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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cell Line, Tumor
  • Cisplatin / administration & dosage
  • Computer Simulation
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration / methods*
  • Female
  • Forecasting
  • Humans
  • Inhibitory Concentration 50
  • Injections, Intralesional
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Cisplatin