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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 11/2016

01-10-2016 | Thoracic Oncology

Impact of Neoadjuvant Chemoradiation on Short-Term Outcomes for Esophageal Squamous Cell Carcinoma Patients: A Meta-analysis

Authors: Suun Sathornviriyapong, MD, Akihisa Matsuda, MD, Masao Miyashita, MD, Satoshi Matsumoto, MD, Nobuyuki Sakurazawa, MD, Yoichi Kawano, MD, Marina Yamada, PhD, Eiji Uchida, MD

Published in: Annals of Surgical Oncology | Issue 11/2016

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Abstract

Background

Neoadjuvant chemoradiation (NCRT) has emerged as a component of the standard treatment for esophageal squamous cell carcinoma (SCC). The primary benefit of NCRT is an improvement in long-term survival; however, the impact of NCRT on short-term outcomes is unclear.

Methods

A comprehensive electronic literature search was performed via the MEDLINE (PubMed), Cochrane Library, and Google Scholar databases through November 2015 for the inclusion of randomized controlled trials (RCTs) that evaluated short-term outcomes of patients administered NCRT followed by surgery compared with surgery alone for resectable esophageal SCC. The main outcome measures were postoperative mortality and morbidity. A meta-analysis was performed using random-effects models to calculate odds ratios (ORs) with 95 % confidence intervals (CIs).

Results

Eight RCTs were included, for a total of 1058 patients. Meta-analysis of the overall postoperative mortality and cardiopulmonary complication rates showed that there was a significant increase for patients administered NCRT followed by surgery compared with surgery alone (OR 1.87, 95 % CI 1.07–3.28, p = 0.03, number of patients needed to harm = 33.3; and OR 2.12, 95 % CI 1.03–4.35, p = 0.04, respectively). Dropout before surgery was higher for patients in the NCRT followed by surgery group compared with patients in the surgery-alone group. NCRT has no statistically impact on anastomosis and other complications compared with surgery alone.

Conclusions

NCRT for esophageal SCC significantly increases postoperative mortality and cardiopulmonary complications.
Appendix
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Literature
1.
Refaely Y, Krasna MJ. Multimodality therapy for esophageal cancer. Surg Clin North Am. 2002;82(4):729–46.PubMedCrossRef
2.
Herskovic A, Martz K, al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992;326(24):1593–98.
3.
Fujiwara Y, Yoshikawa R, Kamikonya N, et al. Trimodality therapy of esophagectomy plus neoadjuvant chemoradiotherapy improves the survival of clinical stage II/III esophageal squamous cell carcinoma patients. Oncol Rep. 2012;28(2):446–52.PubMedPubMedCentral
4.
Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001;19(2):305–13.PubMed
5.
Tepper J, Krasna MJ, Niedzwiecki D, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008;26(7):1086–92.PubMedCrossRef
6.
Lv J, Cao XF, Zhu B, Ji L, Tao L, Wang DD. Effect of neoadjuvant chemoradiotherapy on prognosis and surgery for esophageal carcinoma. World J Gastroenterol. 2009;15(39):4962–68.PubMedPubMedCentralCrossRef
7.
Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12(7):681–92.PubMedCrossRef
8.
Van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84.PubMedCrossRef
9.
Speicher PJ, Wang X, Englum BR, et al. Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer. Dis Esophagus. 2015;28(8):788–96.PubMedCrossRef
10.
Shapiro J, van Lanschot JJ, Hulshof MC, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16(9):1090–98.PubMedCrossRef
11.
Mungo B, Molena D, Stem M, et al. Does neoadjuvant therapy for esophageal cancer increase postoperative morbidity or mortality? Dis Esophagus. 2015;28(7):644–51.PubMedCrossRef
12.
Ruol A, Portale G, Castoro C, et al. Effects of neoadjuvant therapy on perioperative morbidity in elderly patients undergoing esophagectomy for esophageal cancer. Ann Surg Oncol. 2007;14(11):3243–50.PubMedCrossRef
13.
Lin FC, Durkin AE, Ferguson MK. Induction therapy does not increase surgical morbidity after esophagectomy for cancer. Ann Thorac Surg. 2004;78(5):1783–89.PubMedCrossRef
14.
Bosset JF, Gignoux M, Triboulet JP, et al. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997;337(3):161–67.PubMedCrossRef
15.
Hamai Y, Hihara J, Taomoto J, Yamakita I, Ibuki Y, Okada M. Effects of neoadjuvant chemoradiotherapy on postoperative morbidity and mortality associated with esophageal cancer. Dis Esophagus. 2015;28(4):358–64.PubMedCrossRef
16.
Morita M, Masuda T, Okada S, et al. Preoperative chemoradiotherapy for esophageal cancer: factors associated with clinical response and postoperative complications. Anticancer Res. 2009;29(7):2555–62.PubMed
17.
Mariette C, Piessen G, Lamblin A, Mirabel X, Adenis A, Triboulet JP. Impact of preoperative radiochemotherapy on postoperative course and survival in patients with locally advanced squamous cell oesophageal carcinoma. Br J Surg. 2006;93(9):1077–1083.PubMedCrossRef
18.
Morita M, Yoshida R, Ikeda K, et al. Advances in esophageal cancer surgery in Japan: an analysis of 1000 consecutive patients treated at a single institute. Surgery. 2008;143(4):499–508.PubMedCrossRef
19.
Fink U, Stein HJ, Wilke H, Roder JD, Siewert JR. Multimodal treatment for squamous cell esophageal cancer. World J Surg. 1995;19(2):198–204.PubMedCrossRef
20.
Eguchi R, Ide H, Nakamura T, et al. Analysis of postoperative complications after esophagectomy for esophageal cancer in patients receiving neoadjuvant therapy. Jpn J Thorac Cardiovasc Surg. 1999;47(11):552–8.PubMedCrossRef
21.
Abou-Jawde RM, Mekhail T, Adelstein DJ, et al. Impact of induction concurrent chemoradiotherapy on pulmonary function and postoperative acute respiratory complications in esophageal cancer. Chest. 2005;128(1):250–55.PubMedCrossRef
22.
Fiorica F, Di Bona D, Schepis F, et al. Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis. Gut. 2004;53(7):925–30.PubMedPubMedCentralCrossRef
23.
Urschel JD, Vasan H, Blewett CJ. A meta-analysis of randomized controlled trials that compared neoadjuvant chemotherapy and surgery to surgery alone for resectable esophageal cancer. Am J Surg. 2002;183(3):274–279.PubMedCrossRef
24.
Deng J, Wang C, Xiang M, Liu F, Liu Y, Zhao K. Meta-analysis of postoperative efficacy in patients receiving chemoradiotherapy followed by surgery for resectable esophageal carcinoma. Diagn Pathol. 2014;9:151.PubMedPubMedCentralCrossRef
25.
26.
Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet. 2013;381(9864):400–12.PubMedCrossRef
27.
Alexandrou A, Davis PA, Law S, Murthy S, Whooley BP, Wong J. Squamous cell carcinoma and adenocarcinoma of the lower third of the esophagus and gastric cardia: similarities and differences. Dis Esophagus. 2002;15(4):290–95.PubMedCrossRef
28.
Law SY, Fok M, Cheng SW, Wong J. A comparison of outcome after resection for squamous cell carcinomas and adenocarcinomas of the esophagus and cardia. Surg Gynecol Obstet. 1992;175(2):107–12.PubMed
29.
Alexiou C, Khan OA, Black E, et al. Survival after esophageal resection for carcinoma: the importance of the histologic cell type. Ann Thorac Surg. 2006;82(3):1073–77.PubMedCrossRef
30.
Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.PubMedPubMedCentralCrossRef
31.
Moher D, Jadad AR, Nichol G, Penman M, Tugwell P, Walsh S. Assessing the quality of randomized controlled trials: an annotated bibliography of scales and checklists. Control Clin Trials. 1995;16(1):62–73.PubMedCrossRef
32.
33.
Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1–12.PubMedCrossRef
34.
35.
DerSimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials. 2007;28(2):105–114.PubMedCrossRef
36.
DerSimonian R, Laird N. Meta-analysis in clinical trials revisited. Contemp Clin Trials. 2015;45(Pt A):139–145.PubMedCrossRef
37.
McQuay HJ, Moore RA. Using numerical results from systematic reviews in clinical practice. Ann Intern Med. 1997;126(9):712–20.PubMedCrossRef
38.
39.
Wen L, Badgett R, Cornell J. Number needed to treat: a descriptor for weighing therapeutic options. Am J Health Syst Pharm. 2005;62(19):2031–36.PubMedCrossRef
40.
41.
Ioannidis JP. Interpretation of tests of heterogeneity and bias in meta-analysis. J Eval Clin Pract. 2008;14(5):951–57.PubMedCrossRef
42.
43.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–1101.PubMedCrossRef
44.
45.
Cao XF, He XT, Ji L, Xiao J, Lv J. Effects of neoadjuvant radiochemotherapy on pathological staging and prognosis for locally advanced esophageal squamous cell carcinoma. Dis Esophagus. 2009;22(6):477–481.PubMedCrossRef
46.
Apinop C, Puttisak P, Preecha N. A prospective study of combined therapy in esophageal cancer. Hepatogastroenterology. 1994;41(4):391–93.PubMed
47.
Le Prise E, Etienne PL, Meunier B, et al. A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus. Cancer. 1994;73(7):1779–84.PubMedCrossRef
48.
Lee JL, Park SI, Kim SB, et al. A single institutional phase III trial of preoperative chemotherapy with hyperfractionation radiotherapy plus surgery versus surgery alone for resectable esophageal squamous cell carcinoma. Ann Oncol. 2004;15(6):947–54.PubMedCrossRef
49.
Lv J, Cao XF, Zhu B, Ji L, Tao L, Wang DD. Long-term efficacy of perioperative chemoradiotherapy on esophageal squamous cell carcinoma. World J Gastroenterol. 2010;16(13):1649–54.PubMedPubMedCentralCrossRef
50.
Natsugoe S, Okumura H, Matsumoto M, et al. Randomized controlled study on preoperative chemoradiotherapy followed by surgery versus surgery alone for esophageal squamous cell cancer in a single institution. Dis Esophagus. 2006;19(6):468–472.PubMedCrossRef
51.
Nygaard K, Hagen S, Hansen HS, et al. Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. World J Surg. 1992;16(6):1104–109. (discussion 1110).PubMedCrossRef
52.
Law S, Wong KH, Kwok KF, Chu KM, Wong J. Predictive factors for postoperative pulmonary complications and mortality after esophagectomy for cancer. Ann Surg. 2004;240(5):791–800.PubMedPubMedCentralCrossRef
53.
Atkins BZ, Shah AS, Hutcheson KA, et al. Reducing hospital morbidity and mortality following esophagectomy. Ann Thorac Surg. 2004;78(4):1170–76.PubMedCrossRef
54.
D’Journo XB, Michelet P, Avaro JP, et al. Respiratory complications after oesophagectomy for cancer [in French]. Rev Mal Respir. 2008;25(6):683–94.PubMedCrossRef
55.
Whooley BP, Law S, Murthy SC, Alexandrou A, Wong J. Analysis of reduced death and complication rates after esophageal resection. Ann Surg. 2001;233(3):338–44.PubMedPubMedCentralCrossRef
56.
Baba Y, Yoshida N, Shigaki H, et al. Prognostic impact of postoperative complications in 502 patients with surgically resected esophageal squamous cell carcinoma: a retrospective single institution study. Ann Surg. doi:10.​1097/​SLA.​0000000000001510​.
57.
Avendano CE, Flume PA, Silvestri GA, King LB, Reed CE. Pulmonary complications after esophagectomy. Ann Thorac Surg. 2002;73(3):922–26.PubMedCrossRef
58.
Asakura H, Hashimoto T, Zenda S, et al. Analysis of dose-volume histogram parameters for radiation pneumonitis after definitive concurrent chemoradiotherapy for esophageal cancer. Radiother Oncol. 2010;95(2):240–44.PubMedCrossRef
59.
Cui Z, Tian Y, He B, et al. Associated factors of radiation pneumonitis induced by precise radiotherapy in 186 elderly patients with esophageal cancer. Int J Clin Exp Med. 2015;8(9):16646–51.PubMedPubMedCentral
60.
Schallenkamp JM, Miller RC, Brinkmann DH, Foote T, Garces YI. Incidence of radiation pneumonitis after thoracic irradiation: dose-volume correlates. Int J Radiat Oncol Biol Phys. 2007;67(2):410–16.PubMedCrossRef
61.
Lee HK, Vaporciyan AA, Cox JD, et al. Postoperative pulmonary complications after preoperative chemoradiation for esophageal carcinoma: correlation with pulmonary dose-volume histogram parameters. Int J Radiat Oncol Biol Phys. 2003;57(5):1317–22.PubMedCrossRef
62.
Zhao Y, Chen L, Zhang S, et al. Predictive factors for acute radiation pneumonitis in postoperative intensity modulated radiation therapy and volumetric modulated arc therapy of esophageal cancer. Thorac Cancer. 2015;6(1):49–57.PubMedPubMedCentralCrossRef
63.
Ma Z, Zhang Y, Chen X, Liu C, Xu H, Zhao P. Analysis of different fractionations of three-dimensional conformable radiotherapy for esophageal cancer. Int J Clin Exp Med. 2015;8(7):11139–45.PubMedPubMedCentral
64.
Wang SL, Liao Z, Vaporciyan AA, et al. Investigation of clinical and dosimetric factors associated with postoperative pulmonary complications in esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery. Int J Radiat Oncol Biol Phys. 2006;64(3):692–99.PubMedCrossRef
65.
Siewert JR, Ott K. Are squamous and adenocarcinomas of the esophagus the same disease? Semin Radiat Oncol. 2007;17(1):38–44.PubMedCrossRef
66.
Tsutsui S, Morita M, Kuwano H, et al. Influence of preoperative treatment and surgical operation on immune function of patients with esophageal carcinoma. J Surg Oncol. 1992;49(3):176–81.PubMedCrossRef
67.
Hensler T, Hecker H, Heeg K, et al. Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun. 1997;65(6):2283–91.PubMedPubMedCentral
68.
Heidecke CD, Weighardt H, Feith M, et al. Neoadjuvant treatment of esophageal cancer: immunosuppression following combined radiochemotherapy. Surgery. 2002;132(3):495–501.PubMedCrossRef
69.
Westerterp M, Boermeester MA, Omloo JM, et al. Differential responses of cellular immunity in patients undergoing neoadjuvant therapy followed by surgery for carcinoma of the oesophagus. Cancer Immunol Immunother. 2008;57(12):1837–1847.PubMedCrossRef
70.
71.
Napier KJ, Scheerer M, Misra S. Esophageal cancer: a review of epidemiology, pathogenesis, staging workup and treatment modalities. World J Gastrointest Oncol. 2014;6(5):112–20.PubMedPubMedCentralCrossRef
72.
Donington JS, Miller DL, Allen MS, Deschamps C, Nichols FC 3rd, Pairolero PC. Tumor response to induction chemoradiation: influence on survival after esophagectomy. Eur J Cardiothorac Surg. 2003;24(4):631–636. (discussion 636–637)PubMedCrossRef
73.
Chao YK, Chang CB, Chuang WY, et al. Correlation between tumor regression grade and clinicopathological parameters in patients with squamous cell carcinoma of the esophagus who received neoadjuvant chemoradiotherapy. Medicine (Baltimore). 2015;94(34):e1407.PubMedPubMedCentralCrossRef
74.
Berger AC, Farma J, Scott WJ, et al. Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival. J Clin Oncol. 2005;23(19):4330–37.PubMedCrossRef
75.
Tong DK, Law S, Kwong DL, Chan KW, Lam AK, Wong KH. Histological regression of squamous esophageal carcinoma assessed by percentage of residual viable cells after neoadjuvant chemoradiation is an important prognostic factor. Ann Surg Oncol. 2010;17(8):2184–92.PubMedPubMedCentralCrossRef
76.
Rizk NP, Venkatraman E, Bains MS, et al. American Joint Committee on Cancer staging system does not accurately predict survival in patients receiving multimodality therapy for esophageal adenocarcinoma. J Clin Oncol. 2007;25(5):507–12.PubMedCrossRef
77.
Tessier W, Gronnier C, Messager M, et al. Does timing of surgical procedure after neoadjuvant chemoradiation affect outcomes in esophageal cancer? Ann Thorac Surg. 2014;97(4):1181–89.PubMedCrossRef
78.
Kandioler D, Schoppmann SF, Zwrtek R, et al. The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer into 2 subgroups with markedly different outcomes. A p53 Research Group study. J Thorac Cardiovasc. Surg. 2014;148(5):2280–86.PubMedCrossRef
79.
Zingg U, Forberger J, Rajcic B, Langton C, Jamieson GG. Association of C-reactive protein levels and long-term survival after neoadjuvant therapy and esophagectomy for esophageal cancer. J Gastrointest Surg. 2010;14(3):462–69.PubMedCrossRef
80.
Uemura N, Kondo T. Current status of predictive biomarkers for neoadjuvant therapy in esophageal cancer. World J Gastrointest Pathophysiol. 2014;5(3):322–34.PubMedPubMedCentral
81.
Okumura H, Uchikado Y, Setoyama T, et al. Biomarkers for predicting the response of esophageal squamous cell carcinoma to neoadjuvant chemoradiation therapy. Surg Today. 2014;44(3):421–28.PubMedCrossRef
82.
Tao CJ, Lin G, Xu YP, Mao WM. Predicting the response of neoadjuvant therapy for patients with esophageal carcinoma: an in-depth literature review. J Cancer. 2015;6(11):1179–86.PubMedPubMedCentralCrossRef
83.
Honing J, Pavlov KV, Mul VE, et al. CD44, SHH and SOX2 as novel biomarkers in esophageal cancer patients treated with neoadjuvant chemoradiotherapy. Radiother Oncol. 2015;117(1):152–58.PubMedCrossRef
84.
Bollschweiler E, Holscher AH, Schmidt M, Warnecke-Eberz U. Neoadjuvant treatment for advanced esophageal cancer: response assessment before surgery and how to predict response to chemoradiation before starting treatment. Chin J Cancer Res. 2015;27(3):221–30.PubMedPubMedCentral
85.
Bronson NW, Diggs BS, Bakis G, et al. Molecular marker expression is highly heterogeneous in esophageal adenocarcinoma and does not predict a response to neoadjuvant therapy. J Gastrointest Surg. 2015;19(12):2105–110.PubMedCrossRef
86.
Kumagai K, Rouvelas I, Tsai JA, et al. Meta-analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjucant chemotherapy or chemoradiotherapy for resectable oesophageal and gastro-oesophageal junctional cancers. Br J Surg. 2014;101:321–38.PubMedCrossRef
Metadata
Title
Impact of Neoadjuvant Chemoradiation on Short-Term Outcomes for Esophageal Squamous Cell Carcinoma Patients: A Meta-analysis
Authors
Suun Sathornviriyapong, MD
Akihisa Matsuda, MD
Masao Miyashita, MD
Satoshi Matsumoto, MD
Nobuyuki Sakurazawa, MD
Yoichi Kawano, MD
Marina Yamada, PhD
Eiji Uchida, MD
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 11/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5298-9

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