A Mathematical Model to Estimate Chemotherapy Concentration at the Tumor-Site and Predict Therapy Response in Colorectal Cancer Patients with Liver Metastases.
FOLFOX
chemotherapy
colorectal cancer
liver metastases
mathematical model
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
25 Jan 2021
25 Jan 2021
Historique:
received:
11
01
2021
accepted:
21
01
2021
entrez:
28
1
2021
pubmed:
29
1
2021
medline:
29
1
2021
Statut:
epublish
Résumé
Chemotherapy remains a primary treatment for metastatic cancer, with tumor response being the benchmark outcome marker. However, therapeutic response in cancer is unpredictable due to heterogeneity in drug delivery from systemic circulation to solid tumors. In this proof-of-concept study, we evaluated chemotherapy concentration at the tumor-site and its association with therapy response by applying a mathematical model. By using pre-treatment imaging, clinical and biologic variables, and chemotherapy regimen to inform the model, we estimated tumor-site chemotherapy concentration in patients with colorectal cancer liver metastases, who received treatment prior to surgical hepatic resection with curative-intent. The differential response to therapy in resected specimens, measured with the gold-standard Tumor Regression Grade (TRG; from 1, complete response to 5, no response) was examined, relative to the model predicted systemic and tumor-site chemotherapy concentrations. We found that the average calculated plasma concentration of the cytotoxic drug was essentially equivalent across patients exhibiting different TRGs, while the estimated tumor-site chemotherapeutic concentration (eTSCC) showed a quadratic decline from TRG = 1 to TRG = 5 (
Identifiants
pubmed: 33503971
pii: cancers13030444
doi: 10.3390/cancers13030444
pmc: PMC7866038
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : National Science Foundation
ID : DMS-1930583
Organisme : NIH HHS
ID : 1U01CA196403
Pays : United States
Organisme : NIH HHS
ID : 1U01CA213759
Pays : United States
Organisme : NIH HHS
ID : 1R01CA222007
Pays : United States
Organisme : NIH HHS
ID : U54CA210181
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA226537
Pays : United States
Organisme : NIH HHS
ID : 1R01CA226537
Pays : United States
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