Findings from a project that assessed whether life expectancy will improve among adult survivors of childhood and adolescent cancers suggest that advances in the treatment for cancer during the past decades are expected to improve life expectancy for those treated with chemotherapy alone. Despite improvements, survivors remain at risk for shorter lifespans, especially when radiotherapy was included as part of their treatment. The findings highlight the need for continued monitoring of survivors’ health to manage late mortality risks. The results from a model study are published on 2 January 2020 in the JAMA Oncology.
The authors wrote in the study background that advances in the treatment during the past few decades have been associated with remarkable increases in 5-year survival rates, with more than 80% of children and adolescents who receive a diagnosis today expected to live at least 5 years.
As adults, childhood and adolescent cancer survivors face substantially elevated risks of serious long-term morbidity and premature death, with nearly 1 in 3 survivors reporting a severe or life-threatening condition 20 years after diagnosis. Previously published study using a model-based approach estimated that late recurrence and excess mortality risks from secondary cancers, cardiac disease, and other late effects reduced projected life expectancy by as much as 28% among survivors who originally received a diagnosis of childhood and adolescent cancer between 1970 and 1986.
Clinical investigators recognised the risk for life-threatening late effects and focused modern clinical trials to study the outcome of treatments that reduce or eliminate exposure to radiotherapy and/or lower cumulative dose exposures to anthracyclines and other chemotherapies. Lower treatment exposures have been associated with an observed decrease in late mortality among survivors in the 15 years immediately after their cancer diagnosis, but their association with length of life is unknown.
The association of childhood and adolescent cancer with life expectancy after more modern therapy, often chosen based on concerns of late toxic effects, is not known. Therefore, the study team sought to leverage newly available late mortality data on childhood and adolescent cancer survivors who received a diagnosis between 1970 and 1999 to update previous estimates of projected life expectancy.
A microsimulation model of competing mortality risks was developed using data from the Childhood Cancer Survivor Study on 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1999. The model included late recurrence, treatment-related late effects (such as subsequent cancers, cardiac events, pulmonary conditions, and external causes), and US background mortality rates.
In the cohort, 44% participants were female and 56% male with mean (SD) age at diagnosis, 7.3 (5.6) years. Conditional life expectancy was 48.5 years (95% uncertainty interval [UI], 47.6-49.6 years) for 5-year survivors diagnosed in 1970-1979, 53.7 years (95% UI, 52.6-54.7 years) for those diagnosed in 1980-1989, and 57.1 years (95% UI, 55.9-58.1 years) for those diagnosed in 1990-1999.
Compared with individuals without a history of cancer, these results represented a gap in life expectancy of 25% (95% UI, 24%-27%), 16.5 years (95% UI, 15.5-17.5 years) for those diagnosed in 1970-1979, 19% (95% UI, 17%-20%), 12.3 years (95% UI, 11.3-13.4 years) for those diagnosed in 1980-1989, and 14% (95% UI, 13%-16%), 9.2 years (95% UI, 8.3-10.4 years) for those diagnosed in 1990-1999.
During the 3 decades, the proportion of survivors treated with chemotherapy alone increased from 18% in 1970-1979 to 54% in 1990-1999, and the life expectancy gap in this chemotherapy-alone group decreased from 11.0 years (95% UI, 9.0-13.1 years) to 6.0 years (95% UI, 4.5-7.6 years).
In contrast, during the same time frame, only modest improvements in the gap in life expectancy were projected for survivors treated with radiotherapy, 21.0 years (95% UI, 18.5-23.2 years) to 17.6 years (95% UI, 14.2-21.2 years) or with radiotherapy and chemotherapy, 17.9 years (95% UI, 16.7-19.2 years) to 14.8 years (95% UI, 13.1-16.7 years).
For the largest group of survivors by diagnosis (those with acute lymphoblastic leukaemia) the gap in life expectancy decreased from 14.7 years (95% UI, 12.8-16.5 years) in 1970-1979 to 8.0 years (95% UI, 6.2-9.7 years).
Using a simulation model–based approach, this study estimates that children and adolescents who received a diagnosis of and were treated for cancer in the 1990s will live longer into adulthood than those diagnosed in the 1970s. Despite improvements, these individuals remain at risk for a shortened lifespan owing to severe treatment-related late toxic effects. The findings highlight the need for continued monitoring of survivors’ health to manage late mortality risks and underscore the need for new therapeutic approaches to minimise early mortality risks, especially for cancer diagnoses for which radiotherapy remains a key component of therapy.
Yeh JM, Ward ZJ, Chaudhry A, et al. Life Expectancy of Adult Survivors of Childhood Cancer Over 3 Decades. JAMA Oncol; Published online 2 January 2020. doi: 10.1001/jamaoncol.2019.5582.