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However, there are currently no established predictive biomarkers of placebo response. We examined the patterns of association between placebo response and baseline plasma cytokine levels for 10 symptoms in patients with cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is an exploratory analysis of the double-blind, randomized ABCD trial, which compared high-dose dexamethasone to placebo for dyspnea treatment in patients with cancer (clinicaltrials.gov; NCT03367156). The primary outcome was change in dyspnea intensity. Four plasma cytokines (TNF, IL-6, IL-8, and IL-10) and 10 Edmonton Symptom Assessment System symptoms were measured at baseline, day 7, and day 14. Generalized additive models and exploratory analyses were used to examine the patterns of association between baseline cytokine levels and symptom responses on day 7 and day 14 in placebo and dexamethasone groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This analysis included data from 45 patients. In the placebo group, we observed a significant negative association (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) between\u2009\u2265\u20091 of the measured cytokines\u2019 baseline levels across multiple symptoms on day 7 (5\/10 symptoms) and day 14 (3\/10 symptoms), including appetite, drowsiness, nausea, and pain. Exploratory analysis revealed a negative association in the placebo group in 33\/40 cytokine-symptom response combinations for day 7 (\n                      <jats:italic>p\u2009<\/jats:italic>\n                      &lt;\u20090.001) and 29\/40 combinations for day 14 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our preliminary findings suggest patients with high baseline cytokine levels may be less likely to report placebo response for multiple symptoms. Upon further confirmation, these findings may have implications for future clinical trial design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Structured abstract<\/jats:title>\n                    <jats:p>In this exploratory analysis, we observed that patients with cancer were less likely to report placebo response for multiple symptoms if they had higher levels of baseline cytokines. These preliminary findings have important potential implications for placebo-controlled clinical trials, including patient selection, design of interventional controls, and trial interpretation. Additionally, they invite further research on possible mechanistic links between inflammation and placebo effect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00520-026-10689-9","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:10:39Z","timestamp":1776834639000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predictive biomarkers of placebo response in patients with cancer: an exploratory analysis of the ABCD randomized clinical trial"],"prefix":"10.1007","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2733-6607","authenticated-orcid":false,"given":"David","family":"Hui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristofer","family":"Jennings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Ontai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra K.","family":"Hanneman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Bruera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"10689_CR1","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1136\/bmjspcare-2019-002163","volume":"10","author":"R Roji","year":"2020","unstructured":"Roji R, Stone P, Ricciardi F, Candy B (2020) Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression. 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