Dear PAC2

We all know that the survivors of childhood cancer (i.e., alive 5 years after diagnosis) face numerous challenges.  Many of those challenges are related to the effects of the treatment that has saved their lives.  The Childhood Cancer Survivor Study (CCSS) is the largest, nationwide evaluation of the long-term survivors of childhood cancer.  It monitors the long-term health outcomes of over 35,000 survivors diagnosed between 1970 and 1999. 

Previous Work

PAC2 has previously reported on many of the CCSS findings.  One such report, Childhood Cancer - Long-Term Outcomes, used CCSS data to look at the integrated, long-term survival rates for children diagnosed with cancer.  In the report, we looked at a 2008 CCSS report titled Cause-Specific Late Mortality Among 5-Year Survivors of Childhood Cancer: The Childhood Cancer Survivor Study (JNCI J Natl Cancer Inst (2008) 100 (19): 1368-1379. doi: 10.1093/jn...). The term “Late,” or "Excess Mortality" refers to a child dying as the result of recurrence of the original cancer, secondary cancer, or other health effect resulting from the toxicity of treatment, such as chemo or radiation.

This study included 20,483 five-year survivors of childhood cancer that were diagnosed between 1970 and 1986. The study group was searched in the National Death Index for deaths occurring between 1979 and 2002.  The study concluded that for a 5-years survivor the estimated probability of survival 30 years from diagnosis is 82%. Probabilities were 94% at 10 years and 88% at 20 years. Put another way, the projected probability of a 5-year survivor dying within 30 years of diagnosis due to a cancer related cause WAS 18%. In our report, we said: "We HOPE that treatments have IMPROVED in the past 25 years and that the outcomes have changed since then, but this evaluates the available data."

New Data

Well, new data is in and its GOOD NEWS!  Over time, research has allowed the pediatric oncologists to reduce the number of side effects through less harsh, more focused, and even some new treatments.  The most recent findings were presented at the American Society of Clinical Oncology​.  The findings reported at the ASCO meeting titled "Reduction in late mortality among 5-year survivors of childhood can..." are important because they report on the actual improvements in the deaths survivors caused by treatments over time (i.e., as research continues to improve treatments we expect fewer deaths). 

Bottom Line: From 1970 to 1974 about 12.4% of 5 year survivors died from side-effects of treatments and from 1990 to 1994 that number was reduced to about 6%.

Lead author Dr. Greg Armstrong of St. Jude Children's Research Hospital says  “The now decades-long strategy of designing pediatric cancer treatment regimens with a focus on adult health and avoidance of late effects appears to have been successful. Taken along with the promotion of early detection of early late effects and improved treatment of late effects, this approach is now translated to extend the lifespan of many survivors of childhood cancer. Future directions include the need to assess the true impact of screening and early detection of late effects on mortality and the need to determine to what degree temporal changes in treatment have reduced the incidence of late effects, so that we not only extend the lifespan of survivors but their health span as well.”

Until recently, for example, doctors typically recommended that children with aggressive, high-risk leukemias undergo not just chemotherapy, but radiation to the brain. That radiation helped prevent relapses that could be fatal. But radiating the brain — especially when children are very young — can cause learning and memory problems.


Today, studies show that many children with high-risk leukemias can avoid brain radiation, said Jill Ginsberg, a pediatric oncologist and director of the cancer survivorship program at the Children's Hospital of Philadelphia's Cancer Center.  Not all children can avoid aggressive cancer therapies, Ginsberg said. Children with brain tumors still need harsh therapy, because their cancers are so hard to cure.

“For decades, we've strived to avoid the paradox in which children survive cancer, only to become sick or die years later because of the treatment they received,” said ASCO Expert Stephen Hunger, MD, in an ASCO press release.

“By carefully refining pediatric cancer treatment, we have improved long-term care and outcomes by leaps and bounds. Cure rates have increased with parallel decreases in death due to complications of cancer treatment. We hope that the positive trends we're seeing today will continue as our therapeutic approaches continue to improve over time.”

The study Abstract is shown below.  We will review the data and update our Long-Term Health Outcomes shortly.   You will see many many news stories about this report.  While we don't want to appear ungrateful, we should also make sure the world realizes that childhood cancer remains the leading cause of death by disease and that it remains severely under-funded......

Awareness -->Funding-->Research-->CURE!! 

Reduction in late mortality among 5-year survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

Abstract: 

Background: Over the past four decades, treatment of many childhood cancers has been modified with the aim of achieving high survival rates while reducing the risk of life-threatening late-effects, and promoting risk-based follow-up care of survivors. Methods: Late mortality was evaluated in 34,033 5-year survivors (diagnosed < 21 years of age from 1970-1999, median follow-up 21 years, range 5-38) using cumulative incidence and Poisson regression models adjusted for demographic and disease factors to calculate relative risk (RR) and 95% confidence intervals (CI). Mortality due to non-recurrence/non-external (NR/NE) causes, which includes deaths that reflect late-effects of cancer therapy, was evaluated. Results: 1,622 (41%) of the 3,958 deaths were attributable to NR/NE causes, including 751 subsequent neoplasm (SN), 243 cardiac, and 136 pulmonary deaths. Changes in therapy by decade included reduced rates of: cranial radiotherapy (RT) for acute lymphoblastic leukemia (ALL, 86%, 54%, 22%), RT for Wilms tumor (WT, 77%, 54%, 49%) and RT for Hodgkin lymphoma (HL, 96%, 88%, 77%). Reductions in 15 year cumulative NR/NE mortality were observed across treatment eras for ALL (p < .001), HL (p = .005), and WT (p = .005). Cardiac deaths decreased in ALL (p = .002), HL (p = .06), and WT (p = .04), and SN deaths decreased in WT (p < .001). Year of diagnosis (adjusted for age, sex, diagnosis, follow-up time) was significantly associated with a reduced risk of all-cause mortality (RR = 0.85, CI 0.83-0.87), NR/NE death (RR = 0.87, CI 0.84-0.91), death from SN (RR = 0.84, CI 0.80-0.89), cardiac death (RR = 0.78, CI 0.69-0.87) and pulmonary death (RR = 0.79, CI 0.68-0.91). Conclusions: The CCSS cohort provides evidence that the strategy of modifying therapy to reduce the occurrence of late-effects, and promotion of early detection, is successfully translating into a significant reduction in observed late mortality.

Cumulative incidence (%) of death at 15 years from diagnosis.

Treatment

era

All-Cause NR/NE Causes SN Cardiac Pulmonary
1970-74 12.4 3.5 1.8 0.5 0.4
1975-79 9.7 2.8 1.5 0.4 0.2
1980-84 8.8 2.7 1.4 0.3 0.3
1985-89 6.9 2.2 1.3 0.2 0.2
1990-94 6 2.1 1 0.1 0.1

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