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Childhood cancer survivors experience fewer severe health problems
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CHICAGO — Treatment modifications that extended survival for childhood cancer survivors during the past several decades also reduced incidence of serious chronic disease in these individuals later in life, according to study results presented at the ASCO Annual Meeting.
“Our analysis marks the first comprehensive assessment of changes in the rates of chronic health complications over time in a large group of cancer survivors,” Todd M. Gibson, PhD, assistant member at St. Jude Children’s Research Hospital, said in a press release. “From our findings, it is clear that survivors diagnosed and treated in more modern treatment eras are doing better. Not only are more children being cured, but they also have lower risk for developing serious health problems due to cancer treatment later in life.”
The 5-year survival rate among children diagnosed with cancer exceeds 83%, up from 58% in the 1970s. The number of childhood cancer survivors in the United States — which reached 420,000 in 2013 — is expected to reach 500,000 by 2020.
However, the aggressive treatments required to cure children of their cancers often increase their risk for serious health conditions later in life. More than half of childhood cancer survivors will develop at least one severe, disabling, life-threatening or fatal chronic health condition by age of 50 years.
“Accordingly, oncologists have made great efforts in recent decades to modify treatments with the goal of trying to maintain high cure rates while reducing the risk of these devastating late effects,” Gibson said during a press conference. “However, the impact of these modifications on late outcomes of survivors is not yet well established.”
Gibson and colleagues analyzed data from the Childhood Cancer Survivor Study (CCSS) to investigate whether treatment modifications that reduced late mortality of survivors also reduced incidence of chronic disease among those who lived at least 5 years after diagnosis.
CCSS — a federally funded retrospective cohort of individuals diagnosed with common childhood cancers between 1970 and 1999 and treated at one of 31 centers in the United States and Canada — uses surveys to assess long-term health outcomes among childhood cancer survivors.
The analysis included 23,601 survivors (median age at last follow-up, 28 years; range, 5-63) of leukemia, lymphoma, central nervous system malignancies, Wilms tumor, neuroblastoma, soft tissue sarcoma or bone sarcoma.
All survivors received their cancer diagnosis prior to age 21 years, and a median 21 years (range, 5-43) had elapsed since their diagnosis.
Gibson and colleagues used Common Terminology Criteria for Adverse Events to evaluate incidence of severe, disabling, life-threatening or fatal health problems.
Researchers used the CCSS self-reported survey data to calculate 15-year cumulative incidence of chronic health conditions by decade of cancer diagnosis, and they used Cox regression to compare risk across decades. Investigators also used the National Death Index to obtain information about cases in which survivors died due to late effects of treatment.
Results showed the 15-year cumulative incidence of grade 3 to grade 5 conditions declined from 12.7% (95% CI, 11.8-13.6) among survivors diagnosed in the 1970s to 10.1% (95% CI, 9.4-10.7) among those diagnosed in the 1980s, and 8.8% (95% CI, 8.3-9.5) among those diagnosed in the 1990s (HR per 10 years = 0.84; 95% CI, 0.8-0.89).
Analyses adjusted for sex and attained age revealed significant reductions in serious chronic morbidity over time among survivors of Wilms tumor (13% among those diagnosed in the 1970s vs. 5% among those diagnosed in the 1990s; HR = 0.57; 95% CI, 0.46-0.7), Hodgkin lymphoma (18% for 1970s vs. 11% for 1990s; HR = 0.75; 95% CI, 0.65-0.85), astrocytoma (15% for 1970s vs. 9% for 1990s; HR = 0.77; 95% CI, 0.64-0.92), non-Hodgkin lymphoma (10% for 1970s vs. 6% for 1990s; HR = 0.79; 95% CI, 0.63-0.99) and acute lymphoblastic leukemia (9% for 1970s vs. 7% for 1990s; HR = 0.86; 95% CI, 0.76-0.98).
The decline in chronic morbidity over time appeared driven primarily by reduced incidence of endocrine conditions — which occurred at rates of 4% among those diagnosed in the 1970s and 1.6% among those diagnosed in the 1990s (HR = 0.66; 95% CI, 0.59-0.73) — and fewer subsequent malignant neoplasms, which occurred at rates of 2.4% among those diagnosed in the 1970s and 1.6% among those diagnosed in the 1990s (HR = 0.85; 95% CI, 0.76-0.96).
Researchers also observed significant reductions in gastrointestinal conditions (HR = 0.8; 95% CI, 0.66-0.97) and neurological conditions (HR = 0.77; 95% CI, 0.65-0.91).
Results revealed no change in incidence of pulmonary or cardiac conditions.
“We were a little surprised that the incidence of severe cardiovascular disease did not decrease, knowing that deaths from cardiovascular disease dropped among survivors in recent decades,” Gibson said. “This is a reminder that survivors continue to have an increased risk for serious health problems compared to the general population and need to be followed closely.”
When researchers incorporated detailed treatment data into their model, they determined the decline in cumulative incidence of serious chronic conditions was mirrored by a decrease in treatment intensity over time.
“More recent survivors of many childhood cancers have reduced incidence of serious chronic disease later in life,” Gibson said. “These changes correlated with temporal changes in treatment. This demonstrates that the strategy of trying to reduce the intensity of therapy — with the goal of reducing late effects — along with changes in screening and early detection that occurred over the same timeframe have, in fact, translated to reduced incidence of serious late morbidity and improved late health outcomes among survivors of childhood cancer.”– by Mark Leiser
Reference:
Gibson TM, et al. Abstract LBA10500. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure: The NIH funded this study. Gibson reports no relevant financial disclosures. Other researchers report research funding from Merck; honoraria and travel, accommodations or expenses from Sandoz; and consultant or advisory roles with Coleman Supportive Oncology Initiative for Children with Cancer, Oncology Research Information Exchange Network, Pfizer and Princess Maxima Center for Pediatric Oncology.
Perspective
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Timothy D. Gilligan, MD, MSc
It is important to recognize how huge these findings are. I am an adult oncologist, so I would look at these findings in some ways as a parent. If you told me that my child had cancer and the good news was that you would be able to cure my child, but he or she was going to be plagued by health problems for the rest of their life as a result of treatment, thats actually bad news for my child and my entire family. The fact that we are not only seeing increased cure rates but we are also seeing a decline in the problematic health complications that can occur from cancer treatment is really huge progress. These childrens lives are being affected in very important ways by reducing the risk for developing another cancer that is much harder to cure than the first cancer. In the adult oncology world, we often talk about having 6 months of chemotherapy to live another 3 months. A number of patients decline such treatment because they dont think its worth it. Cure is a huge endpoint, so it is very exciting to see this. It also is a reminder of the importance of clinical trials. One of the reasons pediatric oncology has done so well understanding that the biology of the disease is different is because the proportion of pediatric patients with cancer who participate in trials is much higher than in the adult world. Federal funding enables clinical trials of new treatments that are less toxic. It also pays for trials like this that allow us to perform long-term follow-up so we can see whether we are getting better over time.
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Linda Jacobs, PhD, CRNP
This study examined the rate of numerous severe health problems in 23,600 childhood cancer survivors in the Childhood Cancer Survivor Study and showed that the incidence of these problems occurring five or more years after diagnosis has been declining for some cancers. There are many reasons for this that we have been aware of for some time, including advances in treatment and better supportive care. The question remains as to why this is not the case for cancers such as neuroblastoma, acute myeloid leukemia, soft tissue sarcoma and osteosarcoma. The incidence of severe cardiovascular disease did not decrease, although deaths from cardiovascular disease among cancer survivors have dropped. These findings again highlight the importance of lifelong follow-up for all cancer survivors, as well as ongoing examination of morbidity and mortality associated with specific cancer diagnoses and treatments.
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