Abstract：Objective To evaluate the potential influencing factors associated with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Methods A retrospective analysis was performed on the clinical data 265 patients with stage Ⅱ and Ⅲ(the 7th version of AJCC) rectal cancer admitted to our hospital from 2011 to 2013. All patients underwent neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery with/or without induction chemotherapy during the interval between the complete of CCRT and surgery. The predictors associated with pCR were analyzed by univariate and multivariate logistic regression analyses. With the use of the independent predictive variables for pCR from multivariate analysis, a clinical risk score model was established according to the following criteria:no-risk group (0 factor);low-risk group (1 factor);high-risk group (2 factors). Results Among these 265 patients, 50(18.9%) achieved pCR. The univariate analysis showed that carcinoembryonic antigen (CEA) level before CCRT (P=0.017), T stage before CCRT (P=0.001), interval between complete of CCRT and surgery (P=0.000), and the maximum tumor thickness before CCRT (P=0.040) were significantly associated with pCR. The multivariate analysis showed that pre-CCRT CEA level (P=0.021 or 0.446) and interval between the complete of CCRT and surgery (P=0.000 or 3.774) were significant predictors of pCR. When stratifying for smoking status, only low pre-CCRT CEA level was significantly associated with pCR in the non-smoking patients (P=0.044). For the prediction of pCR by the clinical risk score model, the sensitivity was 0.805, the specificity was 0.460, the area under the receiver operating curve was 0.690(95%CI=0.613-0.767), the positive predictive value was35.49%, the negative predictive value was 86.5%, and the predictive accuracy was 73.9%. ConclusionsFor locally advanced rectal cancer, pCR can be achieved in some patients after neoadjuvant therapy. Low pre-CCRT CEA level and long interval time between CCRT and surgery are independent factors associated with pCR, and only low pre-CCRT CEA level is an associated factor in the group of nonsmokers. The clinical risk score model based on pre-CCRT CEA level>5 ng/ml and time interval from CCRT completion to surgery ≤8 weeks can be used to predict pCR after neoadjuvant chemoradiotherapy for LARC.
Chen Yuangui,Xu Benhua,Lu Haijie et al. Predictors of pathologic complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer[J]. Chinese Journal of Radiation Oncology, 2015, 24(6): 627-632.
[1] Kapiteijn E,Marijnen CAM,Nagtegaal ID,et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer[J].N Engl J Med,2001,345(9):638-646.DOI:10.1056/NEJMoa010580. [2] Bosset JF,Collette L,Calais G,et al. Chemotherapy with preoperative radiotherapy in rectal cancer[J].N Engl J Med,2006,355(11):1114-1123.DOI:10.1056/NEJMoa060829. [3] Sauer R,Becker H,Hohenberger W,et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer[J].N Engl J Med,2004,351(17):1731-1740.DOI:10.1056/NEJMoa040694. [4] O’Neill BDP,Brown G,Heald RJ,et al. Non-operative treatment after neoadjuvant chemoradiotherapy for rectal cancer[J].Lancet Oncol,2007,8(7):625-633.DOI:10.1016/S1470-2045(07)70202-4. [5] Capirei C,Valentini V,Cionini L,et al. Prognostic value of pathologic complete response After neoadjuvant therapy in locally advanced rectal cancer:long-term analysis of 566 ypCR patients[J].Int J Radiat Oncol Biol Phys,2008,72(1):99-107.DOI:10.1016/j.ijrobp.2007.12.019. [6] De Campos-Lobato LF,Stocehi L,da Luz Moreira A,et al. Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence[J].Ann Surg Oncol,2011,18(6):1590-1598.DOI:10.1245/s10434-010-1506-1. [7] Wolthuis AM,Penninckx F,Haustermans K,et al. Outcome standards for an organ preservation strategy in stageⅡ and Ⅲrectal adenocarcinoma after neoadjuvant chemoradiation[J].Ann Surg Oncol,2011,18(3):684-690.DOI:10.1245/s10434-010-1324-5. [8] Mass M,Nelemans PJ,Valentini V,et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer:a pooled analysis of individual patient data[J].Lancet Oncol,2010,11(9):835-844.DOI:10.1016/S1470-2045(10)70172-8. [9] Edge S,Byrd DR,Compton CC,et al. AJCC cancer staging manual[M].New York:Springer,2002. [10] Das P,Skibber JM,Rodriguez-Bigas MA,et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer[J].Cancer,2007,109(9):1750-1755.DOI:10.1002/cncr.22625. [11] Moureau-Zabotto L,Farnault B,de Chaisemartin C,et al. Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer[J].Int J Radiat Oncol Biol Phys,2011,80(2):483-491.DOI:10.1016/j.ijrobp.2010.02.025. [12] Lee JH,Kim SH,Jang HS,et al. Preoperative elevation of carcinoembryonic antigen predicts poor tumor response and frequent distant recurrence for patients with rectal cancer who receive preoperative chemoradiotherapy and total mesorectal excision:a multi-institutional analysis in an Asian population[J].Int J Colorectal Dis,2013,28(4):511-517.DOI:10.1007/s00384-012-1584-6. [13] 阿衣古丽·哈热,帕丽达·阿皮孜,伊斯刊达尔·阿布力米提,等.直肠癌新辅助放化疗后pCR的临床因素分析[J].中华放射肿瘤学杂志,2014,23(1):5-8.DOI:10.3760/cma.j.issn.1004-4221.2014.01.002. [14] Alexander JC,Silverman NA,Chretien PB.Effect of age and cigarette smoking on carcinoembryonic antigen levels[J].JAMA,1976,235(18):1975-1979.DOI:10.1001/jama.1976.03260440027017. [15] Sajid KM,Parveen R,Durr-e-Sabih,et al. Carcinoembryonic antigen (CEA) levels in hookah smokers,cigarette smokers and non-smokers[J].J Pak Med Assoc,2007,57(12):595-599. [16] Wallin U,Rothenberger D,Lowry A,et al. CEA-a predictor for pathologic complete response after neoadjuvant therapy for rectal cancer[J].Dis Colon Rectum,2013,56(7):859-868.DOI:10.1097/DCR.0b013e31828e5a72. [17] Tulchinsky H,Shmueli E,Figer A,et al. An Interval>7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease-free survival in patients with locally advanced rectal cancer[J].Ann Surg Oncol,2008,15(10):2661-2667.DOI:10.1245/s10434-008-9892-3. [18] Sloothaak DAM,Geijsen DE,van Leersum NJ,et al. Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer[J].Br J Surg,2013,100(7):933-939.DOI:10.1002/bjs.9112. [19] Stein DE,Mahmoud NN,Anné PR,et al. Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma[J].Dis Colon Rectum,2003,46(4):448-453. [20] Gérard JP,Azria D,Gourgou-Bourgade S,et al. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer:results of the Phase Ⅲ trial ACCORD 12/0405-Prodige 2[J].J Clin Oncol,2010,28(10):1638-1644.DOI:10.1200/JCO.2009.25.8376. [21] Sanghera P,Wong DWY,McConkey CC,et al. Chemoradiotherapy for rectal cancer:an updated analysis of factors affecting pathological response[J].Clin Oncol,2008,20(2):176-183.DOI:10.1016/j.clon.2007.11.013.
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