An analysis of over 34,000 participants in the federally funded Childhood Cancer Survivor Study shows improvement in late mortality achieved over three decades.

Among five-year survivors, all-cause mortality at 15 years of diagnosis dropped from 12.4% to 6%.

This improvement is attributed in part to changes in care that reduced the risk of mortality related to late effects of paediatric cancer treatment, such as subsequent malignancies and cardiac and lung disease.

“Fifty years ago, only one in five children would survive cancer, and today over 80% are alive five years after diagnosis. Yet, these survivors still grow up with increased risk of dying from late effects, like heart disease and second cancers,” said the lead study author Gregory T. Armstrong, MD, MSCE, a paediatric oncologist at St. Jude Children’s Research Hospital.

“Now, we’ve not only helped more children survive their primary cancer, but we’ve also extended their overall lifespan by reducing the overall toxicity of treatment in more modern eras.”

Prior research has shown that up to 18% of five-year childhood cancer survivors die within 30 years of diagnosis.

The deaths are due to three major causes: progression or recurrence of the primary cancer, external causes (accidents, suicide), and other health-related causes.

The latter category primarily consists of mortality due to late effects of cancer therapy.

While the deaths from cancer progression or recurrence plateau over time, mortality from other health-related causes increases with each year survived since diagnosis.

The study analysed data from the Childhood Cancer Survivor Study, which evaluates long-term health outcomes in five year survivors of childhood cancer diagnosed between 1970 and 1999.

Thirty-one US and Canadian hospitals currently participate in the study.

The cohort, initiated in 1994, is an NIH-funded resource ─ any researcher interested in survivorship can request access to the data or banked biologic specimens.

In the current analysis, the National Death Index (a central computerised index of death record information on file in the State vital statistics offices) was used to assess mortality among 34,043 five-year childhood cancer survivors.

All were younger than 21 years at diagnosis.

Major impact from scaling back treatment for many common paediatric cancers

On average, the five-year survivors were followed for 21 years after their diagnosis.

The study found that 3,958 (12%) patients had died during that period, and 41% (1,618) of those deaths were from other health-related causes that include death due to late effects of cancer therapy.

Additionally, all-cause mortality was halved over these two decades – 12.4% of patients diagnosed in the early 1970s died within 15 years of diagnosis, compared to only 6% of those diagnosed in the early 1990s.

During the same time period, the cumulative incidence of deaths from other health-related causes decreased from 3.5% to 2.1%.

Survivors diagnosed in more recent years had a statistically significant lower risk of dying from other health- related causes (including second cancer, and heart or lung disease).

The study team noted that reductions in mortality were due to fewer deaths related to late effects and were most striking among survivors of Wilms tumour, Hodgkin lymphoma, and acute lymphoblastic leukemia (ALL).

Cardiac deaths significantly decreased among survivors of all three cancers.

Deaths due to secondary cancer decreased among Wilms tumor survivors only.

These results are driven by doctors’ gradual refinement of treatment by reducing the intensity of therapy for many paediatric cancers with favourable prognosis, without compromising effectiveness.

For example, in the 1970s, 86% of patients with ALL received cranial radiotherapy, compared to only 22% in the 1990s.

Radiotherapy dose has also been reduced among patients with Hodgkin lymphoma and Wilms tumor.

Furthermore, cumulative dose exposure of anthracycline, a chemotherapy drug strongly associated with cardiotoxicity, has been reduced across these three diseases.

“While the modernisation of cancer therapy has probably made the most significant difference, improvements in supportive care for survivors, and screening, detection, and treatment of late effects, like new cancers and heart and lung disease, have played an important role in extending their lifespan as well,” added Dr Armstrong.

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Source: ASCO