{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:03:18Z","timestamp":1789556598167,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the state of Mecklenburg-Vorpommern","award":["TBI-V-1-241-VBW-084"],"award-info":[{"award-number":["TBI-V-1-241-VBW-084"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Patient-derived xenograft (PDX) models retain clinically relevant features of the donor tumor, but the establishment of colorectal cancer (CRC) PDX models succeeds in only a fraction of attempts. Whether routinely available clinicopathological and experimental variables can predict engraftment for a previously unseen tumor has not been established under a validation design that respects the clustered structure of PDX datasets. Methods: We retrospectively analyzed 1007 first-generation CRC-PDX establishment attempts from 381 specimens (328 patients). Primary analysis used specimen-grouped validation with nested grouped cross-validation; all preprocessing was performed within training folds. Secondary analyses included patient-grouped, attempt-level, specimen-level and temporal validation. Results: Attempt success was 46.3%; 68.8% of specimens yielded \u22651 PDX. Within-specimen correlation was substantial (0.31). Under specimen-grouped validation, pooled AUC was 0.550 (95% CI 0.508\u20130.591), PR-AUC was 0.500, Brier was 0.253, and sensitivity\/specificity was 0.42\/0.64. Patient-grouped validation was similar (0.548), while attempt-level splitting inflated AUC to 0.68\u20130.69, confirming bias from specimen clustering rather than preprocessing leakage. Specimen-level prediction reached 0.636; calendar-time temporal validation yielded 0.584. Sensitivity analyses were stable. Conclusions: Routine variables offer only marginal discrimination for CRC-PDX engraftment in new tumors. Moderate attempt-level performance reflects repeated sampling of the same tumors, not a generalizable signal. These results do not support routine-variable-based triage and identify molecular and tissue-quality factors as the necessary next step.<\/jats:p>","DOI":"10.3390\/cancers18182996","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:09:17Z","timestamp":1789553357000},"page":"2996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Limits of Predicting Colorectal Cancer PDX Engraftment: A Specimen-Grouped Machine Learning Analysis of 1007 Establishment Attempts"],"prefix":"10.3390","volume":"18","author":[{"given":"Menglan","family":"Liu","sequence":"first","affiliation":[{"name":"Molecular Oncology and Immunotherapy, Clinic of General Surgery, University Medical Center Rostock, Schillingallee 35, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Krohn","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Immunotherapy, Clinic of General Surgery, University Medical Center Rostock, Schillingallee 35, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Immunotherapy, Clinic of General Surgery, University Medical Center Rostock, Schillingallee 35, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6746-7260","authenticated-orcid":false,"given":"Maria","family":"Witte","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Immunotherapy, Clinic of General Surgery, University Medical Center Rostock, Schillingallee 35, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Prall","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8054-1402","authenticated-orcid":false,"given":"Michael","family":"Linnebacher","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Immunotherapy, Clinic of General Surgery, University Medical Center Rostock, Schillingallee 35, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. 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