Early increase in circulating carbonic anhydrase IX during neoadjuvant treatment predicts favourable outcome in locally advanced rectal cancer

BMC Cancer

Research Article

Kathrine Røe Redalen¹  Anne Hansen Ree²  Svein Dueland³  Yvonne Andersson⁴  Kjersti Flatmark⁵  Helga Helseth Hektoen⁶ 

[1] Department of Oncology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway;Department of Oncology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway;Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318, Oslo, Norway;Department of Oncology, Oslo University Hospital – Norwegian Radium Hospital, P.O.Box 4950, Nydalen, 0424, Oslo, Norway;Department of Tumour Biology, Oslo University Hospital – Norwegian Radium Hospital, P.O.Box 4950, Nydalen, 0424, Oslo, Norway;Department of Tumour Biology, Oslo University Hospital – Norwegian Radium Hospital, P.O.Box 4950, Nydalen, 0424, Oslo, Norway;Department of Gastroenterological Surgery, Oslo University Hospital – Norwegian Radium Hospital, P.O.Box 4950, Nydalen, 0424, Oslo, Norway;Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318, Oslo, Norway;Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318, Oslo, Norway;Department of Oncology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway;Department of Tumour Biology, Oslo University Hospital – Norwegian Radium Hospital, P.O.Box 4950, Nydalen, 0424, Oslo, Norway;

关键词: Carbonic anhydrase IX;    Chemotherapy;    Metastasis;    Radiotherapy;    Rectal cancer;    Survival;    Tumour microenvironment;   

DOI  :  10.1186/s12885-015-1557-6

 received in 2014-12-07, accepted in 2015-07-14,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundLocally advanced rectal cancer (LARC) comprises heterogeneous tumours with predominant hypoxic components. The hypoxia-inducible metabolic shift causes microenvironmental acidification generated by carbonic anhydrase IX (CAIX) and facilitates metastatic progression, the dominant cause of failure in LARC.MethodsUsing a commercially available immunoassay, circulating CAIX was assessed in prospectively archived serial serum samples collected during combined-modality neoadjuvant treatment of LARC patients and correlated to histologic tumour response and progression-free survival (PFS).ResultsPatients who from their individual baseline level displayed serum CAIX increase above a threshold of 224 pg/ml (with 96 % specificity and 39 % sensitivity) after completion of short-course neoadjuvant chemotherapy (NACT) prior to long-course chemoradiotherapy and definitive surgery had significantly better 5-year PFS (94 %) than patients with below-threshold post-NACT versus baseline alteration (PFS rate of 56 %; p < 0.01). This particular CAIX parameter, ΔNACT, was significantly correlated with histologic ypT0–2 and ypN0 outcome (p < 0.01) and remained an independent PFS predictor in multivariate analysis wherein it was entered as continuous variable (p = 0.04).ConclusionsOur results indicate that low ΔNACT, i.e., a weak increase in serum CAIX level following initial neoadjuvant treatment (in this case two cycles of the Nordic FLOX regimen), might be used as risk-adapted stratification to postoperative therapy or other modes of intensification of the combined-modality protocol in LARC.Trial registrationClinicalTrials.gov NCT00278694

【 授权许可】

Unknown   
© Hektoen et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.