{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:29:54Z","timestamp":1786364994852,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State of Florida James Esther King Award"},{"id":[{"id":"https:\/\/ror.org\/04x1xkh65","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Former and current smokers in lung cancer screening remain at elevated risk for lung cancer despite smoking cessation. We and others have shown that curcumin (CUR) exhibits anti-inflammatory and antiproliferative effects but is limited by poor bioavailability. However, since CUR is lipophilic, co-administration with \u03c9-3 FAs represents a mechanistically rational strategy to enhance delivery and target complementary pathways, including signal transducer and activator of transcription 3 (STAT3) and the transcription factor NF-\u03baB (NF-\u03baB) signaling for lung cancer chemoprevention. Methods: We conducted a randomized, single-blind, placebo-controlled Phase II pilot study evaluating CUR combined with \u03c9-3 FAs in high-risk former and current smokers with CT-detected pulmonary nodules. Participants received intervention agents with active-dose groups (low dose = 3; high dose = 9) or a placebo (n = 7) for 6 months. Primary endpoints included radiologic changes in nodule size, number, and density. Secondary endpoints included safety, adherence to the study agent and exploratory biomarker analyses. Correlation analyses of imaging-derived metrics were performed to assess relationships among LDCT parameters. Results: Nineteen participants were enrolled (intervention, n = 12; placebo, n = 7). Eighteen (11 intervention, 7 placebo) subjects completed post-intervention imaging. One subject was unable to complete follow-up and study-related procedures. Data from the treatment arms were pooled for analysis and comparison with the placebo arm. No statistically significant between-group differences were observed in primary imaging endpoints. The intervention was well tolerated, with predominantly grade 1 adverse events. Exploratory analyses demonstrated consistent positive correlations among established imaging biomarkers, with clustering of size-based metrics (mean diameter, volume, sum of longest diameters) and density-based parameters. Multidimensional scaling supported this structure, indicating internal coherence among imaging-derived endpoints. Conclusions: Although no statistically significant treatment effect on the image biomarkers was observed, this pilot study demonstrates feasibility challenges and identifies coherent imaging biomarkers that may serve as intermediate endpoints in early-phase chemoprevention trials. These results support further investigation of strategies utilizing agent combinations with enhanced bioavailability and safety and refinement of trial design in high-risk lung cancer patient populations.<\/jats:p>","DOI":"10.3390\/cancers18162565","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:38:09Z","timestamp":1786361889000},"page":"2565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multidimensional LDCT Imaging Endpoints for a Randomized Pilot Phase II Trial of Curcumin and Omega-3 Fatty Acids for Lung Cancer Chemoprevention: Results of a Randomized Pilot Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-2627","authenticated-orcid":false,"given":"Nagi B.","family":"Kumar","sequence":"first","affiliation":[{"name":"Cancer Epidemiology Program, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"},{"name":"Genitourinary Oncology Program, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3241-3216","authenticated-orcid":false,"given":"Matthew","family":"Schabath","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Program, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4661-0368","authenticated-orcid":false,"given":"Mark","family":"Alexandrow","sequence":"additional","affiliation":[{"name":"Molecular Biology Program, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhanelle","family":"Gray","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawee","family":"Tanventyanon","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2366-7209","authenticated-orcid":false,"given":"Farah","family":"Khalil","sequence":"additional","affiliation":[{"name":"Pathology, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2003-9653","authenticated-orcid":false,"given":"Jos\u00e9","family":"Laborde","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Program, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4594-6601","authenticated-orcid":false,"given":"Michael J.","family":"Schell","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Program, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Klippenstein","sequence":"additional","affiliation":[{"name":"Thoracic Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1513\/pats.200807-067LC","article-title":"Chemoprevention of lung cancer","volume":"6","author":"Keith","year":"2009","journal-title":"Proc. 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