{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T04:10:49Z","timestamp":1778299849841,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    Conventional RECIST criteria compress heterogeneous metastatic lesions into a single sum\u2010of\u2010diameters endpoint, which can obscure organ\u2010specific pharmacologic effects on response durability and thereby limit the interpretability of efficacy signals used for model\u2010informed drug development and clinical decision making. We developed a lesion\u2010level modeling framework to quantify compartment\u2010dependent therapeutic effects using routinely collected RECIST diameters. Lesion trajectories were characterized using nonlinear mixed\u2010effects modeling to estimate regression\/kill (kkill), regrowth\/progression (kge), and a resistance\u2010like fraction (Fx). We then fit pan\u2010cancer multivariable Cox models (adjusted for cancer lineage, treatment class, and clinical covariates) to quantify the independent contribution of metastatic site to response and progression hazards. Organ site emerged as a consistent determinant of response durability across lineages. Liver metastases frequently showed early shrinkage yet higher progression risk, whereas bone metastases, particularly in prostate cancer, tended to regress more slowly but exhibited more durable control once response occurred. Inter\u2010lesion heterogeneity in progression dynamics was greatest in breast and non\u2010small cell lung cancer and lowest in colorectal and pancreatic cancer. To contextualize site effects, we explored literature\u2010derived estimates of Vascular Perfusion and Leakiness Index (VaPLI) for each organ, along with a broad immune surveillance classification. VaPLI correlated with response probability (\u03c1\u2009=\u20090.44;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01), and immune\u2010tolerant sites showed higher progression hazards (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). With further verification, this analysis can support lesion site\u2010stratified efficacy evaluation by distinguishing true treatment effects from site\u2010driven bias, enabling more balanced interpretation of treatment effects and dose\u2013response relationships.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70260","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T04:01:00Z","timestamp":1773374460000},"page":"1638-1649","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative Lesion\u2010Level Modeling Reveals Organ\u2010Dependent Therapeutic Response"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8205-1569","authenticated-orcid":false,"given":"Ian","family":"Dilley","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3317-0311","authenticated-orcid":false,"given":"Jiawei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Lineberger Comprehensive Cancer Center, School of Medicine University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0707-2763","authenticated-orcid":false,"given":"Quefeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Gillings School of Global Public Health University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3974-9073","authenticated-orcid":false,"given":"Yanguang","family":"Cao","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"},{"name":"Lineberger Comprehensive Cancer Center, School of Medicine University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-025-03072-x"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-009-1685-y"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36121-y"},{"key":"e_1_2_11_4_1","article-title":"Cellular and molecular mechanisms of the tumor stroma in colorectal cancer: insights into disease progression and therapeutic targets","volume":"11","author":"Shakhpazyan N.","year":"2023","journal-title":"Biomedicine"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2025.104744"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12195"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13068"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13128"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12629"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.70095"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyag009"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2953"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13137"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12686"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12384"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12454"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-008-9094-4"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.4274\/Mirt.138"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-011-9232-2"},{"key":"e_1_2_11_20_1","first-page":"90","article-title":"Physiologically based pharmacokinetic (PBPK) model for biodistribution of radiolabeled peptides in patients with neuroendocrine Tumours","volume":"4","author":"Gospavic R.","year":"2016","journal-title":"Asia Ocean. 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