Abstract
Purpose
To investigate the significance of carbohydrate antigen 19-9 (CA19-9) levels for survival in locally advanced pancreatic cancer (LAPC) treated with concurrent chemoradiotherapy (CCRT).
Methods/patients
We retrospectively reviewed data from 97 LAPC patients treated with CCRT between 2000 and 2013. CA19-9 levels (initial and post-CCRT) and their changes [{(post-CCRT CA19-9 level − initial CA19-9 level)/(initial CA19-9 level)} × 100] were analyzed for overall survival. A cut-off point of 37 U/mL was used to analyze initial and post-CCRT CA19-9 levels. In order to define an optimal cut-off point for change in CA19-9 level, the maxstat package of R was applied.
Results
Median overall survival was 14.7 months (95% CI 13.4–16.0), and the 2-year survival rate was 16.5%. The estimated optimal cut-off point of CA19-9 level change was 94.4%. On univariate analyses, CA19-9 level change between initial and post-CCRT was significantly correlated with overall survival (median survival time 9.7 vs 16.3 months, p < 0.001). Multivariate analyses confirmed that CA19-9 level change from initial to post-CCRT was the only prognostic factor (p < 0.001).
Conclusions
Change in CA19-9 level between initial and post-CCRT was a significant prognostic marker for overall survival in LAPC treated with CCRT. A CA19-9 level increase >94.4% might serve as a surrogate marker for poor survival in patients with LAPC undergoing CCRT, and the prognostic power surpassed other CA19-9 variables including initial and post-CCRT values.
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References
Koprowski H, Steplewski Z, Mitchell K et al (1979) Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet 5:957–971
Haas M, Heinemann V, Kullmann F et al (2013) Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy. J Cancer Res Clin Oncol 139:681–689
Bauer TM, El-Rayes BF, Li X et al (2013) Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy. Cancer 119:285–292
Winter JM, Yeo CJ, Brody JR (2013) Diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. J Surg Oncol 107:15–22
Bergquist JR, Puig CA, Shubert CR et al (2016) Carbohydrate antigen 19-9 elevation in anatomically resectable, early-stage pancreatic cancer is independently associated with decreased overall survival and an indication for neoadjuvant therapy: a national cancer database study. J Am Coll Surg 223:52–65
Nazli O, Bozdag AD, Tansug T et al (2000) The diagnostic importance of CEA and CA 19-9 for the early diagnosis of pancreatic carcinoma. Hepato-gastroenterology 47:1750–1752
Ni XG, Bai XF, Mao YL et al (2005) The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer. Eur J Surg Oncol 31:164–169
Goonetilleke KS, Siriwardena AK (2007) Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol 33:266–270
Poruk EK, Gay DZ, Brown K et al (2013) The clinical utility of CA 19-9 in pancreatic adenocarcinoma: diagnostic and prognostic updates. Curr Mol Med 13:340–351
Schlieman MG, Ho HS, Bold RJ (2003) Utility of tumor markers in determining resectability of pancreatic cancer. Arch Surg 138:951–956
Kondo N, Murakami Y, Uemura K et al (2010) Prognostic impact of perioperative serum CA 19-9 levels in patients with resectable pancreatic cancer. Ann Surg Oncol 17:2321–2329
Boone BA, Steve J, Zenati MS et al (2014) Serum CA 19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma. Ann Surg Oncol 21:4351–4358
Tzeng CW, Balachandran A, Ahmad M et al (2014) Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer. HPB (Oxford) 16:430–438
Ballehaninna UK, Chamberlain RS (2011) Serum CA 19-9 as a biomarker for pancreatic cancer − a comprehensive review. Indian J Surg Oncol 2:88–100
Locker GY, Hamilton S, Harris J et al (2006) ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol 24:5313–5327
Mattes MD, Cardinal JS, Jacobson GM (2016) Delayed radiation-induced inflammation accompanying a marked carbohydrate antigen 19-9 elevation in a patient with resected pancreatic cancer. Radiat Oncol J 34:156–159
Berger AC, Garcia M, Hoffman JP et al (2008) Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol 26:5918–5922
Vainshtein JM, Schipper M, Zalupski MM et al (2013) Prognostic significance of carbohydrate antigen 19-9 in unresectable locally advanced pancreatic cancer treated with dose-escalated intensity modulated radiation therapy and concurrent full-dose gemcitabine: analysis of a prospective phase 1/2 dose escalation study. Int J Radiat Oncol Biol Phys 86:96–101
Koom WS, Seong J, Kim YB et al (2009) CA 19-9 as a predictor for response and survival in advanced pancreatic cancer patients treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys 73:1148–1154
Lausen B, Schumacher M (1992) Maximally selected rank statistics. Biometrics 48:73–85
Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267–277
Shaib WL, Ip A, Cardona K et al (2016) Contemporary management of borderline resectable and locally advanced unresectable pancreatic cancer. Oncologist 21:178–187
Huguet F, Andre T, Hammel P et al (2007) Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol 25:326–331
Hammel P, Huguet F, van Laethem JL et al (2016) Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial. JAMA 315:1844–1853
Choi Y, Oh DY, Kim K et al (2015) Concurrent chemoradiotherapy versus chemotherapy alone for unresectable locally advanced pancreatic cancer: a retrospective cohort study. Cancer Res Treat 48:1045–1055
Chen Y, Sun XJ, Jiang TH et al (2013) Combined radiochemotherapy in patients with locally advanced pancreatic cancer: a meta-analysis. World J Gastroenterol 19:7461–7471
Arvold ND, Ryan DP, Niemierko A et al (2012) Long-term outcomes of neoadjuvant chemotherapy before chemoradiation for locally advanced pancreatic cancer. Cancer 118:3026–3035
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. This article does not contain any studies with animals performed by any of the authors.
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Kim, YJ., Koh, H.K., Chie, E.K. et al. Change in carbohydrate antigen 19-9 level as a prognostic marker of overall survival in locally advanced pancreatic cancer treated with concurrent chemoradiotherapy . Int J Clin Oncol 22, 1069–1075 (2017). https://doi.org/10.1007/s10147-017-1129-7
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DOI: https://doi.org/10.1007/s10147-017-1129-7