Great Strides in Survivorship of Childhood Cancer Since the 1970s

More refined treatment and modern screening methods have led to improved long-term survival rates for children and young adults diagnosed with cancer – particularly those with acute lymphocytic leukemia (ALL) and Hodgkin lymphoma, according to an analysis from the Childhood Cancer Survivor Study (CCSS). CCSS is a National Institutes of Health–funded study examining the long-term effects of cancer and its associated therapies on pediatric cancer survivors diagnosed between 1970 and 1999.

“Fifty years ago, only one in five children would survive cancer, and today over 80 percent 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 lead study author Gregory T. Armstrong, MD, MSCE, a pediatric oncologist at St. Jude Children’s Research Hospital in Memphis, Tennessee. “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.”

In the study, presented as a Late-Breaking Abstract at the 2015 American Society of Clinical Oncology Annual Meeting, Dr. Armstrong and colleagues evaluated late mortality in patients who were younger than 21 years old at the time of diagnosis. The National Death Index (a central computerized index of death record information on file in the state vital statistics offices) was used to assess mortality among the more than 34,000 five-year survivors of CCSS. “Late mortality” was defined as death due to non-recurrence or non-extend causes, which included deaths that reflect late effects of cancer therapy (subsequent neoplasm, cardiac disease, and pulmonary disease).

Over a median follow-up of 21 years (range, 5-38), 3,958 deaths occurred – 1,622 (41%) of which were attributable to non-recurrence/non-extend causes, including:

  • 751 subsequent neoplasms deaths
  • 243 cardiac disease-related deaths
  • 136 pulmonary disease-related deaths

All-cause mortality at 15 years after diagnosis dropped by half from the early 1970s to the early 1990s – from 12.4 percent to 6 percent (p<0.001). As seen in the TABLE, the cumulative incidence of deaths from other health-related causes also decreased.

Reductions in mortality were due to fewer deaths related to late effects, Dr. Armstrong and colleagues observed, and were most striking among survivors of ALL (p<0.001), Hodgkin lymphoma (p=0.005), and Wilms tumor (p=0.005).

Year of diagnosis did affect mortality incidence, with survivors diagnosed in more recent years having a 15 percent lower risk for all-cause mortality than patients diagnosed in earlier treatment eras (relative risk [RR]=0.85; 95% CI 0.83-0.87), including:

  • death related to other causes (RR=0.87; 95% CI 0.84-0.91)
  • death from subsequent neoplasms (RR=0.84; 95% CI 0.80-0.89)
  • cardiac death (RR=0.78; 95% CI 0.69-0.87)
  • pulmonary death (RR=0.79; 95% CI 0.68-0.91)

Dr. Armstrong and colleagues attributed the improvement in mortality risk in part to changes in care and the movement toward less-intensive (but equally effective) treatments for many pediatric cancers known to have a favorable prognosis. For example, in each consecutive decade (1970s, 80s, and 90s), use of cranial radiotherapy dropped for ALL (86%, 54%, 22%, respectively), Wilms tumor (77%, 54%, 49%), and Hodgkin lymphoma (96%, 88%, 77%). Furthermore, cumulative dose exposure of anthracycline, a chemotherapy drug strongly associated with cardiotoxicity, has been reduced across these three diseases.

“While the modernization 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,” Dr. Armstrong added.


Reference

Armstrong GT, Yasui Y, Chen Y, et al. Reduction in late mortality among 5-year survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS). Abstract LBA2. Presented at the 2015 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2015; Chicago, IL.

TABLE. Cumulative Incidence (%) of Death at 15 Years from Diagnosis
Treatment era All-cause NR/NE causes Subsequent neoplasm Cardiac disease Pulmonary disease
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 6.0 2.1 1.0 0.1 0.1
p Value <0.001 <0.001 <0.001 0.001 0.02

 

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