Translational study for stereotactic body radiotherapy against non-small cell lung cancer, including oligometastases, considering cancer stem-like cells enable predicting clinical outcome from in vitro data.
Biophysical modeling
Cancer stem-like cells
Cell survival
Tumor control probability
Journal
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
30
09
2022
revised:
15
11
2022
accepted:
06
12
2022
medline:
5
4
2023
entrez:
3
4
2023
pubmed:
4
4
2023
Statut:
ppublish
Résumé
Curative effects of stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) have been evaluated using various biophysical models. Because such model parameters are empirically determined based on clinical experience, there is a large gap between in vitro and clinical studies. In this study, considering the heterogeneous cell population, we performed a translational study to realize the possible linkage based on a modeling approach. We modeled cell-killing and tumor control probability (TCP) considering two populations: progeny and cancer stem-like cells. The model parameters were determined from in vitro survival data of A549 and EBC-1 cells. Based on the cellular parameters, we predicted TCP and compared it with the corresponding clinical data from 553 patients collected at Hirosaki University Hospital. Using an all-in-one developed model, the so-called integrated microdosimetric-kinetic (IMK) model, we successfully reproduced both in vitro survival after acute irradiation and the 3-year TCP with various fractionation schemes (6-10 Gy per fraction). From the conventional prediction without considering cancer stem cells (CSCs), this study revealed that radioresistant CSCs play a key role in the linkage between in vitro and clinical outcomes. This modeling study provides a possible generalized biophysical model that enables precise estimation of SBRT worldwide.
Sections du résumé
BACKGROUND
Curative effects of stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) have been evaluated using various biophysical models. Because such model parameters are empirically determined based on clinical experience, there is a large gap between in vitro and clinical studies. In this study, considering the heterogeneous cell population, we performed a translational study to realize the possible linkage based on a modeling approach.
METHODS
We modeled cell-killing and tumor control probability (TCP) considering two populations: progeny and cancer stem-like cells. The model parameters were determined from in vitro survival data of A549 and EBC-1 cells. Based on the cellular parameters, we predicted TCP and compared it with the corresponding clinical data from 553 patients collected at Hirosaki University Hospital.
RESULTS
Using an all-in-one developed model, the so-called integrated microdosimetric-kinetic (IMK) model, we successfully reproduced both in vitro survival after acute irradiation and the 3-year TCP with various fractionation schemes (6-10 Gy per fraction). From the conventional prediction without considering cancer stem cells (CSCs), this study revealed that radioresistant CSCs play a key role in the linkage between in vitro and clinical outcomes.
CONCLUSIONS
This modeling study provides a possible generalized biophysical model that enables precise estimation of SBRT worldwide.
Identifiants
pubmed: 37011969
pii: S0167-8140(22)04593-5
doi: 10.1016/j.radonc.2022.109444
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109444Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.