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. 2022 Jan 7;12(1):44.
doi: 10.1038/s41598-021-03849-w.

A computational modeling approach for dosing endoscopic intratumoral chemotherapy for advanced non-small cell lung cancer

Vitor Mori  1 , Jason H T Bates  1 , Michael Jantz  2 , Hiren J Mehta  2 , C Matthew Kinsey  3
Affiliations

A computational modeling approach for dosing endoscopic intratumoral chemotherapy for advanced non-small cell lung cancer

Vitor Mori et al. Sci Rep. .

Abstract

We recently developed a computational model of cisplatin pharmacodynamics in an endobronchial lung tumor following ultrasound-guided transbronchial needle injection (EBUS-TBNI). The model suggests that it is more efficacious to apportion the cisplatin dose between injections at different sites rather than giving it all in a single central injection, but the model was calibrated only on blood cisplatin data from a single patient. Accordingly, we applied a modified version of our original model in a set of 32 patients undergoing EBUS-TBNI for non-small cell lung cancer (NSCLC). We used the model to predict clinical responses and compared them retrospectively to actual patient outcomes. The model correctly predicted the clinical response in 72% of cases, with 80% accuracy for adenocarcinomas and 62.5% accuracy for squamous-cell lung cancer. We also found a power-law relationship between tumor volume and the minimal dose needed to induce a response, with the power-law exponent depending on the number of injections administered. Our results suggest that current injection strategies may be significantly over- or under-dosing the agent depending on tumor size, and that computational modeling can be a useful planning tool for EBUS-TBNI of cisplatin in lung cancer.

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Conflict of interest statement

JHTB is a consultant for Johnson & Johnson on matters related to this study, and is co-applicant on the patent application “Methods for computational modeling to guide intratumoral therapy.” U.S. Patent Application No. 62/542,623. Filed: August 8, 2017. CMK is a consultant for Olympus America, Johnson and Johnson, and consultant and equity holder for Quantitative Imaging Solutions. He serves on the steering committee for Nuvaira and the Scientific Advisory Board for Galvanize Therapeutics. He reports grants from the NIH, clinical trial funding through Johnson and Johnson, and is a co-applicant on the patent application "Methods for computational modeling to guide intratumoral therapy". U.S. Patent Application No. 62/542,623. Filed: August 8, 2017.” VM, MJ and HM declare that there are no conflict of interest.

Figures

Figure 1
Figure 1
General structure of the computational model of cisplatin pharmacodynamics following intratumoral injections. Each labeled rectangle represents a single well-mixed compartment and arrows represent cisplatin pathways.
Figure 2
Figure 2
Histogram of the logarithm of 72 h cisplatin IC50 in NSCLC immortalized human cell lines from the Genomics of Drug Sensitivity in Cancer (blue bars) and fitted normal distribution (red curve).
Figure 3
Figure 3
Model results for (A) the complete dataset (B) adenocarcinoma (C) squamous-cell lung cancer.
Figure 4
Figure 4
(A) Minimum cisplatin dose to achieve a therapeutical response according to the model for 1–5 injections in a log–log scale (B–F) Minimum cisplatin dose (circles), and power-law regression of ideal dose versus tumor volume for 1–5 injections.
See this image and copyright information in PMC

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