao Q, Chen QX (2014) Prognostic significance of Glasgow prognostic score in patients undergoing esophagectomy for esophageal squamous cell carcinoma. Saudi J Gastroenterol 20:48–53

    Article  PubMed  PubMed Central  Google Scholar 

  39. Slaviero KA, Clarke SJ, Rivory LP (2003) Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol 4:224–232

    Article  CAS  PubMed  Google Scholar 

  40. Baker SD, van Schaik RH, Rivory LP, Ten Tije AJ, Dinh K, Graveland WJ, Schenk PW, Charles KA, Clarke SJ, Carducci MA, McGuire WP, Dawkins F, Gelderblom H, Verweij J, Sparreboom A (2004) Factors affecting cytochrome P-450 3A activity in cancer patients. Clin Cancer Res 10:8341–8350

    Article  CAS  PubMed  Google Scholar 

  41. Brown DJ, Milroy R, Preston T, McMillan DC (2007) The relationship between an inflammation-based prognostic score (Glasgow Prognostic Score) and changes in serum biochemical variables in patients with advanced lung and gastrointestinal cancer. J Clin Pathol 60:705–708

    Article  CAS  PubMed  Google Scholar 

  42. Wood LJ, Nail LM, Gilster A, Winters KA, Elsea CR (2006) Cancer chemotherapy-related symptoms: evidence to suggest a role for proinflammatory cytokines. Oncol Nurs Forum 33:535–542

    Article  PubMed  Google Scholar 

  43. Lordick F, Mariette C, Haustermans K, Obermannova R, Arnold D, Committee EG (2016) Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 27:v50–v57

    Article  CAS  PubMed  Google Scholar 

  44. Chen Y, Guo L, Cheng X, Wang J, Zhang Y, Wang Y, Ke S, Shi W (2018) With or without consolidation chemotherapy using cisplatin/5-FU after concurrent chemoradiotherapy in stage II-III squamous cell carcinoma of the esophagus: A propensity score-matched analysis. Radiother Oncol 129:154–160

    Article  CAS  PubMed  Google Scholar 

  45. Kim GJ, Koshy M, Hanlon AL, Horiba MN, Edelman MJ, Burrows WM, Battafarano RJ, Suntharalingam M (2016) The Benefit of Chemotherapy in Esophageal Cancer Patients With Residual Disease After Trimodality Therapy. Am J Clin Oncol 39:136–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Nishimura M, Daiko H, Yoshida J, Nagai K (2007) Salvage esophagectomy following definitive chemoradiotherapy. Gen Thorac Cardiovasc Surg 55:461–464; discussion 464–465

  47. Miyata H, Yamasaki M, Takiguchi S, Nakajima K, Fujiwara Y, Nishida T, Mori M, Doki Y (2009) Salvage esophagectomy after definitive chemoradiotherapy for thoracic esophageal cancer. J Surg Oncol 100:442–446

    Article  CAS  PubMed  Google Scholar 

  48. Chao YK, Chan SC, Chang HK, Liu YH, Wu YC, Hsieh MJ, Tseng CK, Liu HP (2009) Salvage surgery after failed chemoradiotherapy in squamous cell carcinoma of the esophagus. Eur J Surg Oncol 35:289–294

    Article  CAS  PubMed  Google Scholar 

  49. Cohen C, Tessier W, Gronnier C, Renaud F, Pasquer A, Thereaux J, Gagniere J, Meunier B, Collet D, Piessen G, Mariette C, Fregat FA (2018) Salvage Surgery for Esophageal Cancer: How to Improve Outcomes? Ann Surg Oncol 25:1277–1286

    Article  PubMed  Google Scholar 

  50. Farinella E, Safar A, Nasser HA, Bouazza F, Liberale G, Paesmans M, Marechal R, Van Laethem JL, Hendlisz A, VanHoutte P, El Nakadi I (2016) Salvage esophagectomy after failure of definitive radiochemotherapy for esophageal cancer. J Surg Oncol 114:833–837

    Article  PubMed  Google Scholar 

  51. Kumagai K, Mariosa D, Tsai JA, Nilsson M, Ye W, Lundell L, Rouvelas I (2016) Systematic review and meta-analysis on the significance of salvage esophagectomy for persistent or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy. Dis Esophagus 29:734–739

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The authors did not receive any funding for this study.

Author information

Authors and Affiliations

  1. Department of Surgery, Gastroenterological Center, Yokohama City University, 4-57 Urafunecho, Minami-ku, Yokohama, 232-0024, Japan

    Nobuhiro Tsuchiya, Chikara Kunisaki, Sho Sato, Yusaku Tanaka, Kei Sato, Jun Watanabe & Kazuhisa Takeda

  2. Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan

    Takashi Kosaka, Hirotoshi Akiyama & Itaru Endo

Authors
  1. Nobuhiro Tsuchiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chikara Kunisaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sho Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yusaku Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kei Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kazuhisa Takeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takashi Kosaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hirotoshi Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Itaru Endo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Nobuhiro Tsuchiya. and Chikara Kunisaki helped in study conception and design and drafting of manuscript. Sho Sato., Yusaku Tanaka., Kei Sato acquired the data. Jun Watanabe., Kazuhisa Takeda., Takashi Kosaka., Hirotoshi Akiyama analyzed and interpreted the data. Itaru Endo critically revised the manuscript.

Corresponding author

Correspondence to Chikara Kunisaki.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tsuchiya, N., Kunisaki, C., Sato, S. et al. Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma. Langenbecks Arch Surg 407, 1911–1921 (2022). https://doi.org/10.1007/s00423-022-02445-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-022-02445-4

Keywords

Search

Navigation