Neoadjuvant Concurrent Chemoradiotherapy for Locally Advanced Esophageal Cancer in a Single High-Volume Center
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Neoadjuvant chemoradiotherapy (CRT) is now considered the standard of care by many centers in the treatment of both squamous cell carcinoma (SCC) and adenocarcinoma of the esophagus. This study evaluates the effectiveness of a neoadjuvant CRT protocol, as regards pathological complete response (pCR) rate and long-term survival.
From 2003 to 2011, at Upper G.I. Surgery Division of Verona University, 155 consecutive patients with locally advanced esophageal cancers (90 SCC, 65 adenocarcinoma) were treated with a single protocol of neoadjuvant CRT (docetaxel, cisplatin, and 5-fluorouracil with 50.4 Gy of concurrent radiotherapy). Response to CRT was evaluated through percentage of pathological complete response (pCR or ypT0N0), overall (OS) and disease-related survival (DRS), and pattern of relapse.
One hundred thirty-one patients (84.5 %) underwent surgery. Radical resection (R0) was achieved in 123 patients (79.3 %), and pCR in 65 (41.9 %). Postoperative mortality was 0.7 % (one case). Five-year OS and DRS were respectively 43 and 49 % in the entire cohort, 52 and 59 % in R0 cases, and 72 and 81 % in pCR cases. Survival did not significantly differ between SCC and adenocarcinoma, except for pCR cases. Forty-nine patients suffered from relapse, which was mainly systemic in adenocarcinoma. Only three out of 26 pCR patients with previous adenocarcinoma developed relapse, always systemic.
This study suggests that patients treated with the present protocol achieve good survival and high pCR rate. Further research is necessary to evaluate whether surgery on demand is feasible in selected patients, such as pCR patients with adenocarcinoma.
- Siegel R, Naishadham D, Jemal A. Cancer statistics, CA Cancer J Clin. 2012;62(1):10–29. CrossRef
- Berrino F, De Angelis R, Sant M, et al. Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995–99: results of the EUROCARE-4 study. Lancet Oncol. 2007;8(9):773–783.
- Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007;8(3):226–234. CrossRef
- 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):4962–8. CrossRef
- 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. CrossRef
- 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(6):538–43. CrossRef
- 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. CrossRef
- Verlato G, Zanoni A, Tomezzoli A, et al. Response to induction therapy in oesophageal and cardia carcinoma using Mandard tumour regression grade or size of residual foci. Br J Surg. 2010;97(5):719–25. CrossRef
- Pasini F, de Manzoni G, Pedrazzani C, et al. High pathological response rate in locally advanced esophageal cancer after neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy schedule with protracted venous infusion of 5-fluorouracil and dose escalation of cisplatin, docetaxel and concurrent radiotherapy. Ann Oncol. Jul 2005;16(7):1133–9. CrossRef
- Marubini E, Valsecchi M. Analysing survival data from clinical trials and observational studies. Chichester: Wiley; 1995.
- Kranzfelder M, Buchler P, Lange K, Friess H. Treatment options for squamous cell cancer of the esophagus: a systematic review of the literature. J Am Coll Surg. 2010;210(3):351–9. CrossRef
- Mariette C, Piessen G, Triboulet JP. Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol. 2007;8(6):545–53. CrossRef
- Samalin E, Ychou M. Neoadjuvant treatment in upper gastrointestinal adenocarcinomas: new paradigms from old concepts? Curr Opin Oncol. 2007;19(4):384–9. CrossRef
- Burmeister BH, Thomas JM, Burmeister EA, et al. Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial. Eur J Cancer. 2011;47(3):354–60. CrossRef
- Stahl M, Walz MK, Stuschke M, et al. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 20 2009;27(6):851–6. CrossRef
- Dimick JB, Pronovost PJ, Cowan JA, Lipsett PA. Surgical volume and quality of care for esophageal resection: do high-volume hospitals have fewer complications? Ann Thorac Surg. 2003;75(2):337–41. CrossRef
- Metzger R, Bollschweiler E, Vallbohmer D, Maish M, DeMeester TR, Holscher AH. High volume centers for esophagectomy: what is the number needed to achieve low postoperative mortality? Dis Esophagus. 2004;17(4):310–14. CrossRef
- Wenner J, Zilling T, Bladstrom A, Alvegard TA. The influence of surgical volume on hospital mortality and 5-year survival for carcinoma of the oesophagus and gastric cardia. Anticancer Res. 2005;25(1B):419–24.
- Choong NW, Mauer AM, Haraf DC, et al. Long-term outcome of a phase II study of docetaxel-based multimodality chemoradiotherapy for locally advanced carcinoma of the esophagus or gastroesophageal junction. Med Oncol. 2011;28(Suppl 1):S152–61. CrossRef
- Knox JJ, Wong R, Visbal AL, et al. Phase 2 trial of preoperative irinotecan plus cisplatin and conformal radiotherapy, followed by surgery for esophageal cancer. Cancer. 2010;116(17):4023–32. CrossRef
- Koo DH, Park SI, Kim YH, et al. Phase II study of use of a single cycle of induction chemotherapy and concurrent chemoradiotherapy containing capecitabine/cisplatin followed by surgery for patients with resectable esophageal squamous cell carcinoma: long-term follow-up data. Cancer Chemother Pharmacol. 2012;69(3):655–63. CrossRef
- Pera M, Gallego R, Montagut C, et al. Phase II trial of preoperative chemoradiotherapy with oxaliplatin, cisplatin, and 5-FU in locally advanced esophageal and gastric cancer. Ann Oncol. 2012;23(3):664–70. CrossRef
- Spigel DR, Greco FA, Meluch AA, et al. Phase I/II trial of preoperative oxaliplatin, docetaxel, and capecitabine with concurrent radiation therapy in localized carcinoma of the esophagus or gastroesophageal junction. J Clin Oncol. 2010;28(13):2213–9. CrossRef
- 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. CrossRef
- Koshy M, Greenwald BD, Hausner P, et al. Outcomes after trimodality therapy for esophageal cancer: the impact of histology on failure patterns. Am J Clin Oncol. 2011;34(3):259–4. CrossRef
- 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(10):1482–96.
- Meguid RA, Hooker CM, Taylor JT, et al. Recurrence after neoadjuvant chemoradiation and surgery for esophageal cancer: does the pattern of recurrence differ for patients with complete response and those with partial or no response? J Thorac Cardiovasc Surg. 2009;138(6):1309–17. CrossRef
- Rohatgi PR, Swisher SG, Correa AM, et al. Failure patterns correlate with the proportion of residual carcinoma after preoperative chemoradiotherapy for carcinoma of the esophagus. Cancer. 2005;104(7):1349–55. CrossRef
- Vallbohmer D, Holscher AH, DeMeester S, et al. A multicenter study of survival after neoadjuvant radiotherapy/chemotherapy and esophagectomy for ypT0N0M0R0 esophageal cancer. Ann Surg. 2010;252(5):744–9. CrossRef
- Orditura M, Galizia G, Morgillo F, et al. Complete response to preoperative chemoradiation and survival in esophageal cancer: a pooled analysis of three single-institution phase II trials. Dis Esophagus. 2012;25(2):130–6. CrossRef
- Park JW, Kim JH, Choi EK, et al. Prognosis of esophageal cancer patients with pathologic complete response after preoperative concurrent chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2011;81(3):691–697. CrossRef
- Scheer RV, Fakiris AJ, Johnstone PA. Quantifying the benefit of a pathologic complete response after neoadjuvant chemoradiotherapy in the treatment of esophageal cancer. Int J Radiat Oncol Biol Phys. 2011;80(4):996–1001. CrossRef
- Bedenne L, Michel P, Bouche O, et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol. 2007;25(10):1160–8. CrossRef
- Stahl M, Stuschke M, Lehmann N, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol. 2005;23(10):2310–7. CrossRef
- Gardner-Thorpe J, Hardwick RH, Dwerryhouse SJ. Salvage oesophagectomy after local failure of definitive chemoradiotherapy. Brit J Surg. 2007;94(9):1059–66. CrossRef
- Dittrick GW, Weber JM, Shridhar R, et al. Pathologic nonresponders after neoadjuvant chemoradiation for esophageal cancer demonstrate no survival benefit compared with patients treated with primary esophagectomy. Ann Surg Oncol. 2012;19(5):1678–84. CrossRef
- Bradbury PA, Kulke MH, Heist RS, et al. Cisplatin pharmacogenetics, DNA repair polymorphisms, and esophageal cancer outcomes. Pharmacogenet Genomics. 2009;19(8):613–25. CrossRef
- Fareed KR, Kaye P, Soomro IN, et al. Biomarkers of response to therapy in oesophago-gastric cancer. Gut. 2009;58(1):127–43. CrossRef
- Warnecke-Eberz U, Metzger R, Bollschweiler E, et al. TaqMan low-density arrays and analysis by artificial neuronal networks predict response to neoadjuvant chemoradiation in esophageal cancer. Pharmacogenomics. 2010;11(1):55–64. CrossRef
- Wu X, Gu J, Wu TT, et al. Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer. J Clin Oncol. 10 2006;24(23):3789–98. CrossRef
- Lordick F, Ott K, Krause BJ, 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(9):797–805. CrossRef
- Piessen G, Briez N, Triboulet JP, Mariette C. Patients with locally advanced esophageal carcinoma nonresponder to radiochemotherapy: who will benefit from surgery? Ann Surg Oncol. 2007;14(7):2036–44. CrossRef
- Neoadjuvant Concurrent Chemoradiotherapy for Locally Advanced Esophageal Cancer in a Single High-Volume Center
Annals of Surgical Oncology
Volume 20, Issue 6 , pp 1993-1999
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- Author Affiliations
- 1. Upper G.I. Surgery Division, University of Verona, Verona, Italy
- 2. Unit of Epidemiology and Medical Statistics, University of Verona, Verona, Italy
- 3. Division of Oncology, Rovigo Hospital, Rovigo, Italy
- 4. Department of General Surgery, Renji Hospital, Shangai Jiaotong University, Shanghai, China