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BMC Cancer. 2016 Jul 25;16:519. doi: 10.1186/s12885-016-2574-9.

Predictive value of vrk 1 and 2 for rectal adenocarcinoma response to neoadjuvant chemoradiation therapy: a retrospective observational cohort study.

Author information

1
Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, 28040, Madrid, Spain.
2
Radiotherapy Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avda Reyes Catolicos, 2, Madrid, 28040, Spain.
3
Pathology Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, Madrid, 28040, Spain.
4
Present address at University Hospital Clinico San Carlos, Profesor Martin Lagos, S/N, Madrid, 28040, Spain.
5
Clinical Biostatistics Unit, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Carretera de Colmenar Viejo km. 9,100, 28034 Madrid, Spain and CIBER of Epidemiology and Public Health (CIBERESP), C/Melchor Fernández Almagro, 3-5, Madrid, Spain.
6
Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, 28040, Madrid, Spain. jesus.garciafoncillas@oncohealth.eu.

Abstract

BACKGROUND:

Neoadjuvant chemoradiotherapy (NACRT) followed by surgical resection is the standard therapy for locally advanced rectal cancer. However, tumor response following NACRT varies, ranging from pathologic complete response to disease progression. We evaluated the kinases VRK1 and VRK2, which are known to play multiple roles in cellular proliferation, cell cycle regulation, and carcinogenesis, and as such are potential predictors of tumor response and may aid in identifying patients who could benefit from NACRT.

METHODS:

Sixty-seven pretreatment biopsies were examined for VRK1 and VRK2 expression using tissue microarrays. VRK1 and VRK2 Histoscores were combined by linear addition, resulting in a new variable designated as "composite score", and the statistical significance of this variable was assessed by univariate and multivariate logistic regression. The Hosmer-Lemeshow goodness-of-fit test and area under the ROC curve (AUC) analysis were carried out to evaluate calibration and discrimination, respectively. A nomogram was also developed.

RESULTS:

Univariate logistic regression showed that tumor size as well as composite score were statistically significant. Both variables remained significant in the multivariate analysis, obtaining an OR for tumor size of 0.65 (95 % CI, 0.45-0.94; p = 0.021) and composite score of 1.24 (95 % CI, 1.07-1.48; p = 0.005). Hosmer-Lemeshow test showed an adequate model calibration (p = 0.630) and good discrimination was also achieved, AUC 0.79 (95 % CI, 0.68-0.90).

CONCLUSIONS:

This study provides novel data on the role of VRK1 and VRK2 in predicting tumor response to NACRT, and we propose a model with high predictive ability which could have a substantial impact on clinical management of locally advanced rectal cancer.

KEYWORDS:

Chemoradiotherapy; Composite score; NACRT; Nomogram; Rectal cancer; Tumor response; VRK1; VRK2

PMID:
27456229
PMCID:
PMC4960836
DOI:
10.1186/s12885-016-2574-9
[Indexed for MEDLINE]
Free PMC Article

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