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Published in: Annals of Surgical Oncology 2/2014

01-02-2014 | Thoracic Oncology

Impact of Neoadjuvant Chemoradiotherapy on Postoperative Course after Curative-intent Transthoracic Esophagectomy in Esophageal Cancer Patients

Authors: Dirk J. Bosch, MD, Christina T. Muijs, MD, Véronique E. M. Mul, MD, Jannet C. Beukema, MD, Geke A. P. Hospers, MD, PhD, Johannes G. M. Burgerhof, MSc, John Th. M. Plukker, MD, PhD

Published in: Annals of Surgical Oncology | Issue 2/2014

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Abstract

Background

Neoadjuvant chemoradiotherapy (CRT) improves locoregional control and overall survival in esophageal cancer patients. Although adverse events are relatively low during neoadjuvant CRT, severe postoperative adverse effects may occur, leading to morbidity and even mortality. We investigated the impact of a more frequently used neoadjuvant CRT regimen of 41.4 Gy/5 weeks radiotherapy with concurrent carboplatin and paclitaxel (CROSS schedule) on the postoperative course.

Methods

Between 2006 and 2012, a total of 96 esophageal cancer patients (staged cT1N+/T2–4a/N0–3 and M0) were treated according to the above neoadjuvant scheme. To reduce bias in this single-center study, we performed a propensity score-matched analysis with patients who underwent surgery alone (n = 230) from a prospectively maintained database (n = 326).

Results

Baseline characteristics between both groups were equally distributed in the matched cohort. In the neoadjuvant treated group, significantly more patients were diagnosed with pneumonia (27.1 vs. 51.0 %; p = 0.001), pleural effusion (12.5 vs. 24.0 %; p = 0.040), and arrhythmia (20.4 vs. 34.4 %; p = 0.008). In addition, in the multivariate analysis, neoadjuvant CRT was significantly associated with an increased risk of pneumonia (p = 0.001, odds ratio 2.896), pleural effusion (p = 0.041, odds ratio 2.268), and arrhythmia (p = 0.023, odds ratio 2.215). Despite these outcomes, no differences were detected in duration of intensive care unit or hospital stay. Short-term mortality did not differ between both groups.

Conclusions

We observed an increase of cardiopulmonary complications in the neoadjuvant CRT group, without any effect on hospital or intensive care unit stay and mortality. Further research is warranted on the limitation of chemoradiation-induced cardiopulmonary toxicity.
Literature
1.
go back to reference Wu PC, Posner MC. The role of surgery in the management of oesophageal cancer. Lancet Oncol. 2003;4:481–8.PubMedCrossRef Wu PC, Posner MC. The role of surgery in the management of oesophageal cancer. Lancet Oncol. 2003;4:481–8.PubMedCrossRef
2.
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;366:2074–84.PubMedCrossRef van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.PubMedCrossRef
3.
go back to reference Courrech Staal EF, Aleman BM, Boot H, van Velthuysen ML, van Tinteren H, van Sandick JW. Systematic review of the benefits and risks of neoadjuvant chemoradiation for oesophageal cancer. Br J Surg. 2010;97:1482–96. Courrech Staal EF, Aleman BM, Boot H, van Velthuysen ML, van Tinteren H, van Sandick JW. Systematic review of the benefits and risks of neoadjuvant chemoradiation for oesophageal cancer. Br J Surg. 2010;97:1482–96.
4.
go back to reference Fogh SE, Yu A, Kubicek GJ, et al. Do elderly patients experience increased perioperative or postoperative morbidity or mortality when given neoadjuvant chemoradiation before esophagectomy? Int J Radiat Oncol Biol Phys. 2011;80:1372–6.PubMedCrossRef Fogh SE, Yu A, Kubicek GJ, et al. Do elderly patients experience increased perioperative or postoperative morbidity or mortality when given neoadjuvant chemoradiation before esophagectomy? Int J Radiat Oncol Biol Phys. 2011;80:1372–6.PubMedCrossRef
5.
go back to reference Merkow RP, Bilimoria KY, McCarter MD, Chow WB, Ko CY, Bentrem DJ. Use of multimodality neoadjuvant therapy for esophageal cancer in the United States: assessment of 987 hospitals. Ann Surg Oncol. 2012;19:357–64.PubMedCrossRef Merkow RP, Bilimoria KY, McCarter MD, Chow WB, Ko CY, Bentrem DJ. Use of multimodality neoadjuvant therapy for esophageal cancer in the United States: assessment of 987 hospitals. Ann Surg Oncol. 2012;19:357–64.PubMedCrossRef
6.
go back to reference Reynolds JV, Ravi N, Hollywood D, et al. Neoadjuvant chemoradiation may increase the risk of respiratory complications and sepsis after transthoracic esophagectomy. J Thorac Cardiovasc Surg. 2006;132:549–55.PubMedCrossRef Reynolds JV, Ravi N, Hollywood D, et al. Neoadjuvant chemoradiation may increase the risk of respiratory complications and sepsis after transthoracic esophagectomy. J Thorac Cardiovasc Surg. 2006;132:549–55.PubMedCrossRef
7.
go back to reference Merritt RE, Whyte RI, D’Arcy NT, Hoang CD, Shrager JB. Morbidity and mortality after esophagectomy following neoadjuvant chemoradiation. Ann Thorac Surg. 2011;92:2034–40.PubMedCrossRef Merritt RE, Whyte RI, D’Arcy NT, Hoang CD, Shrager JB. Morbidity and mortality after esophagectomy following neoadjuvant chemoradiation. Ann Thorac Surg. 2011;92:2034–40.PubMedCrossRef
8.
go back to reference Vande Walle C, Ceelen WP, Boterberg T, et al. Anastomotic complications after Ivor Lewis esophagectomy in patients treated with neoadjuvant chemoradiation are related to radiation dose to the gastric fundus. Int J Radiat Oncol Biol Phys. 2012;82:e513–9. Vande Walle C, Ceelen WP, Boterberg T, et al. Anastomotic complications after Ivor Lewis esophagectomy in patients treated with neoadjuvant chemoradiation are related to radiation dose to the gastric fundus. Int J Radiat Oncol Biol Phys. 2012;82:e513–9.
9.
go back to reference Fiorica F, Di Bona D, Schepis F, et al. Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis. Gut. 2004;53:925–30.PubMedCrossRef Fiorica F, Di Bona D, Schepis F, et al. Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis. Gut. 2004;53:925–30.PubMedCrossRef
10.
go back to reference Geh JI, Crellin AM, Glynne-Jones R. Preoperative (neoadjuvant) chemoradiotherapy in oesophageal cancer. Br J Surg. 2001;88:338–56.PubMedCrossRef Geh JI, Crellin AM, Glynne-Jones R. Preoperative (neoadjuvant) chemoradiotherapy in oesophageal cancer. Br J Surg. 2001;88:338–56.PubMedCrossRef
11.
go back to reference 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;337:161–7.PubMedCrossRef 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;337:161–7.PubMedCrossRef
12.
go back to reference Kaklamanos IG, Walker GR, Ferry K, Franceschi D, Livingstone AS. Neoadjuvant treatment for resectable cancer of the esophagus and the gastroesophageal junction: a meta-analysis of randomized clinical trials. Ann Surg Oncol. 2003;10:754–61.PubMedCrossRef Kaklamanos IG, Walker GR, Ferry K, Franceschi D, Livingstone AS. Neoadjuvant treatment for resectable cancer of the esophagus and the gastroesophageal junction: a meta-analysis of randomized clinical trials. Ann Surg Oncol. 2003;10:754–61.PubMedCrossRef
13.
go back to reference Malthaner RA, Collin S, Fenlon D. Preoperative chemotherapy for resectable thoracic esophageal cancer. Cochrane Database Syst Rev. 2006;(3):CD001556. Malthaner RA, Collin S, Fenlon D. Preoperative chemotherapy for resectable thoracic esophageal cancer. Cochrane Database Syst Rev. 2006;(3):CD001556.
14.
go back to reference 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;12:681–92.PubMedCrossRef 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;12:681–92.PubMedCrossRef
15.
go back to reference Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996;335:462–7.PubMedCrossRef Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996;335:462–7.PubMedCrossRef
16.
go back to reference Zingg U, Smithers BM, Gotley DC, et al. Factors associated with postoperative pulmonary morbidity after esophagectomy for cancer. Ann Surg Oncol. 2011;18:1460–8.PubMedCrossRef Zingg U, Smithers BM, Gotley DC, et al. Factors associated with postoperative pulmonary morbidity after esophagectomy for cancer. Ann Surg Oncol. 2011;18:1460–8.PubMedCrossRef
17.
go back to reference Wang SL, Liao Z, Liu H, et al. Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer. World J Gastroenterol. 2006;12:5501–8.PubMed Wang SL, Liao Z, Liu H, et al. Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer. World J Gastroenterol. 2006;12:5501–8.PubMed
18.
go back to reference 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;57:1317–22.PubMedCrossRef 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;57:1317–22.PubMedCrossRef
19.
go back to reference Darby SC, Ewertz M, Hall P. Ischemic heart disease after breast cancer radiotherapy. N Engl J Med. 2013;368:2527.PubMedCrossRef Darby SC, Ewertz M, Hall P. Ischemic heart disease after breast cancer radiotherapy. N Engl J Med. 2013;368:2527.PubMedCrossRef
20.
go back to reference Urschel JD, Vasan H. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg. 2003;185:538–43.PubMedCrossRef Urschel JD, Vasan H. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg. 2003;185:538–43.PubMedCrossRef
21.
go back to reference Weitzen S, Lapane KL, Toledano AY, Hume AL, Mor V. Principles for modeling propensity scores in medical research: a systematic literature review. Pharmacoepidemiol Drug Saf. 2004;13:841–53.PubMedCrossRef Weitzen S, Lapane KL, Toledano AY, Hume AL, Mor V. Principles for modeling propensity scores in medical research: a systematic literature review. Pharmacoepidemiol Drug Saf. 2004;13:841–53.PubMedCrossRef
22.
go back to reference Pultrum BB, Bosch DJ, Nijsten MW, et al. Extended esophagectomy in elderly patients with esophageal cancer: minor effect of age alone in determining the postoperative course and survival. Ann Surg Oncol. 2010;17:1572–80.PubMedCentralPubMedCrossRef Pultrum BB, Bosch DJ, Nijsten MW, et al. Extended esophagectomy in elderly patients with esophageal cancer: minor effect of age alone in determining the postoperative course and survival. Ann Surg Oncol. 2010;17:1572–80.PubMedCentralPubMedCrossRef
23.
go back to reference Bosch DJ, Pultrum BB, de Bock GH, Oosterhuis JK, Rodgers MG, Plukker JT. Comparison of different risk-adjustment models in assessing short-term surgical outcome after transthoracic esophagectomy in patients with esophageal cancer. Am J Surg. 2011;202:303–9.PubMedCrossRef Bosch DJ, Pultrum BB, de Bock GH, Oosterhuis JK, Rodgers MG, Plukker JT. Comparison of different risk-adjustment models in assessing short-term surgical outcome after transthoracic esophagectomy in patients with esophageal cancer. Am J Surg. 2011;202:303–9.PubMedCrossRef
24.
go back to reference Wei X, Liu HH, Tucker SL, et al. Risk factors for pericardial effusion in inoperable esophageal cancer patients treated with definitive chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2008;70:707–14.PubMedCrossRef Wei X, Liu HH, Tucker SL, et al. Risk factors for pericardial effusion in inoperable esophageal cancer patients treated with definitive chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2008;70:707–14.PubMedCrossRef
25.
go back to reference Bovelli D, Plataniotis G, Roila F; ESMO Guidelines Working Group. Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO clinical practice guidelines. Ann Oncol. 2010;21(Suppl 5):v277–82.PubMedCrossRef Bovelli D, Plataniotis G, Roila F; ESMO Guidelines Working Group. Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO clinical practice guidelines. Ann Oncol. 2010;21(Suppl 5):v277–82.PubMedCrossRef
26.
go back to reference Wang J, Wei C, Tucker SL, et al. Predictors of postoperative complications after trimodality therapy for esophageal cancer. Int J Radiat Oncol Biol Phys. 2013;86:885–91.PubMedCrossRef Wang J, Wei C, Tucker SL, et al. Predictors of postoperative complications after trimodality therapy for esophageal cancer. Int J Radiat Oncol Biol Phys. 2013;86:885–91.PubMedCrossRef
27.
go back to reference Ilson DH. Cancer of the gastroesophageal junction: combined modality therapy. Surg Oncol Clin N Am. 2006;15:803–24.PubMedCrossRef Ilson DH. Cancer of the gastroesophageal junction: combined modality therapy. Surg Oncol Clin N Am. 2006;15:803–24.PubMedCrossRef
28.
go back to reference Blencowe NS, Strong S, McNair AG, et al. Reporting of short-term clinical outcomes after esophagectomy: a systematic review. Ann Surg. 2012;255:658–66.PubMedCrossRef Blencowe NS, Strong S, McNair AG, et al. Reporting of short-term clinical outcomes after esophagectomy: a systematic review. Ann Surg. 2012;255:658–66.PubMedCrossRef
29.
go back to reference Kerr SF, Norton S, Glynne-Jones R. Delaying surgery after neoadjuvant chemoradiotherapy for rectal cancer may reduce postoperative morbidity without compromising prognosis. Br J Surg. 2008;95:1534–40.PubMedCrossRef Kerr SF, Norton S, Glynne-Jones R. Delaying surgery after neoadjuvant chemoradiotherapy for rectal cancer may reduce postoperative morbidity without compromising prognosis. Br J Surg. 2008;95:1534–40.PubMedCrossRef
30.
go back to reference Wang J, Han C, Li XN, et al. Short-term efficacy of intensity-modulated radiotherapy on esophageal carcinoma. Ai Zheng. 2009;28:1138–42.PubMed Wang J, Han C, Li XN, et al. Short-term efficacy of intensity-modulated radiotherapy on esophageal carcinoma. Ai Zheng. 2009;28:1138–42.PubMed
31.
go back to reference Schultz MJ, Haas LE. Antibiotics or probiotics as preventive measures against ventilator-associated pneumonia: a literature review. Crit Care. 2011;15:R18.PubMedCrossRef Schultz MJ, Haas LE. Antibiotics or probiotics as preventive measures against ventilator-associated pneumonia: a literature review. Crit Care. 2011;15:R18.PubMedCrossRef
Metadata
Title
Impact of Neoadjuvant Chemoradiotherapy on Postoperative Course after Curative-intent Transthoracic Esophagectomy in Esophageal Cancer Patients
Authors
Dirk J. Bosch, MD
Christina T. Muijs, MD
Véronique E. M. Mul, MD
Jannet C. Beukema, MD
Geke A. P. Hospers, MD, PhD
Johannes G. M. Burgerhof, MSc
John Th. M. Plukker, MD, PhD
Publication date
01-02-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 2/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-3316-8

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