More than 70 yr after the initial proposition of proton and even heavier ion therapy by R. R. Wilson back in 1946,1 we have reached the critical time of transitioning from a limited number of specialized, mostly research laboratory-based institutions to many predominantly hospital-based particle therapy centers worldwide. To date, 75 particle therapy facilities are clinically operational.2 Moreover, while the majority of patients receiving particle therapy are treated with proton beams, there is a slow but steady increase in the number of clinical centers making use of the higher linear energy transfer (LET) of carbon ions, and a couple of facilities are close to reintroducing helium ions into the clinical landscape. Significantly, the number of particle therapy centers under construction or planning is greater than the number currently in operation.2 Additionally, many centers have only recently come into operation. These factors combined make the current and near-term developments vital because they will impact the greatly increasing number of patients who will soon be treated with particle therapy worldwide. Therefore, we believe that it is crucial at this time to address the open challenges, identify those areas where development is needed, and suggest possible solution paths. Together with the inexorable growth of particle therapy centers, only by addressing these challenges will the particle therapy promise of therapeutic gain be fulfilled for all current and future radiotherapy indications. To this end, we thought of challenges from the medical physics perspective in three main areas: radiobiology, technology, and treatment uncertainties. Each of these overarching challenges, needs, and solution paths is addressed in depth in a series of contributions from internationally renowned authors, seeking for a good balance between more established and emerging scientists, with a good representation of particle therapy experience in the United States, Europe, and Asia. The first contribution “Radiobiological issues in prospective carbon ion therapy trials” addresses challenges at the frontline where clinical practice meets biology, clearly stating the gaps of knowledge in radiobiology which still need to be filled, and the difficulties in the comparison, transfer, and reproduction of clinical results when different underlying biological models are chosen for dose prescription. As a logical continuation, the next contribution “A comparison of mechanism-Inspired models for particle Relative Biological Effectiveness (RBE)” brings together for the first time the principal developers of the three major mechanism-inspired RBE models, highlighting their conceptual similarities and differences, and proposing future experiments which will probe some of the seemingly contradictory aspects of such models. And, while RBE is still the main quantity linking absorbed dose to biological response in clinical practice of particle therapy, the contribution “Radiogenomics” reviews the several genomic changes underlying the response of normal and tumor tissues to radiation, forecasting the integration of radiogenomics into radiation oncology as a crucial step forward toward personalized precision therapy. On the technological side, the contribution “New horizons in particle therapy systems” thoroughly describes the state of the art and the ongoing as well as envisioned development path of particle therapy systems, with the ultimate goal of faster and more accurate dose delivery at reduced cost and size, along with faster responding systems for real-time adaptation. Advancements of beam delivery systems will, in turn, require new detector developments for reliable and fast-responding beam monitors, along with accurate absorbed dose measurements in reference and nonreference conditions, as addressed in depth in “Dose detectors, sensors and their applications.” Furthermore, improvements in the precision and efficiency of beam delivery will have to be matched by corresponding improvements in volumetric image guidance at the treatment site, as addressed in the contribution “Current state and future applications of radiological image guidance for particle therapy.” Progress in beam delivery systems and time-resolved image guidance will also be crucial for tackling the long-standing issue of motion management, especially with advanced beam scanning, as described in “Motion management in particle therapy.” The third challenge entails the reduction and mitigation of treatment uncertainties, which are still perceived as a major obstacle to the full exploitation of the physical and biological advantages of ion beams in clinical practice. To maximize the potential therapeutic gain over photon therapy, we believe the primary goal to be the reduction in uncertainties. These include physical and biological uncertainties. Both types of uncertainties must be addressed as part of patient care. The first step toward reducing these uncertainties should be taken at the stage of treatment planning and treatment plan adaptation. This requires, on the one hand, improved physical and biological accuracy and computational efficiency of dose calculation algorithms underlying treatment planning engines, as addressed in “Computational models and tools.” Furthermore, advanced treatment planning strategies must leverage the unique features of ion beams to enable plans of improved quality and efficacy. This must include mitigation of the reduced, but residual uncertainties with enhanced robustness, making use of prior knowledge and exploiting the different biological properties of the clinically accessible ion species, as presented in the contribution “Advanced treatment planning.” From modeling to treatment, direct verification in the patient can serve as indisputable evidence of greater comprehensive accuracy. The contribution “In-vivo range verification in particle therapy” closes the loop by reviewing and previewing methods at different levels of maturity and clinical testing for patient-specific in vivo range verification, which rely on pretreatment range and tissue probing as well as detection of secondary emissions or physiological changes during and after treatment. Moreover, while we are about to enter the next era of particle therapy, which will eventually enable higher accuracy, more patient treatments, and lower costs for cancer management in radiation oncology, we should be aware of further opportunities of ion beams beyond conventional applications. An example is addressed in the contribution “Non-invasive cardiac arrhythmia ablation with particle beams”, showing the intriguing potential of ion beams for such widely spread noncancer disease, but also the even greater challenges to overcome in terms of elevated fraction doses and highly accurate beam delivery and image guidance in 5D (i.e., including breathing and heart motion). Finally, the special issue concludes with the contribution “What will the medical physics of proton therapy look like ten years from now? A personal view”, which presents the personal vision of an internationally renowned medical physicist spending his entire career with cutting edge technologies in proton therapy. Concluding, this special issue is intended to offer a critical reflection on the remaining challenges but also new horizons and future opportunities of particle therapy, aiming to reach its community among the Medical Physics readership and serve as guidance for the continued and hopefully unified development path powered by clinical centers, industrial providers, and academia all around the world. We thank the American Association of Physicists in Medicine (AAPM) and the editorial team of the Medical Physics Journal, particularly Jeffrey Williamson and Shiva Das, for giving us the opportunity to pursue this special issue as a charge of the AAPM working group 4 (Outreach to Related Communities, chaired by Shiva Das) in relation to particle therapy. We are also indebted to them, along with Elizabeth Brenner from the publisher Wiley, for their continuous support and endurance during the longer than expected journey, which eventually brought to completion of this special issue. Finally, this special issue would not have been possible without the enthusiastic commitment and high-quality manuscripts of the several contributing authors, who took the challenge to provide their thorough reviews and visionary concepts on the assigned topics. Jonathan Farr holds a senior management position at ADAM SA, Meyrin, Switzerland, and is a shareholder in Advanced Oncotherapy, plc, London, UK.
Purpose: To compare clinically relevant dosimetric characteristics of proton therapy fields produced by two uniform scanning systems that have a number of similar hardware components but employ different techniques of beam spreading. Methods: This work compares two technologically distinct systems implementing a method of uniform scanning and layer stacking that has been developed independently at Indiana University (IU) and by Ion Beam Applications, S. A. (IBA). Clinically relevant dosimetric characteristics of fields produced by these systems are studied, such as beam range control, peak‐to‐entrance ratio (PER), lateral penumbra, field flatness, effective source position, precision of dose delivery at different gantry angles, etc. Results: Under comparable conditions, both systems controlled beam range with an accuracy of 0.5 mm and a precision of 0.1 mm. Compared to IBA, the IU system produced pristine peaks with a slightly higher PER (3.23 and 3.45, respectively) and smaller, symmetrical, lateral in‐air penumbra of 1 mm compared to about 1.9/2.4 mm in the inplane/crossplane (IP/CP) directions for IBA. Large field flatness results in the IP/CP directions were similar: 3.0/2.4% for IU and 2.9/2.4% for IBA. The IU system featured a longer virtual source‐to‐isocenter position, which was the same for the IP and CP directions (237 cm), as opposed to 212/192 cm (IP/CP) for IBA. Dose delivery precision at different gantry angles was higher in the IBA system (0.5%) than in the IU system (1%). Conclusions: Each of the two uniform scanning systems considered in this work shows some attractive performance characteristics while having other features that can be further improved. Overall, radiation field characteristics of both systems meet their clinical specifications and show comparable results. Most of the differences observed between the two systems are clinically insignificant.
Particle therapy is rapidly expanding and claiming its position as the treatment modality of choice in teletherapy. However, the rate of expansion continues to be restricted by the size and cost of the associated particle therapy systems and their operation. Additional technical limitations such as dose delivery rate, treatment process efficiency, and achievement of superior dose conformity potentially hinder the complete fulfillment of the promise of particle therapy. These topics are explored in this review considering the current state of particle therapy systems and what improvements are required to overcome the current challenges. Beam production systems (accelerators), beam transport systems including gantries and beam delivery systems are addressed explicitly in these regards.
Multi-element detector arrays were constructed to characterize the properties of active wobbling and energy-stacking proton beam commissioning. A multi-layer ionization chamber (MLIC) array measured depth doses, and a multi-pad ionization chamber (MPIC) array measured lateral profiles. The MLIC consists of 122 chambers with 1.82mm spatial resolution and has an effective physical density about 60% that of water. The MPIC consists of 128 chambers arranged in two 38cm long orthogonal lines with spatial resolution of 5mm within 10cm radius and 7mm outwardly. During performance tests on the MLIC and MPIC, good collection efficiency with superior reproducibility and linearity were achieved. The relative variation on the sensitivity for each individual chamber was carefully calibrated before use for proton beam characterization. The relatively small charge collection area (6mm in diameter) and volume (0.3 cm3) of each chamber has a well guarded lead and allows one to study the effect of field size on depth dose distributions for fields of approximately 2 cm to 10 cm in diameter. The MLIC is calibrated using a pristine proton beam with range 27cm in water. To calibrate the large dimensional MPIC, uniform lateral dose distributions in water within 1% were generated. Analytical functions were applied to fit measured depth dose and lateral distributions in water during the calibrations. With proper calibrations, the uncertainties of measured depth doses and lateral profiles with these multi-element detector arrays were within 1% with respect to ones measured point by point with an ion chamber in a water phantom. Significant time savings for beam measurements were thus achieved.
Purpose Pelvic target dose from intensity-modulated proton therapy (IMPT) is sensitive to patient bowel motion. Robustly optimized plans in regard to bowel filling may improve the dose coverage in the treatment course. Our purpose is to investigate the effect of air volume in large and small bowel and rectum on target dose from IMPT plans.Methods and material Data from 17 cancer patients (11 prostate, 3 gynecologic, 2 colon, and 1 embryonal rhabdomyosarcoma) with planning CT (pCT) and weekly or biweekly scanned quality assurance CTs (QACTs; 82 QACT scans total) were studied. Air in bowels and rectum traversed by proton pencil beams was contoured. The robust treatment plan was made by using 3 CT sets: the pCT set and 2 virtual CT sets that were copies of pCT but in which the fillings of bowels and rectum were overridden to be either air or muscle. Each plan had 2–5 beams with a mean of 3 beams. Targets in the pCT were mapped to the QACTs by deformable image registration, and the dose in QACTs was calculated. Dose coverage (D99 and D95) and correlations between dose coverage and changes in air volume were analyzed. The significance of the correlation was analyzed by t test.Results Mean changes of D99 in QACTs were within 3% of those in the pCT for all prostate and colon cases but >3% in 2 of the 3 gynecologic cases and in the embryonal rhabdomyosarcoma case. Of these three cases with mean change of D99 > 3%, air volume may be the main cause in 2. For the prostate cases, correlation coefficients were <0.7 between change in air volume and change in D99 and D95, because other anatomy changes also contributed to dose deviation. Correlation coefficients in the non-prostate cases were >0.9 between D99 change and rectum and between D95 change and small bowel, indicating a greater effect of the air volume on target dose.Conclusion The air volume may still have an important effect on target dose coverage in treatment plans using 3 CT sets, particularly when the air is traversed by multiple beams.
Abstract Purpose Here, we report the feasibility and long-term efficacy of a granulomatous slack skin disease (GSSD) treatment with combined high-energy photon and proton beams. Patient and methods A GSSD patient with abdominal disease volume 25×15×2–4 cm deep was recommended for treatment at this institution. In addition to photons and electrons, high-energy protons delivered with advanced planning techniques and patient positioning were used. The patient was irradiated to a total dose of 40 Gy by using 20 Gy matched photon and electrons followed by 20 Gy equivalent protons delivered by using innovative range compensation and patient positioning. Results The test patient tolerated the treatment well and is now a 10-year survivor of the disease. Conclusions Treatment of GSSD with protons is feasible. The range and narrow penumbra properties of the proton beam provided an ideal capability to match fields accurately to cover large volumes while also sparing underlying normal tissues.
Abstract Purpose To compare plan quality among photon volumetric modulated arc therapy (VMAT) and intensity‐modulated proton therapy (IMPT) with robustness using three different proton beam delivery systems with various spot size (σ) ranges: cyclotron‐generated proton beams (CPBs) (σ: 2.7–7.0 mm), linear accelerator proton beams (LPBs) (σ: 2.9–5.5 mm), and linear accelerator proton mini beams (LPMBs) (σ: 0.8–3.9 mm) for the treatment of head and neck (HN) cancer with bilateral neck irradiation. Methods Ten patients treated for oropharynx cancer with bilateral neck irradiation were planned using CPBs, LPBs, LPMBs, and VMAT. The homogeneity index (HI), mean body dose, and defined volumetric doses for selected critical organs‐at‐risk (OARs) were compared. Set‐up uncertainties of ±3 mm and ± 3.5% range uncertainties were included in robust evaluation using V 95%Rx > 95% (Volume that covers 95% of the target volume at 95% of the prescription (Rx) dose) to high dose and low dose CTV volumes (CTV_70 Gy and CTV_56 Gy). VMAT and proton plans were compared in terms of OAR doses and mean body dose only. Homogeneity Indices were compared among IMPT plans in addition to OAR doses. The Wilcoxon signed‐rank test was used to evaluate statistical differences between evaluation metrics for VMAT plans and all proton plan types. Results OAR dose metrics were improved by 2% to 30% from CPB plans to LPB or LPMB plans. Compared to photon VMAT plans, all OAR doses except for mandible dose metrics were improved by 2% to 53% for all proton plans. The mean body dose was also improved by 7.5% from CPB to LPB and by 10.8% from CPB to LPMB. In addition, the mean body dose was also improved by 44% from VMAT to CPB, by 48% from VMAT to LPB, and by 50% from VMAT to LPMB plans. Compared to CPB plans, HI was significantly better ( p < 0.05) for the LPB and LPMB plans. HI also improved considerably from VMAT to CPB, LPB, and LPMB. For both CTV_70 Gy and CTV_56 Gy, average robust evaluation across all worst‐case scenarios was slightly better for CPB plans, with an average of V 95%Rx of the CTV_70 Gy of 97.6% ± 1.22%, followed by 97.2% ± 1.31% and 97.2% ± 1.35% for LPB and LPMB plans, respectively. Robustness for CTV_56 Gy showed comparable robustness across all proton plan types, with an average V 95%Rx of 97.4% ± 0.87% for CPB, 97.4% ± 1.21%, and 97.5% ± 1.08% for CPB, LPB, and LPMB plans, respectively. Conclusion With decreased spot size, the LPB and LPMB are excellent alternatives to VMAT and CPB therapy and can significantly reduce the dose to normal tissue.
Two beam profile measurement detectors have been developed at Indiana University Cyclotron Facility to address the need for a tool to efficiently verify dose distributions created with active methods of clinical proton beam delivery. The multipad ionization chamber (MPIC) has 128 ionization chambers arranged in one plane and is designed to measure lateral profiles in fields up to in diameter. The MPIC pads have a pitch for fields up to in diameter and a pitch for larger fields, providing the accuracy of field size determination about . The multilayer ionization chamber (MLIC) detector contains 122 small‐volume ionization chambers stacked at a step (water‐equivalent) for depth‐dose profile measurements. The MLIC detector can measure profiles up to in depth, and determine the 80% distal dose fall‐off with about precision. Both detectors can be connected to the same set of electronics modules, which comprise the detectors’ data acquisition system. The detectors have been tested in clinical proton fields produced with active methods of beam delivery such as uniform scanning and energy stacking. This article describes detector performance tests and discusses their results. The test results indicate that the MPIC and MLIC detectors can be used for dosimetric characterization of clinical proton fields. The detectors offer significant time savings during measurements in actively delivered beams compared with traditional measurements using a water phantom.
