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ASCO 2015: Reduction in Late Mortality Among Childhood Cancer Survivors Linked to Improvements in Cancer Care

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Key Points

  • Survivors of childhood cancer have significantly reduced late mortality that for the first time can be attributed to fewer deaths from treatment-related causes or from late effects of the primary therapy.
  • This includes lower death rates from subsequent malignancies and cardiac deaths.
  • Reductions in mortality related to late effects were most striking among survivors of Wilms tumor, Hodgkin lymphoma, and acute lymphoblastic leukemia.

 

Survivors of childhood cancer in recent eras have shown a significant reduction in late mortality, and “for the first time, we have been able to attribute that to fewer deaths from treatment-related causes or fewer deaths from late effects of the primary therapy,” Gregory T. Armstrong, MD, MSCE, reported at a press briefing at the 2015 ASCO Annual Meeting in Chicago. “This includes lower death rates for subsequent malignant neoplasms and cardiac mortality.” Dr. Armstrong is a pediatric oncologist at St. Jude Children’s Research Hospital, Memphis, and lead author of a study analyzing data from more than 34,000 participants in the federally funded Childhood Cancer Survivor Study. The study showed improvement in late mortality achieved over 3 decades. Dr. Armstrong also presented the study results at today’s Plenary Session (Abstract LBA2).

“Fifty years ago, only one in five children would survive cancer, and today over 80% are alive 5 years after diagnosis. Yet, these survivors still grow up with increased risk of dying from late effects, like heart disease and second cancers. 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,” Dr. Armstrong said.

Survivors Followed for 21 Years 

Prior research has shown that up to 18% of 5-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 after diagnosis.

The Childhood Cancer Survivor Study is evaluating long-term health outcomes in 5-year survivors of childhood cancer diagnosed between 1970 and 1999. Thirty-one U.S. and Canadian hospitals currently participate in the study. The cohort, initiated in 1994, is a National Institutes of Health–funded resource, so any researcher interested in survivorship can request access to the data or banked biologic specimens.

In the current analysis, the National Death Index was used to assess mortality among 34,043 5-year childhood cancer survivors, all younger than 21 years at diagnosis. On average, the 5-year survivors were followed for 21 years after their diagnosis. The study found that 3,958 patients (12%) had died during that period, and 1,618 of those deaths (41%) were from other health-related causes that include death due to late effects of cancer therapy.

All-Cause Mortality Halved

The investigators found that all-cause mortality was halved, with 6% of those diagnosed in the early 1990s vs 12.4% of patients diagnosed in the early 1970s dying within 15 years of diagnosis. 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).

Reductions in mortality related to late effects were most striking among survivors diagnosed in the 1970s vs the 1990s for three types of specific childhood cancers: Wilms tumor (2.2% vs 0.4%, P < .001), Hodgkin lymphoma (4.2% vs 2.1%, P = .02), and acute lymphoblastic leukemia (2.8% vs 1.9%, P < .001). Cardiac deaths significantly decreased among survivors of all three cancers. Deaths due to secondary cancer decreased among Wilms tumor survivors only.

Connecting the Dots

Dr. Armstrong noted that researchers worked “to connect the dots between the reduction in mortality and the reduction in therapy that occurred across this time period.” For example, for acute lymphoblastic leukemia (ALL), “treatment intensity dropped substantially from the 1970s to the 1980s, … largely as a result of the reduction and elimination of cranial irradiation in this population. Simultaneously, we can see the result—a drop in the 15-year cumulative mortality,” Dr. Armstrong said.

Cumulative dose exposure to anthracycline, a chemotherapy drug strongly associated with cardiotoxicity, has been reduced in ALL, Hodgkin lymphoma, and Wilms tumor. Cardiac mortality has also decreased in all three of these groups.

“The strategy of reducing the intensity of therapy to lower the occurrence of late-effects, along with promotion of early detection and improved treatment of late effects has now translated to extend the life span of survivors,” Dr. Armstrong concluded.

“This study really highlights the gains that we have made in the treatment of childhood cancer over the past decades. We have had significant innovations in our understanding of the biology of cancer, but also, pediatric oncologists have been able to collect robust data over the years, and children have been able to go on federally funded trials, translating to cure rates of childhood cancer that have quadrupled in 4 decades,” commented ASCO spokesperson and press briefing moderator Jyoti D. Patel, MD, as well as decreased toxicity of treatment and refined treatment strategies. Dr. Patel is Associate Professor of Medicine, Division of Hematology/Oncology at Northwestern University Feinberg School of Medicine, Chicago.

This study received funding from the National Institutes of Health. For full disclosures of the study authors, view the study abstract at abstract.asco.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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