Global Health Researchers Finding Ways to Improve Children's Cancer Survival Rates

Every child with cancer deserves the greatest opportunity to be cured, no matter where in the world they live. This overarching sense of purpose took Julianne Burns, MD, a third-year pediatric Infectious Diseases fellow, from Children’s Hospital of Philadelphia to the Hospital Infantil Dr. Robert Reid Cabral (HIRRC) in the Dominican Republic for four weeks this summer to conduct much needed infectious disease research.

Her goal is to gain a better understanding of some of the disparities in pediatric cancer patients’ outcomes in low- and middle-income countries. Although survival rates continue to improve for children diagnosed with cancer in high-income countries, increasingly intensive chemotherapy regimens predispose children to frequent life-threatening opportunistic infections. In low-resource settings, death resulting from infection in pediatric cancer patients is up to 10 times higher than in high-income countries.

“Place matters in terms of patients’ outcomes associated with these infections,” Dr. Burns said.

The clinical oncology team at HIRRC, the largest children’s hospital in the Dominican Republic, has a longstanding partnership with Stephen Hunger, MD, chief of the Division of Oncology at CHOP and director of the Center for Childhood Cancer Research. They are the primary provider of oncologic care for a large population of children in the southern half of the Dominican Republic and are part of the Public Ministry of Health system. The dedicated oncologists at HIRRC, led by Dr. Dominga Reyes, are keenly interested in reducing their pediatric patients’ risk for infection requiring hospitalization and infection-related mortality, but due to a high clinical volume, their time to perform research is limited. To hasten improvements in care, Dr. Reyes and her team partner with various groups in the U.S. including Dr. Hunger, St. Jude Global, and the Keira Grace Foundation, and locally with La Fundación Amigos Contra el Cáncer Infantil.

Dr. Hunger enlisted the help of Andrew Steenhoff, MBBCh, DCH, medical director of CHOP’s Global Health Center, which aims to improve pediatric health by addressing topics of importance to the well-being of children in low and middle-income countries. Dr. Steenhoff is also a core faculty member at Clinical Futures, a CHOP Research Institute Center of Emphasis, an attending physician in the Division of Infectious Diseases, and Dr. Burns’ mentor.

Connecting Dr. Burns’ interests in infections in immunocompromised patients and global health, Dr. Steenhoff thought it would be an ideal research study for her to undertake. The first step was to determine the epidemiology of infections in children with cancer in the Dominican Republic, and understand which types of infections are causing poor outcomes, with the goal of identifying interventions to help these children survive.

The project also is a perfect fit for the Master of Science in Clinical Epidemiology (MSCE) program at the Perelman School of Medicine at the University of Pennsylvania that Dr. Burns is pursuing in conjunction with her fellowship. Her MSCE mentor, Brian Fisher, DO, MPH, MSCE, director of the Pediatric Infectious Disease Fellowship Training Program at CHOP and core faculty member of Clinical Futures' Pediatric Infectious Diseases Epidemiology and Antimicrobial Stewardship research group, helped to design the study.

Dr. Burns’ project is based on data collected from a retrospective chart review looking at newly diagnosed pediatric leukemia patients who had been admitted to HIRRC in a two-year period, July 2015 to June 2017. A big challenge of the study is that the hospital does not have an electronic medical record system, so Dr. Burns and F. Jay Garcia, a medical student at the Perelman School of Medicine at the University of Pennsylvania and research associate for this project, traveled to the Dominican Republic to work with Dr. Reyes and her team at HIRRC to systematically abstract data from the oncology admissions logbook, admissions charts, and culture logbooks to inform the aims of the study.

“Importantly, we looked at whether or not an infection was diagnosed during that hospitalization and if there were microbiological studies that supported the diagnosis,” Dr. Burns said. “We also collected data on the antibiotics that the patients received. And we looked at their clinical course — if they needed escalation to care in the ICU — and outcomes, in terms of if they were living at the end of the study period or died, and if the cause of death was infection-related or not.”

Dr. Burns compiled the results in REDCap^TM, a secure data collection tool, and she is in the process of analyzing the data. The results will be the first to describe the epidemiology, outcomes, and risk factors for inpatient infection in pediatric leukemia patients at HIRRC, including infections acquired prior to hospitalization or during the hospital stay. An overview of the data will be presented as a poster at the 10^th Annual Pediatric Global Health Conference being held Oct. 5 and 6, 2018 at the Colket Translational Research Building on CHOP’s Raymond G. Perelman Campus.

“Preliminarily, what we’ve found so far is that infection is a major cause of death in this population,” Dr. Burns said. “The overall goal working with our oncology colleagues at Hospital Infantil Dr. Robert Reid Cabral is to identify risk factors associated with infection, and then design ways to reduce infection in this pediatric cancer population, thereby improving outcomes.”

One of those future directions is to create care modification plans to mitigate demographic and socioeconomic risk factors. Dr. Burns met some families who traveled for hours to get to the national children’s hospital so that their children could receive outpatient cancer therapy treatments. While the families expressed tremendous gratitude for the care their children were receiving, they told her about the hardships of missing work for a few weeks at a time, managing care for their other children far away at home, and paying high out-of-pocket expenses for necessary diagnostic testing and medications.

“Retrospective chart review can be tedious, so meeting the families was motivating,” Dr. Burns said. “These personal connections drive your work forward. I greatly admire our collaborators and colleagues in the Dominican Republic who are every day working with these families to help their children get the best treatment, despite financial and social constraints that make a difficult situation even more challenging to cope with.”

Dr. Burns anticipates the study results could also guide and inform the hospital’s development of a sustainable method of tracking infections through an electronic database, strengthen infection prevention measures in the hospital, and refine their antimicrobial stewardship programs. If successful, these interventions could one day be implemented by other pediatric oncology centers in similar low- and middle-income settings.