Venous Thrombotic Events Are Independently Associated with Inferior Survival Outcome in Pediatric Cancer Patients: A Multicenter Study

Abstract

Background: Venous thrombotic events (VTE) are well recognized complications in pediatric oncology patients. Although risk factors for VTE have been studied the association of VTE with survival in pediatric cancer patients has not been well studied. We hypothesized that pediatric oncology patients who experienced VTE have significantly inferior survival outcome as compared to patients who did not experience VTE.Aim: To determine the association of VTE with survival outcome in pediatric oncology patients.Methods: The population studied were oncology patients from 2000-2015 in Atlantic Canada: 3 Maritime provinces (population= 1.8 million) and from the province of Newfoundland and Labrador (population= 530,000). All pediatric oncology patients from the Maritimes (Nova Scotia, New Brunswick and Prince Edward Island) are treated at the IWK Health Centre (IWK) in a shared care model with regional provincial hospitals. All pediatric oncology patients in Newfoundland and Labrador are treated at the Janeway Children's Health and Rehabilitation Centre (Janeway). This provided a population-based cohort of the total pediatric oncology patients in the 4 Atlantic provinces. Research Ethics Board approval was obtained from each institution.A database of all pediatric oncology patients treated at the IWK was created by amalgamating data from (i) Pediatric oncology hospital database (ii) Cancer in Young People in Canada registry (CYP-C) (iii) pharmacy database and (iv) hospital health records. A database of pediatric oncology patients treated at the Janeway was amalgamated from (i) Janeway written logs (ii) Hospital health records and (iii) CYP-C.Data on patient demographics, diagnosis and date of diagnosis were extracted. Status of every patient, date of last visit or date of death, on or up to December 31, 2015 was reviewed. Brain tumor patients were excluded due to the low incidence of thrombosis.The association between VTE and survival was examined using Kaplan-Meier plots and Cox Proportional Hazards regression. An exploratory survival tree analysis indicated an interaction between cancer type and VTE, and the analysis was therefore stratified by cancer type as group 1: leukemia, lymphoma, other and group 2: sarcoma. Models were adjusted for sex and age at diagnosis. The statistical analysis was performed using R version 3.3.2 and RStudio version 1.0.136.Results: Of the 943 patients included in the study, 70 were diagnosed with thrombosis (7%). The prevalence of thrombosis in group 1 and 2 was 6.9% (n=56) and 10% (n=14) respectively. Cancer types included leukemia (n=356, 38%), lymphoma (n=154, 16%), sarcoma (n=137, 15%), and other (n=296, 31%). Overall mortality was 14%. No patient died directly from VTE. Kaplan-Meier plots showed a showed inferior survival in the presence of VTE in patients in both groups 1 and 2 (Figure 1). Cox proportional hazard model showed a significantly decreased survival for patients in group 1 with a VTE (p<0.001), group 2 without a VTE (p<0.001) and group 2 with a VTE (p<0.001) as compared to patients in group 1 without VTE (Table 1). Patients with a sarcoma did not show a significant difference in patients with and without a VTE due to the overlapping confidence interval (with VTE CI: 4.53 to 20.75, without VTE CI 2.48 to 5.62). Age at diagnosis (p=0.498) and sex (p=0.300) were not associated with survival.Conclusion: In the present study, we demonstrated in a large multi-center population-based cohort of pediatric oncology patients that the survival outcome of patients with leukemia, lymphoma and other types of cancers who develop a VTE is significantly inferior as compared to that of patients who do not develop a VTE. Patients with sarcoma who developed a VTE showed a decrease in survival as compared to those who did not develop VTE. However the results were not statistically significant likely due to the small sample size of these patients. The role of possible confounders such as treatment intensity, chemotherapeutic agents, and central venous catheters were not assessed in the preset study but would be included in future research. Further larger studies are necessary to understand the association between VTE and survival outcome in pediatric oncology patients and determine the prognostic impact of VTE in them. [Display omitted] DisclosuresMoorehead:Baxalta: Honoraria, Speakers Bureau; Bayer: Honoraria; Pfizer: Speakers Bureau; Octapharma: Honoraria; Bioverativ: Honoraria.