Children with cancer in low-, middle-income nations at higher risk for death amid pandemic

Children with cancer who reside in low- and- middle-income countries had a higher risk for mortality due to any cause than those in high-income countries during the first 9 months of the COVID-19 pandemic, according to study results.

The findings, presented during American Association for Cancer Research Annual Meeting and published simultaneously in BMJ Open, also showed treatment delays, interruptions and modifications occurred predominantly in lower- to middle-income countries, suggesting the pandemic may have worsened disparities in health care systems throughout the world, researchers wrote.

Rationale and methods

“Childhood cancers have long been missing from the global child health agenda. Although children have curable cancers, they are often fatal without appropriate and timely diagnosis and treatment,” Muhammed Elhadi, MBBCh, physician at University of Tripoli in Libya, told Healio. “In fact, childhood cancers are the second leading cause of noncommunicable disease deaths for pediatric patients around the world. More than 90% of these deaths occur in low- and- middle-income countries. The inordinately high number of person-years of life lost makes pediatric cancer care a global health priority.”

Elhadi and colleagues suspected the COVID-19 pandemic exacerbated the imbalance in pediatric cancer outcomes between low- and middle-income countries and high-income countries.

“There were reports globally on the cancellation of elective health services — including pediatric surgery and radiotherapy, essential outpatient services, shortage of essential medications, delays in diagnosis, hospital inpatient services being overwhelmed and health care staffing issues,” he said.

To investigate further, researchers examined data from 91 hospitals and cancer centers across the world between March and December 2020. The analysis — which they wrote is the largest international cohort study to date to report COVID-19 outcomes for childhood cancers — included 1,660 patients aged younger than 18 years recently diagnosed with or on active treatment for acute lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, Wilms’ tumor, sarcoma, retinoblastoma, glioma, medullablastoma or neuroblastoma.

Thirty-day and 90-day all-cause mortality served as primary outcomes. Secondary outcomes included identification of changes in cancer services, 30-day COVID-19 infection rate and number of patients managed palliatively.

Key findings

Overall, 66.5% of patients resided in low- and- middle-income countries and 33.5% in high-income countries. Among all children, 219 had their cancer treatments delayed, interrupted or modified due to the COVID-19 pandemic. Univariate and multivariate analyses showed children in lower- and middle-income countries had greater odds of delays or alterations to treatment.

Within the first 30 days of the study, two patients (0.4%) from high-income countries died compared with 45 patients (4.1%) from low- and- middle-income countries. At the 90-day follow-up, five patients (0.9%) vs. 66 patients (6%) had died.

Researchers reported that children in low- to middle-income countries had 12.1 (95% CI, 2.93-50.3) times higher odds of death at 30 days and 7.9 (95% CI, 3.2-19.7) times higher odds of death at 90 days than children in high-income countries.

After adjustment for age, sex, weight, tumor grade and stage, they found children residing in low- and- middle-income countries had 15.6 (95% CI, 3.7-65.8) times higher risk for all-cause mortality at 30 days than those in high-income countries. Data prior to the pandemic showed children in low- to middle-income countries had a four times higher likelihood of death.

The researchers reported several limitations of the study, including the fact that it only included children who had already been diagnosed with cancer; they were not able to determine whether deaths were caused by COVID-19, cancer or other causes; and 18% of patients were lost to follow-up at 90 days.

Elhadi said the adverse impact of the pandemic on pediatric oncology services has affected only a minority of patients receiving treatment.

“Most pediatric patients with cancer have continued to receive the standard of care that they would have received prior to the pandemic,” Elhadi said. “This speaks to the adaptability and resilience of health care systems and health care workers globally. The creation of new legislation, increasing the utilization of technology, and optimizing the allocation of resources are some of the commendable efforts that have mitigated the impact of the pandemic on pediatric patients with cancer.”

Implications

Elhadi said the study “illustrates the stark disparities that continue to exist in children’s cancer care and the multiple impacts that the COVID-19 pandemic has had on health care systems across the globe.”

“Our results underscore the need for a renewed assessment of resource requirements during this pandemic and the sharing of approaches that have minimized the negative effects on pediatric cancer care,” he added. “This pandemic has become the defining crisis of our generation, and its ramifications may stretch beyond the acute crisis and have far-reaching consequences for the future. Understanding its true impact, taking on key lessons and identifying vulnerabilities within health systems helps us develop solutions, which will also prove critical on our path toward equitable global pediatric oncology care.”

Data collection in other countries is necessary, Elhadi added.

“Additional qualitative and quantitative research is needed to identify barriers to care and develop innovative solutions to tackle international inequity in children’s health,” he said. “This work will be primarily led by colleagues in low- and- middle-income countries, as ultimately they are best placed to identify local issues and engage regional stakeholders.”