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Luis Jara-Palomares, MD, PhD; Remedios Otero, MD, PhD; David Jimenez, PhD; Juan Manuel Praena-Fernandez, PhD; Teresa Elias-Hernandez, MD, PhD; Manuel Monreal, MD, PhD
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FINANCIAL/NONFINANCIAL DISCLOSURES: See earlier cited article for author conflicts of interest.

aMedical Surgical Unit of Respiratory Diseases, Virgen del Rocio Hospital, Seville, Spain

bInstituto de Biomedicina de Sevilla, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Seville, Spain

cRespiratory Department, Ramón y Cajal Hospital, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain

dStatistics, Methodology and Research Evaluation Unit, Andalusian Public Foundation for Health Research Management, Hospital Virgen del Rocío, Seville, Spain

eDepartment of Internal Medicine, Hospital Universitari Germans Trias i Pujol de Badalona, Barcelona, Universidad Católica de Murcia, Spain

CORRESPONDENCE TO: Luis Jara-Palomares, MD, PhD, Medical Surgical Unit of Respiratory Diseases, Hospital Virgen del Rocío, CIBERES, Av. Manuel Siurot s/n, Seville, Spain 41013


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(3):728-729. doi:10.1016/j.chest.2016.11.038
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We thank Drs Ferreyro et al for their interest in our article, their insightful comments, and the opportunity to reply. Ferreyro et al published a prognostic score with a final sample of 540 patients with VTE in 2013. Of these patients, 349 (two-thirds) composed the derivation cohort and 191 patients the validation cohort. In the derivation cohort, there were 32 cancers (9.2%) diagnosed during 1 year of follow-up. Moreover, they included a secondary analysis evaluating a combined outcome of cancer or death to address the possibility that death might occur before the identification of an occult cancer. In our opinion, this analysis should be taken with caution, because it is very difficult to assume that all deaths are secondary to occult cancer. In our study, 444 patients (7.6%; 95% CI, 6.90-8.28) were diagnosed with cancer beyond the first 30 days with a follow-up 2 years. One of the major differences with the study by Ferreyro et al is the sample size. As we know, the choice of an adequate sample size for a Cox regression analysis is generally based on the rule of thumb derived from simulation studies of a minimum of 10 events per variable. In the multivariate model, the authors included 3 variables, obtaining for previous VTE ß: 64 (95 CI%, 7.07-579). This large CI suggests that these data are not robust, mostly resulting from few events.

There is some controversy on the influence of prior VTE on the risk of occult cancer. Ferreyro et al found that it increased the risk for occult cancer, but our study revealed the contrary. In a cohort with 854 patients with VTE (of whom 33 had occult cancer), Ihaddadene et al found that prior provoked VTE was associated with an increased risk of occult cancer (hazard ratio, 3.20; 95% CI, 1.19-8.62, P = .022).

Recent surgery has been associated with a lower risk for occult cancer in 2 studies., Older age increased the risk for occult cancer in 3 studies.,, We found chronic lung disease to also be associated with an increased risk and Ihaddadene et al found an association with smoking status, which are closely related. Our data provide with more robust results because the amount of patients with occult cancer is higher and we included more variables, allowing analysis of confounding factors. These similarities should encourage us to get an external validation and search a higher risk population: that is the first step in any screening process.

References

Ferreyro B.L. .Angriman F. .Giunta D. .et al Predictive score for estimating cancer after venous thromboembolism: a cohort study. BMC Cancer. 2013;13:352- [PubMed]journal. [CrossRef] [PubMed]
 
Jara-Palomares L. .Otero R. .Jimenez D. . RIETE investigatorset al Development of a risk prediction score for occult cancer in patients with VTE. Chest. 2017;151:564-571 [PubMed]journal
 
Ogundimu E.O. .Altman D.G. .Collins G.S. . Adequate sample size for developing prediction models is not simply related to events per variable. J Clin Epidemiol. 2016;76:175-182 [PubMed]journal. [CrossRef] [PubMed]
 
Ihaddadene R. .Corsi D.J. .Lazo-Langner A. .et al Risk factors predictive of occult cancer detection in patients with unprovoked venous thromboembolism. Blood. 2016;127:2035-2037 [PubMed]journal. [CrossRef] [PubMed]
 
Beaber E.F. .Kim J.J. .Schapira M.M. . Population-based Research Optimizing Screening through Personalized Regimens Consortiumet al Unifying screening processes within the PROSPR consortium: a conceptual model for breast, cervical, and colorectal cancer screening. J Natl Cancer Inst. 2015;107:djv120- [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Ferreyro B.L. .Angriman F. .Giunta D. .et al Predictive score for estimating cancer after venous thromboembolism: a cohort study. BMC Cancer. 2013;13:352- [PubMed]journal. [CrossRef] [PubMed]
 
Jara-Palomares L. .Otero R. .Jimenez D. . RIETE investigatorset al Development of a risk prediction score for occult cancer in patients with VTE. Chest. 2017;151:564-571 [PubMed]journal
 
Ogundimu E.O. .Altman D.G. .Collins G.S. . Adequate sample size for developing prediction models is not simply related to events per variable. J Clin Epidemiol. 2016;76:175-182 [PubMed]journal. [CrossRef] [PubMed]
 
Ihaddadene R. .Corsi D.J. .Lazo-Langner A. .et al Risk factors predictive of occult cancer detection in patients with unprovoked venous thromboembolism. Blood. 2016;127:2035-2037 [PubMed]journal. [CrossRef] [PubMed]
 
Beaber E.F. .Kim J.J. .Schapira M.M. . Population-based Research Optimizing Screening through Personalized Regimens Consortiumet al Unifying screening processes within the PROSPR consortium: a conceptual model for breast, cervical, and colorectal cancer screening. J Natl Cancer Inst. 2015;107:djv120- [PubMed]journal. [CrossRef] [PubMed]
 
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