The physics of proton therapy

The physics of proton therapy has advanced considerably since it was proposed in 1946. Today analytical equations and numerical simulation methods are available to predict and characterize many aspects of proton therapy. This article reviews the basic aspects of the physics of proton therapy, including proton interaction mechanisms, proton transport calculations, the determination of dose from therapeutic and stray radiations, and shielding design. The article discusses underlying processes as well as selected practical experimental and theoretical methods. We conclude by briefly speculating on possible future areas of research of relevance to the physics of proton therapy.

[1]  J. Ziegler Stopping of energetic light ions in elemental matter , 1999 .

[2]  Daniel W. Miller,et al.  Ion stopping powers and CT numbers. , 2010, Medical dosimetry : official journal of the American Association of Medical Dosimetrists.

[3]  M Scholz,et al.  Tumor therapy and track structure , 1999, Radiation and environmental biophysics.

[4]  W. Newhauser,et al.  Equivalent dose and effective dose from stray radiation during passively scattered proton radiotherapy for prostate cancer , 2008, Physics in medicine and biology.

[5]  W. Leo,et al.  Techniques for Nuclear and Particle Physics Experiments , 1987 .

[6]  P. Almond,et al.  Electron beam dose calculations , 1981, Physics in medicine and biology.

[7]  M. Tadokoro,et al.  Measurement of neutron dose distribution for a passive scattering nozzle at the Proton Medical Research Center (PMRC) , 2006 .

[8]  O. Mawlawi,et al.  Determination of elemental tissue composition following proton treatment using positron emission tomography , 2013, Physics in medicine and biology.

[9]  D. Hoel Second Primary Cancers and Cardiovascular Disease after Radiation Therapy , 2012 .

[10]  H. Paganetti,et al.  Risk of developing second cancer from neutron dose in proton therapy as function of field characteristics, organ, and patient age. , 2008, International journal of radiation oncology, biology, physics.

[11]  H. Bethe Zur Theorie des Durchgangs schneller Korpuskularstrahlen durch Materie , 1930 .

[12]  U. Oelfke,et al.  CT calibration for two-dimensional scaling of proton pencil beams. , 2003, Physics in medicine and biology.

[13]  P Chauvel,et al.  Monte Carlo simulation of a protontherapy platform devoted to ocular melanoma. , 2005, Medical physics.

[14]  Uwe Titt,et al.  Monte Carlo simulations of a nozzle for the treatment of ocular tumours with high-energy proton beams , 2005, Physics in medicine and biology.

[16]  U. Titt,et al.  Patient neutron dose equivalent exposures outside of the proton therapy treatment field. , 2005, Radiation protection dosimetry.

[17]  J. Deye,et al.  Biomedical Particle Accelerators , 1986 .

[18]  R. Mohan,et al.  Assessment of the accuracy of an MCNPX-based Monte Carlo simulation model for predicting three-dimensional absorbed dose distributions , 2008, Physics in medicine and biology.

[19]  Chan Hyeong Kim,et al.  Development of array-type prompt gamma measurement system for in vivo range verification in proton therapy. , 2012, Medical physics.

[20]  R. Howell,et al.  A comparative study on the risks of radiogenic second cancers and cardiac mortality in a set of pediatric medulloblastoma patients treated with photon or proton craniospinal irradiation. , 2014, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[21]  Marco Durante,et al.  Assessing the risk of second malignancies after modern radiotherapy , 2011, Nature Reviews Cancer.

[22]  Proton beam dosimetry for radiosurgery: implementation of the ICRU Report 59 at the Harvard Cyclotron Laboratory. , 2002, Physics in medicine and biology.

[23]  H. Kooy,et al.  Monte Carlo study of the potential reduction in out-of-field dose using a patient-specific aperture in pencil beam scanning proton therapy , 2012, Physics in medicine and biology.

[24]  Stanley J. Rosenthal,et al.  Dosimetric impact of tantalum markers used in the treatment of uveal melanoma with proton beam therapy , 2007, Physics in medicine and biology.

[25]  J. Rosenwald,et al.  Traitement du mélanome choroïdien par disque d'iode 125 et faisceau de protons : indications respectives et comparaison des taux de récidive , 2003 .

[26]  Lev Davidovich Landau,et al.  On the energy loss of fast particles by ionization , 1944 .

[27]  D. Bonnett,et al.  Current developments in proton therapy: a review. , 1993, Physics in medicine and biology.

[28]  R. Sievert,et al.  Book Reviews : Recommendations of the International Commission on Radiological Protection (as amended 1959 and revised 1962). I.C.R.P. Publication 6. 70 pp. PERGAMON PRESS. Oxford, London and New York, 1964. £1 5s. 0d. [TB/54] , 1964 .

[29]  Rui Zhang,et al.  Monte Carlo and analytical model predictions of leakage neutron exposures from passively scattered proton therapy. , 2013, Medical physics.

[30]  Stephanie Weiss,et al.  Fiducial Markers Implanted during Prostate Brachytherapy for Guiding Conformal External Beam Radiation Therapy , 2004, Technology in cancer research & treatment.

[31]  B. A. Ludewigt,et al.  Instrumentation for Treatment of Cancer Using Proton and Light-Ion Beams , 1993 .

[32]  Harald Paganetti,et al.  A review of dosimetry studies on external-beam radiation treatment with respect to second cancer induction , 2008, Physics in medicine and biology.

[33]  W. Newhauser,et al.  Calculations of neutron dose equivalent exposures from range-modulated proton therapy beams , 2005, Physics in medicine and biology.

[34]  A. Pérez-Andújar,et al.  The predicted relative risk of premature ovarian failure for three radiotherapy modalities in a girl receiving craniospinal irradiation , 2013, Physics in medicine and biology.

[35]  G Ciangaru,et al.  Experimental validation of a Monte Carlo proton therapy nozzle model incorporating magnetically steered protons , 2009, Physics in medicine and biology.

[36]  R. Mohan,et al.  An MCNPX Monte Carlo model of a discrete spot scanning proton beam therapy nozzle. , 2010, Medical physics.

[37]  E. Hall,et al.  Intensity-modulated radiation therapy, protons, and the risk of second cancers. , 2006, International journal of radiation oncology, biology, physics.

[38]  J. E. Turner,et al.  Microdosimetry and Its Applications. H. H. Rossi , M. Zaider , 1996 .

[39]  Graham Roger Stevenson,et al.  Radiological safety aspects of the operation of proton accelerators , 1988 .

[40]  Shinichi Shimizu,et al.  Biological effect of dose distortion by fiducial markers in spot-scanning proton therapy with a limited number of fields: a simulation study. , 2012, Medical physics.

[41]  J M Slater,et al.  Dosimetry techniques for narrow proton beam radiosurgery. , 1999, Physics in medicine and biology.

[42]  L. Verhey,et al.  Protons or megavoltage X‐rays as boost therapy for patients irradiated for localized prostatic carcinoma an early phase I/II comparison , 1983, Cancer.

[43]  P. Vaz,et al.  Advanced Monte Carlo for radiation physics, particle transport simulation and applications : proceedings of the Monte Carlo 2000 Conference, Lisbon, 23-26 October 2000 , 2001 .

[44]  R. Mohan,et al.  The risk of developing a second cancer after receiving craniospinal proton irradiation , 2009, Physics in medicine and biology.

[45]  Dragan Mirkovic,et al.  Application of a fast proton dose calculation algorithm to a thorax geometry. , 2010, Radiation measurements.

[46]  P. Petti,et al.  Differential-pencil-beam dose calculations for charged particles. , 1992, Medical physics.

[47]  P Andreo,et al.  Monte Carlo calculated stopping-power ratios, water/air, for clinical proton dosimetry (50-250 MeV). , 1997, Physics in medicine and biology.

[48]  T. Trikalinos,et al.  Systematic Review: Charged-Particle Radiation Therapy for Cancer , 2009, Annals of Internal Medicine.

[49]  S Agosteo,et al.  Secondary neutron and photon dose in proton therapy. , 1998, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[50]  B. Schaffner Proton dose calculation based on in-air fluence measurements , 2008, Physics in medicine and biology.

[51]  R. Mohan,et al.  Monte Carlo simulations of the dosimetric impact of radiopaque fiducial markers for proton radiotherapy of the prostate , 2007, Physics in medicine and biology.

[52]  M Goitein,et al.  The relative costs of proton and X-ray radiation therapy. , 2003, Clinical oncology (Royal College of Radiologists (Great Britain)).

[53]  M Gambaccini,et al.  Dual-energy tissue cancellation in mammography with quasi-monochromatic x-rays. , 2002, Physics in medicine and biology.

[54]  P. Yepes,et al.  Benchmark measurements and simulations of dose perturbations due to metallic spheres in proton beams. , 2013, Radiation measurements.

[55]  U. Titt,et al.  Neutron shielding calculations in a proton therapy facility based on Monte Carlo simulations and analytical models: criterion for selecting the method of choice. , 2005, Radiation protection dosimetry.

[56]  Alfred R. Smith,et al.  Initial beam size study for passive scatter proton therapy. I. Monte Carlo verification. , 2007, Medical physics.

[57]  R. Mohan,et al.  Adjustment of the lateral and longitudinal size of scanned proton beam spots using a pre-absorber to optimize penumbrae and delivery efficiency , 2010, Physics in medicine and biology.

[58]  Todd Pawlicki,et al.  Comprar Quality And Safety In Radiotherapy (Imaging In Medical Diagnosis & Therapy) | P. Scalliet | 9781439804360 | CRC PRESS , 2011 .

[59]  P. Busca,et al.  Prompt gamma imaging with a slit camera for real-time range control in proton therapy: Experimental validation up to 230 MeV with HICAM and development of a new prototype , 2012 .

[60]  Dragan Mirkovic,et al.  Advantages of MCNPX-Based Lattice Tally over Mesh Tally in High-Speed Monte Carlo Dose Reconstruction for Proton Radiotherapy , 2013, Nuclear technology.

[61]  D. Bonnett,et al.  Supplement to the code of practice for clinical proton dosimetry. ECHED (European Clinical Heavy Particle Dosimetry Group). , 1994, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[62]  A M Koehler,et al.  Flattening of proton dose distributions for large-field radiotherapy. , 1977, Medical physics.

[63]  R. Mohan,et al.  Monte Carlo study of neutron dose equivalent during passive scattering proton therapy , 2007, Physics in medicine and biology.

[64]  Y. Lievens,et al.  Health economic controversy and cost-effectiveness of proton therapy. , 2013, Seminars in radiation oncology.

[65]  P. Olko,et al.  Dose perturbation behind tantalum clips in ocular proton therapy , 2010 .

[66]  B W Raaymakers,et al.  Feasibility of MRI guided proton therapy: magnetic field dose effects , 2008, Physics in medicine and biology.

[67]  R. Howell,et al.  Predicted risks of radiogenic cardiac toxicity in two pediatric patients undergoing photon or proton radiotherapy , 2013, Radiation oncology.

[68]  A. Kujawa,et al.  Cancer Survivors in the United States: A Review of the Literature and a Call to Action , 2012, International journal of medical sciences.

[69]  J. Seco,et al.  Comparison of out-of-field photon doses in 6 MV IMRT and neutron doses in proton therapy for adult and pediatric patients , 2010, Physics in medicine and biology.

[70]  J. Ziegler,et al.  SRIM – The stopping and range of ions in matter (2010) , 2010 .

[71]  R. Howell,et al.  Comparison of risk of radiogenic second cancer following photon and proton craniospinal irradiation for a pediatric medulloblastoma patient , 2013, Physics in medicine and biology.

[72]  Harald Paganetti,et al.  The clinical impact of uncertainties in the mean excitation energy of human tissues during proton therapy , 2013, Physics in medicine and biology.

[73]  Uwe Titt,et al.  Monte Carlo investigation of collimator scatter of proton-therapy beams produced using the passive scattering method. , 2008, Physics in medicine and biology.

[74]  J F Ziegler,et al.  Comments on ICRU report no. 49: stopping powers and ranges for protons and alpha particles. , 1999, Radiation research.

[75]  Andrew K. Lee,et al.  Reducing stray radiation dose to patients receiving passively scattered proton radiotherapy for prostate cancer , 2008, Physics in medicine and biology.

[76]  Andrew K. Lee,et al.  Investigation of dose perturbations and the radiographic visibility of potential fiducials for proton radiation therapy of the prostate , 2011, Physics in medicine and biology.

[77]  J. Siebers Application of Monte Carlo to Proton Beam Radiation Therapy , 2001 .

[78]  W. Sweet,et al.  The Bragg peak of a proton beam in intracranial therapy of tumors. , 1962, Transactions of the American Neurological Association.

[79]  N. Rohrig Structural Shielding Design and Evaluation for Megavoltage X- and Gamma-Ray Radiotherapy Facilities, NCRP Report No. 151 , 2006 .

[80]  M Goitein,et al.  Proton beam irradiation of uveal melanomas. Results of 5 1/2-year study. , 1982, Archives of ophthalmology.

[81]  K.-U. Amthor,et al.  Laser-plasma acceleration of quasi-monoenergetic protons from microstructured targets , 2006, Nature.

[82]  Anders Brahme,et al.  Recent advances in light ion radiation therapy. , 2004, International journal of radiation oncology, biology, physics.

[83]  Uwe Titt,et al.  Neutron shielding verification measurements and simulations for a 235-MeV proton therapy center , 2002 .

[84]  R. Mohan,et al.  Monte Carlo simulations of stray neutron radiation exposures in proton therapy , 2007 .

[85]  R. Stewart,et al.  Neutron scattered dose equivalent to a fetus from proton radiotherapy of the mother. , 2006, Medical physics.

[86]  Habib Zaidi,et al.  RapidArc, intensity modulated photon and proton techniques for recurrent prostate cancer in previously irradiated patients: a treatment planning comparison study , 2009, Radiation oncology.

[87]  Radhe Mohan,et al.  Stray radiation dose and second cancer risk for a pediatric patient receiving craniospinal irradiation with proton beams , 2009, Physics in medicine and biology.

[88]  Ravi Vadapalli,et al.  Grid-Enabled Treatment Planning for Proton Therapy Using Monte Carlo Simulations , 2011, Nuclear technology.

[89]  D Sarrut,et al.  Machine learning-based patient specific prompt-gamma dose monitoring in proton therapy , 2013, Physics in medicine and biology.

[90]  E Pedroni,et al.  Experimental characterization and physical modelling of the dose distribution of scanned proton pencil beams , 2005, Physics in medicine and biology.

[91]  Wayne D Newhauser,et al.  Risk of radiogenic second cancers following volumetric modulated arc therapy and proton arc therapy for prostate cancer , 2012, Physics in medicine and biology.

[92]  E. Pedroni,et al.  Dose calculation models for proton treatment planning using a dynamic beam delivery system: an attempt to include density heterogeneity effects in the analytical dose calculation. , 1999, Physics in medicine and biology.

[93]  G. Armstrong,et al.  Late mortality among 5-year survivors of childhood cancer: a summary from the Childhood Cancer Survivor Study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[94]  S. Roy,et al.  Scattered neutron dose equivalent to a fetus from proton therapy of the mother , 2004 .

[95]  U. Linz Ion Beam Therapy , 2012 .

[96]  G H Olivera,et al.  The use of megavoltage CT (MVCT) images for dose recomputations , 2005, Physics in medicine and biology.

[97]  E. Benton,et al.  Leakage and scatter radiation from a double scattering based proton beamline. , 2007, Medical physics.

[98]  T. Mackie,et al.  A generalized 2D pencil beam scaling algorithm for proton dose calculation in heterogeneous slab geometries. , 2013, Medical physics.

[99]  Dieter Schardt,et al.  Heavy-ion tumor therapy: Physical and radiobiological benefits , 2010 .

[100]  Ute Linz,et al.  Ion beam therapy : fundamentals, technology, clinical applications , 2012 .

[101]  Dragan Mirkovic,et al.  A GPU implementation of a track-repeating algorithm for proton radiotherapy dose calculations , 2010, Physics in medicine and biology.

[102]  Icru Prescribing, recording, and reporting photon beam therapy , 1993 .

[103]  Wayne D Newhauser,et al.  Water equivalent thickness values of materials used in beams of protons, helium, carbon and iron ions , 2010, Physics in medicine and biology.

[104]  T R Mackie,et al.  A compact linac for intensity modulated proton therapy based on a dielectric wall accelerator. , 2008, Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics.

[105]  R. Howell,et al.  Analytical model for out-of-field dose in photon craniospinal irradiation , 2013, Physics in medicine and biology.

[106]  D Robertson,et al.  Optimizing a three-stage Compton camera for measuring prompt gamma rays emitted during proton radiotherapy , 2010, Physics in medicine and biology.

[107]  Anatoly B Rosenfeld,et al.  The role of nonelastic reactions in absorbed dose distributions from therapeutic proton beams in different medium. , 2004, Medical physics.

[108]  Z. Zajacova,et al.  Shielding data for 100–250 MeV proton accelerators: Double differential neutron distributions and attenuation in concrete , 2007 .

[109]  Mark Hachey,et al.  Cancer Survivors in the United States: Prevalence across the Survivorship Trajectory and Implications for Care , 2013, Cancer Epidemiology, Biomarkers & Prevention.

[110]  S. Agosteo Radiation protection constraints for use of proton and ion accelerators in medicine. , 2009, Radiation protection dosimetry.

[111]  E Pedroni,et al.  Proton radiography as a tool for quality control in proton therapy. , 1995, Medical physics.

[112]  Pedro Andreo,et al.  On the clinical spatial resolution achievable with protons and heavier charged particle radiotherapy beams , 2009, Physics in medicine and biology.

[113]  C. Johnstone,et al.  Fixed field circular accelerator designs , 1999, Proceedings of the 1999 Particle Accelerator Conference (Cat. No.99CH36366).

[114]  R. Amos,et al.  Proton and Carbon Ion Therapy , 2013 .

[115]  Richard Wilson A Brief History of the Harvard University Cyclotrons , 2004 .

[116]  Wayne D Newhauser,et al.  A Track-Repeating Algorithm for Fast Monte Carlo Dose Calculations of Proton Radiotherapy , 2009, Nuclear technology.

[117]  Harald Paganetti,et al.  Clinical application of in-room positron emission tomography for in vivo treatment monitoring in proton radiation therapy. , 2013, International journal of radiation oncology, biology, physics.

[118]  Design tools for proton therapy nozzles based on the double-scattering foil technique. , 2005, Radiation protection dosimetry.

[119]  M Goitein,et al.  A pencil beam algorithm for proton dose calculations. , 1996, Physics in medicine and biology.

[120]  F. Marti,et al.  A compact superconducting cyclotron for the production of high intensity protons , 1997, Proceedings of the 1997 Particle Accelerator Conference (Cat. No.97CH36167).

[121]  M. E. Rudd,et al.  Secondary electron spectra from charged particle interactions , 1996 .

[122]  Alfred R. Smith,et al.  Benchmarking analytical calculations of proton doses in heterogeneous matter. , 2005, Medical physics.

[123]  A. Kacperek Clinical Proton Dosimetry Part I: Beam Production, Beam Delivery and Measurement of Absorbed Dose (ICRU Report 59) , 2000 .

[124]  T. Merchant Proton Beam Therapy in Pediatric Oncology , 2009, Cancer journal.

[125]  L. Moritz Radiation protection at low energy proton accelerators. , 2001, Radiation protection dosimetry.

[126]  N. Bohr Dr. phil.,et al.  LX. On the decrease of velocity of swiftly moving electrified particles in passing through matter , 1915 .

[127]  K. Tesch,et al.  THE ATTENUATION OF THE NEUTRON DOSE EQUIVALENT IN A LABYRINTH THROUGH AN ACCELERATOR SHIELDING , 1981 .

[128]  Icrp Chapters 3 and 4 , 2007 .

[129]  Nicholas C Koch,et al.  Development and verification of an analytical algorithm to predict absorbed dose distributions in ocular proton therapy using Monte Carlo simulations , 2010, Physics in medicine and biology.

[130]  Philippe Lambin,et al.  How costly is particle therapy? Cost analysis of external beam radiotherapy with carbon-ions, protons and photons. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[131]  H Paganetti,et al.  TOPAS: an innovative proton Monte Carlo platform for research and clinical applications. , 2012, Medical physics.

[132]  S. Y. Lee,et al.  Accelerator Physics , 2019 .

[133]  Anatoly Rosenfeld,et al.  Out-of-field dose equivalents delivered by proton therapy of prostate cancer. , 2007, Medical physics.

[134]  A. Fass,et al.  Radiation Protection for Particle Accelerator Facilities , 2005 .

[135]  A. Koehler,et al.  Measurement of neutron dose equivalent to proton therapy patients outside of the proton radiation field , 2002 .

[136]  Dong Wook Kim,et al.  Microscopic gold particle-based fiducial markers for proton therapy of prostate cancer. , 2009, International journal of radiation oncology, biology, physics.

[137]  F. Bloch,et al.  Zur Bremsung rasch bewegter Teilchen beim Durchgang durch Materie , 1933 .

[138]  H Edwin Romeijn,et al.  A computational implementation and comparison of several intensity modulated proton therapy treatment planning algorithms. , 2008, Medical physics.

[139]  U. Oelfke,et al.  Two-dimensional pencil beam scaling: an improved proton dose algorithm for heterogeneous media. , 2002, Physics in medicine and biology.

[140]  J. Slater,et al.  Treatment of macular degeneration with proton beams. , 1999, Medical physics.

[141]  G. Sandison,et al.  Phantom assessment of lung dose from proton arc therapy. , 1997, International journal of radiation oncology, biology, physics.

[142]  K Parodi,et al.  A Monte Carlo-based treatment planning tool for proton therapy , 2013, Physics in medicine and biology.

[143]  H Paganetti,et al.  Monte Carlo patient study on the comparison of prompt gamma and PET imaging for range verification in proton therapy , 2011, Physics in medicine and biology.

[144]  Steve B. Jiang,et al.  GPU-based fast Monte Carlo dose calculation for proton therapy , 2012, Physics in medicine and biology.

[145]  Torunn I Yock,et al.  Physiologic and radiographic evidence of the distal edge of the proton beam in craniospinal irradiation. , 2007, International journal of radiation oncology, biology, physics.

[146]  W. Newhauser,et al.  Monte Carlo simulations of neutron spectral fluence, radiation weighting factor and ambient dose equivalent for a passively scattered proton therapy unit , 2008, Physics in medicine and biology.

[147]  W. H. Bragg,et al.  XXXIX. On the α particles of radium, and their loss of range in passing through various atoms and molecules , 1905 .

[148]  Katia Parodi,et al.  PET/CT imaging for treatment verification after proton therapy: a study with plastic phantoms and metallic implants. , 2007, Medical physics.

[149]  A. Ahnesjö,et al.  Experimental test of Monte Carlo proton transport at grazing incidence in GEANT4, FLUKA and MCNPX , 2008, Physics in medicine and biology.

[150]  A. Trofimov,et al.  4D Monte Carlo simulation of proton beam scanning: modelling of variations in time and space to study the interplay between scanning pattern and time-dependent patient geometry , 2005, Physics in medicine and biology.

[151]  W. Newhauser,et al.  Dosimetry for ocular proton beam therapy at the Harvard Cyclotron Laboratory based on the ICRU Report 59. , 2002, Medical physics.

[152]  E. Pedroni,et al.  Secondary neutron dose during proton therapy using spot scanning. , 2002, International journal of radiation oncology, biology, physics.

[153]  M. Somerfield,et al.  American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[154]  G. Glasgow,et al.  Structural Shielding Design and Evaluation for Megavoltage X- and Gamma-Ray Radiotherapy Facilities. , 2006, Medical physics.

[155]  D. DavidS.ShimmM. Perez and Brady's Principles and Practice of Radiation Oncology , 2008 .

[156]  George Starkschall,et al.  Determination of output factors for small proton therapy fields. , 2007, Medical physics.

[157]  H Paganetti,et al.  Nuclear interactions in proton therapy: dose and relative biological effect distributions originating from primary and secondary particles. , 2002, Physics in medicine and biology.

[158]  A. Ferrari,et al.  FLUKA: A Multi-Particle Transport Code , 2005 .

[159]  Radhe Mohan,et al.  Can megavoltage computed tomography reduce proton range uncertainties in treatment plans for patients with large metal implants? , 2008, Physics in medicine and biology.

[160]  Andrew K. Lee,et al.  Uncertainty in dose per monitor unit estimates for passively scattered proton therapy: The role of compensator and patient scatter in prostate cases , 2015 .

[161]  E. Pedroni,et al.  The 200-MeV proton therapy project at the Paul Scherrer Institute: conceptual design and practical realization. , 1995, Medical physics.

[162]  Harald Paganetti,et al.  Reduction of the secondary neutron dose in passively scattered proton radiotherapy, using an optimized pre-collimator/collimator , 2009, Physics in medicine and biology.

[163]  Kyounghwa Bae,et al.  Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: long-term results from proton radiation oncology group/american college of radiology 95-09. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[164]  L. Verhey,et al.  The determination of absorbed dose in a proton beam for purposes of charged-particle radiation therapy. , 1979, Radiation research.

[165]  Wayne D Newhauser,et al.  Calculation of water equivalent thickness of materials of arbitrary density , elemental composition and thickness in proton beam irradiation , 2009 .

[166]  Mark Oldham,et al.  Feasibility of using PRESAGE® for relative 3D dosimetry of small proton fields , 2012, Physics in medicine and biology.

[167]  E. Rutherford,et al.  The scattering of alpha and beta particles by matter and the structure of the atom , 1911 .

[168]  E Pedroni,et al.  Monte Carlo dose calculations for spot scanned proton therapy , 2005, Physics in medicine and biology.

[169]  J. Smathers,et al.  The Modern Technology of Radiation Oncology: A Compendium for Medical Physicists and Radiation Oncologists , 1999 .

[170]  W. Newhauser,et al.  Virtual commissioning of a treatment planning system for proton therapy of ocular cancers. , 2005, Radiation protection dosimetry.

[171]  R. Wilson Radiological use of fast protons. , 1946, Radiology.

[172]  L. Verhey,et al.  Computer-assisted positioning of radiotherapy patients using implanted radiopaque fiducials. , 1993, Medical physics.

[173]  Frank Verhaegen,et al.  Monte Carlo Techniques in Radiation Therapy , 2021 .

[174]  N Shandala,et al.  Scope of radiological protection control measures. , 2007, Annals of the ICRP.

[175]  R. Howell,et al.  Second Primary Cancers and Cardiovascular Disease after Radiation Therapy. NCRP Report No. 170. , 2012, Medical physics.

[176]  A. Lomax Charged Particle Therapy: The Physics of Interaction , 2009, Cancer journal.

[177]  P. Yepes,et al.  Intercomparision of Monte Carlo Radiation Transport Codes MCNPX, GEANT4, and FLUKA for Simulating Proton Radiotherapy of the Eye , 2009, Nuclear technology.

[178]  J. Thariat,et al.  Quantification of dose perturbations induced by external and internal accessories in ocular proton therapy and evaluation of their dosimetric impact. , 2013, Medical physics.

[179]  H. Breuer,et al.  Proton Therapy and Radiosurgery , 2000, Springer Berlin Heidelberg.

[180]  A. Pérez-Andújar,et al.  Neutron production from beam-modifying devices in a modern double scattering proton therapy beam delivery system , 2009, Physics in medicine and biology.

[181]  A. Mahajan,et al.  Predicted risks of second malignant neoplasm incidence and mortality due to secondary neutrons in a girl and boy receiving proton craniospinal irradiation , 2010, Physics in medicine and biology.

[182]  Matthias Fippel,et al.  A pencil beam algorithm for intensity modulated proton therapy derived from Monte Carlo simulations , 2005, Physics in medicine and biology.

[183]  T Bortfeld,et al.  An analytical approximation of the Bragg curve for therapeutic proton beams. , 1997, Medical physics.

[184]  R. Ferrand,et al.  Calibration of CT Hounsfield units for proton therapy treatment planning: use of kilovoltage and megavoltage images and comparison of parameterized methods , 2013, Physics in medicine and biology.

[185]  A. Koehler,et al.  Protons in radiation therapy. Comparative dose distributions for protons, photons, and electrons. , 1972, Radiology.

[186]  D. Brenner,et al.  Secondary neutrons in clinical proton radiotherapy: a charged issue. , 2008, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[187]  C Nauraye,et al.  Monte Carlo modelling of the treatment line of the Proton Therapy Center in Orsay , 2009, Physics in medicine and biology.

[188]  R. Vetter ICRP Publication 103, The Recommendations of the International Commission on Radiological Protection , 2008 .

[189]  L. Williams A Brief History of the Harvard University Cyclotrons , 2004 .

[190]  E. Rutherford,et al.  The scattering of α and β particles by matter and the structure of the atom , 2012 .

[191]  W. Sweet,et al.  Stereotaxic instrument for use with the Bragg peak of a proton beam. , 1962, Confinia neurologica.

[192]  N. M. Larson,et al.  ENDF/B-VII.1 Nuclear Data for Science and Technology: Cross Sections, Covariances, Fission Product Yields and Decay Data , 2011 .

[193]  R. Howell,et al.  Risk of second malignant neoplasm following proton versus intensity-modulated photon radiotherapies for hepatocellular carcinoma , 2010, Physics in medicine and biology.

[194]  Wayne D Newhauser,et al.  Monte Carlo fast dose calculator for proton radiotherapy: application to a voxelized geometry representing a patient with prostate cancer , 2009, Physics in medicine and biology.

[195]  Harald Paganetti,et al.  Dosimetric accuracy of planning and delivering small proton therapy fields , 2010, Physics in medicine and biology.

[196]  Rajat J Kudchadker,et al.  Dose perturbations and image artifacts caused by carbon-coated ceramic and stainless steel fiducials used in proton therapy for prostate cancer , 2010, Physics in medicine and biology.

[197]  Brian Wang,et al.  Simulation of organ-specific patient effective dose due to secondary neutrons in proton radiation treatment , 2005, Physics in medicine and biology.

[198]  A. Pérez-Andújar,et al.  An analytic model of neutron ambient dose equivalent and equivalent dose for proton radiotherapy , 2010, Physics in medicine and biology.

[199]  U. Amaldi,et al.  Hadrontherapy in oncology : proceedings of the First International Symposium on Hadrontherapy, Como, Italy, 18-21 October 1993 , 1994 .

[200]  L. Verhey,et al.  Advanced prostate cancer: the results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone. , 1995, International journal of radiation oncology, biology, physics.

[201]  W Schlegel,et al.  An analytical approximation of depth-dose distributions for therapeutic proton beams. , 1996, Physics in medicine and biology.

[202]  Jin Sung Kim,et al.  New concept of a range verification system for proton therapy using a photon counting detector , 2012 .

[203]  Gregory C Sharp,et al.  In vivo proton beam range verification using spine MRI changes. , 2010, International journal of radiation oncology, biology, physics.

[204]  Robert J. Schneider,et al.  Multiple Coulomb scattering of 160 MeV protons , 1993 .

[205]  J H LAWRENCE,et al.  Pituitary irradiation with high-energy proton beams: a preliminary report. , 1958, Cancer research.

[206]  P. V. Vavilov IONIZATION LOSSES OF HIGH-ENERGY HEAVY PARTICLES , 1957 .

[207]  Radhe Mohan,et al.  Monte Carlo simulations for configuring and testing an analytical proton dose-calculation algorithm , 2007, Physics in medicine and biology.

[208]  S. Sarnacki,et al.  Preserving Fertility in Prepubertal Children , 2009, Hormone Research in Paediatrics.

[209]  R. Mohan,et al.  Monte carlo proton radiation therapy planning calculations , 2008 .

[210]  Sjirk N. Boon Dosimetry and quality control of scanning proton beams , 1998 .

[211]  Z. Tochner,et al.  Proton Beam Irradiation in Pediatric Oncology: An Overview , 2005, Journal of pediatric hematology/oncology.

[212]  Gert Moliere,et al.  Theorie der Streuung schneller geladener Teilchen II Mehrfach-und Vielfachstreuung , 1948 .

[213]  S. Peggs,et al.  Conceptual design of a proton computed tomography system for applications in proton radiation therapy , 2004, IEEE Transactions on Nuclear Science.

[214]  Reinhard W. Schulte,et al.  Nuclear Data for Neutron and Proton Radiotherapy and for Radiation Protection , 2001 .

[215]  R. Siddon Fast calculation of the exact radiological path for a three-dimensional CT array. , 1985, Medical physics.

[216]  Bernard Gottschalk,et al.  On the scattering power of radiotherapy protons. , 2009, Medical physics.

[217]  T. Mackie,et al.  Maximum proton kinetic energy and patient-generated neutron fluence considerations in proton beam arc delivery radiation therapy. , 2009, Medical physics.

[218]  D. Bonnett,et al.  Code of practice for clinical proton dosimetry. , 1991, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[219]  Dose Perturbations of Gold Fiducial Markers in the Prostate Cancer Intensity Modulated Proton Radiation Therapy (IMPT) , 2012 .