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While improvements have been made to childhood cancer mortality rates, a recent research study aims to identify how many children die before being able to start treatment, and what interventions can be put in place to improve their chances.
Nearly 8% of childhood cancer deaths in a recent study occurred less than a month after diagnosis, often before treatment could even be started.
The analysis recently published in the Journal of Clinical Oncology reveals that the number of early childhood cancer deaths identified in the study are higher than previous estimates made through clinical trials.
“I was surprised by the number of our patients who die so soon after diagnosis that they’re unable to benefit from the advances that have been made in treatment,” says Adam Green, MD, assistant professor of pediatrics at the University of Colorado School of Medicine in Aurora and attending physician in pediatric hematology/oncology at Children’s Hospital Colorado, and lead author of the study. “I was also surprised by how much more commonly this happens than is reported by clinical trials, indicating that the majority of these patients are likely dying before they can start any treatment, and are also disproportionately not enrolling on trials.”
The study sought to examine why, despite advances in childhood cancer care, some children still die soon after a diagnosis, never making it to treatment or past early interventions.
Researchers used data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program on more than 36,000 patients aged 0 to 19 years who were diagnosed with cancer between 1992 and 2011.
About 1.5% of the children studied died within 1 month of their initial cancer diagnosis, accounting for 7.5% of the total deaths in the entire cohort. Those most at risk of early death were children diagnosed with acute myeloid leukemia (AML), infant acute lymphoblastic leukemia (ALL), hepatoblastoma, and malignant brain tumors. Children aged younger than 1 year at the time of diagnosis also had higher risks of early deaths, as well as children of black or Hispanic ethnicity. Children from counties with lower than median average income levels were found to have higher rates of hematologic cancers, although the percentage of early deaths from hematologic malignancies decreased significantly over the study period.
To date, there has been little research of knowledge about pediatric oncology outcomes outside of clinical trials-an environment in which researchers believe early death may be underreported as these children die before enrollment or become ineligible because of critical illness at the onset of the trial.
Two earlier large-scale studies associated early death in childhood cancer studies with age younger than 1 year; disseminated disease at diagnosis; and certain cancer types such as leukemia, central nervous system (CNS) tumors, liver tumors, and neuroblastoma. Although numerous studies have examined the effect of socioeconomic status on diagnosis and outcomes in pediatric cancer, neither of these 2 studies linked socioeconomic status to a higher risk of early death (defined as death within 1 month of diagnosis).
Compared with those in the cohort who died later after diagnosis, the early death group had higher rates of hematologic cancers (49.9% in the early death group compared with 40.9% who died later) and CNS tumors (27.9% in the early death group compared with 18.3% who died later), and lower rates of solid tumors (22.2% in the early death group compared with 40.7% who died later).
Overall, the researchers found that liver tumors, leukemias, and CNS tumors carried the higher risks of early death when compared with neuroblastoma as a standard, and renal and epithelial cancers carried lower risks of early death. For specific diagnoses, the study revealed that AML, infant ALL, hepatoblastoma, and several types of CNS tumors also carried higher risks of early death than neuroblastoma. Malignant melanoma, Hodgkin lymphoma, osteosarcoma, low-grade glioma, and Wilms tumor carried lower risks of early death than neuroblastoma.
There were no gender differences identified in rates of early death, but the researchers found that infants aged younger than 1 year, children aged 1 to 4 years, and adolescents aged 15 to 19 years had the highest rates of early death.
“Our analysis suggested that while infants who die within a month of diagnosis come equally from all backgrounds, the adolescents to whom this happens are more likely to be of minority race and ethnicity, and to live in disadvantaged areas socioeconomically,” Green says. “This makes me worried that the care these patients are receiving is delayed or inferior compared to other patients.”
In meeting its goal of correctly identifying early death rates, the research team found that early death percentages in this study were consistently higher than early death rates previously reported through clinical trials, ranging from roughly twice the value observed in non-infant ALL to greater by a factor of 12.5 in Wilms tumor.
The study was limited, however, as researchers were not able to determine through the SEER database when during the first month following diagnosis that early deaths actually occurred. The database also didn’t allow researchers to determine the underlying cause of death in early deaths cases. Early deaths did decrease over the study period, and may be attributable to advances in treatment and supportive care.
To combat early death further, the research team recommends better data collection at the time of cancer diagnosis to enable better research and understanding of the causes of early death in childhood cancers, as well as specific initiatives to target risks groups. These interventions might include earlier diagnosis and treatment in high-risk populations, according to the study.
“My hope is that this paper will lead to a better understanding among pediatric oncologists that death before patients can enter treatment is a common event, and which patients (in terms of disease and background) need extra caution right away to prevent this from happening,” Green says. “I also plan to follow up with a prospective study to better identify the problems in the diagnostic process that lead to early death, which will allow us to find ways to address this issue in specific populations, such as public health outreach and education.”