Abstract

Research Article

Causal Mediation Analysis for Childhood Cancer Survival Disparity in Texas, 2005 to 2014

Niaz Morshed* and Russell Weaver and F Benjamin Zhan

Published: 29 March, 2024 | Volume 5 - Issue 1 | Pages: 023-030

This study aimed to examine the disparities of childhood cancer survival among different racial and ethnic groups in Texas. The analysis was mediated by socioeconomic status (SES) and spatial accessibility to Children Oncology Group (COG) hospitals. The relationship between race-ethnicity and overall survival was measured using the Cox proportional hazards model with a robust variance estimator. The counterfactual model measures the total effect of race-ethnicity on survival through all mediating pathways while adjusting for baseline confounders (age, sex, and stage at diagnosis), which are then decomposed into natural direct and indirect effects. Considering all cancer site groups, African Americans showed a statistically significant higher hazard ratio in death (HR = 3.63; 95% CI = 1.87 - 6.62) compared with non-Hispanic White children. At the same time, the mortality hazard ratio among Hispanic children is not significant (HR = 1.23; 95% CI = 0.80 - 1.93) when compared with non-Hispanic White children. Analysis results also suggested that both mediators significantly contribute to racial-ethnic survival disparities for specific cancer site groups such as Leukemia for African American children. This study builds knowledge and understanding about underlying factors (mediators) responsible for the disparities in the outcomes among childhood cancer patients.

Read Full Article HTML DOI: 10.29328/journal.jcmhs.1001044 Cite this Article Read Full Article PDF

Keywords:

Childhood cancer; Race-ethnicity; Disparities; Healthcare access; Socio-economic status; Survival

References

  1. Ness KK, Armstrong GT, Kundu M, Wilson CL, Tchkonia T, Kirkland JL. Frailty in childhood cancer survivors. Cancer. 2015 May 15;121(10):1540-7. doi: 10.1002/cncr.29211. Epub 2014 Dec 19. PMID: 25529481; PMCID: PMC4424063.
  2. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763. PMID: 36633525.
  3. Howlader N, Noone A, Krapcho M, Miller D, Bishop K, Kosary C. Cancer Statistics Review, 1975-2014 - SEER Statistics, National Cancer Institute [Internet]. SEER Cancer Statistics Review, 1975-2014. 2016. https://seer.cancer.gov/csr/1975_2015/
  4. Kaatsch P. Epidemiology of childhood cancer. Cancer Treat Rev. 2010 Jun;36(4):277-85. doi: 10.1016/j.ctrv.2010.02.003. Epub 2010 Mar 15. PMID: 20231056.
  5. Steliarova-Foucher E, Stiller C, Lacour B, Kaatsch P. International Classification of Childhood Cancer, third edition. Cancer. 2005 Apr 1;103(7):1457-67. doi: 10.1002/cncr.20910. PMID: 15712273.
  6. Fluchel MN, Kirchhoff AC, Bodson J, Sweeney C, Edwards SL, Ding Q, Stoddard GJ, Kinney AY. Geography and the burden of care in pediatric cancers. Pediatr Blood Cancer. 2014 Nov;61(11):1918-24. doi: 10.1002/pbc.25170. Epub 2014 Aug 17. PMID: 25131518; PMCID: PMC4749153.
  7. Lund MJ, Eliason MT, Haight AE, Ward KC, Young JL, Pentz RD. Racial/ethnic diversity in children's oncology clinical trials: ten years later. Cancer. 2009 Aug 15;115(16):3808-16. doi: 10.1002/cncr.24437. PMID: 19484783.
  8. Children’s Oncology Group (COG) [Internet]. COG Institution Locations: The world’s childhood cancer experts. Monrovia, CA; 2021 [cited 2021 Jan 1]. https://childrensoncologygroup.org/locations/
  9. Bhatia S, Sather HN, Heerema NA, Trigg ME, Gaynon PS, Robison LL. Racial and ethnic differences in survival of children with acute lymphoblastic leukemia. Blood. 2002 Sep 15;100(6):1957-64. doi: 10.1182/blood-2002-02-0395. PMID: 12200352.
  10. Kadan-Lottick NS, Ness KK, Bhatia S, Gurney JG. Survival variability by race and ethnicity in childhood acute lymphoblastic leukemia. JAMA. 2003 Oct 15;290(15):2008-14. doi: 10.1001/jama.290.15.2008. PMID: 14559954.
  11. Linabery AM, Ross JA. Childhood and adolescent cancer survival in the US by race and ethnicity for the diagnostic period 1975-1999. Cancer. 2008 Nov 1;113(9):2575-96. doi: 10.1002/cncr.23866. PMID: 18837040; PMCID: PMC2765225.
  12. Hamilton EC, Nguyen HT, Chang YC, Eberth JM, Cormier J, Elting LS, Austin MT. Health Disparities Influence Childhood Melanoma Stage at Diagnosis and Outcome. J Pediatr. 2016 Aug;175:182-7. doi: 10.1016/j.jpeds.2016.04.068. Epub 2016 May 24. PMID: 27233520.
  13. Morshed N, Zhan FB. Racial/ethnic, social characteristics and geographic disparities of childhood cancer late-stage diagnosis in Texas, 2005 to 2014. Ann GIS. 2021; 27(4):329–40. https://doi.org/10.1080/19475683.2021.1981999
  14. Luo W, Qi Y. An enhanced two-step floating catchment area (E2SFCA) method for measuring spatial accessibility to primary care physicians. Health Place. 2009 Dec;15(4):1100-7. doi: 10.1016/j.healthplace.2009.06.002. Epub 2009 Jun 18. Erratum in: Health Place. 2011 Jan;17(1):394. PMID: 19576837.
  15. Pearl J. Causality: Models, reasoning, and inference, second edition. Causality: Models, Reasoning, and Inference, Second Edition. New York, NY, USA: Cambridge University Press; 2011.
  16. Tchetgen Tchetgen EJ. Inverse odds ratio-weighted estimation for causal mediation analysis. Stat Med. 2013 Nov 20;32(26):4567-80. doi: 10.1002/sim.5864. Epub 2013 Jun 7. PMID: 23744517; PMCID: PMC3954805.
  17. Lange T, Vansteelandt S, Bekaert M. A simple unified approach for estimating natural direct and indirect effects. Am J Epidemiol. 2012 Aug 1;176(3):190-5. doi: 10.1093/aje/kwr525. Epub 2012 Jul 10. PMID: 22781427.
  18. Robins JM, Greenland S. Identifiability and exchangeability for direct and indirect effects. Epidemiology. 1992 Mar;3(2):143-55. doi: 10.1097/00001648-199203000-00013. PMID: 1576220.
  19. Pearl J. Direct and indirect effects. In: Proceedings of the American Statistical Association Joint Statistical Meetings [Internet]. Brentwood, MO: MIRA Digital Publishing; 2005; 1572–81. http://dl.acm.org/citation.cfm?id=2074073
  20. Vanderweele TJ, Vansteelandt S. Odds ratios for mediation analysis for a dichotomous outcome. Am J Epidemiol. 2010 Dec 15;172(12):1339-48. doi: 10.1093/aje/kwq332. Epub 2010 Oct 29. PMID: 21036955; PMCID: PMC2998205.
  21. VanderWeele TJ. Causal mediation analysis with survival data. Epidemiology. 2011 Jul;22(4):582-5. doi: 10.1097/EDE.0b013e31821db37e. PMID: 21642779; PMCID: PMC3109321.
  22. Rochon J, du Bois A, Lange T. Mediation analysis of the relationship between institutional research activity and patient survival. BMC Med Res Methodol. 2014 Jan 22;14:9. doi: 10.1186/1471-2288-14-9. PMID: 24447677; PMCID: PMC3917547.
  23. Kaplan EL, Meier P. Nonparametric Estimation from Incomplete Observations. Am Stat Assoc [Internet]. 1958;53(282):457–81. http://www.jstor.org/stable/2281868
  24. R Core Team. R: A language and environment for statistical computing (Version 3.2.4) [Software] [Internet]. R Foundation for Statistical Computing, Vienna, Austria; 2018. https://cran.r-project.org/bin/windows/base/old/3.2.4/
  25. Therneau TM, Lumley T. Survival Analysis: A package for survival analysis in R. 2018. https://github.com/therneau/survival
  26. Højsgaard S, Halekoh U, Yan J. The R Package geepack for Generalized Estimating Equations. J Stat Softw [Internet]. 2006;15(2):1–11. https://cran.r-project.org/web/packages/geepack/geepack.pdf%0Ahttp://www.jstatsoft.org/v15/i02/
  27. Harrell FE. Regression Modeling Strategies: Package “rms” [Internet]. 2018. http://biostat.mc.vanderbilt.edu/rms
  28. International Classification of Childhood Cancer (ICCC): National Cancer Institute, SEER Cancer Statistics Review 1975-2011. 2011;103(7):34. https://seer.cancer.gov/archive/csr/1975_2011/results_merged/topic_icccrecode.pdf
  29. US Department of Health and Human Services. Secretary’s Advisory Committee on Health Promotion and Disease Prevention Objectives for 2030. [Internet]. Healthy People 2030 - Building a healthier future for all. 2022. Available from: https://www.cdc.gov/nchs/healthy_people/hp2030/hp2030.htm
  30. Bhatia S. Disparities in cancer outcomes: lessons learned from children with cancer. Pediatr Blood Cancer. 2011 Jun;56(6):994-1002. doi: 10.1002/pbc.23078. Epub 2011 Feb 15. PMID: 21328525; PMCID: PMC3369622.
  31. Gupta S, Wilejto M, Pole JD, Guttmann A, Sung L. Low socioeconomic status is associated with worse survival in children with cancer: a systematic review. PLoS One. 2014 Feb 26;9(2):e89482. doi: 10.1371/journal.pone.0089482. PMID: 24586813; PMCID: PMC3935876.
  32. Holmes L, Vandenberg J, McClarin L, Dabney K. Epidemiologic, Racial and Healthographic Mapping of Delaware Pediatric Cancer: 2004-2014. Int J Environ Res Public Health. 2015 Dec 22;13(1):ijerph13010049. doi: 10.3390/ijerph13010049. PMID: 26703649; PMCID: PMC4730440.
  33. Dang-Tan T, Trottier H, Mery LS, Morrison HI, Barr RD, Greenberg ML, Franco EL. Determinants of delays in treatment initiation in children and adolescents diagnosed with leukemia or lymphoma in Canada. Int J Cancer. 2010 Apr 15;126(8):1936-1943. doi: 10.1002/ijc.24906. PMID: 19795458.
  34. Martin S, Ulrich C, Munsell M, Taylor S, Lange G, Bleyer A. Delays in cancer diagnosis in underinsured young adults and older adolescents. Oncologist. 2007 Jul;12(7):816-24. doi: 10.1634/theoncologist.12-7-816. PMID: 17673613.
  35. Marquant F, Goujon S, Faure L, Guissou S, Orsi L, Hémon D, Lacour B, Clavel J. Risk of Childhood Cancer and Socio-economic Disparities: Results of the French Nationwide Study Geocap 2002-2010. Paediatr Perinat Epidemiol. 2016 Nov;30(6):612-622. doi: 10.1111/ppe.12313. Epub 2016 Aug 24. PMID: 27555468.
  36. Sedgwick P. How to read a Kaplan-Meier survival plot. BMJ. 2014 Sep 12;349:g5608. doi: 10.1136/bmj.g5608. PMID: 25216915.

Figures:

Similar Articles

Recently Viewed

Read More

Most Viewed

Read More

Help ?