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Purpose The heavy‐ion medical machine (HIMM), which is the first commercial medical accelerator designed and built independently by the institute of modern physics (IMP) in Wuwei, Gansu Province, China, had officially completed clinical trials at the time of this article's writing. Three types of detector systems were developed based on the ionization‐chamber principle to monitor the beam parameters during treatment in real time, quickly verify the beam performance during a routine checkup, and ensure patient safety. Methods and materials The above‐mentioned detector systems were used for beam monitoring and quality assurance in the treatment system. The beam‐monitoring system is composed of three integral ionization chambers (ICs) and two multistrip ionization chambers (MSICs) as a redundant design. The irradiation dose, beam position, and homogeneity of a lateral profile are monitored online by the beam‐monitoring system, and safety interlocks are established to keep the test results under the predefined tolerance limitation. The quality‐assurance equipment was composed of one MSIC and one IC stack. The IC stack was used for energy verification. Results The off‐axis response of ICs is within a tolerance of 2%, and the dose interlock system (DIS) response time is less than 7 ms during the treatment process. The positioning resolution of MSICs reached 73 µm. The IC stack can verify the beam range within one spill and the measurement resolution is less than 0.2 mm. Conclusions The beam‐monitoring system (BMS) and quality‐assurance equipment (QAE) have been installed and run successfully within HIMM for two years and are associated with the HIMM treatment system to deliver the right dose to the correct position precisely. Furthermore, the daily QA task is simplified by it. Above all, the system has passed the performance test of the China Food and Drug Administration (CFDA).

Background The purpose of this study was to evaluate the use of raster-scanned intensity-controlled carbon ion therapy (ICCT) in the treatment of mucosal melanoma of the paranasal sinus. Methods Patients received combined intensity-modulated radiotherapy (IMRT) plus carbon ion (C12). Records of 18 consecutive patients treated between 2009 and 2013 were analyzed retrospectively regarding toxicity (Common Terminology Criteria for Adverse Events, version 4), treatment response (Response Evaluation Criteria in Solid Tumors [RECIST]), and control/survival rates. Results Most patients had advanced disease (T4, 94%; gross residual disease, 78%). Median dose was 74 GyE (median boost volume = 157 mL). C12 treatments were planned as ICCT, no concurrent chemotherapy was administered. Grade III or higher late toxicity was not observed. Overall survival (OS), progression-free survival (PFS), and locoregional control at 3 years were 16.2%, 0%, and 58.3%, respectively (median follow-up, 18 months). Resection status did not impact locoregional control or survival rates. Conclusion ICCT results in promising locoregional control at mild toxicity. OS is poor because of the occurrence of distant metastases; therefore, addition of systemic components to primary treatment should be investigated. © 2015 Wiley Periodicals, Head Neck, 2015

Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalent uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon therapy, the optimization by biological objective functions resulted in slightly superior treatment plans in terms of final EUD for the organs at risk (OARs) compared to voxel-based optimization approaches. This observation was made independent of the underlying objective function metric. An absolute gain in OAR sparing was observed for quadratic objective functions, whereas intersecting DVHs were found for logistic approaches. Even for considerable under- or overestimations of the used effect- or dose–volume parameters during the optimization, treatment plans were obtained that were of similar quality as the results of a voxel-based optimization. Conclusions: EUD-based optimization with either of the presented concepts can successfully be applied to treatment plan optimization. This makes EUE-based optimization for carbon ion therapy a useful tool to optimize more specifically in the sense of biological outcome while voxel-to-voxel variations of the biological effectiveness are still properly accounted for. This may be advantageous in terms of computational cost during treatment plan optimization but also enables a straight forward comparison of different fractionation schemes or treatment modalities.

BACKGROUND The current study was performed to evaluate the safety and effectiveness of irradiation with carbon ions using raster scanning as well as prognostic factors in patients with skull base chondrosarcomas. METHODS Between 1998 and 2008, 79 patients with chondrosarcoma of the skull base were treated using carbon ions in raster scanning. The applied median total dose was 60 gray equivalent (GyE) at 3 GyE per fraction. Local control and overall survival (OS) were evaluated using the Kaplan-Meier method. Long-term toxicity was quantitatively assessed using questionnaires. RESULTS The median follow-up after irradiation was 91 months (range, 3 months-175 months). Within the follow-up, 10 patients developed local disease recurrence. The 3-year, 5-year, and 10-year local control rates were 95.9%, 88%, and 88%, respectively; the corresponding OS rates were 96.1%, 96.1%, and 78.9%, respectively. With a median follow-up of 110 months after first diagnosis, the corresponding 3-year, 5-year, and 10-year OS rates were 97.5%, 97.5%, and 91.5%, respectively. Age ≤ 45 years and boost volume ≤ 55 mL were associated with significantly better local control rates. We observed a clinically relevant improvement in cranial nerve deficits 7 to 10 years after treatment (range, 45.5%-53.3%) compared with the baseline (73.4%). During follow-up, none of the patients in the current study developed a secondary malignancy. CONCLUSIONS Carbon ion therapy is a safe and effective treatment in patients with chondrosarcoma of the skull base. For further evaluation, a prospective randomized phase 3 trial comparing protons versus carbon ions has been recruiting patients with low-grade and intermediate-grade chondrosarcoma of the skull base since 2009. Cancer 2014;120:1579–1585. © 2014 American Cancer Society.

BACKGROUND: The objective of this study was to evaluate the clinical outcome of proton and carbon ion therapy for hepatocellular carcinoma (HCC). METHODS: In total, 343 consecutive patients with 386 tumors, including 242 patients (with 278 tumors) who received proton therapy and 101 patients (with 108 tumors) who received carbon ion therapy, were treated on 8 different protocols of proton therapy (52.8-84.0 gray equivalents [GyE] in 4-38 fractions) and on 4 different protocols of carbon ion therapy (52.8-76.0 GyE in 4-20 fractions). RESULTS: The 5-year local control and overall survival rates for all patients were 90.8% and 38.2%, respectively. Regarding proton and carbon ion therapy, the 5-year local control rates were 90.2% and 93%, respectively, and the 5-year overall survival rates were 38% and 36.3%, respectively. These rates did not differ significantly between the 2 therapies. Univariate analysis identified tumor size as an independent risk factor for local recurrence in proton therapy, carbon ion therapy, and in all patients. Multivariate analysis identified tumor size as the only independent risk factor for local recurrence in proton therapy and in all patients. Child-Pugh classification was the only independent risk factor for overall survival in proton therapy, in carbon ion therapy, and in all patients according to both univariate and multivariate analyses. No patients died of treatment-related toxicities. CONCLUSIONS: Proton and carbon ion therapies for HCC were comparable in terms of local control and overall survival rates. These therapies may represent innovative alternatives to conventional local therapies for HCC. Cancer 2011;. © 2011 American Cancer Society.

The number of proton and carbon ion therapy centers is increasing; however, since the publication of the International Commission on Radiation Units and Measurements report, there has been no dedicated report dealing with proton therapy quality assurance. The purpose of this article is to describe the quality assurance procedures performed on the passively scattered proton therapy beams at The University of Texas M. D. Anderson Cancer Center Proton Therapy Center in Houston. The majorities of these procedures are either adopted from procedures outlined in the American Association of Physicists in Medical Task Group (TG) 40 report or are a modified version of the TG 40 procedures. In addition, new procedures, which were designed specifically to be applicable to the synchrotron at the author's center, have been implemented. The authors' procedures were developed and customized to ensure patient safety and accurate operation of synchrotron to within explicit limits. This article describes these procedures and can be used by others as a guideline for developing QA procedures based on particle accelerator specific parameters and local regulations pertinent to any new facility.

This book describes the advantages, limitations and similarities between proton beams and carbon ion beams for cancer therapy at an entry level. The author was an associate professor at University of Sao Paulo (USP), Sao Paulo, Brazil, who is known for his electrophysiological studies on biological membranes, applications of thermodynamics of irreversible processes in membranes, and the development of electron paramagnetic resonance to study the behavior of molecular components of the biological membranes. After retirement, the author has devoted himself to writing books in nuclear medicine and advanced physics. This article is protected by copyright. All rights reserved.

Purpose: Although radiation therapy is frequently used to cure Hodgkin lymphoma (HL), young patients treated with radiation have an increased risk to develop secondary malignant neoplasms. The purpose of this study was to determine whether using carbon ion therapy instead of proton therapy would show a difference in the predicted risk of radiation‐induced second cancers in the breast for female HL patients. Methods: We retrospectively selected 6 female HL patients who were previously treated with proton therapy and limited our study to patients with supradiaphragmatic disease. We designed scanned proton and scanned carbon ion treatment plans to deliver 36 Gy (RBE) to the HL target using a single anterior‐posterior beam for each patient. We calculated relative predicted risks of second cancer in the breast using a linear‐no‐threshold tumor induction model and a linear‐quadratic breast cell inactivation model, and we explicitly modeled RBE values for both of these competing processes. Results: For all patients, we found that the predicted risk for second cancer incidence in the breast was slightly lower using carbon ions instead of protons. For individual patients, we observed large variations in predicted risk given the plausible range of RBE for cancer induction for protons and carbon ions. Conclusion: Our findings are indicative that a higher or lower risk of second cancer in the breast might be expected for some patients using carbon therapy instead of proton therapy, depending on RBE for tumor induction, which implicitly depends on the α/β ratio of breast tissue, as well as on the physical dose distribution. UT MD Anderson Rosalie B. Hite Fellowship

This article reviews Proton and Carbon Ion Therapy. by C.-M. Ma, T. Lomax, William R. Hendee , Taylor & Francis Group, Boca Raton, FL, 2013. 250 pp. (hardcover). Price: $129.95. ISBN: 9781439816073.

Objective : Carbon ion particle therapy delivers sharp Bragg's peaks, and hence can produce dosedelivery of very high precision and conformality. To complement this characteristic, particle therapy centers implement a number of technologies unique to these centers, and are not commonly known to the medical physics community. This work outlines these adopted technologies.Methods : Particle therapy centers develop technologies to meet the needs of patient safety,dosedelivery accuracy, and imaging requirements complementing these state‐of‐the‐art centers. Through the use of literature reviews and publicly available documents, we produced a compilation of some of these innovations, a number of them unique to the centers themselves. Results : The centers based in Bloomington, USA, Chiba, Japan, Harima Japan, Gunma, Japan, Heidelberg, Germany, and Pavia, Italy were reviewed. Interestingly, 60% of centers reviewed developed in‐house innovations to address the needs of particle therapy, and all but one had at least one technology unique to its center. For example, Bloomington's MPRI developed a 3D dosimeter used in particle beam measurement. The patient couch systems implemented in Chiba, Japan and now Gunma, Japan are unique to the centers. Heidelberg's HIT developed the world's first carbon ion gantry. Italy's CNAO has a unique patient positioning system.Conclusions : Particle therapy centers, despite being at the forefront of technology in delivering radiation to patients, have not widely disclosed treatmentdelivery strategies and dosimetry techniques, despite the material being potentially useful to the radiotherapy community. This work is an effort in comparing and contrasting these innovations.

The relative biological effectiveness (RBE) is defined as the ratio of the doses required by two radiations to cause the same level of effect. Thus, the RBE needs to be considered if dose constraints from photon therapy are to be adopted. Proton therapy has been based on the use of a generic RBE of 1.1, which is applied to all treatments independent of dose/fraction, position in the irradiated volume, beam energy or the tissue. Quantitative dependencies of the RBE on various physical and biological properties are disregarded. The variability of RBE in clinical situations is believed to be within 10%. Elevated RBE values might be expected particularly near the edges of the high‐dose volume because doses may be deposited by high‐LET particles. Furthermore, the increase in RBE as a function of depth in the patient results in an extension of the bio‐effective range of the beam, which is being considered in treatment planning. The magnitude of RBE values and their variations is significantly larger in Carbon ion therapy than in proton therapy. Heavy ions have a potential advantage compared to protons when it comes to their therapeutic ratio due to an elevated RBE in the tumor (based on the oxygen enhancement ratio and higher average LET values) compared to the surrounding tissue. However, there are considerable variations in RBE within the irradiated volume that have to be considered in treatment planning and delivery. At present there are still considerable uncertainties in RBE values and their dependencies on dose, LET, and alpha/beta ratio. This presentation will illustrate the magnitude of RBE variations in proton and Carbon beams. Furthermore, it will demonstrate the clinical significance for proton therapytreatments involving tissues with low alpha/beta ratio and show a method for biologically optimized treatment planning in proton therapy.

The dose localization advantages of proton beams derive primarily from the Bragg peak in the proton stopping distribution. Therefore, the potential clinical gains expected form proton beams are based on physical, rather than biological, considerations. The rationale for proton therapy is based on the hypothesis that the superior dose distributions of proton beams will lead to increased local control; increased disease‐free survival; decreased treatment‐related morbidity; and improved quality of life. The degree to which each of these end‐points can be changed by proton therapy will depend upon the particular disease site, patient population, and other factors. In the last few years there has been a significant increase in interest in proton therapy and as a consequence, many new facilities are being planned and built. There are currently over 25 institutions worldwide treating patients with proton beams and over 55,000 patients have been treated. There are at least 25 new facilities in various stages of planning and building. We will discuss the rationale for proton therapy, the current status of proton therapy,proton physics and dosimetry, and technology for the acceleration and delivery of proton beams. We will also discuss new developments in proton therapy accelerators and treatmentdelivery systems. Technologies for carbon ion therapy will also be discussed. We will address issues related to the cost of protontreatments relative to the cost of photontreatments and discuss various ways in which the cost of proton therapy can be decreased. Learning Objectives: Understand 1. rationale for proton therapy; 2. current status of proton therapy; 3. physical characteristics of proton beams; 4. beam production and treatmentdelivery technology for proton beams; 5. acceptance testing and clinical commissioning of proton therapy beams; and 6. QA for protontreatments