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Objective The purpose of this work is the clinical commissioning of a recently developed in-vivo range verification system for the head treatment of pediatric medulloblastoma patients. Inaccurate beam range for such treatment could lead to either inadequate dose coverage of the target volume or excessive dose to the head skin resulting permanent alopecia. Methods The in-vivo range verification system is designed to perform pre-treatment range verification and adjustment. An array of Si-diode detectors is to be placed on the patient immobilization mask in the exit direction of a whole-brain field; signal is analyzed, and the extracted water equivalent path length (WEPL) is compared to the expected one, revealing if a range correction is needed. The method was tested in solid water and anthropomorphic head phantom, with validation based on independent WEPL measurements. The measured WEPL were compared to those computed by the treatment planning system (TPS). Results The accuracy for the WEPL measurements by the diode system in both solid water and anthropomorphic head phantom were on average within a millimeter from more accurate measurement by the dose-extinction technique, with the error range for the two phantoms as (0–1 ​mm) and (0–1.3 ​mm), respectively. When compared to the WEPL calculated by the treatment planning system, the measured values were on average within 1 ​% (range 0–3%) of the beam range. The accuracy of dose measurements by the diodes in the fall-off part of the depth dose profile was validated against the reference Markus chamber. No need for further correction (due to different beam parameters and detector dose ageing effects) was found. Conclusions The range verification workflow was successfully tested in the anthropomorphic head phantom. The performance of the in-vivo range verification system and related workflow meet the clinical requirements in terms of the needed WEPL accuracy for pretreatment range verification.

Purpose To quantify and compare the impact of interfractional setup and anatomic variations on proton therapy (PT) and intensity modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials Twenty patients with low-risk or intermediate-risk prostate cancer randomized to receive passive-scattering PT (n=10) and IMRT (n=10) were selected. For both modalities, clinical treatment plans included 50.4 Gy(RBE) to prostate and proximal seminal vesicles, and prostate-only boost to 79.2 Gy(RBE) in 1.8 Gy(RBE) per fraction. Implanted fiducials were used for prostate localization and endorectal balloons were used for immobilization. Patients in PT and IMRT arms received weekly computed tomography (CT) and cone beam CT (CBCT) scans, respectively. The planned dose was recalculated on each weekly image, scaled, and mapped onto the planning CT using deformable registration. The resulting accumulated dose distribution over the entire treatment course was compared with the planned dose using dose-volume histogram (DVH) and γ analysis. Results The target conformity index remained acceptable after accumulation. The largest decrease in the average prostate D 98 was 2.2 and 0.7 Gy for PT and IMRT, respectively. On average, the mean dose to bladder increased by 3.26 ± 7.51 Gy and 1.97 ± 6.84 Gy for PT and IMRT, respectively. These values were 0.74 ± 2.37 and 0.56 ± 1.90 for rectum. Differences between changes in DVH indices were not statistically significant between modalities. All volume indices remained within the protocol tolerances after accumulation. The average pass rate for the γ analysis, assuming tolerances of 3 mm and 3%, for clinical target volume, bladder, rectum, and whole patient for PT/IMRT were 100/100, 92.6/99, 99.2/100, and 97.2/99.4, respectively. Conclusion The differences in target coverage and organs at risk dose deviations for PT and IMRT were not statistically significant under the guidelines of this protocol.

Purpose For prostate treatments, robust evidence regarding the superiority of either intensity modulated radiation therapy (IMRT) or proton therapy is currently lacking. In this study we investigated the circumstances under which proton therapy should be expected to outperform IMRT, particularly the proton beam orientations and relative biological effectiveness (RBE) assumptions. Methods and materials For 8 patients, 4 treatment planning strategies were considered: (A) IMRT; (B) passively scattered standard bilateral (SB) proton beams; (C) passively scattered anterior oblique (AO) proton beams, and (D) AO intensity modulated proton therapy (IMPT). For modalities (B)-(D) the dose and linear energy transfer (LET) distributions were simulated using the TOPAS Monte Carlo platform and RBE was calculated according to 3 different models. Results Assuming a fixed RBE of 1.1, our implementation of IMRT outperformed SB proton therapy across most normal tissue metrics. For the scattered AO proton plans, application of the variable RBE models resulted in substantial hotspots in rectal RBE weighted dose. For AO IMPT, it was typically not possible to find a plan that simultaneously met the tumor and rectal constraints for both fixed and variable RBE models. Conclusion If either a fixed RBE of 1.1 or a variable RBE model could be validated in vivo, then it would always be possible to use AO IMPT to dose-boost the prostate and improve normal tissue sparing relative to IMRT. For a cohort without rectum spacer gels, this study (1) underlines the importance of resolving the question of proton RBE within the framework of an IMRT versus proton debate for the prostate and (2) highlights that without further LET/RBE model validation, great care must be taken if AO proton fields are to be considered for prostate treatments.

Purpose This study aimed to assess the clinical impact of spot size and the addition of apertures and range compensators on the treatment quality of pencil beam scanning (PBS) proton therapy and to define when PBS could improve on passive scattering proton therapy (PSPT). Methods and Materials The patient cohort included 14 pediatric patients treated with PSPT. Six PBS plans were created and optimized for each patient using 3 spot sizes (∼12-, 5.4-, and 2.5-mm median sigma at isocenter for 90- to 230-MeV range) and adding apertures and compensators to plans with the 2 larger spots. Conformity and homogeneity indices, dose-volume histogram parameters, equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and integral dose were quantified and compared with the respective PSPT plans. Results The results clearly indicated that PBS with the largest spots does not necessarily offer a dosimetric or clinical advantage over PSPT. With comparable target coverage, the mean dose (D mean ) to healthy organs was on average 6.3% larger than PSPT when using this spot size. However, adding apertures to plans with large spots improved the treatment quality by decreasing the average D mean and EUD by up to 8.6% and 3.2% of the prescribed dose, respectively. Decreasing the spot size further improved all plans, lowering the average D mean and EUD by up to 11.6% and 10.9% compared with PSPT, respectively, and eliminated the need for beam-shaping devices. The NTCP decreased with spot size and addition of apertures, with maximum reduction of 5.4% relative to PSPT. Conclusions The added benefit of using PBS strongly depends on the delivery configurations. Facilities limited to large spot sizes (>∼8 mm median sigma at isocenter) are recommended to use apertures to reduce treatment-related toxicities, at least for complex and/or small tumors.

Pediatric rhabdomyosarcoma (RMS) is highly curable, however, cure may come with significant radiation related toxicity in developing tissues. Proton therapy (PT) can spare excess dose to normal structures, potentially reducing the incidence of adverse effects.Between 2005 and 2012, 54 patients were enrolled on a prospective multi-institutional phase II trial using PT in pediatric RMS. As part of the protocol, intensity modulated radiation therapy (IMRT) plans were generated for comparison with clinical PT plans.Target coverage was comparable between PT and IMRT plans with a mean CTV V95 of 100% for both modalities (p=0.82). However, mean integral dose was 1.8 times higher for IMRT (range 1.0-4.9). By site, mean integral dose for IMRT was 1.8 times higher for HN (p0.01) and GU (p=0.02), 2.0 times higher for trunk/extremity (p0.01), and 3.5 times higher for orbit (p0.01) compared to PT. Significant sparing was seen with PT in 26 of 30 critical structures assessed for orbital, head and neck, pelvic, and trunk/extremity patients.Proton radiation lowers integral dose and improves normal tissue sparing when compared to IMRT for pediatric RMS. Correlation with clinical outcomes is necessary once mature long-term toxicity data are available.

Given concerns of excess malignancies following adjuvant radiation for seminoma, we evaluated photon and proton beam therapy (PBT) treatment plans to assess dose distributions to organs at risk and model rates of second cancers.Ten stage I seminoma patients who were treated with conventional para-aortic AP-PA photon radiation to 25.5 Gy at Massachusetts General Hospital had PBT plans generated (AP-PA, PA alone). Dose differences to critical organs were examined. Risks of second primary malignancies were calculated.PBT plans were superior to photons in limiting dose to organs at risk. PBT decreased dose by 46% (8.2 Gy) and 64% (10.2 Gy) to the stomach and large bowel, respectively (p0.01). Notably, PBT was found to avert 300 excess second cancers among 10,000 men treated at a median age of 39 and surviving to 75 (p0.01).In this study, the use of protons provided a favorable dose distribution with an ability to limit unnecessary exposure to critical normal structures in the treatment of early-stage seminoma. It is expected that this will translate into decreased acute toxicity and reduced risk of second cancers, for which prospective studies are warranted.

The spin structure functions g 1 for the proton and the deuteron have been measured over a wide kinematic range in x and Q 2 using 1.6 and 5.7 GeV longitudinally polarized electrons incident upon polarized NH3 and ND3 targets at Jefferson Lab. Scattered electrons were detected in the CEBAF Large Acceptance Spectrometer, for 0.05 Q 2 5 GeV 2 and W 3 GeV . The first moments of g 1 for the proton and deuteron are presented – both have a negative slope at low Q 2 , as predicted by the extended Gerasimov–Drell–Hearn sum rule. The first extraction of the generalized forward spin polarizability of the proton γ 0 p is also reported. This quantity shows strong Q 2 dependence at low Q 2 . Our analysis of the Q 2 evolution of the first moment of g 1 shows agreement in leading order with Heavy Baryon Chiral Perturbation Theory. However, a significant discrepancy is observed between the γ 0 p data and Chiral Perturbation calculations for γ 0 p , even at the lowest Q 2 .

We report results for the virtual photon asymmetry A{sub 1} on the nucleon from new Jefferson Lab measurements. The experiment, which used the CEBAF Large Acceptance Spectrometer and longitudinally polarized proton ({sup 15}NH{sub 3}) and deuteron ({sup 15}ND{sub 3}) targets, collected data with a longitudinally polarized electron beam at energies between 1.6 GeV and 5.7 GeV. In the present paper, we concentrate on our results for A{sub 1}(x,Q{sup 2}) and the related ratio g{sub 1}/F{sub 1}(x,Q{sup 2}) in the resonance and the deep inelastic regions for our lowest and highest beam energies, covering a range in momentum transfer Q{sup 2} from 0.05 to 5.0 GeV{sup 2} and in final-state invariant mass W up to about 3 GeV. Our data show detailed structure in the resonance region, which leads to a strong Q{sup 2}--dependence of A{sub 1}(x,Q{sup 2}) for W below 2 GeV. At higher W, a smooth approach to the scaling limit, established by earlier experiments, can be seen, but A{sub 1}(x,Q{sup 2}) is not strictly Q{sup 2}--independent. We add significantly to the world data set at high x, up to x = 0.6. Our data exceed the SU(6)-symmetric quark model expectation for both the proton and the deuteron whilemore » being consistent with a negative d-quark polarization up to our highest x. This data set should improve next-to-leading order (NLO) pQCD fits of the parton polarization distributions.« less