PMID- 36370084 OWN - NLM STAT- MEDLINE DCOM- 20230209 LR - 20231113 IS - 1460-2105 (Electronic) IS - 0027-8874 (Print) IS - 0027-8874 (Linking) VI - 115 IP - 2 DP - 2023 Feb 8 TI - Premature aging as an accumulation of deficits in young adult survivors of pediatric cancer. PG - 200-207 LID - 10.1093/jnci/djac209 [doi] AB - BACKGROUND: We aimed to characterize premature aging as an accumulation of deficits in survivors of pediatric cancer compared with community controls and examine associations with host and treatment factors, neurocognition, and mortality. METHODS: Pediatric cancer survivors (n = 4000, median age = 28.6, interquartile range [IQR] = 23-35 years; 20 years postdiagnosis: IQR = 15-27), and community participants without a history of cancer serving as controls (n = 638, median age = 32, IQR = 25-40 years) completed clinical assessments and questionnaires and were followed for mortality through April 30, 2020 (mean [SD] follow-up = 7.0 [3.4] years). A deficit accumulation index (DAI) score was calculated from 44 aging-related items including self-reported daily function, psychosocial symptoms, and health conditions. Items were weighted from 0 (absent) to 1 (present and/or most severe), summed and divided by the total yielding a ratio (higher = more deficits). Scores less than 0.20 are robust, and 0.06 is a clinically meaningful difference. Linear regression compared the DAI in survivors and controls with an age*survivor or control interaction. Logistic regression and Cox-proportional hazards estimated the risk of neurocognitive impairment and death. Models were minimally adjusted for age, sex, and race and ethnicity. RESULTS: The adjusted mean DAI among survivors at age 30 years was 0.16 corresponding to age 63 years in controls (33 years premature aging; beta = 0.07, 95% confidence interval [CI] = 0.06 to 0.08; P < .001). Cranial and abdominal radiation, alkylators, platinum, and neurosurgery were associated with worse DAI (P /= 0.35, hazard ratio = 5.08, 95% CI = 3.52 to 7.34). CONCLUSION: Pediatric cancer survivors experience clinically significant premature aging. The DAI may be used to identify survivors at greatest risk of poor health outcomes. CI - (c) The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Williams, AnnaLynn M AU - Williams AM AUID- ORCID: 0000-0002-7042-5851 AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. AD - Current affiliation: Department of Surgery, Division of Supportive Care in Cancer, University of Rochester Medical Center, James P. Wilmot Cancer Institute, Rochester, NY, USA. FAU - Mandelblatt, Jeanne AU - Mandelblatt J AD - Department of Oncology, Georgetown University, Washington, DC, USA. FAU - Wang, Mingjuan AU - Wang M AD - Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Armstrong, Gregory T AU - Armstrong GT AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. AD - Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Bhakta, Nickhill AU - Bhakta N AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. AD - Department Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Brinkman, Tara M AU - Brinkman TM AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. AD - Department of Psychology, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Chemaitilly, Wassim AU - Chemaitilly W AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. AD - Department of Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Ehrhardt, Matthew J AU - Ehrhardt MJ AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. AD - Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Mulrooney, Daniel A AU - Mulrooney DA AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. AD - Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Small, Brent J AU - Small BJ AUID- ORCID: 0000-0002-7444-4689 AD - School of Aging Studies, University of South Florida, Tampa, FL, USA. FAU - Wang, Zhaoming AU - Wang Z AUID- ORCID: 0000-0001-7556-3869 AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Srivastava, Deokumar AU - Srivastava D AD - Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Robison, Leslie L AU - Robison LL AUID- ORCID: 0000-0001-7460-8578 AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Hudson, Melissa M AU - Hudson MM AUID- ORCID: 0000-0001-6984-2407 AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. AD - Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Ness, Kirsten K AU - Ness KK AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Krull, Kevin R AU - Krull KR AUID- ORCID: 0000-0002-0476-7001 AD - Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. AD - Department of Psychology, St. Jude Children's Research Hospital, Memphis, TN, USA. LA - eng GR - R00 CA256356/CA/NCI NIH HHS/United States GR - P30 CA021765/CA/NCI NIH HHS/United States GR - U01 CA195547/CA/NCI NIH HHS/United States GR - R35 CA197289/CA/NCI NIH HHS/United States GR - K99 CA256356/CA/NCI NIH HHS/United States GR - K00 CA222742/CA/NCI NIH HHS/United States GR - K00CA222742/NH/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Natl Cancer Inst JT - Journal of the National Cancer Institute JID - 7503089 SB - IM MH - Humans MH - Child MH - Young Adult MH - Adult MH - Middle Aged MH - *Aging, Premature MH - *Neoplasms/psychology MH - Survivors MH - *Cancer Survivors MH - Ethnicity PMC - PMC9905971 EDAT- 2022/11/13 06:00 MHDA- 2023/02/10 06:00 PMCR- 2023/11/12 CRDT- 2022/11/12 08:23 PHST- 2022/06/09 00:00 [received] PHST- 2022/09/26 00:00 [revised] PHST- 2022/11/08 00:00 [accepted] PHST- 2022/11/13 06:00 [pubmed] PHST- 2023/02/10 06:00 [medline] PHST- 2022/11/12 08:23 [entrez] PHST- 2023/11/12 00:00 [pmc-release] AID - 6825315 [pii] AID - djac209 [pii] AID - 10.1093/jnci/djac209 [doi] PST - ppublish SO - J Natl Cancer Inst. 2023 Feb 8;115(2):200-207. doi: 10.1093/jnci/djac209.