Approaching Oxygen-Guided Intensity-Modulated Radiation Therapy

Abstract

The outcome of cancer radiation treatment is strongly correlated with tumor oxygenation. The aim of this study is to use oxygen tension distributions in tumors obtained using Electron Paramagnetic Resonance (EPR) imaging to devise better tumor radiation treatment. The proposed radiation plan is delivered in two steps. In the first step, a uniform 50% tumor control dose (TCD50) is delivered to the whole tumor. For the second step an additional dose boost is delivered to radioresistant, hypoxic tumor regions. FSa fibrosarcomas grown in the gastrocnemius of the legs of C3H mice were used. Oxygen tension images were obtained using a 250 MHz pulse imager and injectable partially deuterated trityl OX63 (OX71) spin probe. Radiation was delivered with a novel animal intensity modulated radiation therapy (IMRT) XRAD225Cx microCT/radiation therapy delivery system. In a simplified scheme for boost dose delivery, the boost area is approximated by a sphere, whose radius and position are determined using an EPR O2 image. The sphere that irradiates the largest fraction of hypoxic voxels in the tumor was chosen using an algorithm based on Receiver Operator Characteristic (ROC) analysis. We used the fraction of irradiated hypoxic volume as the true positive determinant and the fraction of irradiated normoxic volume as the false positive determinant in the terms of that analysis. The most efficient treatment is the one that demonstrates the shortest distance from the ROC curve to the upper left corner of the ROC plot. The boost dose corresponds to the difference between TCD90 and TCD50 values. For the control experiment an identical radiation dose to the normoxic tumor area is delivered.

Direct and indirect assessment of cancer metabolism explored by MRI

“…Although most clinically used therapeutic regimens involving fractionated doses are likely to influence the intra‐tumor oxygenation pattern, the results support the clinical value of pO 2 imaging in predicting the treatment efficacy of radiation therapy. Based on this observation, the group is currently investigating the clinical feasibility of oxygen‐guided radiation therapy, where an additional boost dose of radiation is delivered to the hypoxic area determined by EPRI to achieve improved treatment efficacy …”

Triarylmethyl Radicals: An EPR Study of 13C Hyperfine Coupling Constants

“…In particular, TAMs are widely used as in vivo spin probes for EPR oxymetry [5–9]. Compared to nitroxides, TAMs have several important advantages, namely: (i) extremely narrow EPR line, especially for deuterated analogues (5 μT); (ii) very long electron spin relaxation times even at room temperatures: T 1 up to 20 μs and T m up to 3 μs [10, 11]; (iii) very high stability against reduction in biological systems (tissues and blood).…”

In Vivo pO2 Imaging of Tumors

“…A trial comparing the tumor control using such a boost with treatment to a well oxygenated shell of similar volume (an “anti-boost”) is underway. 87 …”