Dataset Information

Development and Validation of a Clinical Score for Cardiovascular Risk Stratification of Long-Term Childhood Cancer Survivors.

ABSTRACT:

Background

Long-term childhood cancer survivors (CCS) are at increased risk of adverse cardiovascular events; however, there is a paucity of risk-stratification tools to identify those at higher-than-normal risk.

Subjects, materials, and methods

This was a population-based study using data from the Surveillance, Epidemiology, and End Results Program (1973-2013). Long-term CCS (age at diagnosis ?19 years, survival ?5 years) were followed up over a median time period of 12.3 (5-40.9) years. Independent predictors of cardiovascular mortality (CVM) were combined into a risk score, which was developed in a derivation set (n?=?22,374), and validated in separate patient registries (n?=?6,437).

Results

In the derivation registries, older age at diagnosis (?10 years vs. reference group of 1-5 years), male sex, non-white race, a history of lymphoma, and a history of radiation were independently associated with an increased risk of CVM among long-term CCS (p?p?p_log-rank?p_log-rank?ConclusionWe propose a simple risk score that can be applied in everyday clinical practice to identify long-term CCS at increased cardiovascular risk, who may benefit from early cardiovascular screening, and risk-reduction strategies.

Implications for practice

Childhood cancer survivors (CCS) are known to be at increased cardiovascular risk. Currently available prognostic tools focus on treatment-related adverse events and late development of congestive heart failure, but there is no prognostic model to date to estimate the risk of cardiovascular mortality among long-term CCS. A simple clinical tool is proposed for cardiovascular risk stratification of long-term CCS based on easily obtainable information from their medical history. This scoring system may be used as a first-line screening tool to assist health care providers in identifying those who may benefit from closer follow-up and enable timely deployment of preventive strategies.

SUBMITTER: Oikonomou EK

PROVIDER: S-EPMC6156177 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

Development and Validation of a Clinical Score for Cardiovascular Risk Stratification of Long-Term Childhood Cancer Survivors.

Oikonomou Evangelos K EK Athanasopoulou Sofia G SG Kampaktsis Polydoros N PN Kokkinidis Damianos G DG Papanastasiou Christos A CA Feher Attila A Steingart Richard M RM Oeffinger Kevin C KC Gupta Dipti D

The oncologist 20180328 8

<h4>Background</h4>Long-term childhood cancer survivors (CCS) are at increased risk of adverse cardiovascular events; however, there is a paucity of risk-stratification tools to identify those at higher-than-normal risk.<h4>Subjects, materials, and methods</h4>This was a population-based study using data from the Surveillance, Epidemiology, and End Results Program (1973-2013). Long-term CCS (age at diagnosis ≤19 years, survival ≥5 years) were followed up over a median time period of 12.3 (5-40.9 ...[more]

PMID: 29593100

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Project description:Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTS) may provide important insight into the biology of GBM. We identified 7 patients with GBM treated at Memorial Sloan-Kettering Cancer Center (MSKCC) with survival greater than 48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTS in two independent cohorts (TCGA and REMBRANDT) and analyzed the transcriptomal characteristics of these LTS. The median overall survival of our cohort was 62.5 months. LTS were distributed between the proneural (n=2), neural (n=2), classical (n=2) and mesenchymal (n=1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identity. The majority of the MSKCC LTS (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutations, and IDH mutation occurred in a minority of the TCGA LTS as well. A set of 42 genes was found to be differentially expressed in the MSKCC and TCGA LTS. While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression. All tumors (n = 7) were obtained following surgical resection at the MSKCC as part of routine clinical care, and snap frozen. Tumors were obtained in accordance with Institutional Review Board policies at the MSKCC. Each sample was examined histologically by 3 independent neuropathologists and confirmed to be World Health Organization (WHO) grade IV glioma (GBM). Before analysis, tumors were sectioned and microdissected. Genomic DNA or RNA was extracted using the DNeasy kit (Qiagen) or RNeasy Lipid Tissue Mini Kit (Qiagen) as per the manufacturer’s instructions. Expression analysis of tumors was performed using the Affymetrics U133 2.0 microarray (Affymetrix). Affymetrix CEL files were imported into the Partek Genomics Suite (Partek). The TCGA gene expression data (HT-HG-U133A) was accessed from the TCGA data repositories (http://cancergenome.nih.gov, date of download 12/2013).

Dataset Information

Development and Validation of a Clinical Score for Cardiovascular Risk Stratification of Long-Term Childhood Cancer Survivors.

Background

Subjects, materials, and methods

Results

Implications for practice

Publications

Development and Validation of a Clinical Score for Cardiovascular Risk Stratification of Long-Term Childhood Cancer Survivors.

Similar Datasets

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