A. Trofimov

Final report of the E821 muon anomalous magnetic moment measurement at BNL

We present the final report from a series of precision measurements of the muon anomalous magnetic moment, a(mu)=(g-2)/2. The details of the experimental method, apparatus, data taking, and analysis are summarized. Data obtained at Brookhaven National Laboratory, using nearly equal samples of positive and negative muons, were used to deduce a(mu)(Expt)=11659208.0(5.4)(3.3)x10(-10), where the statistical and systematic uncertainties are given, respectively. The combined uncertainty of 0.54 ppm represents a 14-fold improvement compared to previous measurements at CERN. The standard model value for a(mu) includes contributions from virtual QED, weak, and hadronic processes. While the QED processes account for most of the anomaly, the largest theoretical uncertainty, approximate to 0.55 ppm, is associated with first-order hadronic vacuum polarization. Present standard model evaluations, based on e(+)e(-) hadronic cross sections, lie 2.2-2.7 standard deviations below the experimental result.

Measurement of the negative muon anomalous magnetic moment to 0.7 ppm

The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement for the negative muon. The result a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is statistical and the second is systematic, is consistent with previous measurements of the anomaly for the positive and the negative muon. The average of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10) (0.5 ppm).

A unified approach for inversion problems in intensity-modulated radiation therapy.

We propose and study a unified model for handling dose constraints (physical dose, equivalent uniform dose (EUD), etc) and radiation source constraints in a single mathematical framework based on the split feasibility problem. The model does not impose on the constraints an exogenous objective (merit) function. The optimization algorithm minimizes a weighted proximity function that measures the sum of the squares of the distances to the constraint sets. This guarantees convergence to a feasible solution point if the split feasibility problem is consistent (i.e., has a solution), or, otherwise, convergence to a solution that minimally violates the physical dose constraints and EUD constraints. We present computational results that demonstrate the validity of the model and the power of the proposed algorithmic scheme.

Precise Measurement of the Positive Muon Anomalous Magnetic Moment

A precise measurement of the anomalous g value, a(mu) = (g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron. The result a(mu+) = 11 659 202(14) (6) x 10(-10) (1.3 ppm) is in good agreement with previous measurements and has an error one third that of the combined previous data. The current theoretical value from the standard model is a(mu)(SM) = 11 659 159.6(6.7) x 10(-10) (0.57 ppm) and a(mu)(exp) - a(mu)(SM) = 43(16) x 10(-10) in which a(mu)(exp) is the world average experimental value.

PROTON RADIOTHERAPY FOR CHILDHOOD EPENDYMOMA : INITIAL CLINICAL OUTCOMES AND DOSE COMPARISONS

PURPOSE To report preliminary clinical outcomes for pediatric patients treated with proton beam radiation for intracranial ependymoma and compare the dose distributions of intensity-modulated radiation therapy with photons (IMRT), three-dimensional conformal proton radiation, and intensity-modulated proton radiation therapy (IMPT) for representative patients. METHODS AND MATERIALS All children with intracranial ependymoma confined to the supratentorial or infratentorial brain treated at the Francis H. Burr Proton Facility and Harvard Cyclotron between November 2000 and March 2006 were included in this study. Seventeen patients were treated with protons. Proton, IMRT, and IMPT plans were generated with similar clinical constraints for representative infratentorial and supratentorial ependymoma cases. Tumor and normal tissue dose-volume histograms were calculated and compared. RESULTS At a median follow-up of 26 months from the start date of radiation therapy, local control, progression-free survival, and overall survival rates were 86%, 80%, and 89%, respectively. Subtotal resection was significantly associated with decreased local control (p = 0.016). Similar tumor volume coverage was achieved with IMPT, proton therapy, and IMRT. Substantial normal tissue sparing was seen with proton therapy compared with IMRT. Use of IMPT will allow for additional sparing of some critical structures. CONCLUSIONS Preliminary disease control with proton therapy compares favorably with the literature. Dosimetric comparisons show the advantage of proton radiation compared with IMRT in the treatment of ependymoma. Further sparing of normal structures appears possible with IMPT. Superior dose distributions were accomplished with fewer beam angles with the use of protons and IMPT.

Proton vs carbon ion beams in the definitive radiation treatment of cancer patients.

BACKGROUND AND PURPOSE Relative to X-ray beams, proton [(1)H] and carbon ion [(12)C] beams provide superior distributions due primarily to their finite range. The principal differences are LET, low for (1)H and high for (12)C, and a narrower penumbra of (12)C beams. Were (12)C to yield a higher TCP for a defined NTCP than (1)H therapy, would LET, fractionation or penumbra width be the basis? METHODS Critical factors of physics, radiation biology of (1)H and (12)C ion beams, neutron therapy and selected reports of TCP and NTCP from (1)H and (12)C irradiation of nine tumor categories are reviewed. RESULTS Outcome results are based on low dose per fraction (1)H and high dose per fraction (12)C therapy. Assessment of the role of LET and dose distribution vs dose fractionation is not now feasible. Available data indicate that TCP increases with BED with (1)H and (12)C TCPs overlaps. Frequencies of GIII NTCPs were higher after (1)H than (12)C treatment. CONCLUSIONS Assessment of the efficacy of (1)H vs(12)C therapy is not feasible, principally due to the dose fractionation differences. Further, there is no accepted policy for defining the CTV-GTV margin nor definition of TCP. Overlaps of (1)H and (12)C ion TCPs at defined BED ranges indicate that TCPs are determined in large measure by dose, BED. Late GIII NTCP was higher in (1)H than (12)C patients, indicating LET as a significant factor. We recommend trials of (1)H vs(12)C with one variable, i.e. LET. The resultant TCP vs NTCP relationship will indicate which beam yields higher TCP for a specified NTCP at a defined dose fractionation.

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.

Improved limit on the muon electric dipole moment

G.W. Bennett, B. Bousquet, H.N. Brown, G. Bunce, R.M. Carey, P. Cushman, G.T. Danby, P.T. Debevec, M. Deile, H. Deng, W. Deninger, S.K. Dhawan, V.P. Druzhinin, L. Duong, E. Efstathiadis, F.J.M. Farley, G.V. Fedotovich, S. Giron, F.E. Gray, D. Grigoriev, M. Grosse-Perdekamp, A. Grossmann, M.F. Hare, D.W. Hertzog, X. Huang, V.W. Hughes, M. Iwasaki, K. Jungmann, D. Kawall, M. Kawamura, B.I. Khazin, J. Kindem, F. Krienen, I. Kronkvist, A. Lam, R. Larsen, Y.Y. Lee, I. Logashenko, R. McNabb, W. Meng, J. Mi, J.P. Miller, Y. Mizumachi, W.M. Morse, D. Nikas, C.J.G. Onderwater, Y. Orlov, C.S. Özben, J.M. Paley, Q. Peng, C.C. Polly, J. Pretz, R. Prigl, G. zu Putlitz, T. Qian, S.I. Redin, O. Rind, B.L. Roberts, N. Ryskulov, S. Sedykh, Y.K. Semertzidis, P. Shagin, Yu.M. Shatunov, E.P. Sichtermann, E. Solodov, M. Sossong, A. Steinmetz, L.R. Sulak, C. Timmermans, A. Trofimov, D. Urner, P. von Walter, D. Warburton, D. Winn, A. Yamamoto and D. Zimmerman (Muon (g − 2) Collaboration) Department of Physics, Boston University, Boston, MA 02215 Brookhaven National Laboratory, Upton, NY 11973 Budker Institute of Nuclear Physics, 630090 Novosibirsk, Russia LEPP, Cornell University, Ithaca, NY 14853 Fairfield University, Fairfield, CT 06430 6 Kernfysisch Versneller Instituut, University of Groningen, NL-9747 AA, Groningen, The Netherlands 7 Physikalisches Institut der Universität Heidelberg, 69120 Heidelberg, Germany 8 Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801 9 KEK, High Energy Accelerator Research Organization, Tsukuba, Ibaraki 305-0801, Japan Department of Physics, University. of Minnesota., Minneapolis, MN 55455 11 Science University of Tokyo, Tokyo, 153-8902, Japan 12 Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8551, Japan 13 Department of Physics, Yale University, New Haven, CT 06520 † Deceased

Including robustness in multi-criteria optimization for intensity-modulated proton therapy

We present a method to include robustness in a multi-criteria optimization (MCO) framework for intensity-modulated proton therapy (IMPT). The approach allows one to simultaneously explore the trade-off between different objectives as well as the trade-off between robustness and nominal plan quality. In MCO, a database of plans each emphasizing different treatment planning objectives, is pre-computed to approximate the Pareto surface. An IMPT treatment plan that strikes the best balance between the different objectives can be selected by navigating on the Pareto surface. In our approach, robustness is integrated into MCO by adding robustified objectives and constraints to the MCO problem. Uncertainties (or errors) of the robust problem are modeled by pre-calculated dose-influence matrices for a nominal scenario and a number of pre-defined error scenarios (shifted patient positions, proton beam undershoot and overshoot). Objectives and constraints can be defined for the nominal scenario, thus characterizing nominal plan quality. A robustified objective represents the worst objective function value that can be realized for any of the error scenarios and thus provides a measure of plan robustness. The optimization method is based on a linear projection solver and is capable of handling large problem sizes resulting from a fine dose grid resolution, many scenarios, and a large number of proton pencil beams. A base-of-skull case is used to demonstrate the robust optimization method. It is demonstrated that the robust optimization method reduces the sensitivity of the treatment plan to setup and range errors to a degree that is not achieved by a safety margin approach. A chordoma case is analyzed in more detail to demonstrate the involved trade-offs between target underdose and brainstem sparing as well as robustness and nominal plan quality. The latter illustrates the advantage of MCO in the context of robust planning. For all cases examined, the robust optimization for each Pareto optimal plan takes less than 5 min on a standard computer, making a computationally friendly interface possible to the planner. In conclusion, the uncertainty pertinent to the IMPT procedure can be reduced during treatment planning by optimizing plans that emphasize different treatment objectives, including robustness, and then interactively seeking for a most-preferred one from the solution Pareto surface.

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.