Monte Carlo study of the potential reduction in out-of-field dose using a patient-specific aperture in pencil beam scanning proton therapy

This study is aimed at identifying the potential benefits of using a patientspecific aperture in proton beam scanning. For this purpose, an accurate Monte Carlo model of the pencil beam scanning (PBS) proton therapy (PT) treatment head at Massachusetts General Hospital (MGH) was developed based on an existing model of the passive double-scattering (DS) system. The Monte Carlo code specifies the treatment head at MGH with sub-millimeter accuracy. The code was configured based on the results of experimental measurements performed at MGH. This model was then used to compare out-of-field doses in simulated DS treatments and PBS treatments. For the conditions explored, the penumbra in PBS is wider than in DS, leading to higher absorbed doses and equivalent doses adjacent to the primary field edge. For lateral distances greater than 10 cm from the field edge, the doses in PBS appear to be lower than those observed for DS. We found that placing a patient-specific aperture at nozzle exit during PBS treatments can potentially reduce doses lateral to the primary radiation field by over an order of magnitude. In conclusion, using a patient-specific aperture has the potential to further improve the normal tissue sparing capabilities of PBS

Pencil beam scanning proton therapy: the significance of secondary particles

The bulk of the energy deposition from a proton beam occurs at depth in the Bragg peak. The _nite range of protons in tissue makes them an ideal candidate for the treatment of deep seated tumours and gives improved tissue sparing distal to the target volume compared to photons. However, the production of secondary neutrons and photons has the potential to deliver unwanted dose far outside the intended treatment volume. The _ndings of this thesis show that the magnitude of the doses from secondary neutrons and photons are small. The risk of second cancer from proton therapy treatments has been shown to be lower compared to photon techniques despite the presence of secondary neutrons. This thesis also demonstrates the potential advantages of using pencil beam scanning (PBS) compared to double scattering proton therapy. The neutron doses from PBS is signi_cantly lower than double scattering even far from the primary _eld. The rationale for using protons to treat cancer was examined. Treatment planning comparisons at a number of di_erent clinical sites have shown the potential usefulness of proton therapy. A treatment planning comparison has demonstrated the potential use of protons for the treatment of prostate cancer. Through comparison of proton treatment plans with the best achievable photon plans, it was observed that protons can potentially deliver the same dose to the prostate target volume whilst reducing the dose in normal tissue. Secondary neutrons deposit dose via charged secondary particles which often have high linear energy transfer (LET). The high range of neutrons in tissue combined with the production of high-LET secondaries gives the potential of second malignancy induction external to the primary target volume. Secondary neutrons are produced in proton therapy through nuclear interactions in the treatment nozzle and or in the patient directly. The amount of neutron production in the patient is governed by the interaction cross-section. Phantoms which are used to represent human tissue in experimental studies need to be characterised as they have di_erent chemical compositions which alters the amount of neutron production and the neutron energy spectrum. Monte Carlo simulations were used to determine the variation in neutron absorbed dose and dose equivalent from internally produced secondary neutrons in a series of di_erent tissues and phantom materials. Large variations were observed in the neutron doses in the di_erent materials suggesting the choice of phantom material for neutron dosimetry studies is signi_cant for experimental studies, particularly in regions where the total dose is dominated by secondary neutrons generated internally. A dedicated Monte Carlo code was developed for simulation of PBS treatments us- ing the Geant4 Monte Carlo toolkit. The scanning treatment nozzle at Massachusetts General Hospital was included in the simulation code. Out-of-_eld doses in scanning treatments were previously approximated in Monte Carlo simulations by simulating a double scattering beamline and ignoring the contribution of secondary particles generated in the treatment nozzle. The dose deposition from protons, neutrons and photons was simulated for a _eld designed for the treatment of a deep seated tumour incident upon a Lucite phantom. The results of the simulations showed that the approximation used in previous studies is not valid close to the _eld edge where the wider penumbra from scanning plays a signi_cant role. Further out-of-_eld, the approximation is more acceptable, as the total dose is dominated by internally produced secondary particles. The absorbed dose and dose equivalent out-of-_eld in scanning is approximately an order of magnitude lower than that delivered in double scattering. Employing a patient-speci_c aperture in scanning reduces the penumbral width and the dose close to the _eld edge compared to scanning without an aperture by an order of magnitude. The radiation _eld external to the target volume for a clinical pancreatic _eld was characterised using a _E-E detector. Comparisons were made between double scattering and PBS. Distal to the spread out Bragg peak (SOBP), the neutron uence is higher in double scattering, primarily due to the high amount of neutron production in the treatment nozzle for this modality. The wide penumbra in PBS leads to a higher particle uence upon the detector close to the _eld edge. Further from the _eld edge, the neutron uence is signi_cantly higher from double scattering compared to scanning. Close to the primary _eld, the orientation of the detector was determined to be signi_cant for double scattering. Depending on the chosen orientation, when operated in coincidence mode, the results are biased towards either detection of scattered protons from the primary _eld or neutrons generated in the treatment nozzle. The time to undertake any treatment is important for radiotherapy and the efficiency of patient throughput. The time required for a PBS treatment has not been investigated previously. A series of equations are presented which allow calculation of the time required to deliver a pencil beam scanning treatment based on the system hardware. An SOBP is produced from a database of individual Bragg peaks generated from Monte Carlo simulations. Using a constant distance spacing between individual Bragg peaks in the SOBP allows the required dose conformality to be achieved with the fewest number of layers. The e_ect of each of the parameters in a clinical pencil beam scanning system on the total irradiation time was ascertained. Both a cyclotron and synchrotron were considered as possible beam sources. The equations allow optimisation of the irradiation time by observing the e_ect of altering the system hardware. The equations presented are facility independent and can be applied to any scanning system which uses two perpendicular scanning magnets to scan the beam laterally. KEYWORDS: proton therapy, Monte Carlo, pencil beam scanning, secondary neutron

A comparison of proton therapy and IMRT treatment plans for prostate radiotherapy

Proton therapy (PT) is becoming a more widely available treatment option on the world stage and there is some interest in investment in this treatment option in Australia. The benefit of PT has been shown for a number of tumour sites, particularly for paediatric patients. The workload from these patients may not completely fill the maximum yearly workload of a machine. This work aims to ascertain if prostate cancer would be a suitable candidate to fill the rest of the workload at an Australian PT facility. Passive and intensity modulated proton therapy (IMPT) plans were generated for a prostate patient. These were compared to 7 field sliding window and step and shoot IMRT plans. All plans used a prescription dose of 78 CGE. IMRT and IMPT plans used inverse planning for optimisation. Homogeneity in the PTV was best for the IMPT plan. IMPT also gave the best rectal sparing. The bladder and femoral heads were exposed to less dose in both proton plans. Proton plans exposed normal tissue outside the PTV to less than 50% of the dose given by the IMRT plans. PT, particularly IMPT, is a suitable treatment option for the prostate cancer patient presented here

Perforin and Gamma Interferon-Mediated Control of Coronavirus Central Nervous System Infection by CD8 T Cells in the Absence of CD4 T Cells

Infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus produces acute and chronic demyelination. The contributions of perforin-mediated cytolysis and gamma interferon (IFN-γ) secretion by CD8(+) T cells to the control of infection and the induction of demyelination were examined by adoptive transfer into infected SCID recipients. Untreated SCID mice exhibited uncontrolled virus replication in all CNS cell types but had little or no demyelination. Memory CD8(+) T cells from syngeneic wild-type (wt), perforin-deficient, or IFN-γ-deficient (GKO) donors all trafficked into the infected CNS in the absence of CD4(+) T cells and localized to similar areas. Although CD8(+) T cells from all three donors suppressed virus replication in the CNS, GKO CD8(+) T cells expressed the least antiviral activity. A distinct viral antigen distribution in specific CNS cell types revealed different mechanisms of viral control. While wt CD8(+) T cells inhibited virus replication in all CNS cell types, cytolytic activity in the absence of IFN-γ suppressed the infection of astrocytes, but not oligodendroglia. In contrast, cells that secreted IFN-γ but lacked cytolytic activity inhibited replication in oligodendroglia, but not astrocytes. Demyelination was most severe following viral control by wt CD8(+) T cells but was independent of macrophage infiltration. These data demonstrate the effective control of virus replication by CD8(+) T cells in the absence of CD4(+) T cells and support the necessity for the expression of distinct effector mechanisms in the control of viral replication in distinct CNS glial cell types