{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:43:29Z","timestamp":1785527009958,"version":"3.56.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      EPOCH demonstrated superior progression free survival using yttrium-90 [\n                      <jats:sup>90<\/jats:sup>\n                      Y] glass microspheres radioembolization plus chemotherapy versus chemotherapy in colorectal cancer patients with liver metastases who had progressed following first-line oxaliplatin or irinotecan-based chemotherapy. Exploratory post-hoc analyses and theoretical modeling assessed the potential impact of dosimetry on safety outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>Liver-related treatment-emergent adverse event (TEAE) frequency and\/or severity, and bilirubin increase were explored in participating patients. For hypothesis generation, a theoretical model was constructed to understand EPOCH dosimetry in the absence of multicompartment dosimetry data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Liver-related TEAEs were reported in 93\/186 (50%) patients, TEAEs\u2009\u2265\u2009grade 3 in 44\/186 (24%) patients. A total of 26\/186 patients (14%) experienced a bilirubin increase TEAE of any grade, in five of which assessed as related to glass [\n                      <jats:sup>90<\/jats:sup>\n                      Y]Y-radioembolization with a median fractional tumour involvement of 2.3% (range 1.4\u20134.1%). Under the theoretical assumption of a T\/N ratio of 2\u201310, most patients in EPOCH (62% had a fractional tumour involvement\u2009&lt;\u200910%) received a normal liver absorbed dose of at least 75 Gy. In this model, at &lt;\u20094.1% fractional tumour involvement, the normal liver absorbed dose approximates 120 Gy at any T\/N ratio.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>When treatment is same-day whole liver at 120 Gy average absorbed dose, the normal liver absorbed dose is dependent on fractional tumour involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT01483027.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-07948-6","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T01:29:47Z","timestamp":1780018187000},"page":"5994-5998","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Post-hoc analysis of adverse events during the EPOCH trial: reconsidering dosimetry"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4902-9790","authenticated-orcid":false,"given":"Marnix","family":"Lam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kersting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline","family":"Boucher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Garin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk","family":"Fowers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riad","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"7948_CR1","doi-asserted-by":"publisher","unstructured":"Mulcahy MF, Mahvash A, Pracht M, Montazeri AH, Bandula S, Martin RCG 2, et al. Radioembolization With Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial. J Clin Oncol. 2021;39:3897\u2013907. https:\/\/doi.org\/10.1200\/JCO.21.01839.","DOI":"10.1200\/JCO.21.01839"},{"key":"7948_CR2","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.remnie.2021.12.004","volume":"41","author":"A Ruiz-Casado","year":"2022","unstructured":"Ruiz-Casado A, Gutierrez Sanz L, Franco Perez F, Sanchez Ruiz AC. Treatment of colorectal liver metastases with y-90: the problem is the toxicity. Rev Esp de Med Nucl Imagen Mol. 2022;41:66\u20138. https:\/\/doi.org\/10.1016\/j.remnie.2021.12.004.","journal-title":"Rev Esp de Med Nucl Imagen Mol"},{"key":"7948_CR3","doi-asserted-by":"publisher","first-page":"3887","DOI":"10.1200\/JCO.21.01993","volume":"39","author":"RW Lentz","year":"2021","unstructured":"Lentz RW, Messersmith WA. Transarterial Radioembolization in Patients With Unresectable Colorectal Cancer Liver Metastases. J Clin Oncol. 2021;39:3887\u20139. https:\/\/doi.org\/10.1200\/JCO.21.01993.","journal-title":"J Clin Oncol"},{"key":"7948_CR4","doi-asserted-by":"publisher","first-page":"156","DOI":"10.3348\/kjr.2021.0867","volume":"23","author":"H Kim","year":"2022","unstructured":"Kim H. Role of Yttrium-90 Radioembolization for Colorectal Hepatic Metastasis. Korean J Radiol. 2022;23:156\u20138. https:\/\/doi.org\/10.3348\/kjr.2021.0867.","journal-title":"Korean J Radiol"},{"key":"7948_CR5","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.remnie.2022.02.003","volume":"41","author":"J Orcajo-Rincon","year":"2022","unstructured":"Orcajo-Rincon J, Rodriguez-Fraile M. Is everything said in the treatment of colorectal cancer liver metastases with radioembolization, after the EPOCH results? Rev Esp Med Nucl Imagen Mol. 2022;41:69\u201370. https:\/\/doi.org\/10.1016\/j.remnie.2022.02.003.","journal-title":"Rev Esp Med Nucl Imagen Mol"},{"key":"7948_CR6","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1093\/oncolo\/oyae128","volume":"29","author":"R Salem","year":"2024","unstructured":"Salem R, Garin E, Boucher E, Fowers K, Lam M, Padia S, et al. Optimal patient selection for yttrium-90 glass plus chemotherapy in the treatment of colorectal liver metastases: additional quality of life, efficacy, and safety analyses from the EPOCH study. Oncologist. 2024;29:681\u20139. https:\/\/doi.org\/10.1093\/oncolo\/oyae128.","journal-title":"Oncologist"},{"key":"7948_CR7","doi-asserted-by":"publisher","first-page":"3820","DOI":"10.1007\/s00259-025-07229-8","volume":"52","author":"M Lam","year":"2025","unstructured":"Lam M, Salem R, Toskich B, Kappadath SC, Chiesa C, Fowers K, et al. Clinical and dosimetric considerations for yttrium-90 glass microspheres radioembolization of intrahepatic cholangiocarcinoma, metastatic colorectal carcinoma, and metastatic neuroendocrine carcinoma: recommendations from an international multidisciplinary working group. Eur J Nucl Med Mol Imaging. 2025;52:3820\u201332. https:\/\/doi.org\/10.1007\/s00259-025-07229-8.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"7948_CR8","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.2967\/jnumed.120.255745","volume":"62","author":"AA Alsultan","year":"2021","unstructured":"Alsultan AA, van Roekel C, Barentsz MW, Smits MLJ, Kunnen B, Koopman M, et al. Dose-Response and Dose-Toxicity Relationships for Glass (90)Y Radioembolization in Patients with Liver Metastases from Colorectal Cancer. 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EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds. 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DK reports a research grant from Pfizer, personal fees from GE Healthcare and Novartis, travel grants from Life Molecular Imaging and Sanofi and speaker honoraria from Pfizer, outside the submitted work. WH reports research support from Astra Zeneca, Eureka Therapeutics and Pfizer, consultancy for Boston Scientific. EB and KF are employees of Boston Scientific. EG reports consultancy for Boston Scientific. RS reports consultancy for Cook, Siemens, Sirtex, Bard, AstraZeneca, Eisai, TriSalus, Genentech and Boston Scientific.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"EPOCH involved human participants and was conducted in accordance with the International Conference on Harmonization guidelines for Good Clinical Practice and the principles of the Declaration of Helsinki. All patients provided informed consent. The Protocol was approved by each institution\u2019s review board.","order":2,"name":"Ethics","label":"Compliance with ethical standards","group":{"name":"EthicsHeading","label":"Declarations"}}]}}