{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T22:00:25Z","timestamp":1775167225230,"version":"3.50.1"},"reference-count":19,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Clin Cancer Inform"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Health-related quality of life (HRQoL) is a valuable counterpart to other end points in oncology trials. However, when analyzing the effect of treatment on HRQoL, results are often mixed. Cancer and its treatment can have direct and indirect effects on symptoms such as pain, nausea, and fatigue. These, in turn, can affect the patients' physical and social functioning and ultimately their HRQoL. This causal cascade requires methodologies, such as structural equation modeling, to estimate direct, indirect, and total effects of symptoms on more distal HRQoL outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Data were obtained from two multicenter, randomized trials available from Project Data Sphere, LLC. One trial included patients with non\u2013small cell lung cancer; the other included patients with metastatic breast cancer. Structural equation models were evaluated; models included symptom items from the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire, QLQ-C30 (version 3). A causal cascade of individual symptoms at two time points was hypothesized to affect fatigue, which, in turn, had direct and indirect effects on the functional and HRQoL measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Results showed a logical, causal ordering among EORTC QLQ-C30 outcomes. In the final model, the effects of most symptoms on functional domains and the quality of life (QoL) scale were through their direct effect on fatigue, which, in turn, affected patient functioning and HRQoL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Results strongly suggest that when examining the effects of symptoms on EORTC QLQ-C30 functional scales or HRQoL, symptoms would generally not show direct effects on these more distal outcomes. The results from the two clinical trials demonstrated that anticipating a causal cascade from specific symptoms to functional domains and HRQoL would yield more meaningful results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/cci-25-00127","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T21:00:13Z","timestamp":1769202013000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Causal Cascade of Symptoms on Patient Functioning and Health-Related Quality of Life in Non\u2013Small Cell Lung Cancer and Metastatic Breast Cancer"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9808-5417","authenticated-orcid":true,"given":"Donald E.","family":"Stull","sequence":"first","affiliation":[{"name":"Patient Centered Solutions, IQVIA, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2018.09.2842"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.585"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2016.09.2295"},{"key":"e_1_3_5_5_2","unstructured":"Stull DE Houghton K Ainsworth C et al: The effects of disease and treatment-associated cancer symptoms on health-related quality-of-life: The mediating effect of fatigue in non-small cell lung cancer and metastatic breast cancer. Presented at the ISPOR 22nd Annual International Meeting Boston MA USA 2017"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.35.15_suppl.1060"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/03637750903310360"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/0002764296039003008"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2009.12.006"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac138"},{"key":"e_1_3_5_11_2","doi-asserted-by":"crossref","unstructured":"Bollen KA Pearl J. Eight myths about causality and structural equation models in Morgan SL (ed): Handbook of Causal Analysis for Social Research. Dordrecht the Netherlands: Springer pp 301\u2010328 2013","DOI":"10.1007\/978-94-007-6094-3_15"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-011-0082-6"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2015.08.007"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.5981"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.937"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/85.5.365"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.4135\/9781412983600"},{"key":"e_1_3_5_18_2","unstructured":"Muthen LK Muthen BO: Mplus User\u2019s Guide (ed 8). Los Angeles CA Muth\u00e9n & Muth\u00e9n pp 1998-2021 2017"},{"key":"e_1_3_5_19_2","volume-title":"Principles and Practice of Structural Equation Modeling","author":"Kline R","year":"2023","unstructured":"Kline R: Principles and Practice of Structural Equation Modeling (ed 5). New York, NY, Guildford Press, 2023","edition":"5"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv391"}],"container-title":["JCO Clinical Cancer Informatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/CCI-25-00127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T21:31:23Z","timestamp":1775165483000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/CCI-25-00127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1200\/CCI-25-00127"],"URL":"https:\/\/doi.org\/10.1200\/cci-25-00127","relation":{},"ISSN":["2473-4276"],"issn-type":[{"value":"2473-4276","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-05-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-31","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2500127"}}