Stanley Rosenthal

Proton Beams to Replace Photon Beams in Radical Dose Treatments

With proton beam radiation therapy a smaller volume of normal tissues is irradiated at high dose levels for most anatomic sites than is feasible with any photon technique. This is due to the Laws of Physics, which determine the absorption of energy from photons and protons. In other words, the dose from a photon beam decreases exponentially with depth in the irradiated material. In contrast, protons have a finite range and that range is energy dependent. Accordingly, by appropriate distribution of proton energies, the dose can be uniform across the target and essentially zero deep to the target and the atomic composition of the irradiated material. The dose proximal to the target is lower compared with that in photon techniques, for all except superficial targets. This resultant closer approximation of the planning treatment volume (PTV) to the CTV/GTV (grossly evident tumor volume/subclinical tumor extensions) constitutes a clinical gain by definition; i.e. a smaller treatment volume that covers the target three dimensionally for the entirety of each treatment session provides a clinical advantage. Several illustrative clinical dose distributions are presented and the clinical outcome results are reviewed briefly. An important technical advance will be the use of intensity modulated proton radiation therapy, which achieves contouring of the proximal edge of the SOBP (spread out bragg peak) as well as the distal edge. This technique uses pencil beam scanning. To permit further progressive reductions of the PTV, 4-D treatment planning and delivery is required. The fourth dimension is time, as the position and contours of the tumor and the adjacent critical normal tissues are not constant. A potentially valuable new method for assessing the clinical merits of each of a large number of treatment plans is the evaluation of multidimensional plots of the complication probabilities for each of ‘n’ critical normal tissues/structures for a specified tumor control probability. The cost of proton therapy compared with that of very high technology photon therapy is estimated and evaluated. The differential is estimated to be ≈1.5 provided there were to be no charge for the original facility and that there were sufficient patients for operating on an extended schedule (6–7 days of 14–16 h) with ≥ two gantries and one fixed horizontal beam.

Neuroendocrine tumors of the sinonasal tract. Results of a prospective study incorporating chemotherapy, surgery, and combined proton-photon radiotherapy.

The authors report the results of a prospective study of patients with malignant neuroendocrine tumors of the sinonasal tract who received multimodality treatment incorporating high‐dose proton‐photon radiotherapy.

Moving targets: detection and tracking of internal organ motion for treatment planning and patient set-up.

BACKGROUND AND PURPOSE Clinical target volumes of the thorax and abdomen are typically expanded to account for inter- and intrafractional organ motion. Usually, such expansions are based on clinical experience and planar observations of target motion during simulation. More precise, 4-dimensional motion margins for a specific patient may improve dose coverage of mobile targets and yet limit unnecessarily large field expansions. We are studying approaches to targeting moving tumors throughout the entire treatment process, from treatment planning to beam delivery. MATERIAL AND METHODS Radio-opaque markers were implanted under CT guidance in the liver at the gross tumor periphery. Organ motion during light respiration was volumetrically imaged by 4D Computed Tomography. Marker motion was also acquired by fluoroscopy and compared with 4DCT data. During treatment, daily diagnostic x-ray images were captured at end-exhale and -inhale for patient setup and target localization. RESULTS Based on the time-resolved CT data, target volumes can be designed to account for respiratory motion during treatment. Motion of the tumor as derived from 4DCT was consistent with fluoroscopic motion analysis. Radiographs acquired in the treatment room enabled millimeter-level patient set-up and assessment of target position relative to bony anatomy. Daily positional variations between bony anatomy and implanted markers were observed. CONCLUSIONS Image guided therapy, based on 4DCT imaging, fluoroscopic imaging studies, and daily gated diagonstic energy set-up radiographs is being developed to improve beam delivery precision. Monitoring internal target motion throughout the entire treatment process will ensure adequate dose coverage of the target while sparing the maximum healthy tissue.

The measurement of proton stopping power using proton-cone-beam computed tomography

A cone-beam computed tomography (CT) system utilizing a proton beam has been developed and tested. The cone beam is produced by scattering a 160 MeV proton beam with a modifier that results in a signal in the detector system, which decreases monotonically with depth in the medium. The detector system consists of a Gd2O2S:Tb intensifying screen viewed by a cooled CCD camera. The Feldkamp-Davis-Kress cone-beam reconstruction algorithm is applied to the projection data to obtain the CT voxel data representing proton stopping power. The system described is capable of reconstructing data over a 16 x 16 x 16 cm3 volume into 512 x 512 x 512 voxels. A spatial and contrast resolution phantom was scanned to determine the performance of the system. Spatial resolution is significantly degraded by multiple Coulomb scattering effects. Comparison of the reconstructed proton CT values with x-ray CT derived proton stopping powers shows that there may be some advantage to obtaining stopping powers directly with proton CT. The system described suggests a possible practical method of obtaining this measurement in vivo.

A precision cranial immobilization system for conformal stereotactic fractionated radiation therapy

PURPOSE Conformal radiotherapy has been shown to benefit from precision alignment of patient target to therapy beam (1, 6, 13). This work describes an optimized immobilization system for the fractionated treatment of intracranial targets. A study of patient motion demonstrates the high degree of immobilization which is available. METHODS AND MATERIALS A system using dental fixation and a thermoplastic mask that relocates on a rigid frame is described. The design permits scanning studies using computed tomography (CT) and magnetic resonance imaging (MR), conventional photon radiotherapy, and high precision stereotactic proton radiotherapy to be performed with minimal repositioning variation. Studies of both intratreatment motion and daily setup reliability are performed on patients under treatment for paranasal sinus carcinoma. Multiple radiographs taken during single treatments provide the basis for a three-dimensional (3D) motion analysis. Additionally, studies of orthogonal radiographs used to setup for proton treatments and verification port films from photon treatments are used to establish day to day patient position variation in routine use. RESULTS Net 3D patient motion during any treatment is measured to be 0.9 +/- 0.4 mm [mean +/- standard deviation (SD)] and rotation about any body axis is 0.14 +/- 0.67 degrees (mean +/- SD). Day-to-day setup accuracy to laser marks is limited to 2.3 mm (mean) systematic error and 1.6 mm (mean) random error. CONCLUSION We conclude that the most stringent immobilization requirements of 3D conformal radiotherapy adjacent to critical normal structures can be met with a high precision system such as the one described here. Without the use of pretreatment verification, additional developments in machine and couch design are needed to assure that patient repositioning accuracy is comparable to the best level of patient immobility achievable.

Dosimetric impact of tantalum markers used in the treatment of uveal melanoma with proton beam therapy

Metallic fiducial markers are frequently implanted in patients prior to external-beam radiation therapy to facilitate tumor localization. There is little information in the literature, however, about the perturbations in proton absorbed-dose distribution these objects cause. The aim of this study was to assess the dosimetric impact of perturbations caused by 2.5 mm diameter by 0.2 mm thick tantalum fiducial markers when used in proton therapy for treating uveal melanoma. Absorbed dose perturbations were measured using radiochromic film and confirmed by Monte Carlo simulations of the experiment. Additional Monte Carlo simulations were performed to study the effects of range modulation and fiducial placement location on the magnitude of the dose shadow for a representative uveal melanoma treatment. The simulations revealed that the fiducials caused perturbations in the absorbed-dose distribution, including absorbed-dose shadows of 22% to 82% in a typical proton beam for treating uveal melanoma, depending on the marker depth and orientation. The clinical implication of this study is that implanted fiducials may, in certain circumstances, cause dose shadows that could lower the tumor dose and theoretically compromise local tumor control. To avoid this situation, fiducials should be positioned laterally or distally with respect to the target volume.

The prediction of output factors for spread-out proton Bragg peak fields in clinical practice

The reliable prediction of output factors for spread-out proton Bragg peak (SOBP) fields in clinical practice remained unrealized due to a lack of a consistent theoretical framework and the great number of variables introduced by the mechanical devices necessary for the production of such fields. These limitations necessitated an almost exclusive reliance on manual calibration for individual fields and empirical, ad hoc, models. We recently reported on a theoretical framework for the prediction of output factors for such fields. In this work, we describe the implementation of this framework in our clinical practice. In our practice, we use a treatment delivery nozzle that uses a limited, and constant, set of mechanical devices to produce SOBP fields over the full extent of clinical penetration depths, or ranges, and modulation widths. This use of a limited set of mechanical devices allows us to unfold the physical effects that affect the output factor. We describe these effects and their incorporation into the theoretical framework. We describe the calibration and protocol for SOBP fields, the effects of apertures and range-compensators and the use of output factors in the treatment planning process.

Comparison of proton and x‐ray conformal dose distributions for radiosurgery applications

Highly focused dose distributions for radiosurgery applications are successfully achieved using either multiple static high-energy particle beams or multiple-arc circular x-ray beams from a linac. It has been suggested that conformal x-ray techniques using dynamically shaped beams with a moving radiation source would offer advantages compared to the use of only circular beams. It is also thought that, generally, charged particle beams such as protons offer dose deposition advantages compared to x-ray beams. A comparison of dose distributions was made between a small number of discrete proton beams, multiple-arc circular x-ray beams, and conformal x-ray techniques. Treatment planning of a selection of radiosurgery cases was done for these three techniques. Target volumes ranged from 1.0-25.0 cm3. Dose distributions and dose volume histograms of the target and surrounding normal brain were calculated. The advantages and limitations of each technique were primarily dependent upon the shape and size of the target volume. In general, proton dose distributions were superior to x-ray distributions; both shaped proton and shaped x-ray beams delivered dose distributions which were more conformal than x-ray techniques using circular beams; and the differences between all proton and x-ray distributions were negligible for the smallest target volumes, and greatest for the larger target volumes.

Anatomic feature-based registration for patient set-up in head and neck cancer radiotherapy

Modern radiotherapy equipment is capable of delivering high precision conformal dose distributions relative to isocentre. One of the barriers to precise treatments is accurate patient re-positioning before each fraction of treatment. At Massachusetts General Hospital, we perform daily patient alignment using radiographs, which are captured by flat panel imaging devices and sent to an analysis program. A trained therapist manually selects anatomically significant features in the skeleton, and couch movement is computed based on the image coordinates of the features. The current procedure takes about 5 to 10 min and significantly affects the efficiency requirement in a busy clinic. This work presents our effort to develop an improved, semi-automatic procedure that uses the manually selected features from the first treatment fraction to automatically locate the same features on the second and subsequent fractions. An implementation of this semi-automatic procedure is currently in clinical use for head and neck tumour sites. Radiographs collected from 510 patient set-ups were used to test this algorithm. A mean difference of 1.5 mm between manual and automatic localization of individual features and a mean difference of 0.8 mm for overall set-up were seen.

Recent Performance of the NPTC Equipment Compared with the Clinical Specifications

The construction of the Northeast Proton Therapy Center (NPTC) at Massachusetts General Hospital is nearing completion. Preliminary beam tests have begun and clinical acceptance testing is soon to follow. Preliminary measurements have been made to determine the properties of the system as compared to the clinical requirements. These results will be discussed. The procedures and instrumentation to be used for testing will also be described.