Science1 publisher2 min readPublished
Platinum chemotherapy left hundreds of adult-type mutations in children's healthy liver cells
A study in Science compared liver and blood samples from children treated with platinum for hepatoblastoma with samples from children given other therapies. The platinum-exposed tissue carried mutations normally seen in adult livers.
The Scientist · Science desk
What happened
- A study published Thursday in the journal Science examined the long-term effects of platinum chemotherapy in children treated for hepatoblastoma, a rare liver cancer most often diagnosed in childhood.
- Those results were compared against samples taken from children who had been given different treatments.
- Samples exposed to platinum carried hundreds of mutations of a kind usually found in adult livers, making the treated children's liver cells resemble those of adults.
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Why it matters
- constraint A mutation count is not an incidence rate, so no surveillance schedule for these survivors follows from the result as reported.
- decision Oncologists weighing platinum against other regimens now have a measured biological cost on one side of the comparison and still no risk figure to set against a cure rate.
- capability Sequencing healthy tissue taken during treatment gives clinicians a readout of collateral damage long before a second tumor could appear.
The comparison is what makes the result readable. Children in the study had platinum therapy and then surgery to remove the tumor, and the researchers took healthy liver tissue, cancerous liver tissue and blood from them [4]. They then compared those results against samples from children who had been given different treatments [5].
Without that second group, a pile of mutations in a treated child's liver could be attributed to the disease, to the surgery, or to nothing in particular about childhood liver tissue that anyone had bothered to measure. With it, you can see whether the untreated children's samples carry the same pattern.
The platinum-exposed samples carried hundreds of mutations of a kind usually found in adult livers, and STAT's account of the work describes the effect as platinum aging the treated children's liver cells so that they resemble adult cells [6][7]. The study was published Thursday in Science [1].
The thing this does not tell you is how many of these children will get a second cancer. STAT's report on the study gives no cohort size, no per-patient mutation burden and no quantified risk estimate; "hundreds of mutations" is the only quantity in it [8]. Mutations in healthy tissue are the mechanism you would expect to sit upstream of a later tumor.
The clinical stakes cut both ways. Hepatoblastoma is a rare liver cancer, most often diagnosed in childhood [3]. STAT reported that platinum-based treatment for children with certain cancers can be a lifeline, while also mutating healthy cells and potentially raising the risk of new cancers later in life [2]. A cure rate and a mutation count are not in the same units, so this finding cannot be traded against the first one in a treatment decision.
The finding is useful after treatment. The measurement came from tissue that was removed during treatment, which means the damage is legible at the time it happens rather than years later in a survivorship clinic. STAT said its full report covers what the study means for long-term monitoring and treatment [9].
What to watch
- The paper's cohort size and whether mutation burden scaled with cumulative platinum dose.
- Follow-up that links mutation burden measured at treatment to second cancers actually diagnosed in these survivors.
- Whether the same adult-type mutation pattern turns up in children given platinum for cancers other than hepatoblastoma.