TY - JOUR
T1 - Simulating drug penetration during hyperthermic intraperitoneal chemotherapy
AU - Löke, Daan R.
AU - Helderman, Roxan F. C. P. A.
AU - Franken, Nicolaas A. P.
AU - Oei, Arlene L.
AU - Tanis, Pieter J.
AU - Crezee, Johannes
AU - Kok, H. Petra
N1 - Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
KW - Hyperthermic intrapertioneal chemotherapy (HIPEC)
KW - cancer biology
KW - computational fluid dynamics (CFD)
KW - computational modeling
KW - drug dynamics
KW - interstitial fluidpressure (IFP)
KW - treatment planning software
UR - http://www.scopus.com/inward/record.url?scp=85100069786&partnerID=8YFLogxK
U2 - https://doi.org/10.1080/10717544.2020.1862364
DO - https://doi.org/10.1080/10717544.2020.1862364
M3 - Article
C2 - 33427507
SN - 1071-7544
VL - 28
SP - 145
EP - 161
JO - Drug Delivery
JF - Drug Delivery
IS - 1
ER -