B. Clasie

Should positive phase III clinical trial data be required before proton beam therapy is more widely adopted? No

PURPOSE Evaluate the rationale for the proposals that prior to a wider use of proton radiation therapy there must be supporting data from phase III clinical trials. That is, would less dose to normal tissues be an advantage to the patient? METHODS Assess the basis for the assertion that proton dose distributions are superior to those of photons for most situations. Consider the requirements for determining the risks of normal tissue injury, acute and remote, in the examination of the data from a trial. Analyze the probable cost differential between high technology photon and proton therapy. Evaluate the rationale for phase III clinical trials of proton vs photon radiation therapy when the only difference in dose delivered is a difference in distribution of low LET radiation. RESULTS The distributions of biological effective dose by protons are superior to those by X-rays for most clinical situations, viz. for a defined dose and dose distribution to the target by protons there is a lower dose to non-target tissues. This superiority is due to these physical properties of protons: (1) protons have a finite range and that range is exclusively dependent on the initial energy and the density distribution along the beam path; (2) the Bragg peak; (3) the proton energy distribution may be designed to provide a spread out Bragg peak that yields a uniform dose across the target volume and virtually zero dose deep to the target. Importantly, proton and photon treatment plans can employ beams in the same number and directions (coplanar, non-co-planar), utilize intensity modulation and employ 4D image guided techniques. Thus, the only difference between protons and photons is the distribution of biologically effective dose and this difference can be readily evaluated and quantified. Additionally, this dose distribution advantage should increase the tolerance of certain chemotherapeutic agents and thus permit higher drug doses. The cost of service (not developmental) proton therapy performed in 3-5 gantry centers operating 14-16 h/day and 6 days/week is likely to be equal to or less than twice that of high technology X-ray therapy. CONCLUSIONS Proton therapy provides superior distributions of low LET radiation dose relative to that by photon therapy for treatment of a large proportion of tumor/normal tissue situations. Our assessment is that there is no medical rationale for clinical trials of protons as they deliver lower biologically effective doses to non-target tissue than do photons for a specified dose and dose distribution to the target. Based on present knowledge, there will be some gain for patients treated by proton beam techniques. This is so even though quantitation of the clinical gain is less secure than the quantitation of reduction in physical dose. Were proton therapy less expensive than X-ray therapy, there would be no interest in conducting phase III trails. The talent, effort and funds required to conduct phase III clinical trials of protons vs photons would surely be more productive in the advancement of radiation oncology if employed to investigate real problems, e.g. the most effective total dose, dose fractionation, definition of CTV and GTV, means for reduction of PTV and the gains and risks of combined modality therapy.

-Measurement of the proton's electric to magnetic form factor ratio from 1H(over -->)(e(over -->),e'p).

We report the first precision measurement of the proton electric to magnetic form factor ratio from spin-dependent elastic scattering of longitudinally polarized electrons from a polarized hydrogen internal gas target. The measurement was performed at the MIT-Bates South Hall Ring over a range of four-momentum transfer squared Q2 from 0.15 to 0.65 (GeV/c)(2). Significantly improved results on the proton electric and magnetic form factors are obtained in combination with existing cross-section data on elastic electron-proton scattering in the same Q2 region.

Measurement of the proton's electric to magnetic form factor ratio from H→1(e→,e′p)

We report the first precision measurement of the proton electric to magnetic form factor ratio from spin-dependent elastic scattering of longitudinally polarized electrons from a polarized hydrogen internal gas target. The measurement was performed at the MIT-Bates South Hall Ring over a range of four-momentum transfer squared Q2 from 0.15 to 0.65 (GeV/c)(2). Significantly improved results on the proton electric and magnetic form factors are obtained in combination with existing cross-section data on elastic electron-proton scattering in the same Q2 region.

New Measurements of the European Muon Collaboration Effect in Very Light Nuclei

J. Seely, A. Daniel, D. Gaskell, J. Arrington, ∗ N. Fomin, P. Solvignon, R. Asaturyan, † F. Benmokhtar, W. Boeglin, B. Boillat, P. Bosted, A. Bruell, M.H.S. Bukhari, M.E. Christy, B. Clasie, S. Connell, ‡ M.M. Dalton, D. Day, J. Dunne, D. Dutta, 12 L. El Fassi, R. Ent, H. Fenker, B.W. Filippone, H. Gao, 12 C. Hill, R.J. Holt, T. Horn, 3 E. Hungerford, M.K. Jones, J. Jourdan, N. Kalantarians, C.E. Keppel, D. Kiselev, M. Kotulla, C. Lee, A.F. Lung, S. Malace, D.G. Meekins, T. Mertens, H. Mkrtchyan, T. Navasardyan, G. Niculescu, I. Niculescu, H. Nomura, Y. Okayasu, A.K. Opper, C. Perdrisat, D.H. Potterveld, V. Punjabi, X. Qian, P.E. Reimer, J. Roche, V.M. Rodriguez, O. Rondon, E. Schulte, E. Segbefia, K. Slifer, G.R. Smith, V. Tadevosyan, S. Tajima, L. Tang, G. Testa, R. Trojer, V. Tvaskis, W.F. Vulcan, F.R. Wesselmann, S.A. Wood, J. Wright, L. Yuan, and X. Zheng Laboratory for Nuclear Science, Massachusetts Institute of Technology, Cambridge, MA, USA University of Houston, Houston, TX, USA Thomas Jefferson National Laboratory, Newport News, VA, USA Physics Division, Argonne National Laboratory, Argonne, IL, USA University of Virginia, Charlottesville, VA, USA Yerevan Physics Institute, Armenia University of Maryland, College Park, MD, USA Florida International University, Miami, FL, USA Basel University, Basel, Switzerland Hampton University, Hampton, VA, USA Mississippi State University, Jackson, MS, USA Triangle Universities Nuclear Laboratory, Duke University, Durham, NC, USA Kellogg Radiation Laboratory, California Institute of Technology, Pasadena, CA, USA University of the Witwatersrand, Johannesburg, South Africa James Madison University, Harrisonburg, VA, USA Tohoku University, Sendai, Japan Ohio University, Athens, OH, USA College of William and Mary, Williamsburg, VA, USA Norfolk State University, Norfolk, VA, USA (Dated: October 27, 2009)

New Measurements of High-Momentum Nucleons and Short-Range Structures in Nuclei

We present new measurements of electron scattering from high-momentum nucleons in nuclei. These data allow an improved determination of the strength of two-nucleon correlations for several nuclei, including light nuclei where clustering effects can, for the first time, be examined. The data also include the kinematic region where three-nucleon correlations are expected to dominate.

Parity-Violating Electron Deuteron Scattering and the Proton's Neutral Weak Axial Vector Form Factor

We report on a new measurement of the parity-violating asymmetry in quasielastic electron scattering from the deuteron at backward angles at Q2=0.038 (GeV/c)2. This quantity provides a determination of the neutral weak axial vector form factor of the nucleon, which can potentially receive large electroweak corrections. The measured asymmetry A=-3.51+/-0.57 (stat)+/-0.58 (syst) ppm is consistent with theoretical predictions. We also report on updated results of the previous experiment at Q2=0.091 (GeV/c)2, which are also consistent with theoretical predictions.

Out-of-Field Dose Equivalents Delivered by Passively Scattered Therapeutic Proton Beams for Clinically Relevant Field Configurations

PURPOSE Microdosimetric measurements were performed at Massachusetts General Hospital, Boston, MA, to assess the dose equivalent external to passively delivered proton fields for various clinical treatment scenarios. METHODS AND MATERIALS Treatment fields evaluated included a prostate cancer field, cranial and spinal medulloblastoma fields, ocular melanoma field, and a field for an intracranial stereotactic treatment. Measurements were completed with patient-specific configurations of clinically relevant treatment settings using a silicon-on-insulator microdosimeter placed on the surface of and at various depths within a homogeneous Lucite phantom. The dose equivalent and average quality factor were assessed as a function of both lateral displacement from the treatment field edge and distance downstream of the beams distal edge. RESULTS Dose-equivalent value range was 8.3-0.3 mSv/Gy (2.5-60-cm lateral displacement) for a typical prostate cancer field, 10.8-0.58 mSv/Gy (2.5-40-cm lateral displacement) for the cranial medulloblastoma field, 2.5-0.58 mSv/Gy (5-20-cm lateral displacement) for the spinal medulloblastoma field, and 0.5-0.08 mSv/Gy (2.5-10-cm lateral displacement) for the ocular melanoma field. Measurements of external field dose equivalent for the stereotactic field case showed differences as high as 50% depending on the modality of beam collimation. Average quality factors derived from this work ranged from 2-7, with the value dependent on the position within the phantom in relation to the primary beam. CONCLUSIONS This work provides a valuable and clinically relevant comparison of the external field dose equivalents for various passively scattered proton treatment fields.

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 patient-specific 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.

The Charge Form Factor of the Neutron at Low Momentum Transfer from the H-2-polarized (e-polarized, e-prime n) p Reaction

We report new measurements of the neutron charge form factor at low momentum transfer using quasielastic electrodisintegration of the deuteron. Longitudinally polarized electrons at an energy of 850 MeV were scattered from an isotopically pure, highly polarized deuterium gas target. The scattered electrons and coincident neutrons were measured by the Bates Large Acceptance Spectrometer Toroid (BLAST) detector. The neutron form factor ratio GEn/GMn was extracted from the beam-target vector asymmetry AedV at four-momentum transfers Q2=0.14, 0.20, 0.29, and 0.42 (GeV/c)2.

The Charge Form Factor of the Neutron at Low Momentum Transfer from the

We report new measurements of the neutron charge form factor at low momentum transfer using quasielastic electrodisintegration of the deuteron. Longitudinally polarized electrons at an energy of 850 MeV were scattered from an isotopically pure, highly polarized deuterium gas target. The scattered electrons and coincident neutrons were measured by the Bates Large Acceptance Spectrometer Toroid (BLAST) detector. The neutron form factor ratio GEn/GMn was extracted from the beam-target vector asymmetry AedV at four-momentum transfers Q2=0.14, 0.20, 0.29, and 0.42 (GeV/c)2.