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Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as\u2009\u2265\u200950% viability reduction and p\u2009&lt;\u20090.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16\/17 (94.1%) sites undergoing comparative 37\u00b0 and 42\u00b0 treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12\/16 (75%) tumors and an average viability of 38% (5\u201368%). Heated MMC demonstrated efficacy in 7\/16 (43.8%) tumors with an average treatment viability of 51% (17\u201392.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC.<\/jats:p>","DOI":"10.1038\/s41598-023-38545-4","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T10:14:42Z","timestamp":1689761682000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cisplatin exhibits superiority over MMC as a perfusion agent in a peritoneal mesothelioma patient specific organoid HIPEC platform"],"prefix":"10.1038","volume":"13","author":[{"given":"Steven D.","family":"Forsythe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Erali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Edenhoffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Meeker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem","family":"Wajih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia R.","family":"Schaaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preston","family":"Laney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian D.","family":"Vanezuela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"Levine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shay","family":"Soker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos I.","family":"Votanopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"38545_CR1","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1007\/s10552-009-9328-9","volume":"20","author":"SH Moolgavkar","year":"2009","unstructured":"Moolgavkar, S. H., Meza, R. & Turim, J. Pleural and peritoneal mesotheliomas in SEER: Age effects and temporal trends, 1973\u20132005. Cancer Causes Control 20, 935\u2013944. https:\/\/doi.org\/10.1007\/s10552-009-9328-9 (2009).","journal-title":"Cancer Causes Control"},{"key":"38545_CR2","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1002\/jso.21167","volume":"99","author":"D Rodriguez","year":"2009","unstructured":"Rodriguez, D., Cheung, M. C., Housri, N. & Koniaris, L. G. Malignant abdominal mesothelioma: Defining the role of surgery. J. Surg. Oncol. 99, 51\u201357. https:\/\/doi.org\/10.1002\/jso.21167 (2009).","journal-title":"J. Surg. Oncol."},{"key":"38545_CR3","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1245\/s10434-014-3978-x","volume":"22","author":"JH Helm","year":"2015","unstructured":"Helm, J. H. et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: A systematic review and meta-analysis. Ann. Surg. Oncol. 22, 1686\u20131693. https:\/\/doi.org\/10.1245\/s10434-014-3978-x (2015).","journal-title":"Ann. Surg. Oncol."},{"key":"38545_CR4","first-page":"25","volume":"4","author":"AU Blackham","year":"2012","unstructured":"Blackham, A. U. & Levine, E. A. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma. Eur. J. Clin. Med. Oncol. 4, 25\u201332 (2012).","journal-title":"Eur. J. Clin. Med. Oncol."},{"key":"38545_CR5","doi-asserted-by":"publisher","first-page":"2720","DOI":"10.1245\/s10434-010-1080-6","volume":"17","author":"AU Blackham","year":"2010","unstructured":"Blackham, A. U., Shen, P., Stewart, J. H., Russell, G. B. & Levine, E. A. Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for malignant peritoneal mesothelioma: Mitomycin versus cisplatin. Ann. Surg. Oncol. 17, 2720\u20132727. https:\/\/doi.org\/10.1245\/s10434-010-1080-6 (2010).","journal-title":"Ann. Surg. 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Lung Cancer 64, 211\u2013218. https:\/\/doi.org\/10.1016\/j.lungcan.2008.08.013 (2009).","journal-title":"Lung Cancer"},{"key":"38545_CR8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.ejca.2016.06.002","volume":"65","author":"V Kepenekian","year":"2016","unstructured":"Kepenekian, V. et al. Diffuse malignant peritoneal mesothelioma: Evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE Database: Multi-Institutional Retrospective Study. Eur. J. Cancer 65, 69\u201379. https:\/\/doi.org\/10.1016\/j.ejca.2016.06.002 (2016).","journal-title":"Eur. J. Cancer"},{"key":"38545_CR9","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1245\/s10434-019-08143-8","volume":"27","author":"KI Votanopoulos","year":"2020","unstructured":"Votanopoulos, K. I. et al. Model of patient-specific immune-enhanced organoids for immunotherapy screening: Feasibility study. Ann. Surg. 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