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Late mortality rates have declined in pediatric cancer survivors
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CHICAGO — The modification of therapy to reduce late treatment effects has led to a reduction in all-cause mortality over the past 3 decades among survivors of pediatric cancer, according to findings from the phase 3 Childhood Cancer Survivor Study presented at the plenary session of the ASCO Annual Meeting.
Among 5-year survivors, all-cause mortality at 15 years from diagnosis declined from 12.4% for those treated between 1970 and 1974 to 6% for those treated between 1990 and 1994.
“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,” Gregory T. Armstrong, MD, MSCE, associate member of the faculty of the department of epidemiology and cancer control in the division of neuro-oncology at St. Jude Children’s Research Hospital in Memphis and a HemOnc Today Editorial Board member, said in a press release. “Now, we’ve not only helped more children survive their primary cancer, but we’ve also extended their overall lifespan by reducing their overall toxicity of treatment in more modern eras.”
Prior data have indicated that approximately 18% of 5-year pediatric cancer survivors die within 30 years of their diagnosis, according to the press release. Survivors of pediatric cancer are at risk for death from progression or recurrence of their primary cancer, as well as from other health-related issues that may be linked to late effects of their cancer treatment. The risk for death from these late effects often increases with time, according to the researchers.
Armstrong and colleagues evaluated data from 34,033 5-year survivors of all pediatric cancers (aged younger than 21 years at diagnosis) who were diagnosed between 1970 and 1999.
Median follow-up was 21 years (range, 5-38).
Overall, 3,958 deaths (12%) occurred in the population. Researchers linked 41% of those deaths to non-recurrence/non-external causes, which included late effects of cancer therapy.
The most common causes of death were secondary cancer (46.3%), heart disease (15%) and lung disease (8.4%).
Other than the decline in all-cause mortality rates from 12.4% to 6% (P ˂ .001), the cumulative incidence of death at 15 years from diagnosis from non-recurrence/non-external causes also decreased from 3.5% for patients treated between 1970 and 1974 to 2.1% for those treated between 1990 and 1994 (P ˂ .001).
Researchers also observed significant declines in deaths from subsequent neoplasms (1.8% vs. 1%; P ˂ .001), cardiac deaths (P ˂ .001) and pulmonary deaths (P = .02).
Researchers attributed these declines in part due to a refinement in treatment approaches to reduce treatment intensity in order to spare patients from late effects.
For patients with acute lymphoblastic leukemia, the use of cranial radiotherapy decreased from 86% in the 1970s to 54% in the 1980s and then to 22% in the 1990s. The use of radiotherapy also decreased over those 3 decades for patients with Wilms’ tumor (77% vs. 54% vs. 49%) and Hodgkin’s lymphoma (96% vs. 88% vs. 77%).
Fifteen-year cumulative mortality rates from non-recurrence/non-external causes also decreased when stratified by disease for patients with ALL (P < .001), Hodgkin’s lymphoma (P = .005) and Wilms’ tumor (P = .005). Cardiac deaths decreased in each malignancy (ALL, P = .002; Hodgkin’s lymphoma, P = .06; Wilms’ tumor P = .04); however, only survivors of Wilms’ tumors experienced a significant decrease in mortality from secondary cancers (P < .001).
“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,” Armstrong added in the release.
In analyses adjusted for age, sex, diagnosis and follow-up time, year of diagnosis was significantly associated with all-cause mortality (RR = 0.85; 95% CI, 0.83-0.87), non-recurrence/non-external death (RR = 0.87; 95% CI, 0.84-0.91), death from a secondary neoplasm (RR = 0.84; 95% CI 0.8-0.89), death from heart disease (RR = 0.78; 95% CI, 0.69-0.87) and death from lung disease (RR = 0.79; 95% CI, 0.68-0.91).
“For leukemia, we had big changes with a drop or reduction in the use of cranial radiotherapy and anthracyclines,” Armstrong said at a press briefing. “For Hodgkin’s lymphoma there have been reductions and/or the elimination of chest radiation and anthracyclines, and for Wilms’ tumor there has been a reduction in abdominal radiation in dose and in volume as well as a reduction in anthracyclines. This reduction is important because there is a strong established relationship with long-term cardiotoxicity with anthracyclines.” – by Anthony SanFilippo
Reference: Armstrong GT, et al. Abstract LBA2. Presented at: ASCO Annual Meeting; May 30-June 2, 2015; Chicago.
Disclosure: One research reports research funding from Merck.
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Stephen Hunger, MD
This is a very important study. When I was in training 25 years ago, I treated a 16-year-old young woman with very advanced-stage Hodgkin’s lymphoma, and she was cured of Hodgkin’s lymphoma with her therapy. About 3 years ago when she was in her late 30s and had several children, she died of metastatic breast cancer caused by the radiation used to treat her Hodgkin’s lymphoma. That’s the reality of the statistics. This does happen. It leads to premature deaths in people who are in the prime of their lives, so I think this is a very important study because it shows that modifications of therapy have been made to allow us to continue to increase cure rates from the primary cancer and also decrease the risks for dying from the treatment itself.
You have to see the movie to the end. We can’t know what’s going to happen 15 or 20 years later until we get there, but there have been a number of significant trends in pediatric cancers since the early 1990s. For example, in the early 1990s more than half of children with acute lymphoblastic leukemia received prophylactic cranial radiation. Today that’s down to the 15% range. The dose also is lower and there’s an active debate among the pediatric leukemia specialists about whether you can avoid cranial radiation in all patients with leukemia. One of the hopes of molecular medicine is to better identify the patients who can be cured with relatively limited therapy and reserve the more intensive or experimental therapies for those who have a significant risk of failure with low intensity therapy. I’m optimistic that we will continue to see this improvement.
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