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

Vitor Mori,Hiren J Mehta,Michael Jantz,Jason H T Bates,C Matthew Kinsey

doi:10.1038/s41598-021-03849-w

Vitor Mori, Hiren J Mehta + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-03849-w

Copy DOI

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.

Highlights

We recently developed a computational model of cisplatin pharmacodynamics in an endobronchial lung tumor following ultrasound-guided transbronchial needle injection (EBUS-TBNI)
We screened 37 patients treated for lung cancer with EBUS-TBNI of cisplatin, the inclusion criteria b eing[7] age 18–80 years, pathologically confirmed non-small cell lung cancer, histologic or cytologic recurrence of cancer following therapy at initial diagnosis, recurrence in an EBUS-accessible site, and computed tomography (CT) scans performed less than five weeks prior to treatment
Of the 22 patients treated at the University of Florida, 1 received 2 injections and 21 received 4 injections according to the injected dose, which was 20 or 40 mg, respectively

Summary

Introduction

We recently developed a computational model of cisplatin pharmacodynamics in an endobronchial lung tumor following ultrasound-guided transbronchial needle injection (EBUS-TBNI). 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. Endobronchial ultrasound-guided transbronchial needle injection (EBUS-TBNI) of cisplatin has recently emerged as a safe alternative to systemic delivery for treating recurrent centrally located non-small cell lung cancer (NSCLC)[3,4]. There would seem to be significant opportunity to advance the efficacy of EBUS-TBNI of cisplatin by determining the dose that achieves the best tradeoff between cytotoxicity and systemic side-effects, and by employing an injection strategy that ensures all tumor cells receive a lethal concentration of agent. We used the model to estimate the minimal cisplatin dose required to induce a positive response in each tumor, as well as how this dose depends on the number of spatially distributed injections, with the goal of establishing an initial foundation upon which to set rationalized guidelines for cisplatin dose as a function of tumor volume and delivery strategy

Objectives

Methods

Results

Conclusion