A scientific breakthrough has enabled experts to predict relapse in a common childhood cancer and means doctors can tailor treatment for each individual child and improve prognosis.

Researchers at Newcastle University in the U.K. say that experts can identify the time, nature, and outcome of medulloblastoma relapse from the biology of the disease at diagnosis and the initial therapy received. Their study “Time, pattern, and outcome of medulloblastoma relapse and their association with tumor biology at diagnosis and therapy: a multicenter cohort study”, published today in The Lancet Child & Adolescent Health, shows that different biological and treatment groups within the disease relapse at different times and with different patterns of spread throughout the body.

“We aimed to establish whether the clinical and molecular characteristics of the disease at diagnosis are associated with the nature of relapse and subsequent disease course, and whether these associations could inform clinical management,” write the investigators.

“In this multicenter cohort study we comprehensively surveyed the clinical features of medulloblastoma relapse (time to relapse, pattern of relapse, time from relapse to death, and overall outcome) in centrally reviewed patients who relapsed following standard upfront therapies, from 16 U.K. Children’s Cancer and Leukemia Group institutions and four collaborating centers. We compared these relapse-associated features with clinical and molecular features at diagnosis, including established and recently described molecular features, prognostic factors, and treatment at diagnosis and relapse.

“This study suggests that the nature and outcome of medulloblastoma relapse are biology and therapy dependent, providing translational opportunities for improved disease management through biology-directed disease surveillance, post-relapse prognostication, and risk-stratified selection of second-line treatment strategies.”

Medulloblastoma is the most common malignant brain tumors in children and relapse following initial treatment (surgery, radiotherapy, and chemotherapy) has a grave prognosis.

Around 70 children are diagnosed with the cancer each year in the U.K. Relapse occurs in around 30% of children, usually within five years of diagnosis.

The Newcastle research identifies which patients are most at risk of continuing problems with the disease and provides the ability to fine-tune treatment and surveillance to improve the child’s prognosis.

Steve Clifford, PhD, director of Newcastle University’s Centre for Cancer, who led the research, said the findings can be applied immediately in medical clinics to help disease monitoring, advance treatment decisions and improve quality of life after relapse.

“Our research is a very exciting development for the treatment of medulloblastoma patients and it will help improve clinical outcomes,” he explained. “Our study allowed us to undertake biology-directed disease surveillance after initial treatment, in other words to gather and analyze a large amount of data on patients’ tumors, looking out for particular types of relapse in particular groups of patients.”

This revealed, “that some patient biological groups relapse later and therefore need to be monitored longer as it is not a one-size-fits-all approach to tackling this kind of brain tumor,” Clifford continued. “Our findings also mean that we can now predict the course of the disease following a relapse and tailor treatments, enabling us to improve how we manage these patients through more personalized approaches based on understanding their individual disease.”

For the study, 247 young patients around the globe with relapsed medulloblastoma were monitored.

“For a while we thought these differences in medulloblastoma relapse might exist,” Clifford said. “To test this we gathered the largest set of data worldwide on these relapsed patients to allow us to investigate possible relationships and define the nature of the cancer accurately for clinical application.

“We now need to understand the biological mechanisms which underlie these findings, and whether these give rise to opportunities to develop new, more effective therapies for the disease.”

Case study

Four-year-old Evan Wharton was diagnosed with medulloblastoma at the age of 15 months following severe balance problems. Within 24 hours of the discovery, Evan spent nine hours in surgery at Newcastle’s Great North Children’s Hospital to remove a brain tumor the size of a golf ball.

Months of chemotherapy followed and in September 2018 he was given all clear. But 10 months later, his cancer relapsed; more surgery and a course of proton therapy

In October this year, Evan had a brain scan to monitor his health and there was no sign of the cancer. He has hearing problems, is not yet walking or talking, but is back at nursery.

“It is amazing and encouraging to hear of this breakthrough by scientists at Newcastle University,” says Lindsey Sparrow, Evan’s mother. “Evan has a lot of long-term health issues due to the type of treatment he received which, yes, saved his life but has also altered his life.’

With more tailor-based options available, this will hopefully lessen the long-term side effects and harsh treatments that children have to endure.

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