Abstract
Background
The purpose of this study was to evaluate the impact of neoadjuvant chemoradiotherapy (NCR) on perioperative outcomes, tumor pathology, and survival following surgical resection of clinical stage II and III esophageal cancer.
Methods
Patients undergoing esophagectomy for clinical stage II and III cancer were divided into two groups: those who received NCR and those who underwent primary surgery (1991–2011).
Results
A total of 173 (50.9 %) of 340 stage II/III patients received NCR, 108 (31.8 %) patients underwent primary surgery, and 59 (17.4 %) underwent neoadjuvant chemotherapy followed by surgery. Patients who received NCR were younger but had a similar Charlson comorbidity index and incidence of adenocarcinoma. There were no differences between groups in the incidence of complications, in-hospital mortality, and ICU stay, but patients who received NCR demonstrated a reduced length of hospital stay. NCR was associated with a reduced the incidence of positive pathological lymph node status and positive resection margin (3.1 vs. 21.1 %) in stage III esophageal cancer. No overall survival benefit was seen with use of NCR, although a nonsignificant improvement in survival of 22 months (p = 0.06) was noted in patients with adenocarcinoma. Negative resection margin was associated with an improved survival in both stage II and III patients.
Conclusions
This study highlights the importance of planning operations to optimize the opportunity to provide negative surgical resection margins and to identify patients not responding to NCR to allow them to proceed directly to surgery. Additional assessment of the effect of NCR on patients with adenocarcinoma is warranted.
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References
Powell J, McConkey CC. The rising trend in oesophageal adenocarcinoma and gastric cardia. Eur J Cancer Prev. 1992;1:265–9.
Siegel R, Naishadham D, Jemal A. Cancer statistics 2012. CA Cancer J Clin. 2012;62:10–29.
Courrech Staal EFW, Aleman BMP, Boot H, van Velthuysen MLF, 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.
Leichman L, Steiger Z, Seydel HG, Vaitkevicius VK. Combined preoperative chemotherapy and radiation therapy for cancer of the esophagus: the Wayne State University, Southwest Oncology group and Radiation Therapy Oncology Group experience. Semin Oncol. 1984;11:178–85.
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.
Kesler KA, Helft PR, Werner EA, Jain NP, Brooks JA, DeWitt JM, et al. A retrospective analysis of locally advanced esophageal cancer patients treated with neoadjuvant chemoradiation therapy followed by surgery or surgery alone. Ann Thorac Surg. 2005;79:1116–21.
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.
Van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal and junctional cancer. N Engl J Med. 2012;366:2074–84.
Luu TD, Gaur P, Force SD, Stanley CA, Mansour KA, Miller JL Jr, et al. Neoadjuvant chemoradiation versus chemotherapy for patients undergoing esophagectomy for esophageal cancer. Ann Thorac Surg. 2008;85:127–33.
Reynolds JV, Ravi N, Hollywood D, Kennedy MJ, Rowley S, Ryan A, et al. Neoadjuvant chemoradiation may increase the risk of respiratory complications and sepsis after transthoracic esophagectomy. J Thorac Cardiovasc Surg. 2006;132:549–55.
Bailey SH, Bull DA, Harpole DH, Rentz JJ, Neumayer LA, Pappas TN, et al. Outcomes after esophagectomy: a ten-year prospective cohort. Ann Thorac Surg. 2003;75:217–22.
Ruol A, Portale G, Castoro C, Merigliano S, Cagol M, Cavallin F, et al. Effects of neoadjuvant therapy on perioperative morbidity in elderly patients undergoing esophagectomy for esophageal cancer. Ann Surg Oncol. 2007;14:3243–50.
Wright CD, Kucharczuk JC, O’Brien SM, Grab JD, Allen MS, Society of Thoracic Surgeons General Thoracic Surgery Database. Predictors of major morbidity and mortality after esophagectomy for esophageal cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database risk adjustment model. J Thorac Cardiovasc Surg. 2009;137:587–95.
Ajani JA, Bentrem DJ, Besh S, D’Amico TA, Das P, Denlinger C et al. Esophageal and esophagogastric junction cancers (excluding the proximal 5 cm of the stomach). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) version 2.2012.
Low DE, Kunz S, Schembre D, Otero H, Malpass T, Hsi A, et al. Esophagectomy—it’s not just about mortality anymore: standardized perioperative clinical pathways improve outcomes in patients with esophageal cancer. J Gastrointest Surg. 2007;11:1395–402.
Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.
Vallbohmer D, Hollscher AH, DeMeester S, DeMeester T, Salo J, Peters J, et al. A multicenter study of survival after neoadjuvant radiotherapy/chemotherapy and esophagectomy for ypT0N0M0R0 esophageal cancer. Ann Surg. 2010;252:744–9.
Malaisrie SC, Untch B, Aranha GV, Mohideen N, Hantel A, Pickleman J. Neoadjuvant chemoradiotherapy for locally advanced esophageal cancer. Arch Surg. 2004;139:532–9.
Hurmuzlu M, Aarstad HJ, Aarstad AK, Hjermstad MJ, Viste A. Health-related quality of life in long-term survivors after high-dose chemoradiotherapy followed by surgery in esophageal cancer. Dis Esophagus. 2011;24:39–47.
Courrech Staal EF, van Sandick JW, van Tinteren H, Cats A, Aaronson NK. Health-related quality of life in long-term esophageal cancer survivors after curative treatment. J Thorac Cardiovasc Surg. 2010;140:777–83.
Donahue JM, Nichols FC, Li Z, Schomas DA, Allen MS, Cassivi SD, et al. Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg. 2009;87:392–9.
Meredith KL, Weber JM, Turaga KK, Siegel EM, McLoughlin J, Hoffe S, et al. Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol. 2010;17:1159–67.
Metzger R, Bollschweiler E, Drebber U, Monig SP, Schroder W, Alakus H, et al. Neoadjuvant chemoradiotherapy for esophageal cancer: impact on extracapsular lymph node involvement. World J Gastroenterol. 2010;16:1986–92.
Rice TW, Mason DP, Murthy SC, Zuccaro G Jr, Adelsten DJ, Rybicki LA, et al. T2N0M0 esophageal cancer. J Thorac Cardiovasc Surg. 2007;133:317–24.
Lordick F, Ott K, Krause BJ, Weber WA, Becker K, Stein HJ, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007;8:797–805.
Acknowledgment
The authors acknowledge the Ryan Hill Research Foundation for their support for this work and David Nickinovich, PhD, Health Science Matrix, Medical Outcomes Research Design & Analysis for the statistical analysis to support this study.
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Markar, S.R., Bodnar, A., Rosales, J. et al. The Impact of Neoadjuvant Chemoradiotherapy on Perioperative Outcomes, Tumor Pathology, and Survival in Clinical Stage II and III Esophageal Cancer. Ann Surg Oncol 20, 3935–3941 (2013). https://doi.org/10.1245/s10434-013-3137-9
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DOI: https://doi.org/10.1245/s10434-013-3137-9