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

Purpose: Spatial and temporal patterns of response of human glioblastoma to fractionated chemoradiation are described by changes in the bioscales of residual tumor volume, tumor cell volume fraction and tumor cell kill, as derived from tissue sodium concentration measured by quantitative sodium magnetic resonance imaging 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 tissue sodium concentration obtained from serial quantitative sodium magnetic resonance imaging 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 to times to disease progression and survival. Results: Residual tumor volume following tumor resection showed decreased cell volume fraction due to disruption of normal cell packing by edema and infiltrating tumor cells. Cell volume fraction showed either increases back towards 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.

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