453: Pain Phenotyping for Precision Care in Childhood Cancer Survivors: A St. Jude Lifetime Cohort Study

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic cancer related pain, Psychology, Epidemiology, Pain in special populations (e.g. neonates, children, teens, elderly, neurodegenerative diseases)

Background and Aims: Survival after childhood cancer has improved substantially, yet chronic pain remains a prevalent and insufficiently characterized late effect. Pain presentations among survivors vary widely across affective, cognitive, sleep, and somatic symptoms, making the identification of risk factors and long‑term functional consequences challenging. No prior reports have applied a comprehensive multidimensional framework to characterize pain in this population, limiting opportunities for precision survivorship care. Leveraging pain models from non-cancer chronic pain populations, this project aimed to identify multidimensional pain phenotypes, their associations with clinical and sociodemographic predictors, and evaluate associations with social and health outcomes among adult survivors of childhood cancer.

Methods: Participants were enrolled in the St. Jude Lifetime Cohort Study (n=1,006; mean age=34.7; cancer diagnosis age=9.2; 33% leukemia; 12% CNS tumor) and reported pain or prescription analgesic use, and completed self-report and objective assessments across affective, somatic/sensory, cognitive, and sleep domains. Latent class analysis utilized 27 indicators across these 4 domains to derive pain phenotypes. Clinical (diagnosis and treatment) and sociodemographic factors were examined as predictors of class membership using multinomial logistic regression. Multivariable regression models examined associations between pain class and social and health outcomes (chronic health conditions). Results are presented as odds ratios(OR) with 95% CIs.

Results: Four pain phenotypes emerged: Cognitive-problems (9%), Distressed-somatic (30%), Cancer-worry (40%); Resilient (Referent: 21%).
CNS tumor diagnosis (vs. leukemia: 2.23[1.07-4.65]) and cranial radiation (vs. no radiation: 3.21[1.69-6.09]) were associated with Cognitive-problems; non-cranial radiation (vs. no radiation) with Distressed-somatic (2.04[1.22-3.40]) and Cancer-worry (1.72[1.06-2.78]) phenotypes.
Cognitive-problems and Distressed-somatic pain phenotypes were at risk for poor social (low education [14.19(5.56-36.21);2.97(1.49-5.92)]; unemployment [3.02(1.74-5.23); 2.30(1.5-3.42)]; no driver’s license [Cognitive-problems=2.62(1.27-5.40)]), and health (grade≥2 gastrointestinal [3.26(1.57-6.79); 2.68(1.50-4.81)], neurologic [3.45(1.96-6.08); 2.43(1.58-3.72)], musculoskeletal [Cognitive-problems=1.83(1.03-3.27)] conditions; frail health status [13.39(4.86-36.91);10.47(4.50-24.39)]) outcomes.
The Cancer-worry phenotype was at risk of non-independent living (0.65[0.42-1.00]) and gastrointestinal conditions (1.87[1.05-3.34]).

Conclusions: This study provides a novel multidimensional characterization of pain phenotypes in adult survivors of childhood cancer and identified predictors and outcomes that distinguish high vulnerability from resilient profiles. Diagnosis, treatment exposures, and socioeconomic disadvantage predicted distinct pain phenotypes with differential cognitive, affective, somatic, and functional patterns—phenotypes that, in turn, conferred elevated risk for adverse social and health outcomes. High-vulnerability profiles, marked by cognitive problems and distressed-somatic pain features, were linked to impaired functioning, multimorbidity, and social role attainment. These findings highlight survivorship pain heterogeneity and the need for phenotype-informed, mechanism-based strategies for screening, intervention, and multidisciplinary care.

References: 1. Bhakta N, Liu Q, Ness KK, Baassiri M, Eissa H, Yeo F, Chemaitilly W, Ehrhardt MJ, Bass J, Bishop MW, et al. The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE). Lancet. 2017;390:2569-2582. doi: 10.1016/S0140-6736(17)31610-0

2. Brinkman TM, Recklitis CJ, Michel G, Grootenhuis MA, Klosky JL. Psychological Symptoms, Social Outcomes, Socioeconomic Attainment, and Health Behaviors Among Survivors of Childhood Cancer: Current State of the Literature. J Clin Oncol. 2018;36:2190-2197. doi: 10.1200/JCO.2017.76.5552

3. Robison LL, Hudson MM. Survivors of childhood and adolescent cancer: Life-long risks and responsibilities. In; 2014:61-70.

4. Melzack R, Casey K. Sensory, Motivational, and Central Control Determinants of Pain: A New Conceptual Model. 1968.

5. Schulte FSM, Patton M, Alberts NM, Kunin-Batson A, Olson-Bullis BA, Forbes C, Russell KB, Neville A, Heathcote LC, Karlson CW, et al. Pain in long-term survivors of childhood cancer: A systematic review of the current state of knowledge and a call to action from the Children's Oncology Group. In: John Wiley and Sons Inc; 2020:35-44.

6. Karlson CW, Alberts NM, Liu W, Brinkman TM, Annett RD, Mulrooney DA, Schulte F, Leisenring WM, Gibson TM, Howell RM, et al. Longitudinal pain and pain interference in long-term survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. In: John Wiley and Sons Inc.; 2020:2915-2923.

7. Tonning Olsson I, Alberts NM, Li C, Ehrhardt MJ, Mulrooney DA, Liu W, Pappo AS, Bishop MW, Anghelescu DL, Srivastava D, et al. Pain and functional outcomes in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort study. In: John Wiley and Sons Inc; 2021:1679-1689.

8. Huang IC, Brinkman TM, Kenzik K, Gurney JG, Ness KK, Lanctot J, Shenkman E, Robison LL, Hudson MM, Krull KR. Association between the prevalence of symptoms and health-related quality of life in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort study. J Clin Oncol. 2013;31:4242-4251. doi: 10.1200/JCO.2012.47.8867

9. Alberts NM, Gagnon MM, Stinson JN. Chronic pain in survivors of childhood cancer: a developmental model of pain across the cancer trajectory. Pain. 2018;159:1916-1927. doi: 10.1097/j.pain.0000000000001261

10. Lu Q, Krull KR, Leisenring W, Owen JE, Kawashima T, Tsao JCI, Zebrack B, Mertens A, Armstrong GT, Stovall M, et al. Pain in long-term adult survivors of childhood cancers and their siblings: A report from the Childhood Cancer Survivor Study. In; 2011:2616-2624.

11. Chua GWY, Vig PS. Overview of radiotherapy-induced chronic pain in childhood cancer survivors: A narrative review. Paediatr Neonatal Pain. 2023;5:1-9. doi: 10.1002/pne2.12094

12. Grundy R, Hulse RP. Chronic pain and childhood cancer survivorship. Current Opinion in Physiology. 2019;11:58-61. doi: 10.1016/j.cophys.2019.06.002

13. Khan RB, Hudson MM, Ledet DS, Morris EB, Pui CH, Howard SC, Krull KR, Hinds PS, Crom D, Browne E, et al. Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross-sectional study. J Cancer Surviv. 2014;8:688-696. doi: 10.1007/s11764-014-0375-1

14. Patton M, Racine N, Afzal AR, Russell KB, Forbes C, Trépanier L, Khu M, Neville A, Noel M, Reynolds K, et al. The Pain of Survival: Prevalence, Patterns, and Predictors of Pain in Survivors of Childhood Cancer. In: American Psychological Association; 2021:784-792.

15. Reinfjell T, Zeltzer L. A systematic review of self-reported pain in childhood cancer survivors. Acta Paediatr. 2020;109:56-70. doi: 10.1111/apa.14977

16. Brinkman TM, Zhu L, Zeltzer LK, Recklitis CJ, Kimberg C, Zhang N, Muriel AC, Stovall M, Srivastava DK, Robison LL, et al. Longitudinal patterns of psychological distress in adult survivors of childhood cancer. Br J Cancer. 2013;109:1373-1381. doi: 10.1038/bjc.2013.428

17. McDonnell GA, Brinkman TM, Wang M, Gibson TM, Heathcote LC, Ehrhardt MJ, Srivastava DK, Robison LL, Hudson MM, Alberts NM. Prevalence and predictors of cancer-related worry and associations with health behaviors in adult survivors of childhood cancer. Cancer. 2021;127:2743-2751. doi: 10.1002/cncr.33563

18. Rakel BA, Zimmerman BM, Geasland K, Embree J, Clark CR, Noiseux NO, Callaghan JJ, Herr K, Walsh D, Sluka KA. Transcutaneous electrical nerve stimulation for the control of pain during rehabilitation after total knee arthroplasty: A randomized, blinded, placebo-controlled trial. Pain. 2014;155:2599-2611. doi: 10.1016/j.pain.2014.09.025

19. Jamison RN, Edwards RR, Liu X, Ross EL, Michna E, Warnick M, Wasan AD. Relationship of negative affect and outcome of an opioid therapy trial among low back pain patients. Pain Pract. 2013;13:173-181. doi: 10.1111/j.1533-2500.2012.00575.x

20. Carroll IR, Younger JW, Mackey SC. Pain Quality Predicts Lidocaine Analgesia among Patients with Suspected Neuropathic Pain. Pain Medicine. 2010;11:617-621.

21. Gammaitoni AR, Smugar SS, Jensen MP, Galer BS, Bolognese JA, Alon A, Hewitt DJ. Predicting Response to Pregabalin from Pretreatment Pain Quality: Clinical Applications of the Pain Quality Assessment Scalepme_. Pain Medicine. 2013;14.

22. Bouhassira D, Wilhelm S, Schacht A, Perrot S, Kosek E, Cruccu G, Freynhagen R, Tesfaye S, Lledo A, Choy E, et al. Neuropathic pain phenotyping as a predictor of treatment response in painful diabetic neuropathy: data from the randomized, double-blind, COMBO-DN study. Pain. 2014;155:2171-2179. doi: 10.1016/j.pain.2014.08.020

23. Vinik A, Emir B, Parsons B, Cheung R. Prediction of Pregabalin-Mediated Pain Response by Severity of Sleep Disturbance in Patients with Painful Diabetic Neuropathy and Post-Herpetic Neuralgia. 2014;15:661-670.

24. Turner JA, Holtzman S, Mancl L. Mediators, moderators, and predictors of therapeutic change in cognitive-behavioral therapy for chronic pain. Pain. 2007;127:276-286. doi: 10.1016/j.pain.2006.09.005

25. De Baets L, Matheve T, Meeus M, Struyf F, Timmermans A. The influence of cognitions, emotions and behavioral factors on treatment outcomes in musculoskeletal shoulder pain: a systematic review. Clin Rehabil. 2019;33:980-991. doi: 10.1177/0269215519831056

26. Edwards RR, Dworkin RH, Turk DC, Angst MS, Dionne R, Freeman R, Hansson P, Haroutounian S, Arendt-Nielsen L, Attal N, et al. Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations. PAIN Reports. 2021;6. doi: 10.1097/pr9.0000000000000896

27. Patton M, Forster VJ, Forbes C, Stokoe M, Noel M, Carlson LE, Birnie KA, Reynolds K, Schulte F. Characterizing pain in long-term survivors of childhood cancer. In: Springer Science and Business Media Deutschland GmbH; 2022:295-303.

28. Robison LL, Green DM, Hudson M, Meadows AT, Mertens AC, Packer RJ, Sklar CA, Strong LC, Yasui Y, Zeltzer LK. Long-term outcomes of adult survivors of childhood cancer. Cancer. 2005;104:2557-2564. doi: 10.1002/cncr.21249

29. Krull KR, Hardy KK, Kahalley LS, Schuitema I, Kesler SR. Neurocognitive Outcomes and Interventions in Long-Term Survivors of Childhood Cancer. J Clin Oncol. 2018;36:2181-2189. doi: 10.1200/JCO.2017.76.4696

30. Hudson MM, Mertens AC, Yasui Y, Hobbie W, Chen H, Gurney JG, Yeazel M, Recklitis CJ, Marina N, Robison LR, et al. Health status of adult longterm survivors of childhood cancer: a report from the childhood cancer survivor study. JAMA. 2003;290(12):1583‐1592. JAMA. 2003;290:1583-1592.

31. Morgan GB. Mixed Mode Latent Class Analysis: An Examination of Fit Index Performance for Classification. Structural Equation Modeling: A Multidisciplinary Journal. 2015;22:76-86. doi: 10.1080/10705511.2014.935751

Presenting Author: Cassie Mae Argenbright, PhD
Submitting Author: Cassie Argenbright

Senior Author: Tara M. Brinkman, PhD

IASP 2026 Global Year theme of Neuropathic Pain: No

• Cassie Mae Argenbright: PhD - Department of Psychology and Biobehavioral Sciences, St. Jude Children’s Research Hospital
• Lei Wang: MS - Department of Biostatistics, St. Jude Children’s Research Hospital
• Kendrick Li: PhD - Department of Biostatistics, St. Jude Children’s Research Hospital
• Michael Frett: MD - Department of Pediatric Medicine, Anesthesiology Division, St. Jude Children’s Research Hospital
• Ryan James: PhD - Department of Psychology and Biobehavioral Sciences, St. Jude Children’s Research Hospital
• Daniel A. Mulrooney: MD - Department of Oncology, St. Jude Children’s Research Hospital
• Jerlym S. Porter: PhD, MPH - Department of Psychology and Biobehavioral Sciences, St. Jude Children’s Research Hospital
• Kirsten K. Ness: PhD - Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital
• Melissa M. Hudson: MD - Department of Oncology, St. Jude Children’s Research Hospital
• Deo Kumar Srivastava: PhD - Department of Biostatistics, St. Jude Children’s Research Hospital
• Kevin R. Krull: PhD - Department of Psychology and Biobehavioral Sciences, St. Jude Children’s Research Hospital
• Tara M. Brinkman: PhD - Department of Psychology and Biobehavioral Sciences, St. Jude Children’s Research Hospital