Considerable evidence now exists to show that that the relative biological effectiveness (RBE) changes considerably along the proton depth-dose distribution, with progressively higher RBE values at the distal part of the modulated, or spread out Bragg peak (SOBP) and in the distal dose fall-off (DDF). However, the highly variable nature of the existing studies (with regards to cell lines, and to the physical properties and dosimetry of the various proton beams) precludes any consensus regarding the RBE weighting factor at any position in the depth-dose profile. We have thus conducted a systematic study on the variation in RBE for cell killing for two clinical modulated proton beams at Indiana University and have determined the relationship between the RBE and the dose-averaged linear energy transfer (LETd) of the protons at various positions along the depth-dose profiles. Clonogenic assays were performed on human Hep2 laryngeal cancer cells and V79 cells at various positions along the SOBPs of beams with incident energies of 87 and 200 MeV. There was a marked variation in the radiosensitivity of both cell lines along the SOBP depth-dose profile of the 87 MeV proton beam. Using Hep2 cells, the D(0.1) isoeffect dose RBE values (normalized against (60)Co) were 1.46 at the middle of SOBP, 2.1 at the distal end of the SOBP and 2.3 in the DDF. For V79 cells, the D(0.1) isoeffect RBE for the 87 MEV beam were 1.23 for the proximal end of the SOBP: 1.46 for the distal SOBP and 1.78 for the DDF. Similar D(0.1) isoeffect RBE values were found for Hep2 cells irradiated at various positions along the depth-dose profile of the 200 MeV beam. Our experimentally derived RBE values were significantly correlated (P = 0.001) with the mean LETd of the protons at the various depths, which confirmed that proton RBE is highly dependent on LETd. These in vitro data suggest that the RBE of the proton beam at certain depths is greater than 1.1, a value currently used in most treatment planning algorithms. Thus, the potential for increased cell killing and normal tissue damage in the distal regions of the proton SOBP may be greater than originally thought.

A proton beam delivery system on a gantry with continuous uniform scanning and dose layer stacking at the Midwest Proton Radiotherapy Institute has been commissioned and accepted for clinical use. This paper was motivated by a lack of guidance on the testing and characterization for clinical uniform scanning systems. As such, it describes how these tasks were performed with a uniform scanning beam delivery system. This paper reports the methods used and important dosimetric characteristics of radiation fields produced by the system. The commissioning data include the transverse and longitudinal dose distributions, penumbra, and absolute dose values. Using a 208 MeV cyclotron's proton beam, the system provides field sizes up to 20 and 30 cm in diameter for proton ranges in water up to 27 and 20 cm, respectively. The dose layer stacking method allows for the flexible construction of spread-out Bragg peaks with uniform modulation of up to 15 cm in water, at typical dose rates of 1 -3 Gy/ min. For measuring relative dose distributions, multielement ion chamber arrays, small-volume ion chambers, and radiographic films were employed. Measurements during the clinical commissioning of the system have shown that the lateral and longitudinal dose uniformity of 2.5% or better can be achieved for all clinically important field sizes and ranges. The measured transverse penumbra widths offer a slight improvement in comparison to those achieved with a double scattering beam spreading technique at the facility. Absolute dose measurements were done using calibrated ion chambers, thermoluminescent and alanine detectors. Dose intercomparisons conducted using various types of detectors traceable to a national standards laboratory indicate that the measured dosimetry data agree with each other within 5%.

Two beam profile measurement detectors have been developed at Indiana University Cyclotron Facility to address the need for a tool to efficiently verify dose distributions created with active methods of clinical proton beam delivery. The multipad ionization chamber (MPIC) has 128 ionization chambers arranged in one plane and is designed to measure lateral profiles in fields up to 38 cm in diameter. The MPIC pads have a 5 mm pitch for fields up to 20 cm in diameter and a 7 mm pitch for larger fields, providing the accuracy of field size determination about 0.5 mm. The multilayer ionization chamber (MLIC) detector contains 122 small-volume ionization chambers stacked at a 1.82 mm step (water-equivalent) for depth-dose profile measurements. The MLIC detector can measure profiles up to 20 cm in depth, and determine the 80% distal dose fall-off with about 0.1 mm precision. Both detectors can be connected to the same set of electronics modules, which comprise the detectors' data acquisition system. The detectors have been tested in clinical proton fields produced with active methods of beam delivery such as uniform scanning and energy stacking. This article describes detector performance tests and discusses their results. The test results indicate that the MPIC and MLIC detectors can be used for dosimetric characterization of clinical proton fields. The detectors offer significant time savings during measurements in actively delivered beams compared with traditional measurements using a water phantom.

Purpose: To compare clinically relevant dosimetric characteristics of proton therapy fields produced by two uniform scanning systems that have a number of similar hardware components but employ different techniques of beam spreading. Methods: This work compares two technologically distinct systems implementing a method of uniform scanning and layer stacking that has been developed independently at Indiana University (IU) and by Ion Beam Applications, S. A. (IBA). Clinically relevant dosimetric characteristics of fields produced by these systems are studied, such as beam range control, peak-to-entrance ratio (PER), lateral penumbra, field flatness, effective source position, precision of dose delivery at different gantry angles, etc. Results: Under comparable conditions, both systems controlled beam range with an accuracy of 0.5 mm and a precision of 0.1 mm. Compared to IBA, the IU system produced pristine peaks with a slightly higher PER (3.23 and 3.45, respectively) and smaller, symmetrical, lateral in-air penumbra of 1 mm compared to about 1.9/2.4 mm in the inplane/crossplane (IP/CP) directions for IBA. Large field flatness results in the IP/CP directions were similar: 3.0/2.4% for IU and 2.9/2.4% for IBA. The IU system featured a longer virtual source-to-isocenter position, which was the same for the IP and CP directions (237 cm), as opposed to 212/192 cm (IP/CP) for IBA. Dose delivery precision at different gantry angles was higher in the IBA system (0.5%) than in the IU system (1%). Conclusions: Each of the two uniform scanning systems considered in this work shows some attractive performance characteristics while having other features that can be further improved. Overall, radiation field characteristics of both systems meet their clinical specifications and show comparable results. Most of the differences observed between the two systems are clinically insignificant.

A number of designs have been proposed for ridge filters and range modulators used in proton therapy to modify the beam in order to spread out the Bragg peak. Despite the variety of solutions, no simple design capable of providing large fields and easy variation of the spread out Bragg peak (SOBP) length in a pulsed beam has been developed. We propose a compact ridge filter that can be used in a proton beam of any time structure. It allows the production of depth dose distributions that meet the requirements of therapy dose fields.