Purpose To examine the potential use of BOLD (Blood Oxygenation Level Dependent) and TOLD (Tissue Oxygenation Level Dependent) contrast MRI to assess tumor oxygenation and predict radiation response. Methods BOLD and TOLD MRI were performed on Dunning R3327-AT1 rat prostate tumors during hyperoxic gas breathing challenge at 4.7 T. Animals were divided into two groups. In Group 1 (n=9), subsequent 19F MRI based on spin lattice relaxation of hexafluorobenzene reporter molecule provided quantitative oximetry for comparison. For Group 2 rats (n=13) growth delay following a single dose of 30 Gy was compared with pre-irradiation BOLD and TOLD assessments. Results Oxygen (100%O2) and carbogen (CB; 95%O2/5%CO2) challenge elicited similar BOLD, TOLD and pO2 responses. Strong correlations were observed between BOLD or R2* response and quantitative 19F pO2 measurements. TOLD response showed a general trend with weaker correlation. Irradiation caused a significant tumor growth delay and tumors with larger changes in TOLD and R1 values upon oxygen breathing exhibited significantly increased tumor growth delay. Conclusion These results provide further insight into the relationships between oxygen sensitive (BOLD/TOLD) MRI and tumor pO2. Moreover, a larger increase in R1 response to hyperoxic gas challenge coincided with greater tumor growth delay following irradiation.

Purpose This study was designed to provide the foundation for combining immunotherapy to induce tumor antigen-specific T cells with proton radiation therapy to exploit the activity of those T cells. We have recently defined “immunogenic modulation,” a mechanism distinct from immunogenic cell death, whereby tumor cells surviving photon radiation therapy nonetheless become more susceptible to cytotoxic T lymphocyte (CTL)-mediated lysis. However, to our knowledge, there are no prior studies examining the role of proton radiation on tumor immune sensitivity. Materials and Methods Using cell lines of tumors frequently treated with proton radiation, such as prostate, breast, lung, and chordoma, we examined the effect of proton radiation on the viability and induction of immunogenic modulation in tumor cells by flow cytometric and immunofluorescent analysis of surface phenotype and the functional immune consequences. Results These studies show for the first time that a) proton and photon radiation induced comparable upregulation of surface molecules involved in immune recognition (HLA, ICAM-1, and the tumor-associated antigens CEA and MUC-1), b) proton radiation mediated calreticulin cell-surface expression, increasing sensitivity to cytotoxic T-lymphocyte killing of tumor cells, and c) cancer stem cells (CSCs), which are resistant to the direct cytolytic activity of proton radiation, nonetheless upregulated calreticulin after radiation in a manner similar to non-CSCs. Conclusions These findings offer a rationale for the use of proton radiation in combination with immunotherapy, including for patients who have failed radiation therapy alone or have limited treatment options.

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Small animal irradiation provides an important tool used by preclinical studies to assess and optimize new treatment strategies such as stereotactic ablative radiotherapy. Characterization of radiation beams that are clinically and geometrically scaled for the small animal model is uniquely challenging for orthovoltage energies and minute field sizes. The irradiator employs a commercial x-ray device (XRAD 320, Precision x-ray, Inc.) with a custom collimation system to produce 1-10 mm diameter beams and a 50 mm reference beam. Absolute calibrations were performed using the AAPM TG-61 methodology. Beam's half-value layer (HVL) and timer error were measured with an ionization chamber. Percent depth dose (PDD), output factors (OFs) and off-axis ratios were measured using radiochromic film, a diode and a pinpoint ionization chamber at 19.76 and 24.76 cm source-to-surface distance (SSD). PDD measurements were also compared with Monte Carlo (MC) simulations. In-air and in-water absolute calibrations for the reference 50 mm diameter collimator at 19.76 cm SSD were measured as 20.96 and 20.79 Gy min(-1), respectively, agreeing within 0.8%. The HVL at 250 kVp and 15 mAs was measured to be 0.45 mm Cu. The reference field PDD MC simulation results agree with measured data within 3.5%. PDD data demonstrate typical increased penetration with increasing field size and SSD. For collimators larger than 5 mm in diameter, OFs measured using film, an ion chamber and a diode were within 3% agreement.

This paper summarizes clinical commissioning of the world's first commercial, clinically utilized installation of a compact, image‐guided, pencil‐beam scanning, intensity‐modulated proton therapy system, the IBA Proteus® ONE, at the Willis‐Knighton Cancer Center (WKCC) in Shreveport, LA. The Proteus® ONE is a single‐room, compact‐gantry system employing a cyclotron‐generated proton beam with image guidance via cone‐beam CT as well as stereoscopic orthogonal and oblique planar kV imaging. Coupling 220° of gantry rotation with a 6D robotic couch capable of in plane patient rotations of over 180° degrees allows for 360° of treatment access. Along with general machine characterization, system commissioning required: (a) characterization and calibration of the proton beam, (b) treatment planning system commissioning including CT‐to‐density curve determination, (c) image guidance system commissioning, and (d) safety verification (interlocks and radiation survey). System readiness for patient treatment was validated by irradiating calibration TLDs as well as prostate, head, and lung phantoms from the Imaging and Radiation Oncology Core (IROC), Houston. These results confirmed safe and accurate machine functionality suitable for patient treatment. WKCC also successfully completed an on‐site dosimetry review by an independent team of IROC physicists that corroborated accurate Proteus® ONE dosimetry.