ArticlesTemporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970–99: a report from the Childhood Cancer Survivor Study cohort
Introduction
In the USA, there are more than 420 000 survivors of childhood cancer and this number is estimated to exceed half a million by 2020.1 More than 80% of children diagnosed with a malignancy now achieve 5-year survival, but these individuals have substantial risks of morbidity and mortality later in life because of the late effects of cancer and its treatments.1, 2, 3, 4 A previous study in the Childhood Cancer Survivor Study (CCSS) reported that 54% of long-term childhood cancer survivors, diagnosed between 1970 and 1986, developed at least one severe, disabling, life-threatening, or fatal chronic health condition by the age of 50 years, representing a 5-times increased risk compared with siblings.5 In a retrospective cohort study from a single institution, Hudson and colleagues6 reported that 81% of survivors who underwent systematic clinical assessment were identified with at least one severe, disabling, or life-threatening chronic health condition by the age of 45 years.
Associations between specific cancer therapies and increased risk of late effects in survivors have led to modifications in treatment regimens with the goal of maintaining or improving the proportion of patients who achieve long-term survival, while reducing the risk and severity of late adverse events. For some cancers, elimination of radiotherapy or or combinations of conformal fields and reduced radiotherapy doses were able to minimise exposure to healthy tissues, while maintaining therapeutic activity.7, 8, 9, 10 Furthermore, risk-adapted therapy has allowed reduced treatment exposures for children with a lower risk of relapse or recurrence of their primary cancer.7, 8 These changes contributed to reductions in late mortality from late adverse events in survivors treated more recently across the three decades between 1970 and 1999.11, 12, 13 By contrast, over the same time period, more recently treated survivors reported reduced health status, emphasising the need to further examine temporal changes in chronic health conditions in this population.14 Optimum survivorship should include both extended lifespan and improvements in overall health; therefore, the goal of our analysis was to examine associations between treatment era and the incidence of severe, disabling, life-threatening, or fatal chronic health conditions, using the expanded CCSS cohort of childhood cancer patients who were diagnosed from 1970 to 1999 and survived at least 5-years after diagnosis.
Section snippets
Study design and participants
The CCSS is a multi-institutional, retrospective, cohort study with longitudinal follow-up of survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) diagnosed before the age of 21 years at one of 27 institutions in the USA and Canada. Survivors were eligible if they were diagnosed with cancer between Jan 1, 1970, and Dec 31, 1999, and survived at least 5 years after
Results
The cohort included 23 601 5-year survivors (66% of all eligible; appendix p 2) and 5051 siblings (62% of all eligible; appendix p 3). Among survivors, 6223 were diagnosed in 1970–79, 9420 in 1980–89, and 7958 in 1990–99 (table 1). Median follow-up time for all survivors was 21 years (IQR 15–25), and median follow-up by decade of diagnosis was 29 years (24–33) for 1970–79, 22 years (18–24) for 1980–89, and 15 years (13–18) for 1990–99. Median age at diagnosis was 6 years (IQR 3–13) and median
Discussion
In this study, 5-year survivors of childhood cancer diagnosed and treated between 1970 and 1999 had declining risks across treatment decades for severe, disabling, life-threatening, or fatal chronic health conditions by 20 years post-diagnosis. Treatments for childhood cancer have evolved in recent decades, with the aim of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. Increased understanding of cancer biology, along with
References (30)
- et al.
Neuroblastoma
Lancet
(2007) - et al.
Gonadal function and fertility among survivors of childhood cancer
Endocrinol Metab Clin North Am
(2015) - et al.
Survivors of childhood and adolescent cancer: life-long risks and responsibilities
Nat Rev Cancer
(2014) SEER Cancer Statistics Review (CSR)
(1975-2014)- et al.
Medical assessment of adverse health outcomes in long-term survivors of childhood cancer
JAMA
(2007) - et al.
Risk stratification of childhood cancer survivors necessary for evidence-based clinical long-term follow-up
Br J Cancer
(2017) - et al.
Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study
J Clin Oncol
(2014) - et al.
Clinical ascertainment of health outcomes among adults treated for childhood cancer
JAMA
(2013) - et al.
Relevance of historical therapeutic approaches to the contemporary treatment of pediatric solid tumors
Pediatr Blood Cancer
(2013) - et al.
Lessons from the past: opportunities to improve childhood cancer survivor care through outcomes investigations of historical therapeutic approaches for pediatric hematological malignancies
Pediatr Blood Cancer
(2012)
Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma
JAMA
Treating childhood acute lymphoblastic leukemia without cranial irradiation
N Engl J Med
Reduction in late mortality among 5-year survivors of childhood cancer
N Engl J Med
Long term cause specific mortality among 34489 five year survivors of childhood cancer in Great Britain: population based cohort study
BMJ
Late and very late mortality in 5-year survivors of childhood cancer: changing pattern over four decades–experience from the Nordic countries
Int J Cancer
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