Residual Tumor Volume, Cell Volume Fraction, and Tumor Cell Kill During Fractionated Chemoradiation Therapy of Human Glioblastoma using Quantitative Sodium MR Imaging.

TitleResidual Tumor Volume, Cell Volume Fraction, and Tumor Cell Kill During Fractionated Chemoradiation Therapy of Human Glioblastoma using Quantitative Sodium MR Imaging.
Publication TypeJournal Article
Year of Publication2019
AuthorsThulborn KR, Lu A, Atkinson IC, Pauliah M, Beal K, Chan TA, Omuro A, Yamada J, Bradbury MS
JournalClin Cancer Res
Volume25
Issue4
Pagination1226-1232
Date Published2019 Feb 15
ISSN1557-3265
KeywordsAdult, Aged, Cell Size, Chemoradiotherapy, Disease Progression, Dose Fractionation, Radiation, Female, Glioblastoma, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neoplasm, Residual, Sodium, Tumor Burden
Abstract

PURPOSE: Spatial and temporal patterns of response of human glioblastoma to fractionated chemoradiation are described by changes in the bioscales of residual tumor volume (RTV), tumor cell volume fraction (CVF), and tumor cell kill (TCK), as derived from tissue sodium concentration (TSC) measured by quantitative sodium MRI at 3 Tesla. These near real-time patterns during treatment are compared with overall survival.

EXPERIMENTAL DESIGN: Bioscales were mapped during fractionated chemoradiation therapy in patients with glioblastomas (n = 20) using TSC obtained from serial quantitative sodium MRI at 3 Tesla and a two-compartment model of tissue sodium distribution. The responses of these parameters in newly diagnosed human glioblastomas undergoing treatment were compared with time-to-disease progression and survival.

RESULTS: RTV following tumor resection showed decreased CVF due to disruption of normal cell packing by edema and infiltrating tumor cells. CVF showed either increases back toward normal as infiltrating tumor cells were killed, or decreases as cancer cells continued to infiltrate and extend tumor margins. These highly variable tumor responses showed no correlation with time-to-progression or overall survival.

CONCLUSIONS: These bioscales indicate that fractionated chemoradiotherapy of glioblastomas produces variable responses with low cell killing efficiency. These parameters are sensitive to real-time changes within the treatment volume while remaining stable elsewhere, highlighting the potential to individualize therapy earlier in management, should alternative strategies be available.

DOI10.1158/1078-0432.CCR-18-2079
Alternate JournalClin Cancer Res
PubMed ID30487127
PubMed Central IDPMC7462306
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
R01 CA129553 / CA / NCI NIH HHS / United States