Predictors of pathological complete response to neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma

World Journal of Surgical Oncology

Yun-Hen Liu³  Sheng-Chieh Chan⁶  Chen-Kan Tseng⁴  Hsien-Kun Chang⁵  Yu-Wen Wen¹  Yin-Kai Chao³  Ren-Wen Huang² 

[1] Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, Taiwan;Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Division of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Division of Hematology/Oncology, Chang Gung Memorial Hospital, Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Nuclear Medicine, Chang Gung Memorial Hospital, Keelung, College of Medicine, Chang Gung University, Taoyuan, Taiwan

关键词: Neoadjuvant chemoradiotherapy;    Predictors;    Esophageal cancer;    Pathological complete response;   

Others  :  811122
DOI  :  10.1186/1477-7819-12-170

 received in 2014-01-27, accepted in 2014-05-06,  发布年份 2014

【 摘 要 】

Backgrounds

In this study, we evaluated the factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma (ESCC).

Methods

Pre-nCRT parameters in ESCC patients treated between 1999 and 2006 were analyzed to identify predictors of pCR. All patients received 5-fluorouracil/cisplatin-based chemotherapy and external beam radiation followed by scheduled esophagectomy. Variables were analyzed using univariate and multivariate analyses with pCR as the dependent variable. Estimated pCR rate was calculated with a regression model.

Results

Fifty-nine (20.9%) of 282 patients achieved pCR. Univariate analysis identified four patient factors (age, smoking status, drinking history and hypertension), one pre-nCRT parameter (tumor length) as significant predictors of pCR (all P <0.05). On multivariate analysis, tumor length ≤3 cm (favorable, odds ratio (OR): 4.85, P = 0.001), patient age >55 years (favorable, OR: 1.95, P = 0.035), and being a non-smoker (favorable, OR: 3.6, P = 0.003) were independent predictors of pCR. The estimated pCR rates based on a logistic regression including those three predictors were 71%, 35 to approximately 58%, 19 to approximately 38%, and 12% for patients with 3, 2, 1 and 0 predictors, respectively.

Conclusion

Age, smoking habit and tumor length were important pCR predictors. These factors may be used to predict outcomes for ESCC patients receiving nCRT, to develop risk-adapted treatment strategies, and to select patients who could participate in trials on new therapies.

【 授权许可】

   
2014 Huang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Enzinger PC, Mayer RJ: Esophageal cancer. N Engl J Med 2003, 349:2241-2252.
• [2]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, 335:462-467.
• [3]Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V: Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 2011, 12:681-692.
• [4]Berger AC, Farma J, Scott WJ, Freedman G, Weiner L, Cheng JD, Wang H, Goldberg M: Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival. J Clin Oncol 2005, 23:4330-4337.
• [5]Donahue JM, Nichols FC, Li Z, Schomas DA, Allen MS, Cassivi SD, Jatoi A, Miller RC, Wigle DA, Shen KR, Deschamps C: Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg 2009, 87:392-398. discussion 398–399
• [6]Meredith KL, Weber JM, Turaga KK, Siegel EM, McLoughlin J, Hoffe S, Marcovalerio M, Shah N, Kelley S, Karl R: Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol 2010, 17:1159-1167.
• [7]Dittrick GW, Weber JM, Shridhar R, Hoffe S, Melis M, Almhanna K, Barthel J, McLoughlin J, Karl RC, Meredith KL: Pathologic nonresponders after neoadjuvant chemoradiation for esophageal cancer demonstrate no survival benefit compared with patients treated with primary esophagectomy. Ann Surg Oncol 2012, 19:1678-1684.
• [8]Rohatgi P, Swisher SG, Correa AM, Wu TT, Liao Z, Komaki R, Walsh GL, Vaporciyan AA, Rice DC, Roth JA, Ajani JA: Characterization of pathologic complete response after preoperative chemoradiotherapy in carcinoma of the esophagus and outcome after pathologic complete response. Cancer 2005, 104:2365-2372.
• [9]Schauer M, Janssen KP, Rimkus C, Raggi M, Feith M, Friess H, Theisen J: Microarray-based response prediction in esophageal adenocarcinoma. Clin Cancer Res 2010, 16:330-337.
• [10]Maher SG, Gillham CM, Duggan SP, Smyth PC, Miller N, Muldoon C, O'Byrne KJ, Sheils OM, Hollywood D, Reynolds JV: Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer. Ann Surg 2009, 250:729-737.
• [11]Duong C, Greenawalt DM, Kowalczyk A, Ciavarella ML, Raskutti G, Murray WK, Phillips WA, Thomas RJ: Pretreatment gene expression profiles can be used to predict response to neoadjuvant chemoradiotherapy in esophageal cancer. Ann Surg Oncol 2007, 14:3602-3609.
• [12]Luthra R, Wu TT, Luthra MG, Izzo J, Lopez-Alvarez E, Zhang L, Bailey J, Lee JH, Bresalier R, Rashid A, Swisher SG, Ajani JA: Gene expression profiling of localized esophageal carcinomas: association with pathologic response to preoperative chemoradiation. J Clin Oncol 2006, 24:259-267.
• [13]Shimada H, Hoshino T, Okazumi S, Matsubara H, Funami Y, Nabeya Y, Hayashi H, Takeda A, Shiratori T, Uno T, Ito H, Ochiai T: Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma. Br J Cancer 2002, 86:552-557.
• [14]Warnecke-Eberz U, Metzger R, Miyazono F, Baldus SE, Neiss S, Brabender J, Schaefer H, Doerfler W, Bollschweiler E, Dienes HP, Mueller RP, Danenberg PV, Hoelscher AH, Schneider PM: High specificity of quantitative excision repair cross-complementing 1 messenger RNA expression for prediction of minor histopathological response to neoadjuvant radiochemotherapy in esophageal cancer. Clin Cancer Res 2004, 10:3794-3799.
• [15]Hothorn T, Hornik K, Zeileis A: Unbiased recursive partitioning: a conditional inference framework. J Comput Graph Stat 2006, 15:651-674.
• [16]Oze I, Matsuo K, Ito H, Wakai K, Nagata C, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Sasazuki S, Inoue M, Tsugane S, Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan: Cigarette smoking and esophageal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol 2012, 42:63-73.
• [17]Shitara K, Matsuo K, Hatooka S, Ura T, Takahari D, Yokota T, Abe T, Kawai H, Tajika M, Kodaira T, Shinoda M, Tajima K, Muro K, Tanaka H: Heavy smoking history interacts with chemoradiotherapy for esophageal cancer prognosis: a retrospective study. Cancer Sci 2010, 101:1001-1006.
• [18]Sundelof M, Lagergren J, Ye W: Patient demographics and lifestyle factors influencing long-term survival of oesophageal cancer and gastric cardia cancer in a nationwide study in Sweden. Eur J Cancer 2008, 44:1566-1571.
• [19]Nozoe T, Korenaga D, Kabashima A, Sugimachi K: Smoking-related increase of O(6)-methylguanine-DNA methyltransferase expression in squamous cell carcinoma of the esophagus. Cancer Lett 2002, 184:49-55.
• [20]Ohba T, Kometani T, Shoji F, Yano T, Yoshino I, Taguchi K, Kuraoka I, Oda S, Maehara Y: Expression of an X-family DNA polymerase, pol lambda, in the respiratory epithelium of non-small cell lung cancer patients with habitual smoking. Mutat Res 2009, 677:66-71.
• [21]Sobin LH, Hermanek P, Hutter RV: TNM classification of malignant tumors. A comparison between the new (1987) and the old editions. Cancer 1988, 61:2310-2314.
• [22]Wang BY, Goan YG, Hsu PK, Hsu WH, Wu YC: Tumor length as a prognostic factor in esophageal squamous cell carcinoma. Ann Thorac Surg 2011, 91:887-893.
• [23]Eloubeidi MA, Desmond R, Arguedas MR, Reed CE, Wilcox CM: Prognostic factors for the survival of patients with esophageal carcinoma in the U.S.: the importance of tumor length and lymph node status. Cancer 2002, 95:1434-1443.
• [24]Willett CG, Warland G, Coen J, Shellito PC, Compton CC: Rectal cancer: the influence of tumor proliferation on response to preoperative irradiation. Int J Radiat Oncol Biol Phys 1995, 32:57-61.
• [25]Turkyilmaz A, Eroglu A, Subasi M, Karaoglanoglu N: Clinicopathological features and prognosis of esophageal cancer in young patients. Is there a difference in outcome? Dis Esophagus 2009, 22:211-215.
• [26]Lin MY, Chen MC, Wu IC, Wu DC, Cheng YJ, Wu CC, Chai CY, Lee JM, Wu MT: Areca users in combination with tobacco and alcohol use are associated with younger age of diagnosed esophageal cancer in Taiwanese men. PLoS One 2011, 6:e25347.