Quantitative assessment of anatomical change using a virtual proton depth radiograph for adaptive head and neck proton therapy.

The aim of this work is to demonstrate the feasibility of using water-equivalent thickness (WET) and virtual proton depth radiographs (PDRs) of intensity corrected cone-beam computed tomography (CBCT) to detect anatomical change and patient setup error to trigger adaptive head and neck proton therapy. The planning CT (pCT) and linear accelerator (linac) equipped CBCTs acquired weekly during treatment of a head and neck patient were used in this study. Deformable image registration (DIR) was used to register each CBCT with the pCT and map Hounsfield units (HUs) from the planning CT (pCT) onto the daily CBCT. The deformed pCT is referred as the corrected CBCT (cCBCT). Two dimensional virtual lateral PDRs were generated using a ray-tracing technique to project the cumulative WET from a virtual source through the cCBCT and the pCT onto a virtual plane. The PDRs were used to identify anatomic regions with large variations in the proton range between the cCBCT and pCT using a threshold of 3 mm relative difference of WET and 3 mm search radius criteria. The relationship between PDR differences and dose distribution is established. Due to weight change and tumor response during treatment, large variations in WETs were observed in the relative PDRs which corresponded spatially with an increase in the number of failing points within the GTV, especially in the pharynx area. Failing points were also evident near the posterior neck due to setup variations. Differences in PDRs correlated spatially to differences in the distal dose distribution in the beam's eye view. Virtual PDRs generated from volumetric data, such as pCTs or CBCTs, are potentially a useful quantitative tool in proton therapy. PDRs and WET analysis may be used to detect anatomical change from baseline during treatment and trigger further analysis in adaptive proton therapy.

Proton Therapy Equipment Installation, Upgrades, and Building Design.

PURPOSE: This work aims at reviewing challenges and pitfalls in proton facility design related to equipment upgrade or replacement. Proton therapy was initially developed at research institutions in the 1950s which ushered in the use of hospital-based machines in 1990s. We are approaching an era where older commercial machines are reaching the end of their life and require replacement. The future widespread application of proton therapy depends on cost reduction; customized building design and installation are significant expenses. METHODS AND MATERIALS: We take this opportunity to discuss how commercial proton machines have been installed and how buildings housing the equipment have been designed. RESULTS: Data on dimensions and weights of the larger components of proton systems (cyclotron main magnet and gantries) are presented and innovative, non-gantry-based, patient positioning systems are discussed. CONCLUSIONS: We argue that careful consideration of the building design to include larger elevators, hoistways from above, wide corridors and access slopes to below grade installations, generic vault and treatment room layouts to accommodate multiple vendor's equipment, and modular system design can provide specific benefits during planning, installation, maintenance, and replacement phases of the project. Room temperature magnet coils can be constructed in a more modular manner: a potential configuration is presented. There is scope for constructing gantries and magnet yokes from smaller modular sub-units. These considerations would allow a hospital to replace a commercial machine at its end of life in a manner similar to a linac.

Comparison of secondary neutron dose in proton therapy resulting from the use of a tungsten alloy MLC or a brass collimator system.

PURPOSE: To apply the dual ionization chamber method for mixed radiation fields to an accurate comparison of the secondary neutron dose arising from the use of a tungsten alloy multileaf collimator (MLC) as opposed to a brass collimator system for defining the shape of a therapeutic proton field. METHODS: Hydrogenous and nonhydrogenous ionization chambers were constructed with large volumes to enable measurements of absorbed doses below 10(-4) Gy in mixed radiation fields using the dual ionization chamber method for mixed-field dosimetry. Neutron dose measurements were made with a nominal 230 MeV proton beam incident on a closed tungsten alloy MLC and a solid brass block. The chambers were cross-calibrated against a (60)Co-calibrated Farmer chamber in water using a 6 MV x-ray beam and Monte Carlo simulations were performed to account for variations in ionization chamber response due to differences in secondary neutron energy spectra. RESULTS: The neutron and combined proton plus γ-ray absorbed doses are shown to be nearly equivalent downstream from either a closed tungsten alloy MLC or a solid brass block. At 10 cm downstream from the distal edge of the collimating material the neutron dose from the closed MLC was (5.3 ± 0.4) × 10(- 5) Gy/Gy. The neutron dose with brass was (6.4 ± 0.7) × 10(- 5) Gy/Gy. Further from the secondary neutron source, at 50 cm, the neutron doses remain close for both the MLC and brass block at (6.9 ± 0.6) × 10(- 6) Gy/Gy and (6.3 ± 0.7) × 10(- 6) Gy/Gy, respectively. CONCLUSIONS: The dual ionization chamber method is suitable for measuring secondary neutron doses resulting from proton irradiation. The results of measurements downstream from a closed tungsten alloy MLC and a brass block indicate that, even in an overly pessimistic worst-case scenario, secondary neutron production in a tungsten alloy MLC leads to absorbed doses that are nearly equivalent to those seen from brass collimators. Therefore, the choice of tungsten alloy in constructing the leaves of a proton MLC is appropriate, and does not lead to a substantial increase in the secondary neutron dose to the patient compared to that generated in a brass collimator.

Analytical shielding calculations for a proton therapy facility.

The University of Pennsylvania is building a proton therapy facility in collaboration with Walter Reed Army Medical Center. The proposed facility has four gantry rooms, a fixed beam room and a research room, and will use a cyclotron as the source of protons. In this study, neutron shielding considerations for the proposed proton therapy facility were investigated using analytical techniques and Monte Carlo simulated neutron spectra. Neutron spectra calculations were done using the GEANT4 (v6.2) simulation code for various materials: water, carbon, iron, nickel and tantalum to estimate the neutron production at proton beam energies of 100, 175 and 250 MeV. Dose equivalent calculations were performed using analytical methods at various critical points within the facility, by folding the GEANT4 produced neutron spectra with dose equivalent rate data from the National Council on Radiation Protection and Measurements (NCRP) Report #144.

Intensity modulated neutron radiotherapy for the treatment of adenocarcinoma of the prostate.

PURPOSE: This study investigates the enhanced conformality of neutron dose distributions obtainable through the application of intensity modulated neutron radiotherapy (IMNRT) to the treatment of prostate adenocarcinoma. METHODS AND MATERIALS: An in-house algorithm was used to optimize individual segments for IMNRT generated using an organ-at-risk (OAR) avoidance approach. A number of beam orientation schemes were investigated in an attempt to approach an optimum solution. The IMNRT plans were created retrospectively for 5 patients previously treated for prostate adenocarcinoma using fast neutron therapy (FNT), and a comparison of these plans is presented. Dose distributions and dose-volume histograms (DVHs) were analyzed and plans were evaluated based on percentage volumes of rectum and bladder receiving 95%, 80%, and 50% (V(95), V(80), V(50)) of the prescription dose, and on V(60) for both the femoral heads and GM(muscle) group. RESULTS: Plans were normalized such that the IMNRT DVHs for prostate and seminal vesicles were nearly identical to those for conventional FNT plans. Use of IMNRT provided reductions in rectum V(95) and V(80) of 10% (2-27%) and 13% (5-28%), respectively, and reductions in bladder V(95) and V(80) of 12% (3-26%) and 4% (7-10%), respectively. The average decrease in V(60) for the femoral heads was 4.5% (1-18%), with no significant change in V(60) for the GM(muscle) group. CONCLUSIONS: This study provides the first analysis of the application of intensity modulation to neutron radiotherapy. The IMNRT technique provides a substantial reduction in normal tissue dose in the treatment of prostate cancer. This reduction should result in a significant clinical advantage for this and other treatment sites.

Boron neutron capture enhancement of fast neutron radiotherapy utilizing a moderated fast neutron beam.

An investigation of the therapeutic potential of boron neutron capture (BNC) enhancement of fast neutron therapy utilizing the Harper University Hospital superconducting cyclotron-produced d(48.5)+Be fast neutron therapy beam is presented. A technique for modification of the fast neutron beam to increase the BNC enhancement is presented along with an evaluation of the effects of beam moderation on the biological effectiveness of the absorbed dose. Characteristics of the photon, neutron, and boron neutron capture components of the absorbed dose are presented. Results demonstrate the possibility of therapeutic gains greater than 50% over conventional fast neutron therapy at depths required to treat brain lesions. This enhancement is estimated assuming currently achievable boron concentrations, and is more than adequate to provide a therapeutic window for the effective treatment of Glioblastoma Multiforme without prohibitive toxicity to the normal brain.

Responsiveness of experimental prostate carcinoma bone tumors to neutron or photon radiation combined with cytokine therapy.

PURPOSE: To improve the outcome of radiotherapy for prostate carcinoma bone tumors, we investigated bone tumor irradiation with photons or neutrons followed by interleukin 2 (IL-2) therapy in a tumor model. METHODS AND MATERIALS: Implantation of PC-3 cells in nude mouse femur cavity induced a bone tumor that progressed to the formation of a palpable tumor, at the hip joint, by Day 20. Established bone tumors were irradiated with photons or neutrons, and a day later, mice were treated with IL-2 therapy for 3 weekly cycles. RESULTS: PC-3 bone tumors responded to radiation with photons or neutrons in a dose-dependent manner. Combination of photon or neutron radiation with IL-2 therapy increased tumor growth delay, compared to that with photons or neutrons alone. Radiation alone or combined with IL-2 significantly increased mouse survival compared to that with IL-2 or no treatment. After combined therapy, a complete inhibition of bone tumor growth was observed in 45% to 50% of the mice. Histologically, the combined therapy resulted in greater tumor destruction associated with fibrosis, new bone formation, and inflammatory infiltrates than that observed with each modality alone. CONCLUSIONS: The efficacy of tumor irradiation with neutrons or photons was enhanced by IL-2 therapy for the treatment of prostate carcinoma bone tumors.

Design considerations for a computer controlled multileaf collimator for the Harper Hospital fast neutron therapy facility.

The d(48.5) + Be neutron beam from the Harper Hospital superconducting cyclotron is collimated using a unique multirod collimator (MRC). A computer controlled multileaf collimator (MLC) is being designed to improve efficiency and allow for the future development of intensity modulated radiation therapy with neutrons. For the current study the use of focused or unfocused collimator leaves has been studied. Since the engineering effort associated with the leaf design and materials choice impacts significantly on cost, it was desirable to determine the clinical impact of using unfocused leaves in the MLC design. The MRC is a useful tool for studying the effects of using focused versus unfocused beams on beam penumbra. The effects of the penumbra for the different leaf designs on tumor and normal tissue DVHs in two selected sites (prostate and head and neck) was investigated. The increase in the penumbra resulting from using unfocused beams was small (approximately 1.5 mm for a 5 x 5 cm2 field and approximately 7.6 mm for a 25 x 25 cm2 field at 10 cm depth) compared to the contribution of phantom scatter to the penumbra width (5.4 and 20 mm for the small and large fields at 10 cm depth, respectively). Comparison of DVHs for tumor and critical normal tissue in a prostate and head and neck case showed that the dosimetric disadvantages of using an unfocused rather than focused beam were minimal and only significant at shallow depths. For the rare cases, where optimum penumbra conditions are required, a MLC incorporating tapered leaves and, thus, providing focused collimation in one plane is necessary.

Microdosimetric intercomparison of BNCT beams at BNL and MIT.

Microdosimetric measurements have been performed at the clinical beam intensities in two epithermal neutron beams, the Brookhaven Medical Research Reactor and the M67 beam at the Massachusetts Institute of Technology Research Reactor, which have been used to treat patients with Boron Neutron Capture Therapy (BNCT). These measurements offer an independent assessment of the dosimetry used at these two facilities, as well as provide information about the radiation quality not obtainable from conventional macrodosimetric techniques. Moreover, they provide a direct measurement of the absorbed dose resulting from the BNC reaction. BNC absorbed doses measured within this study are approximately 15% lower than those estimated using foil activation at both MIT and BNL. Finally, an intercomparison of the characteristics and radiation quality of these two clinical beams is presented. The techniques described here allow an accurate quantitative comparison of the physical absorbed dose as well as a measure of the biological effectiveness of the absorbed dose delivered by different epithermal beams. No statistically significant differences were observed in the predicted RBEs of these two beams. The methodology presented here can help to facilitate the effective sharing of clinical results in an effort to demonstrate the clinical utility of BNCT.

Characterization of miniature tissue-equivalent proportional counters for neutron radiotherapy applications.

A miniature tissue-equivalent proportional counter (TEPC) system has been developed to facilitate microdosimetric measurements in high-flux mixed fields. Counters with collecting volumes of 12.3 and 2.65 mm3 have been constructed using various tissue-equivalent wall materials, including those loaded with 10B for evaluation of the effects of the boron neutron capture reaction. These counters provide a measure of both the absorbed dose and associated radiation quality, allowing an assessment of the utility and relative effectiveness of various neutron radiotherapy techniques such as boron neutron capture therapy (BNCT), boron neutron capture enhanced fast neutron therapy (BNCEFNT) and intensity modulated neutron radiotherapy (IMNRT). An evaluation of the physical parameters affecting the measured microdosimetric spectrum, the gas multiplication characteristics and the measurement of absorbed dose is presented. In addition, important aspects of the calibration and low energy extrapolation techniques for the microdosimetric spectrum are provided.

Fast neutron irradiation for prostate cancer.

The purpose of this study was to summarize the progress made using fast neutron irradiation in the treatment of prostate cancer at Wayne State University between 1991 and the year 2001. The results of three Phase II studies and one Phase III st udy involving nearly 700 patients is summarized in this paper. The Phase II studies weredose finding studies looking at doses of 15, 9, 10, and 11 nGy, respectively. The randomized protocol was a study of sequence looking at the results of treating patients with neutron first versus neutron radiation last. The results demonstrated that the best combination of tumor control probabilities and normal tissue complications was found in a mix of approximately 50% neutrons and 50% photons. Thus, the standard doses become 10 nGy and 40 Gy of photons. The randomized trial demonstrated that the sequence has significant importance and the disease-free survival was 93% for patients treated with neutrons first versus 73% for patients treated with neutrons last. There was no difference in the rate of acute or chronic complications. Finally, an analysis was performed demonstrating which patients may best benefit from the use of neutron irradiation. It was shown that patients with one, two, or three adverse risk factors had a significant improvement in disease-free survival when part of the treatment included neutron radiation versus standard photon radiation alone. Neutron radiation can be delivered safely with effort to see that it is superior to that which can be achieved by conformal photon irradiation by itself. Future work will be done to expand the role of neutron radiation in other clinical disease sites.