ABSTRACT
In pediatric oncology, the diagnosis of a hematologic malignancy and presence of a central venous catheter (CVC) have been identified as significant risk factors for the development of a venous thromboembolism (VTE). There remain little data regarding CVC factors associated with CVC-related VTE. Using the VTE and oncology database in a quaternary care center, a retrospective cohort study was conducted in children below 18 years old with hematologic cancer from November 5, 2012 to April 4, 2016. Patient, CVC factors, and VTE occurrence were analyzed to identify significant patient and CVC factors associated with the development of clinically identified CVC-related VTE. Utilizing the χ, Mann-Whitney, and the Fisher exact tests, patient factors were compared across VTE yes/no groups. Of the 198 study patients, 22 VTE cases were identified. Eighteen VTE events were CVC-associated, occurring in 9% of study population. Peripherally inserted central catheter lines and older ages were associated with VTE. The use of tissue-plasminogen activator for CVC occlusion was associated with decreased VTE rates, suggesting a protective potential.
Subject(s)
Central Venous Catheters/adverse effects , Hematologic Neoplasms/epidemiology , Thromboembolism/epidemiology , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Hematologic Neoplasms/drug therapy , Humans , Male , Retrospective Studies , Thromboembolism/etiology , Thromboembolism/prevention & control , Tissue Plasminogen Activator/administration & dosageABSTRACT
Purpose: Preclinical models have shown that the effectiveness of GL-ONC1, a modified oncolytic vaccinia virus, is enhanced by radiation and chemotherapy. The purpose of this study was to determine the safety of GL-ONC1 when delivered intravenously with chemoradiotherapy to patients with primary, nonmetastatic head and neck cancer.Experimental Design: Patients with locoregionally advanced unresected, nonmetastatic carcinoma of the head/neck, excluding stage III-IVA p16-positive oropharyngeal cancers, were treated with escalating doses and cycles of intravenous GL-ONC1, along with radiotherapy and chemotherapy. The primary aims were to define the MTD and dose-limiting toxicities, and to recommend a dose for phase II trials.Results: Between May 2012 and December 2014, 19 patients were enrolled. The most frequent adverse reactions included grade 1-2 rigors, fever, fatigue, and rash. Grade 3 adverse reactions included hypotension, mucositis, nausea, and vomiting. In 2 patients, the rash was confirmed as viral in origin by fluorescence imaging and viral plaque assay. In 4 patients, viral presence in tumor was confirmed on midtreatment biopsy by quantitative PCR. In 1 patient, live virus was confirmed in a tongue tumor 7 days after receiving the first dose of virus. The MTD was not reached. With median follow-up of 30 months, 1-year (2-year) progression-free survival and overall survival were 74.4% (64.1%) and 84.6% (69.2%), respectively.Conclusions: Delivery of GL-ONC1 is safe and feasible in patients with locoregionally advanced head/neck cancer undergoing standard chemoradiotherapy. A phase II study is warranted to further investigate this novel treatment strategy. Clin Cancer Res; 23(19); 5696-702. ©2017 AACR.
Subject(s)
Carcinoma, Squamous Cell/drug therapy , Cisplatin/administration & dosage , Head and Neck Neoplasms/drug therapy , Oncolytic Virotherapy , Adult , Aged , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Cisplatin/adverse effects , Combined Modality Therapy , Disease-Free Survival , Female , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/radiotherapy , Humans , Male , Middle Aged , Neoplasm Staging , Oncolytic Viruses/genetics , Vaccinia virus/geneticsABSTRACT
OBJECTIVES: To identify patient, hospital, and central venous catheter factors that may influence the use of low-dose heparin infusion for central venous catheter patency in critically ill children. DESIGN: Secondary analysis of an international multicenter observational study. SETTING: Fifty-nine PICUs over four study dates in 2012, involving seven countries. PATIENTS: Children less than 18 years old with a central venous catheter who were admitted to a participating unit and enrolled in the completed Prophylaxis against Thrombosis Practice study were included. All overflow patients were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 2,484 patients in the Prophylaxis against Thrombosis Practice study, 1,312 patients had a central venous catheter. Five hundred seven of those patients used low-dose heparin infusion. The frequency of low-dose heparin infusion was compared across various patient, hospital, and central venous catheter factors using chi-square, Mann-Whitney U, and Fisher exact tests. In the multivariate analysis, age was not a significant factor for low-dose heparin infusion use. Patients with pulmonary hypertension had decreased low-dose heparin infusion use, whereas those with active surgical or trauma diagnoses had increased low-dose heparin infusion use. All centrally inserted central venous catheters were more likely to use low-dose heparin infusion when compared with peripherally inserted central venous catheters. The Asia-Pacific region showed increased low-dose heparin infusion use, along with community hospitals and smaller ICUs (< 10 beds). CONCLUSIONS: Patient, central venous catheter, and hospital factors are associated with the use of low-dose heparin infusion in critically ill children. Further study is needed to evaluate the efficacy and persistence of low-dose heparin infusion use.