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Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. (c) 2021 Elsevier Inc. All rights reserved.

Purpose Photon radiation therapy (x-ray radiation therapy [XRT] and gamma-ray radiation therapy [GRT]) of tumors close to ovaries causes reproductive and endocrine sequelae due to ovarian primordial follicle depletion. Given its finite range, proton radiation therapy (PRT) can preserve ovarian function when ovaries are positioned distal to the spread-out Bragg peak (SOBP) in tumors of the abdominopelvic region. This study compared anti-Mullerian hormone (AMH) levels (a biomarker of ovarian function) and primordial follicle survival after in vivo mouse pelvic GRT versus PRT. Methods and Materials One hundred twenty-four female prepubertal mice received sham, GRT, or PRT with ovaries positioned at various depth with respect to the proton SOBP, with single doses of 1.8 or 0.2 Gy. AMH was measured at baseline, 1, 3, and 8 weeks after treatment, and the total number of surviving primordial follicles was counted. Multivariable linear mixed-effects modeling was used to assess the relationship between radiation therapy modality and dose on AMH and primordial follicle survival. Results For ovaries beyond the SOBP, ovarian function (P = .5) and ovarian primordial follicle (OPF; P = 1.0) were spared relative to sham controls. For ovaries in the SOBP plateau, ovarian function and primordial follicle reserve 8 weeks after treatment were reduced for all groups: 1.8 Gy GRT (βAMH = –4.9 ng/mL; βOPF = –728.2/animal), 1.8 Gy (relative biological effectiveness [RBE] = 1.1) PRT (βAMH = –5.1 ng/mL; βOPF = –728.2/animal), 0.2 Gy GRT (βAMH = –2.5 ng/mL; βOPF = –595.1/animal), and 0.2 Gy (RBE = 1.1) PRT (βAMH = –3.0 ng/mL; βOPF = –555.4/animal) relative to sham controls (all differences P Conclusions This study uses an animal model to demonstrate the safety of proton therapy in sparing fertility. Ovaries positioned beyond the SOBP during PRT maintain ovarian reserve, suggesting that a proton beam has no energy and exit dose beyond SOBP. This study proposes that proton therapy is much safer than photon radiation therapy to protect ovarian follicles with the same dose, and it supports further testing of proton therapy for abdominopelvic tumors in young women.

Purpose Developing a quantitative decision-support strategy estimating the impact of normal tissue complications from definitive radiation therapy (RT) for head and neck cancer (HNC). We developed this strategy to identify patients with oropharyngeal HNC who may benefit most from receiving proton RT. Methods and Materials Recent normal tissue complication probability (NTCP) models for dysphagia, esophagitis, hypothyroidism, xerostomia, and oral mucositis were used to estimate NTCP for 33 patients with oropharyngeal HNC previously treated with photon intensity modulated radiation therapy (IMRT). Comparative proton therapy plans were generated using clinical protocols for HNC RT at a collaborating proton center. Organ-at-risk (OAR) doses from photon and proton RT plans were used to calculate NTCPs; Monte Carlo sampling 10,000 times was used for each patient to account for model parameter uncertainty. The latency and duration of each complication were modeled from calculated NTCP, accounting for age-, sex-, smoking- and p16-specific conditional survival probability. Complications were then assigned quality-adjustment factors based on severity to calculate quality-adjusted life years (QALYs) lost from each complication. Results Based on our institutional-delivered photon IMRT doses and the achievable proton therapy doses, the average QALY reduction from all HNC RT complications for photon and proton therapy was 1.52 QALYs versus 1.15 QALYs, with proton therapy sparing 0.37 QALYs on average (composite 95% confidence interval, 0.27-2.53 QALYs). Long-term complications (dysphagia and xerostomia) contributed most to the QALY reduction. The QALYs spared with proton RT varied considerably among patients, ranging from 0.06 to 0.84 QALYs. Younger patients with p16-positive tumors who smoked ≤10 pack-years may benefit most from proton therapy, although this finding should be validated using larger patient series. A sensitivity analysis reducing photon IMRT doses to all OARs by 20% resulted in no overall estimated benefit with proton therapy with –0.02 QALYs spared, although some patients still had an estimated benefit in this scenario, ranging from −0.50 to 0.43 QALYs spared. Conclusions This quantitative decision-support strategy allowed us to identify patients with oropharyngeal cancer who might benefit the most from proton RT, although the estimated benefit of proton therapy ultimately depends on the OAR doses achievable with modern photon IMRT solutions. These results can help radiation oncologists and proton therapy centers optimize resource allocation and improve quality of life for patients with HNC.

Results of radiation tests of Hamamatsu 2.0 x 2.0~mm2 through-silicon-via (S13360-2050VE) multi-pixel photon counters, or MPPCs [1], are presented. Distinct sets of eight MPPCs were exposed to four different 1~MeV neutron equivalent doses of 200 MeV protons. Measurements of the breakdown voltage, gain and noise rates at different bias overvoltages, photoelectron thresholds, and LED illumination levels were taken before and after irradiation. No significant deterioration in performance was observed for breakdown voltage, gain, and response. Noise rates increased significantly with irradiation. These studies were undertaken in the context of MPPC requirements for the Cosmic Ray Veto detector of the Mu2e experiment at the Fermi National Accelerator Laboratory., Nucl. Inst. and Meth

Purpose As patients with mediastinal lymphoma are typically young with curable disease, advanced radiation techniques such as proton therapy are often considered to minimize subacute and late toxicity. However, it is unclear which mediastinal lymphoma patients are treated with proton therapy. Within a prospective, multi-institutional proton registry, we characterized mediastinal lymphoma patients treated with proton therapy and assessed concordance with consensus recommendations published in 2018 by the International Lymphoma Radiation Oncology Group (ILROG). Methods Eligible patients included those with lymphoma of the mediastinum treated exclusively with proton therapy for whom digital imaging and communications in medicine (DICOM) treatment data were available for review. Given the challenge with reliably visualizing the left mainstem coronary artery, the inferior-most aspect of the left pulmonary artery (PA) was used as a surrogate. Extent of disease was characterized as upper mediastinum (above level of left PA), middle mediastinum (below left PA but at or above level of T8), or low mediastinum (below T8). Results Between November 2012 and April 2019, 56 patients were treated and met inclusion criteria. Patients treated with proton therapy were young (median, 24 y; range: 12 to 88), with over half being female (55%). Patients were most commonly treated at initial diagnosis (86%) and had Hodgkin lymphoma (79%). Most patients (96%) had mediastinal disease that extended down to the level of the heart: 48% had middle and 48% had low mediastinal involvement. Nearly all patients (96%) met the ILROG consensus recommendations: 95% had lower mediastinal disease, 46% were young females, and 9% were heavily pretreated. Heart (mean) and lung dose (mean, V5, V20) were significantly associated with lowest extent of mediastinal disease. Conclusions Mediastinal lymphoma patients treated with proton therapy are typically young with lower mediastinal involvement. Within a prospective, multi-institutional proton registry, nearly all treated patients fit the ILROG consensus recommendations regarding which mediastinal lymphoma patients may most benefit from proton therapy.

Background Proton therapy is a promising advancement in radiation oncology especially in terms of reducing normal tissue toxicity, although it is currently expensive and of limited availability. Here we estimated the individual quality of life benefit and cost-effectiveness of proton therapy in patients with oropharyngeal cancer treated with definitive radiation therapy (RT), as a decision-making tool for treatment individualization. Methods and materials Normal tissue complication probability models were used to estimate the risk of dysphagia, esophagitis, hypothyroidism, xerostomia and oral mucositis for 33 patients, comparing delivered photon intensity-modulated RT (IMRT) plans to intensity-modulated proton therapy (IMPT) plans. Quality-adjusted life years (QALYs) lost were calculated for each complication while accounting for patient-specific conditional survival probability and assigning quality-adjustment factors based on complication severity. Cost-effectiveness was modeled based on upfront costs of IMPT and IMRT, and the cost of acute and/or long-term management of treatment complications. Uncertainties in all model parameters and sensitivity analyses were included through Monte Carlo sampling. Results The incremental cost-effectiveness ratios (ICERs) showed considerable variability in the cost of QALYs spared between patients, with median $361,405/QALY for all patients, varying from $54,477/QALY to $1,508,845/QALY between individual patients. Proton therapy was more likely to be cost-effective for patients with p16-positive tumors ($234,201/QALY), compared to p16-negative tumors ($516,297/QALY). For patients with p16-positive tumors treated with comprehensive nodal irradiation, proton therapy is estimated to be cost-effective in ≥ 50% of sampled cases for 8/9 patients at $500,000/QALY, compared to 6/24 patients who either have p16-negative tumors or receive unilateral neck irradiation. Conclusions Proton therapy cost-effectiveness varies greatly among oropharyngeal cancer patients, and highlights the importance of individualized decision-making. Although the upfront cost, societal willingness to pay and healthcare administration can vary greatly among different countries, identifying patients for whom proton therapy will have the greatest benefit can optimize resource allocation and inform prospective clinical trial design.

Purpose GRID therapy is an effective treatment for bulky tumors. Linear accelerator (Linac)-produced photon beams collimated through blocks or multileaf collimators (MLCs) are the most common methods used to deliver this therapy. Utilizing the newest proton delivery method of pencil beam scanning (PBS) can further improve the efficacy of GRID therapy. In this study, we developed a method of delivering GRID therapy using proton PBS, evaluated the dosimetry of this novel technique and applied this method in two clinical cases. Materials/methods In the feasibility study phase, a single PBS proton beam was optimized to heterogeneously irradiate a shallow 20 × 20 × 12 cm3 target volume centered at a 6 cm depth in a water phantom. The beam was constrained to have an identical spot pattern in all layers, creating a "beamlet" at each spot position. Another GRID treatment using PBS was also performed on a deep 15 × 15 × 8 cm3 target volume centered at a 14 cm depth in a water phantom. Dosimetric parameters of both PBS dose distributions were compared with typical photon GRID dose distributions. In the next phase, four patients have been treated at our center with this proton GRID technique. The planning, dosimetry, and measurements for two representative patients are reported. Results For the shallow phantom target, the depth-dose curve of the PBS plan was uniform within the target (variation 95% with a gamma index criterion of 3%/3 mm). Patients tolerated the treatment well without significant skin toxicity (radiation dermatitis grade ≤ 1). Conclusions Proton GRID therapy using a PBS delivery method was successfully developed and implemented clinically. Proton GRID therapy offers many advantages over photon GRID techniques. The use of protons provides a more uniform beamlet dose within the tumor and spares normal tissues located beyond the tumor. This new PBS method will also reduce the dose to proximal organs when treating a deep-seated tumor.

Purpose/Objective(s) Proton Beam Craniospinal Irradiation (CSI) requires multiple isocenters to cover the entire brain and spine target. These matching fields can lead to treatment field overlap or gap to yield dose heterogeneity. To ensure acceptable dose heterogeneity, we previously acquired KV-images at all isocenters to adjust patient posture before treating the first brain field. This process requires extra setup time and additional radiation exposure to the patient. We present a novel setup workflow using surface imaging in combination with IGRT to reduce the number of KV-images for proton CSI setup. Materials/Methods The patient is first setup at the cranial isocenter where head position is confirmed with KV-imaging. The lower body posture is adjusted based on guidance from the surface imaging system. The patient is shifted to lower isocenters where spine position can be fine-tuned with KV imaging if needed. The residual corrections, i.e., shifts required per KV-imaging after using surface imaging guidance, are recorded. If spine position determined by the surface imaging is within set-up tolerance verified by the X-rays for the first three fractions, we will no longer shift patient and verify spine isocenters with KV-imaging before treating the brain field. We will only verify setup by KV-imaging before each field delivery. Results Setup of 127 treatment fractions were analyzed. The setup method is found to be beneficial for 9 out of 13 proton CSI patients. Among the 9 patients using surface imaging, the average magnitude of the residual shifts for X, Y, and Z directions were 0.17 ± 0.15 cm, 0.24 ± 0.18 cm, and 0.14 ± 0.16 cm respectively. The average KV-imaging count was reduced from 8 to 5 per fraction with reduced setup time. For surface imaging, the reference surface image auto-generated from planning CT images was found to be accurate, however, one may request an in-room setup capture due to the change of correlation between the skin and the bony anatomy. Setup using surface imaging for patients with high body mass index is less accurate due to the poor correlation between surface and bony anatomy. Conclusion For proton CSI, while setting up the patient for the brain and cervical spine treatment, surface imaging provides a useful guidance for the setup of the spine. Overall, surface imaging provides a larger field of view than KV-imaging with no additional imaging dose. For treatment with target size larger than imaging field, surface imaging can potentially reduce the amount of setup images thus reduce imaging dose and increase setup efficiency.

We are exploring low-dose proton radiography and computed tomography (pCT) as techniques to improve the accuracy of proton treatment planning and to provide artifact-free images for verification and adaptive therapy at the time of treatment. Here we report on comprehensive beam test results with our prototype pCT head scanner. The detector system and data acquisition attain a sustained rate of more than a million protons individually measured per second, allowing a full CT scan to be completed in six minutes or less of beam time. In order to assess the performance of the scanner for proton radiography as well as computed tomography, we have performed numerous scans of phantoms at the Northwestern Medicine Chicago Proton Center including a custom phantom designed to assess the spatial resolution, a phantom to assess the measurement of relative stopping power, and a dosimetry phantom. Some images, performance, and dosimetry results from those phantom scans are presented together with a description of the instrument, the data acquisition system, and the calibration methods., Comment: Conference on the Application of Accelerators in Research and Industry, CAARI 2016, 30 October to 4 November 2016, Ft. Worth, TX, USA

Proton computed tomography (pCT) is a novel medical imaging modality for mapping the distribution of proton relative stopping power (RSP) in medical objects of interest. Compared to conventional X-ray computed tomography, where range uncertainty margins are around 3.5%, pCT has the potential to provide more accurate measurements to within 1%. This improved efficiency will be beneficial to proton-therapy planning and pre-treatment verification. A prototype pCT imaging device has recently been developed capable of rapidly acquiring low-dose proton radiographs of head-sized objects. We have also developed an advanced, fast image reconstruction software based on distributed computing that utilizes parallel processors and graphical processing units. The combination of fast data acquisition and fast image reconstruction will enable the availability of RSP images within minutes for use in clinical settings. The performance of our image reconstruction software has been evaluated using data collected by the prototype pCT scanner from several phantoms., Comment: Paper presented at Conference on the Application of Accelerators in Research and Industry, CAARI 2016, 30 October to 4 November 2016, Ft. Worth, TX, USA

Author(s): Dickmann, J; Rit, S; Pankuch, M; Johnson, RP; Schulte, RW; Parodi, K; Dedes, G; Landry, G | Abstract: PurposeFluence-modulated proton computed tomography (FMpCT) using pencil beam scanning aims at achieving task-specific image noise distributions by modulating the imaging proton fluence spot-by-spot based on an object-specific noise model. In this work, we present a method for fluence field optimization and investigate its performance in dose reduction for various phantoms and image variance targets.MethodsThe proposed method uses Monte Carlo simulations of a proton CT (pCT) prototype scanner to estimate expected variance levels at uniform fluence. Using an iterative approach, we calculate a stack of target variance projections that are required to achieve the prescribed image variance, assuming a reconstruction using filtered backprojection. By fitting a pencil beam model to the ratio of uniform fluence variance and target variance, relative weights for each pencil beam can be calculated. The quality of the resulting fluence modulations is evaluated by scoring imaging doses and comparing them to those at uniform fluence, as well as evaluating conformity of the achieved variance with the prescription. For three different phantoms, we prescribed constant image variance as well as two regions-of-interest (ROI) imaging tasks with inhomogeneous image variance. The shape of the ROIs followed typical beam profiles for proton therapy.ResultsPrescription of constant image variance resulted in a dose reduction of 8.9% for a homogeneous water phantom compared to a uniform fluence scan at equal peak variance level. For a more heterogeneous head phantom, dose reduction increased to 16.0% for the same task. Prescribing two different ROIs resulted in dose reductions between 25.7% and 40.5% outside of the ROI at equal peak variance levels inside the ROI. Imaging doses inside the ROI were increased by 9.2% to 19.2% compared to the uniform fluence scan, but can be neglected assuming that the ROI agrees with the therapeutic dose region. Agreement of resulting variance maps with the prescriptions was satisfactory.ConclusionsWe developed a method for fluence field optimization based on a noise model for a real scanner used in pCT. We demonstrated that it can achieve prescribed image variance targets. A uniform fluence field was shown not to be dose optimal and dose reductions achievable with the proposed method for FMpCT were considerable, opening an interesting perspective for image guidance and adaptive therapy.

IntroductionA broad range of stakeholders have called for randomised evidence on the potential clinical benefits and harms of proton therapy, a type of radiation therapy, for patients with breast cancer. Radiation therapy is an important component of curative treatment, reducing cancer recurrence and extending survival. Compared with photon therapy, the international treatment standard, proton therapy reduces incidental radiation to the heart. Our overall objective is to evaluate whether the differences between proton and photon therapy cardiac radiation dose distributions lead to meaningful reductions in cardiac morbidity and mortality after treatment for breast cancer.MethodsWe are conducting a large scale, multicentre pragmatic randomised clinical trial for patients with breast cancer who will be followed longitudinally for cardiovascular morbidity and mortality, health-related quality of life and cancer control outcomes. A total of 1278 patients with non-metastatic breast cancer will be randomly allocated to receive either photon or proton therapy. The primary outcomes are major cardiovascular events, defined as myocardial infarction, coronary revascularisation, cardiovascular death or hospitalisation for unstable angina, heart failure, valvular disease, arrhythmia or pericardial disease. Secondary endpoints are urgent or unanticipated outpatient or emergency room visits for heart failure, arrhythmia, valvular disease or pericardial disease. The Radiotherapy Comparative Effectiveness (RadComp) Clinical Events Centre will conduct centralised, blinded adjudication of primary outcome events.Ethics and disseminationThe RadComp trial has been approved by the institutional review boards of all participating sites. Recruitment began in February 2016. Current version of the protocol is A3, dated 08 November 2018. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets.Trial registration numberNCT02603341

Argonne National Laboratory (ANL) and the Department of Radiation and Cellular Oncology at the University of Chicago (UChicago) are investigating the feasibility of developing an innovative heavy ion therapy center by combining an advanced compact heavy ion linac (ACCIL) designed at Argonne with real-time image-guided therapy. The proposed technology will not only be the first linac-based heavy-ion therapy technology in the world, with the advantage of much desired fast energy and ion switching capability, but also the first real-time image-guided heavy ion therapy modality. ANL has a prime location to house such a development within existing infrastructure and radiation enclosure at the former Intense Pulsed Neutron Source (IPNS) site. The cost of developing the technology and building a linac-based ion therapy facility on the existing ANL site will be significantly lower than the “green field” carbon ion therapy centers proposed elsewhere. Such a facility would prove a unique platform to stage the development of pre-clinical studies to prepare for Federal Drug Administration (FDA) clearance for carbon and other ion beam therapies in the US, and pave the way to establishing a clinical therapy facility in the Chicago area. In addition to discovery science in high-gradient accelerator physics and the development of superconducting heavy-ion gantry for therapy delivery coupled with real-time guidance, the proposed facility will enable a breadth of research and applications, and as such, will serve as the advanced particle therapy research center in the US. Potential research topics include cellular radiobiology comparative studies of different ion beam therapies and the development of real-time imaging for precise and accurate dose delivery. The ANL/UChicago Advanced Heavy Ion Therapy Center initiative has recently grown to include the regional and nationwide interest, support and collaboration of Northwestern University, the Chicago Proton Center, the Hines Illinois branch of the Department of Veteran Affairs (VA), as well as the National Center for Particle Beam Radiation Therapy Research.

Purpose: To evaluate the potential of proton therapy in sparing cardiac/coronary structures when compared with 3-dimensional conformal radiation therapy (3DCRT), helical tomotherapy (HT), and intensity-modulated radiation therapy using volumetric modulated arc therapy (VMAT). Materials and Methods: Comparative treatment planning was performed using computed tomography scans of 10 patients with left-sided stage III breast cancer after mastectomy, targeting the chest wall, axilla levels I to III, and the supraclavicular and internal mammary nodes (IMN) to 50.4 Gy (radiobiologic equivalent [RBE]) in 28 fractions. Organs at risk were heart, lungs, contralateral breast, unspecified healthy tissues, and coronary arteries. Plans were also compared that included IMNs for protons, but not for photons. Results: Mean heart dose of 1.2 Gy (RBE) was lowest with protons when compared with 6.8, 10.2, and 8.2 Gy for 3DCRT, HT, and VMAT, respectively (P

Purpose: Randomized evidence for extreme hypofractionation in prostate cancer is lacking. We aimed to identify differences in toxicity and quality-of-life outcomes between standard fractionation and extreme hypofractionated radiation in a phase 3 randomized trial. Methods and materials: We analyzed the results of the first 75 patients in our phase 3 trial, comparing 38 Gy relative biologic effectiveness (RBE) in 5 fractions (n = 46) versus 79.2 Gy RBE in 44 fractions (n = 29). Patients received proton radiation using fiducials and daily image guidance. We evaluated American Urological Association Symptom Index (AUASI), adverse events (AEs), and Expanded Prostate Index Composite (EPIC) domains. The primary endpoint of this interim analysis was the cumulative incidence of grade 2 (G2) or higher AEs. The randomized patient allocation scheme was a 2:1 ratio favoring the 38 Gy RBE arm. Results: The median follow-up was 36 months; 30% of patients reached 48-month follow-up. AUASI scores differed

Purpose: We describe the design and use of a daily QA device for proton therapy. The device is designed for therapists to check the readiness of the IBA Proton Therapy System (IBA, Louvain‐la‐Neuve, Belgium) during morning QA. The checks include connectivity, positioning, mechanical, imaging and dosimetric parameters of the proton therapy system. Methods: The device consists of a commercial QA device, (rf‐DailyQA3 ‐Sun Nuclear Corporation, Melbourne, FL), in conjunction with a home‐made acrylic phantom and mechanical indexing jig. The indexing jig indexes the rf‐DailyQA3 to treatment couch. Fiducial markers embedded in the phantom are used for checking the x‐ray image and alignment accuracy of the imaging system (VeriSuite, MedCom, Darmstadt‐ Germany). The rf‐ DailyQA3 is used to check the proton beam output, range and symmetry, which are acquired during one single beam delivery of 100 monitor units. We developed in‐house software to calculate the variation of beam range and symmetry, based on readings from the various ion chambers inside the rf‐DailyQA3. Results: The device has been employed to perform daily QA since June 2010 at two operational protontreatment centers and will soon be implemented at ProCure's New Jersey center. All QA tests are performed by radiation therapists and reviewed by the medical physicist on duty. Due to the simplicity of the device and the associated processing software, the QA time is less than 20 minutes per room. The measurement data collected by the device during daily QA are recorded in the OIS. The integrity of the data is validated by comparing against other independent measurements. Conclusions: The daily QA device has been proven to be robust, reliable and user‐friendly. The performance of this system has been proven to be stable and accurate using trend analyses. Key words:proton therapy, daily QA, output, range, symmetry

In order to address dosimetry demands during proton therapy treatments utilizing pencil beam scanning and/or pulsed beam accelerators, we have developed a xenon-filled Gas Scintillation Detector (GSD) that can monitor delivered dose and two-dimensional beam centroid position pulse-by-pulse in real time, with high response linearity up to high instantaneous dose rates. We present design considerations for the GSD and results of beam tests carried out at operating proton therapy clinics. In addition to demonstrating spatial resolution with σ of a few hundred microns in each transverse dimension and relative dose precision better than 1% over large treatment areas, the test beam results also reveal the dependence of the GSD dose normalization on dose rate, beam energy, and gas impurities. The results demonstrate the promise of the GSD technology to provide an important addition to dosimetry approaches for next-generation ion beam therapy.

Purpose This study evaluates acute toxicity outcomes in breast cancer patients treated with adjuvant proton beam therapy (PBT). Methods From 2011 to 2016, 91 patients (93 cancers) were treated with adjuvant PBT targeting the intact breast/chest wall and comprehensive regional nodes including the axilla, supraclavicular fossa, and internal mammary lymph nodes. Toxicity was recorded weekly during treatment, one month following treatment, and then every 6months according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Charts were retrospectively reviewed to verify toxicities, patient parameters, disease and treatment characteristics, and disease-related outcomes. Results Median follow-up was 15.5months. Median PBT dose was 50.4 Gray relative biological effectiveness (GyRBE), with subsequent boost as clinically indicated ( N =61, median 10 GyRBE). Chemotherapy, when administered, was given adjuvantly ( N =42) or neoadjuvantly ( N =46). Grades 1, 2, and 3 dermatitis occurred in 23%, 72%, and 5%, respectively. Eight percent required treatment breaks owing to dermatitis. Median time to resolution of dermatitis was 32days. Grades 1, 2, and 3 esophagitis developed in 31%, 33%, and 0%, respectively. Conclusions PBT displays acceptable toxicity in the setting of comprehensive regional nodal irradiation.

In spite of a slow take off within the proton radiation community for breast cancer as a disease site, proton therapy is an increasingly employed radiation treatment alternative to standard photon and photon/electron treatments for both locally advanced and early stage breast cancer [1–3]. Though most patients do well with standard radiation, risks of cardiopulmonary complications and of radiation-induced malignancy are seen in long-term survivors. Breast cancer outcomes compare favorably to most other malignancies. The longevity that these patients are likely to experience leads to a greater concern for late complications. For both patients and physicians, a late chronic side effect attributable to therapy after surviving a cancer diagnosis can be devastating. For breast cancer patients, the most concerning late side effect of radiation is cardiac morbidity and mortality. Cardiac injury from radiation therapy is thought to occur by direct damage to the myocardium and/or to coronary vessels in close proximity to the chest wall. This includes the mid- and distal left anterior descending coronary artery for patients with left-sided breast cancer and right coronary artery for those with right-sided advanced breast cancer receiving radiation to the internal mammary lymph nodes [4, 5]. Darby et al. demonstrated a direct correlation of major cardiac events and mean radiation dose to the heart [6]. Rates of major coronary events increased linearly with mean heart dose (7.4 % per Gray) with no apparent threshold.

Proton therapy facilities use high-energy proton beams to destroy cancerous cells with greater specificity than photon-based approaches. However, due to the high energy of these protons, secondary radiation is produced through interactions with the patient and surroundings. These secondary neutrons and photons need to be accurately characterized for the benefit of patients and medical personnel. Experiments have been performed at a Chicago Proton Center proton therapy treatment beamline. Continuous-operation pencil beams of 155- and 200-MeV protons were used to irradiate three tissue-equivalent phantoms provided by CIRS Inc: soft tissue, compact bone, and trabecular bone. Secondary particles were detected using an array of organic scintillation detectors: three 7.6-cm diameter by 7.6-cm thick EJ-309 liquid scintillators and one 5-cm diameter by 7.6-cm thick stilbene crystalline scintillator. Pulse shape discrimination was applied to each detector using a charge-integration technique. Preliminary analysis has shown clear separation in the measured neutron and photon pulses.

Purpose We evaluated sparing of normal structures using 3-dimensional (3D) treatment planning for proton therapy of ocular melanomas. Methods and Materials We evaluated 26 consecutive patients with choroidal melanomas on a prospective registry. Ophthalmologic work-up included fundoscopic photographs, fluorescein angiography, ultrasonographic evaluation of tumor dimensions, and magnetic resonance imaging of orbits. Three tantalum clips were placed as fiducial markers to confirm eye position for treatment. Macula, fovea, optic disc, optic nerve, ciliary body, lacrimal gland, lens, and gross tumor volume were contoured on treatment planning compute tomography scans. 3D treatment planning was performed using noncoplanar field arrangements. Patients were typically treated with 3 fields, with at least 95% of planning target volume receiving 50 GyRBE in 5 fractions. Results Tumor stage was T1a in 10 patients, T2a in 10 patients, T2b in 1 patient, T3a in 2 patients, T3b in 1 patient, and T4a in 2 patients. Acute toxicity was mild. All patients completed treatment as planned. Mean optic nerve dose was 10.1 Gy relative biological effectiveness (RBE). Ciliary body doses were higher for nasal (mean: 11.4 GyRBE) than temporal tumors (5.8 GyRBE). Median follow-up was 31 months (range: 18-40 months). Six patients developed changes which required intraocular bevacizumab or corticosteroid therapy, but only 1 patient developed neovascular glaucoma. Five patients have since died: 1 from metastatic disease and 4 from other causes. Two patients have since required enucleation: 1 due to tumor and 1 due to neovascular glaucoma. Conclusions 3D treatment planning can be used to obtain appropriate coverage of choroidal melanomas. This technique is feasible with relatively low doses to anterior structures, and appears to have acceptable rates of local control with low risk of enucleation. Further evaluation and follow-up is needed to determine optimal dose-volume relationships for organs at risk to decrease complications rates.

We have investigated methods of reconstructing beam profiles in the penumbral region using a set of axially symmetric chambers, differing only in the detector radius. In principal, the transfer functions, or kernels, of such chambers should be functions of radius only. Three chambers of radii 0.297, 0.556, and 0.714 cm have been used. The transfer functions of the chambers can be determined by deconvolving the profiles measured with each detector with the PPMC profile. The results indicate that the transfer functions can be parametrized accurately as a Gaussian cutoff at 1.75 , with the average radius of the chamber. Deconvolution of the measured profiles with the transfer functions yields a profile that agrees with the PPMC profile to {+-}0.5 mm over the 20-80% penumbra.

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. It introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: 1.Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. 2.The current state of volumetric image guidance equipment in proton therapy. 3.Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.

The goal of this session is to introduce the audience to the physics, dosimetry, treatment planning techniques, and quality assurances (QA) procedures used in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Challenges involved in the motion management in proton therapy will also be discussed. It will also include the methodology for proton beam dosimetry for clinical commissioning, beam calibration, and quality assurance checks. Learning Objectives: 1. Gain knowledge on physics, dosimetry, and treatment planning for proton therapy including intensity modulated proton therapy. 2. Be acquainted with the procedures involved in machine and patient treatment field specific QA. 3. Understand the uncertainties associated with proton therapy and currently used strategies for their mitigation in treatment planning.

Purpose: The objective was to develop a method for dose distribution calculation of spatially-fractionated-GRID-radiotherapy (SFGRT) in Eclipse treatment-planning-system (TPS). Methods: Patient treatment-plans with SFGRT for bulky tumors were generated in Varian Eclipse version11. A virtual structure based on the GRID pattern was created and registered to a patient CT image dataset. The virtual GRID structure was positioned on the iso-center level together with matching beam geometries to simulate a commercially available GRID block made of brass. This method overcame the difficulty in treatment-planning and dose-calculation due to the lack o-the option to insert a GRID block add-on in Eclipse TPS. The patient treatment-planning displayed GRID effects on the target, critical structures, and dose distribution. The dose calculations were compared to the measurement results in phantom. Results: The GRID block structure was created to follow the beam divergence to the patient CT images. The inserted virtual GRID block made it possible to calculate the dose distributions and profiles at various depths in Eclipse. The virtual GRID block was added as an option to TPS. The 3D representation of the isodose distribution of the spatially-fractionated beam was generated in axial, coronal, and sagittal planes. Physics of GRID can be different from that for fields shaped by regular blocks because the charge-particle-equilibrium cannot be guaranteed for small field openings. Output factor (OF) measurement was required to calculate the MU to deliver the prescribed dose. The calculated OF based on the virtual GRID agreed well with the measured OF in phantom. Conclusion: The method to create the virtual GRID block has been proposed for the first time in Eclipse TPS. The dosedistributions, in-plane and cross-plane profiles in PTV can be displayed in 3D-space. The calculated OF's based on the virtual GRID model compare well to the measured OF's for SFGRT clinical use.

Purpose: The objective was to utilize and evaluate diagnostic CT-MAR technique for radiation therapy treatment planning. Methods: A Toshiba-diagnostic-CT acquisition with SEMAR(Single-energy-MAR)-algorism was performed to make the metal-artifact-reduction (MAR) for patient treatment planning. CT-imaging datasets with and without SEMAR were taken on a Catphan-phantom. Two sets of CT-numbers were calibrated with the relative electron densities (RED). A tissue characterization phantom with Gammex various simulating material rods was used to establish the relationship between known REDs and corresponding CT-numbers. A GE-CT-sim acquisition was taken on the Catphan for comparison. A patient with bilateral hip arthroplasty was scanned in the radiotherapy CT-sim and the diagnostic SEMAR-CT on a flat panel. The derived SEMAR images were used as a primary CT dataset to create contours for the target, critical-structures, and for planning. A deformable registration was performed with VelocityAI to track voxel changes between SEMAR and CT-sim images. The SEMAR-CT images with minimal artifacts and high quality of geometrical and spatial integrity were employed for a treatment plan. Treatment-plans were evaluated based on deformable registration of SEMAR-CT and CT-sim dataset with assigned CT-numbers in the metal artifact regions in Eclipse v11 TPS. Results: The RED and CT-number relationships were consistent for the datasets in CT-sim and CT's with and without SEMAR. SEMAR datasets with high image quality were used for PTV and organ delineation in the treatment planning process. For dose distribution to the PTV through the DVH analysis, the plan using CT-sim with the assigned CT-number showed a good agreement to those on deformable CT-SEMAR. Conclusion: A diagnostic-CT with MAR-algorithm can be utilized for radiotherapy treatment planning with CT-number calibrated to the RED. Treatment planning comparison and DVH shows a good agreement in the PTV and critical organs between the plans on CT-sim with assigned CT-number and the deformable SEMAR CT datasets.

X‐ray photoemission spectra of the core levels of passive films for an amorphous Al90Fe7Ce3 alloy ribbon are presented. Passive films were induced by anodizing below the pitting potential in an aqueous 0.9 wt % NaCl solution for 60 min using potentiodynamic polarization techniques. Survey scan (with pass energy of 89.45) and medium resolution multiplexes (with pass energy of 35.75 eV) of the C 1s, O 1s, Na 1s, and KL1L2,3 (Auger line), Al 2p, Cl 2s, 2p, and LM2,3M2,3 (Auger line), Fe 2p, 3s, and 3p, and Ce 3d and 4p photoelectron lines were collected on a Perkin‐Elmer/Physical Electronics model ♯ 5400 photoelectron spectrometer using monochromatized Al x rays. For comparison purposes, spectra of the native oxide film chemistry prior to anodization have been published previously [A. N. Mansour, S. J. Poon, Y. He, and G. J. Shiflet, Surf. Sci. Spectra 2, 31 (1993)]. Analysis of XPS data for the potentiodynamically anodized surface reveals the following conclusions: (i) the Fe and Ce concentrations of the pa...

“In situ” laser Raman spectra of the corrosion films on iron have been observed in aerated 5 M KOH and 0.15 M NaCl solutions via surface enhancement by the electrodeposition of a silver overlayer. Essentially the same spectra are observed in the two solutions as a function of applied potential in spite of a breakdown of passivity on iron in the chloride solution. Fe(OH)2 and Fe3O4 are found in the prepassive potential region while FeOOH is present in the passive region. A film which is very difficult to reduce appears to be always present on the electrode surface even at hydrogen evolution potentials; this film is believed to be α-FeOOH. Surface enhanced Raman spectra of the corrosion films on chromium have also been obtained in NaCl solution for the first time. The passive film has a composition that corresponds most closely to an amorphous form of Cr2O3, with some Cr(OH)3 also present. The film is converted in the transpassive region to a higher oxide form, presumably CrO2−4. Reversible reduction of this species to Cr2O3 is indicated.

The structure of the higher oxide forms of nickel (where Ni has a valency greater than +2) is interesting from the standpoint of developing advanced nickel batteries for consumer applications and for electric vehicle propulsion. Xanes spectra of nickel K-edge and X-ray diffraction patterns of several nickel oxycompounds were measured. The shift in energy of the Ni K-absorption edge toward higher values correlates well with the increase in the oxidation state of nickel from +2 to +4 in the compounds studied. The inflection point energy of the Ni pre-edge structure shifts approximately 1 eV per unit change in valency. The results provide evidence which support the assignment that the valency of Ni in [beta]-NiOOH is +3; Ni[sub 3]O[sub 2](OH)[sub 4] and commercial nickel peroxide (NiO[sub 2]) likewise contain trivalent nickel. The edge shift for quadrivalent nickel in KNilO[sub 6] is reported for the first time.

“In situ” laser Raman spectra of the corrosion films on iron have been observed in aerated 5 M KOH and 0.15 M NaCl solutions via surface enhancement by the electrodeposition of a silver overlayer. Essentially the same spectra are observed in the two solutions as a function of applied potential in spite of a breakdown of passivity on iron in the chloride solution. Fe(OH)2 and Fe3O4 are found in the prepassive potential region while FeOOH is present in the passive region. A film which is very difficult to reduce appears to be always present on the electrode surface even at hydrogen evolution potentials; this film is believed to be α-FeOOH. Surface enhanced Raman spectra of the corrosion films on chromium have also been obtained in NaCl solution for the first time. The passive film has a composition that corresponds most closely to an amorphous form of Cr2O3, with some Cr(OH)3 also present. The film is converted in the transpassive region to a higher oxide form, presumably CrO2−4. Reversible reduction of this species to Cr2O3 is indicated.

The composition of the surface film on nickel in the passive potential region has been determined using the technique of surface-enhanced Raman spectroscopy with electrodeposited silver. Both Ni(OH)2 and NiO were found to be present. The formation of these species is correlated for the first time with the two anodic waves in the voltammogram of nickel in all the solutions studied from pH 2.7 to 12. Ni(OH)2 is formed first, and then NiO at a more anodic potential. A duplex-type film consisting of an inner NiO layer and an outer Ni(OH)2 layer appears to be the most consistent model for the passive film on nickel.

Purpose: Implement a center wide communication system that increases interdepartmental transparency and accountability while decreasing redundant work and treatment delays by actively monitoring treatment planning workflow. Methods: Intake Management System (IMS), a program developed by ProCure Treatment Centers Inc., is a multi-function database that stores treatment planning process information. It was devised to work with the oncology information system (Mosaiq) to streamline interdepartmental workflow.Each step in the treatment planning process is visually represented and timelines for completion of individual tasks are established within the software. The currently active step of each patient's planning process is highlighted either red or green according to whether the initially allocated amount of time has passed for the given process. This information is displayed as a Treatment Planning Process Monitor (TPPM), which is shown on screens in the relevant departments throughout the center. This display also includes the individuals who are responsible for each task.IMS is driven by Mosaiq's quality checklist (QCL) functionality. Each step in the workflow is initiated by a Mosaiq user sending the responsible party a QCL assignment. IMS is connected to Mosaiq and the sending or completing of a QCL updates the associated field in the TPPM to the appropriate status. Results: Approximately one patient a week is identified during the workflow process as needing to have his/her treatment start date modified or resources re-allocated to address the most urgent cases. Being able to identify a realistic timeline for planning each patient and having multiple departments communicate their limitations and time constraints allows for quality plans to be developed and implemented without overburdening any one department. Conclusion: Monitoring the progression of the treatment planning process has increased transparency between departments, which enables efficient communication. Having built-in timelines allows easy prioritization of tasks and resources and facilitates effective time management.

We have investigated methods of reconstructing beam profiles in the penumbral region using a set of axially symmetric chambers, differing only in the detector radius. In principal, the transfer functions, or kernels, of such chambers should be functions of radius only. Three chambers of radii 0.297, 0.556, and 0.714 cm have been used. The transfer functions of the chambers can be determined by deconvolving the profiles measured with each detector with the PPMC profile. The results indicate that the transfer functions can be parametrized accurately as a Gaussian cutoff at 1.75(r), with (r) the average radius of the chamber. Deconvolution of the measured profiles with the transfer functions yields a profile that agrees with the PPMC profile to +/- 0.5 mm over the 20-80% penumbra.