Skip to main content
Top
Published in: Journal of Gastrointestinal Surgery 9/2016

01-09-2016 | Original Article

Pathologic Complete Response Is an Independent Predictor of Improved Survival Following Neoadjuvant Chemoradiation for Esophageal Adenocarcinoma

Authors: Raed M. Alnaji, William Du, Emmanuel Gabriel, Smit Singla, Kristopher Attwood, Hector Nava, Usha Malhotra, Steven N. Hochwald, Moshim Kukar

Published in: Journal of Gastrointestinal Surgery | Issue 9/2016

Login to get access

Abstract

Introduction

Reports of improved survival in patients with pathologic complete response (pCR) to neoadjuvant therapy for esophageal and gastroesophageal junction (GEJ) adenocarcinoma is extrapolated from heterogeneous studies that include squamous cell histology. We sought to determine if pCR is associated with a survival advantage in a homogenous group of patients with esophageal adenocarcinoma.

Methods

This is a single institution analysis of all patients with T2–T4 or node positive esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy and esophagectomy between 2004 and 2014. Patients were divided into two groups based on pathological response, pCR vs. incomplete pathological response (iPR). Survival outcomes were evaluated using standard Kaplan-Meier methods and multivariable Cox regression models.

Results

A total of 205 patients were included in the study: 38 (19 %) patients with pCR and 167 patients (81 %) with iPR. The two groups were similar with respect to clinical stage, age, gender, comorbid conditions, ECOG status, smoking, and alcohol use. Patients in the pCR group had a higher percentage of tumors located in middle third of esophagus (11 vs. 2 %, p = 0.04) while tumor grade was similar in both groups. Median follow-up was 50 months, range 2–109 months. The 3-year overall (OS) and recurrence-free survival (RFS) for iPR was 48 and 39 %, respectively, vs. 86 and 80 % for pCR group, respectively.

Conclusion

This analysis of a cohort of homogeneous patients with esophageal adenocarcinoma undergoing multimodality therapy showed that pCR is an independent predictor of improved RFS and OS. This data contributes to a growing body of evidence highlighting the benefits of neoadjuvant therapy specific to esophageal adenocarcinoma particularly when pCR is achieved.
Literature
3.
go back to reference Donahue JM, Nichols FC, Li Z, et al. Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg. 2009;87(2):392-8. Medline: 19161745CrossRefPubMedPubMedCentral Donahue JM, Nichols FC, Li Z, et al. Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg. 2009;87(2):392-8. Medline: 19161745CrossRefPubMedPubMedCentral
4.
go back to reference Kukar M, Alnaji RM, Jabi F, et al. Role of Repeat 18F-Fluorodeoxyglucose Positron Emission Tomography Examination in Predicting Pathologic Response Following Neoadjuvant Chemoradiotherapy for Esophageal Adenocarcinoma. JAMA Surg. 2015;150(6):555-62. Medline: 25902198CrossRefPubMed Kukar M, Alnaji RM, Jabi F, et al. Role of Repeat 18F-Fluorodeoxyglucose Positron Emission Tomography Examination in Predicting Pathologic Response Following Neoadjuvant Chemoradiotherapy for Esophageal Adenocarcinoma. JAMA Surg. 2015;150(6):555-62. Medline: 25902198CrossRefPubMed
5.
go back to reference 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):4330-7. Medline: 15781882CrossRefPubMed 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):4330-7. Medline: 15781882CrossRefPubMed
6.
go back to reference Meredith KL, Weber JM, Turaga KK, et al. Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol. 2010;17(4):1159-67. Medline: 20140529CrossRefPubMed Meredith KL, Weber JM, Turaga KK, et al. Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol. 2010;17(4):1159-67. Medline: 20140529CrossRefPubMed
7.
go back to reference Hammoud ZT, Kesler KA, Ferguson MK, et al. Survival outcomes of resected patients who demonstrate a pathologic complete response after neoadjuvant chemoradiation therapy for locally advanced esophageal cancer. Dis Esophagus. 2006;19(2):69-72. Medline: 16643172CrossRefPubMed Hammoud ZT, Kesler KA, Ferguson MK, et al. Survival outcomes of resected patients who demonstrate a pathologic complete response after neoadjuvant chemoradiation therapy for locally advanced esophageal cancer. Dis Esophagus. 2006;19(2):69-72. Medline: 16643172CrossRefPubMed
8.
go back to reference Rohatgi PR, Swisher SG, Correa AM, et al. Histologic subtypes as determinants of outcome in esophageal carcinoma patients with pathologic complete response after preoperative chemoradiotherapy. Cancer. 2006;106(3):552-8. Medline: 16353210CrossRefPubMed Rohatgi PR, Swisher SG, Correa AM, et al. Histologic subtypes as determinants of outcome in esophageal carcinoma patients with pathologic complete response after preoperative chemoradiotherapy. Cancer. 2006;106(3):552-8. Medline: 16353210CrossRefPubMed
9.
go back to reference Davies AR, Gossage JA, Zylstra J, et al. Tumor stage after neoadjuvant chemotherapy determines survival after surgery for adenocarcinoma of the esophagus and esophagogastric junction. J Clin Oncol. 2014;32(27):2983-90. Medline: 25071104CrossRefPubMed Davies AR, Gossage JA, Zylstra J, et al. Tumor stage after neoadjuvant chemotherapy determines survival after surgery for adenocarcinoma of the esophagus and esophagogastric junction. J Clin Oncol. 2014;32(27):2983-90. Medline: 25071104CrossRefPubMed
10.
go back to reference Donington JS, Miller DL, Allen MS, Deschamps C, Nichols FC, Pairolero PC. Tumor response to induction chemoradiation: influence on survival after esophagectomy. Eur J Cardiothorac Surg. 2003;24(4):631-6. Medline: 14500086CrossRefPubMed Donington JS, Miller DL, Allen MS, Deschamps C, Nichols FC, Pairolero PC. Tumor response to induction chemoradiation: influence on survival after esophagectomy. Eur J Cardiothorac Surg. 2003;24(4):631-6. Medline: 14500086CrossRefPubMed
11.
go back to reference 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. Medline: 22646630CrossRefPubMed 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. Medline: 22646630CrossRefPubMed
12.
go back to reference Piessen G, Petyt G, Duhamel A, Mirabel X, Huglo D, Mariette C. Ineffectiveness of 18F-fluorodeoxyglucose positron emission tomography in the evaluation of tumor response after completion of neoadjuvant chemoradiation in esophageal cancer. Ann Surg. 2013;258(1):66-76. Medline: 23470576CrossRefPubMed Piessen G, Petyt G, Duhamel A, Mirabel X, Huglo D, Mariette C. Ineffectiveness of 18F-fluorodeoxyglucose positron emission tomography in the evaluation of tumor response after completion of neoadjuvant chemoradiation in esophageal cancer. Ann Surg. 2013;258(1):66-76. Medline: 23470576CrossRefPubMed
13.
go back to reference Bollschweiler E, Metzger R, Drebber U, et al. Histological type of esophageal cancer might affect response to neo-adjuvant radiochemotherapy and subsequent prognosis. Ann Oncol. 2009;20(2):231-8. Medline: 18836090CrossRefPubMed Bollschweiler E, Metzger R, Drebber U, et al. Histological type of esophageal cancer might affect response to neo-adjuvant radiochemotherapy and subsequent prognosis. Ann Oncol. 2009;20(2):231-8. Medline: 18836090CrossRefPubMed
14.
go back to reference Macguill M, Mulligan E, Ravi N, et al. Clinicopathologic factors predicting complete pathological response to neoadjuvant chemoradiotherapy in esophageal cancer. Dis Esophagus. 2006;19(4):273-6. Medline: 16866859CrossRefPubMed Macguill M, Mulligan E, Ravi N, et al. Clinicopathologic factors predicting complete pathological response to neoadjuvant chemoradiotherapy in esophageal cancer. Dis Esophagus. 2006;19(4):273-6. Medline: 16866859CrossRefPubMed
15.
go back to reference Schmidt M, Bollschweiler E, Dietlein M, et al. Mean and maximum standardized uptake values in [18F]FDG-PET for assessment of histopathological response in oesophageal squamous cell carcinoma or adenocarcinoma after radiochemotherapy. Eur J Nucl Med Mol Imaging. 2009;36(5):735-44. Medline 19096843CrossRefPubMed Schmidt M, Bollschweiler E, Dietlein M, et al. Mean and maximum standardized uptake values in [18F]FDG-PET for assessment of histopathological response in oesophageal squamous cell carcinoma or adenocarcinoma after radiochemotherapy. Eur J Nucl Med Mol Imaging. 2009;36(5):735-44. Medline 19096843CrossRefPubMed
16.
go back to reference Monjazeb AM, Riedlinger G, Aklilu M, et al. Outcomes of patients with esophageal cancer staged with [18F]fluorodeoxyglucose positron emission tomography (FDG-PET): can postchemoradiotherapy FDG-PET predict the utility of resection?. J Clin Oncol. 2010;28(31):4714-21. Medline: 20876421CrossRefPubMedPubMedCentral Monjazeb AM, Riedlinger G, Aklilu M, et al. Outcomes of patients with esophageal cancer staged with [18F]fluorodeoxyglucose positron emission tomography (FDG-PET): can postchemoradiotherapy FDG-PET predict the utility of resection?. J Clin Oncol. 2010;28(31):4714-21. Medline: 20876421CrossRefPubMedPubMedCentral
17.
go back to reference Ben-david K, Sarosi GA, Cendan JC, Hochwald SN. Technique of minimally invasive Ivor Lewis esophagogastrectomy with intrathoracic stapled side-to-side anastomosis. J Gastrointest Surg. 2010;14(10):1613-8. Medline: 20532663CrossRefPubMed Ben-david K, Sarosi GA, Cendan JC, Hochwald SN. Technique of minimally invasive Ivor Lewis esophagogastrectomy with intrathoracic stapled side-to-side anastomosis. J Gastrointest Surg. 2010;14(10):1613-8. Medline: 20532663CrossRefPubMed
18.
go back to reference Hochwald SN, Ben-david K. Minimally invasive esophagectomy with cervical esophagogastric anastomosis. J Gastrointest Surg. 2012;16(9):1775-81. Medline: 22549264CrossRefPubMed Hochwald SN, Ben-david K. Minimally invasive esophagectomy with cervical esophagogastric anastomosis. J Gastrointest Surg. 2012;16(9):1775-81. Medline: 22549264CrossRefPubMed
19.
go back to reference Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11-20. Medline: 16822992CrossRefPubMed Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11-20. Medline: 16822992CrossRefPubMed
20.
go back to reference Ronellenfitsch U, Schwarzbach M, Hofheinz R, et al. Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer. 2013;49(15):3149-58. Medline: 23800671CrossRefPubMed Ronellenfitsch U, Schwarzbach M, Hofheinz R, et al. Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer. 2013;49(15):3149-58. Medline: 23800671CrossRefPubMed
21.
go back to reference 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. 2014. Medline: 25212528. 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. 2014. Medline: 25212528.
22.
go back to reference Gabriel E, Attwood K, Du W, et al. Association Between Clinically Staged Node-Negative Esophageal Adenocarcinoma and Overall Survival Benefit From Neoadjuvant Chemoradiation. JAMA Surg. 2015;:1-12. Medline: 26559488 Gabriel E, Attwood K, Du W, et al. Association Between Clinically Staged Node-Negative Esophageal Adenocarcinoma and Overall Survival Benefit From Neoadjuvant Chemoradiation. JAMA Surg. 2015;:1-12. Medline: 26559488
23.
go back to reference Rohatgi P, Swisher SG, Correa AM, et al. Characterization of pathologic complete response after preoperative chemoradiotherapy in carcinoma of the esophagus and outcome after pathologic complete response. Cancer. 2005;104(11):2365-72. Medline: 16245310CrossRefPubMed Rohatgi P, Swisher SG, Correa AM, et al. Characterization of pathologic complete response after preoperative chemoradiotherapy in carcinoma of the esophagus and outcome after pathologic complete response. Cancer. 2005;104(11):2365-72. Medline: 16245310CrossRefPubMed
24.
go back to reference Lin SH, Wang J, Allen PK, et al. A nomogram that predicts pathologic complete response to neoadjuvant chemoradiation also predicts survival outcomes after definitive chemoradiation for esophageal cancer. J Gastrointest Oncol. 2015;6(1):45-52. Medline: 25642337PubMedPubMedCentral Lin SH, Wang J, Allen PK, et al. A nomogram that predicts pathologic complete response to neoadjuvant chemoradiation also predicts survival outcomes after definitive chemoradiation for esophageal cancer. J Gastrointest Oncol. 2015;6(1):45-52. Medline: 25642337PubMedPubMedCentral
25.
go back to reference Nieman DR, Peyre CG, Watson TJ, et al. Neoadjuvant treatment response in negative nodes is an important prognosticator after esophagectomy. Ann Thorac Surg. 2015;99(1):277-83. Medline: 25442991CrossRefPubMed Nieman DR, Peyre CG, Watson TJ, et al. Neoadjuvant treatment response in negative nodes is an important prognosticator after esophagectomy. Ann Thorac Surg. 2015;99(1):277-83. Medline: 25442991CrossRefPubMed
26.
go back to reference Francis AM, Sepesi B, Correa AM, et al. The influence of histopathologic tumor viability on long-term survival and recurrence rates following neoadjuvant therapy for esophageal adenocarcinoma. Ann Surg. 2013;258(3):500-7. Medline 24022442CrossRefPubMed Francis AM, Sepesi B, Correa AM, et al. The influence of histopathologic tumor viability on long-term survival and recurrence rates following neoadjuvant therapy for esophageal adenocarcinoma. Ann Surg. 2013;258(3):500-7. Medline 24022442CrossRefPubMed
27.
go back to reference Sogaard M, Thomsen RW, Bossen KS, Sørensen HT, Nørgaard M. The impact of comorbidity on cancer survival: a review. Clin Epidemiol. 2013;5(Suppl 1):3-29. Medline: 24227920CrossRefPubMedPubMedCentral Sogaard M, Thomsen RW, Bossen KS, Sørensen HT, Nørgaard M. The impact of comorbidity on cancer survival: a review. Clin Epidemiol. 2013;5(Suppl 1):3-29. Medline: 24227920CrossRefPubMedPubMedCentral
28.
go back to reference Dolan JP, Kaur T, Diggs BS, et al. Impact of comorbidity on outcomes and overall survival after open and minimally invasive esophagectomy for locally advanced esophageal cancer. Surg Endosc. 2013;27(11):4094-103. Medline: 23846365CrossRefPubMed Dolan JP, Kaur T, Diggs BS, et al. Impact of comorbidity on outcomes and overall survival after open and minimally invasive esophagectomy for locally advanced esophageal cancer. Surg Endosc. 2013;27(11):4094-103. Medline: 23846365CrossRefPubMed
29.
go back to reference Iversen LH. Aspects of survival from colorectal cancer in Denmark. Dan Med J. 2012;59(4):B4428. Medline: 22459726PubMed Iversen LH. Aspects of survival from colorectal cancer in Denmark. Dan Med J. 2012;59(4):B4428. Medline: 22459726PubMed
Metadata
Title
Pathologic Complete Response Is an Independent Predictor of Improved Survival Following Neoadjuvant Chemoradiation for Esophageal Adenocarcinoma
Authors
Raed M. Alnaji
William Du
Emmanuel Gabriel
Smit Singla
Kristopher Attwood
Hector Nava
Usha Malhotra
Steven N. Hochwald
Moshim Kukar
Publication date
01-09-2016
Publisher
Springer US
Published in
Journal of Gastrointestinal Surgery / Issue 9/2016
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-016-3177-0

Other articles of this Issue 9/2016

Journal of Gastrointestinal Surgery 9/2016 Go to the issue