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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.

Author information

Thulborn KR1, Lu A2, Atkinson IC2, Pauliah M3, Beal K4, Chan TA4, Omuro A5, Yamada J4, Bradbury MS3,6.
1
Center for Magnetic Resonance Research, University of Illinois at Chicago, Chicago, Illinois. mrix@ameritech.net.
2
Center for Magnetic Resonance Research, University of Illinois at Chicago, Chicago, Illinois.
3
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
4
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
5
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.
6
Molecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, New York, New York.