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Will the observed shortened life expectancy of adult survivors of childhood cancer lengthen over time given improvements in treatment and care?
Using a simulation model–based approach, this study estimates that children 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.
Evolving treatment approaches are projected to be associated with improved life expectancy after treatment for pediatric cancer, in particular among individuals who did not receive radiotherapy during childhood cancer treatment.
Advances in childhood and adolescent cancer treatment have been associated with increased rates of cure during the past 3 decades; however, improvement in adult life expectancy for these individuals has not yet been reported.
To project long-term survival and assess whether life expectancy will improve among adult survivors of childhood cancer who were treated in more recent decades.
Design, Setting, and Participants
A microsimulation model of competing mortality risks was developed using data from the Childhood Cancer Survivor Study on 5-year survivors of childhood cancer diagnosed between 1970 and 1999. The model included (1) late recurrence, (2) treatment-related late effects (health-related [subsequent cancers, cardiac events, pulmonary conditions, and other] and external causes), and (3) US background mortality rates.
Treatment subgroups (no treatment or surgery only, chemotherapy alone, radiotherapy alone, and radiotherapy with chemotherapy) and individuals with acute lymphoblastic leukemia during childhood by era (1970-1979, 1980-1989, and 1990-1999).
Main Outcomes and Measures
Conditional life expectancy (defined as the number of years a 5-year survivor can expect to live), cumulative cause-specific mortality risk, and 10-year mortality risks conditional on attaining ages of 30, 40, 50, and 60 years.
Among the hypothetical cohort of 5-year survivors of childhood cancer representative of the Childhood Cancer Survivor Study participants (44% female and 56% male; 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 leukemia—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).
Conclusions and Relevance
Evolving treatment approaches are projected to be associated with improved life expectancy after treatment for pediatric cancer, in particular among those who received chemotherapy alone for their childhood cancer diagnosis. Despite improvements, survivors remain at risk for shorter lifespans, especially when radiotherapy was included as part of their childhood cancer treatment.
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Accepted for Publication: October 3, 2019.
Corresponding Author: Jennifer M. Yeh, PhD, Division of General Pediatrics, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115 (firstname.lastname@example.org).
Published Online: January 2, 2020. doi:10.1001/jamaoncol.2019.5582
Author Contributions: Dr Yeh had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Yeh, Ward, Armstrong, Hudson, Leisenring, Oeffinger, Diller.
Acquisition, analysis, or interpretation of data: Yeh, Ward, Chaudhry, Liu, Yasui, Armstrong, Gibson, Howell, Hudson, Krull, Oeffinger, Diller.
Drafting of the manuscript: Yeh, Oeffinger, Diller.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Yeh, Ward, Liu, Yasui, Leisenring.
Obtained funding: Yeh, Armstrong.
Administrative, technical, or material support: Yeh, Ward, Chaudhry, Armstrong, Krull, Leisenring.
Supervision: Yeh, Armstrong, Diller.
Conflict of Interest Disclosures: Dr Yeh reported receiving grants from the American Cancer Society and the National Cancer Institute during the conduct of the study. Dr Armstrong reported receiving grants from the National Institutes of Health during the conduct of the study. Drs Gibson, Krull, Leisenring, and Yasui reported receiving grants from the National Cancer Institute during the conduct of the study. No other disclosures were reported.
Funding/Support: This work was supported by the American Cancer Society (Research Scholar Grant RSG-16-018-01–CPHPS, Dr Yeh, principal investigator) and the National Cancer Institute (CA55727, Dr Armstrong, principal investigator). Support to St Jude Children’s Research Hospital was also provided by the Cancer Center Support (CORE) grant (CA21765) and the American Lebanese-Syrian Associated Charities.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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