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Simulating drug penetration during hyperthermic intraperitoneal chemotherapy

Hyperthermic intraperitoneal chemotherapy (HIPEC) is administered to treat residual microscopic disease after debulking cytoreductive surgery. During HIPEC, a limited number of catheters are used to administer and drain fluid containing chemotherapy (41–43 °C), yielding heterogeneities in the perito...

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Autores principales: Löke, Daan R., Helderman, Roxan F. C. P. A., Franken, Nicolaas A. P., Oei, Arlene L., Tanis, Pieter J., Crezee, Johannes, Kok, H. Petra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808385/
https://www.ncbi.nlm.nih.gov/pubmed/33427507
http://dx.doi.org/10.1080/10717544.2020.1862364
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author Löke, Daan R.
Helderman, Roxan F. C. P. A.
Franken, Nicolaas A. P.
Oei, Arlene L.
Tanis, Pieter J.
Crezee, Johannes
Kok, H. Petra
author_facet Löke, Daan R.
Helderman, Roxan F. C. P. A.
Franken, Nicolaas A. P.
Oei, Arlene L.
Tanis, Pieter J.
Crezee, Johannes
Kok, H. Petra
author_sort Löke, Daan R.
collection PubMed
description Hyperthermic intraperitoneal chemotherapy (HIPEC) is administered to treat residual microscopic disease after debulking cytoreductive surgery. During HIPEC, a limited number of catheters are used to administer and drain fluid containing chemotherapy (41–43 °C), yielding heterogeneities in the peritoneum. Large heterogeneities may lead to undertreated areas, increasing the risk of recurrences. Aiming at intra-abdominal homogeneity is therefore essential to fully exploit the potential of HIPEC. More insight is needed into the extent of the heterogeneities during treatments and assess their effects on the efficacy of HIPEC. To that end we developed a computational model containing embedded tumor nodules in an environment mimicking peritoneal conditions. Tumor- and treatment-specific parameters affecting drug delivery like tumor size, tumor shape, velocity, temperature and dose were assessed using three-dimensional computational fluid dynamics (CFD) to demonstrate their effect on the drug distribution and accumulation in nodules. Clonogenic assays performed on RKO colorectal cell lines yielded the temperature-dependent IC50 values of cisplatin (19.5–6.8 micromolar for 37–43 °C), used to compare drug distributions in our computational models. Our models underlined that large nodules are more difficult to treat and that temperature and velocity are the most important factors to control the drug delivery. Moderate flow velocities, between 0.01 and 1 m/s, are optimal for the delivery of cisplatin. Furthermore, higher temperatures and higher doses increased the effective penetration depth with 69% and 54%, respectively. We plan to extend the software developed for this study toward patient-specific treatment planning software, capable of mapping and assist in reducing heterogeneous flow patterns.
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spelling pubmed-78083852021-01-29 Simulating drug penetration during hyperthermic intraperitoneal chemotherapy Löke, Daan R. Helderman, Roxan F. C. P. A. Franken, Nicolaas A. P. Oei, Arlene L. Tanis, Pieter J. Crezee, Johannes Kok, H. Petra Drug Deliv Research Article Hyperthermic intraperitoneal chemotherapy (HIPEC) is administered to treat residual microscopic disease after debulking cytoreductive surgery. During HIPEC, a limited number of catheters are used to administer and drain fluid containing chemotherapy (41–43 °C), yielding heterogeneities in the peritoneum. Large heterogeneities may lead to undertreated areas, increasing the risk of recurrences. Aiming at intra-abdominal homogeneity is therefore essential to fully exploit the potential of HIPEC. More insight is needed into the extent of the heterogeneities during treatments and assess their effects on the efficacy of HIPEC. To that end we developed a computational model containing embedded tumor nodules in an environment mimicking peritoneal conditions. Tumor- and treatment-specific parameters affecting drug delivery like tumor size, tumor shape, velocity, temperature and dose were assessed using three-dimensional computational fluid dynamics (CFD) to demonstrate their effect on the drug distribution and accumulation in nodules. Clonogenic assays performed on RKO colorectal cell lines yielded the temperature-dependent IC50 values of cisplatin (19.5–6.8 micromolar for 37–43 °C), used to compare drug distributions in our computational models. Our models underlined that large nodules are more difficult to treat and that temperature and velocity are the most important factors to control the drug delivery. Moderate flow velocities, between 0.01 and 1 m/s, are optimal for the delivery of cisplatin. Furthermore, higher temperatures and higher doses increased the effective penetration depth with 69% and 54%, respectively. We plan to extend the software developed for this study toward patient-specific treatment planning software, capable of mapping and assist in reducing heterogeneous flow patterns. Taylor & Francis 2021-01-11 /pmc/articles/PMC7808385/ /pubmed/33427507 http://dx.doi.org/10.1080/10717544.2020.1862364 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Löke, Daan R.
Helderman, Roxan F. C. P. A.
Franken, Nicolaas A. P.
Oei, Arlene L.
Tanis, Pieter J.
Crezee, Johannes
Kok, H. Petra
Simulating drug penetration during hyperthermic intraperitoneal chemotherapy
title Simulating drug penetration during hyperthermic intraperitoneal chemotherapy
title_full Simulating drug penetration during hyperthermic intraperitoneal chemotherapy
title_fullStr Simulating drug penetration during hyperthermic intraperitoneal chemotherapy
title_full_unstemmed Simulating drug penetration during hyperthermic intraperitoneal chemotherapy
title_short Simulating drug penetration during hyperthermic intraperitoneal chemotherapy
title_sort simulating drug penetration during hyperthermic intraperitoneal chemotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808385/
https://www.ncbi.nlm.nih.gov/pubmed/33427507
http://dx.doi.org/10.1080/10717544.2020.1862364
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