Mandatory in several countries, in vivo dosimetry has been recognized as one of the next milestones in radiation oncology. Our department has implemented clinically an EPID based in vivo dosimetry ...system, EPIgray, by DOSISOFT S.A., since 2006. An analysis of the measurements per linac and energy over a two‐year period was performed, which included a more detailed examination per technique and treatment site over a six‐month period. A comparison of the treatment planning system doses and the doses estimated by EPIgray shows a mean of the differences of 1.9% (±5.2%) for the two‐year period. The 3D conformal treatment plans had a mean dose difference of 2.0% (±4.9%), while for intensity‐modulated radiotherapy and volumetric‐modulated arc therapy treatments the mean dose difference was −3.0 (±5.3%) and −2.5 (±5.2%), respectively. In addition, root cause analyses were conducted on the in vivo dosimetry measurements of two breast cancer treatment techniques, as well as prostate treatments with intensity‐modulated radiotherapy and volumetric‐modulated arc therapy. During the breast study, the dose differences of breast treatments in supine position were correlated to patient setup and EPID positioning errors. Based on these observations, an automatic image shift correction algorithm is developed by DOSIsoft S.A. The prostate study revealed that beams and arcs with out‐of‐tolerance in vivo dosimetry results tend to have more complex modulation and a lower exposure of the points of interest. The statistical studies indicate that in vivo dosimetry with EPIgray has been successfully implemented for classical and complex techniques in clinical routine at our institution. The additional breast and prostate studies exhibit the prospects of EPIgray as an easy supplementary quality assurance tool. The validation, the automatization, and the reduction of false‐positive results represent an important step toward adaptive radiotherapy with EPIgray.
PACS number(s): 87.53.Bn, 87.55.Qr, 87.56.Fc, 87.57.uq
To assess the planning, treatment, and follow-up strategies worldwide in dedicated proton therapy ocular programs.
Ten centers from 7 countries completed a questionnaire survey with 109 queries on ...the eye treatment planning system (TPS), hardware/software equipment, image acquisition/registration, patient positioning, eye surveillance, beam delivery, quality assurance (QA), clinical management, and workflow.
Worldwide, 28,891 eye patients were treated with protons at the 10 centers as of the end of 2014. Most centers treated a vast number of ocular patients (1729 to 6369). Three centers treated fewer than 200 ocular patients. Most commonly, the centers treated uveal melanoma (UM) and other primary ocular malignancies, benign ocular tumors, conjunctival lesions, choroidal metastases, and retinoblastomas. The UM dose fractionation was generally within a standard range, whereas dosing for other ocular conditions was not standardized. The majority (80%) of centers used in common a specific ocular TPS. Variability existed in imaging registration, with magnetic resonance imaging (MRI) rarely being used in routine planning (20%). Increased patient to full-time equivalent ratios were observed by higher accruing centers (P=.0161). Generally, ophthalmologists followed up the post-radiation therapy patients, though in 40% of centers radiation oncologists also followed up the patients. Seven centers had a prospective outcomes database. All centers used a cyclotron to accelerate protons with dedicated horizontal beam lines only. QA checks (range, modulation) varied substantially across centers.
The first worldwide multi-institutional ophthalmic proton therapy survey of the clinical and technical approach shows areas of substantial overlap and areas of progress needed to achieve sustainable and systematic management. Future international efforts include research and development for imaging and planning software upgrades, increased use of MRI, development of clinical protocols, systematic patient-centered data acquisition, and publishing guidelines on QA, staffing, treatment, and follow-up parameters by dedicated ocular programs to ensure the highest level of care for ocular patients.
(1) Background: Our purpose is to describe the design of a phase II clinical trial on 5-fraction proton therapy for chordomas and chondrosarcomas of the skull base and to present early results in ...terms of local control and clinical tolerance of the first prospective series. (2) Methods: A dose of 37.5 GyRBE in five fractions was proposed for chordomas and 35 GyRBE in five fractions for chondrosarcomas. The established inclusion criteria are age ≥ 18 years, Karnofsky Performance Status ≥ 70%, clinical target volume up to 50 cc, and compliance with dose restrictions to the critical organs. Pencil beam scanning was used for treatment planning, employing four to six beams. (3) Results: A total of 11 patients (6 chordomas and 5 chondrosarcomas) were included. The median follow-up was 12 months (9-15 months) with 100% local control. Acute grade I-II headache (64%), grade I asthenia and alopecia (45%), grade I nausea (27%), and grade I dysphagia (18%) were described. Late toxicity was present in two patients with grade 3 temporal lobe necrosis. (4) Conclusions: Hypofractionated proton therapy is showing encouraging preliminary results. However, to fully assess the efficacy of this therapeutic approach, future trials with adequate sample sizes and extended follow-ups are necessary.
Proton therapy has advantages and pitfalls comparing with photon therapy in radiation therapy. Among the limitations of protons in clinical practice we can selectively mention: uncertainties in ...range, lateral penumbra, deposition of higher LET outside the target, entrance dose, dose in the beam path, dose constraints in critical organs close to the target volume, organ movements and cost. In this review, we combine proposals under study to mitigate those pitfalls by using individually or in combination: (a) biological approaches of beam management in time (very high dose rate "FLASH" irradiations in the order of 100 Gy/s) and (b) modulation in space (a combination of mini-beams of millimetric extent), together with mechanical approaches such as (c) rotational techniques (optimized in partial arcs) and, in an effort to reduce cost, (d) gantry-less delivery systems. In some cases, these proposals are synergic (e.g., FLASH and minibeams), in others they are hardly compatible (mini-beam and rotation). Fixed lines have been used in pioneer centers, or for specific indications (ophthalmic, radiosurgery,…), they logically evolved to isocentric gantries. The present proposals to produce fixed lines are somewhat controversial. Rotational techniques, minibeams and FLASH in proton therapy are making their way, with an increasing degree of complexity in these three approaches, but with a high interest in the basic science and clinical communities. All of them must be proven in clinical applications.
After years of lethargy, studies on two non-conventional microstructures in time and space of the beams used in radiation therapy are enjoying a huge revival. The first effect called "FLASH" is based ...on very high dose-rate irradiation (pulse amplitude ≥10
Gy/s), short beam-on times (≤100 ms) and large single doses (≥10 Gy) as experimental parameters established so far to give biological and potential clinical effects. The second effect relies on the use of arrays of minibeams (
0.5-1 mm, spaced 1-3.5 mm). Both approaches have been shown to protect healthy tissues as an endpoint that must be clearly specified and could be combined with each other (
minibeams under FLASH conditions). FLASH depends on the presence of oxygen and could proceed from the chemistry of peroxyradicals and a reduced incidence on DNA and membrane damage. Minibeams action could be based on abscopal effects, cell signalling and/or migration of cells between "valleys and hills" present in the non-uniform irradiation field as well as faster repair of vascular damage. Both effects are expected to maintain intact the tumour control probability and might even preserve antitumoural immunological reactions. FLASH
experiments involving Zebrafish, mice, pig and cats have been done with electron beams, while minibeams are an intermediate approach between X-GRID and synchrotron X-ray microbeams radiation. Both have an excellent rationale to converge and be applied with proton beams, combining focusing properties and high dose rates in the beam path of pencil beams, and the inherent advantage of a controlled limited range. A first treatment with electron FLASH (cutaneous lymphoma) has recently been achieved, but clinical trials have neither been presented for FLASH with protons, nor under the minibeam conditions. Better understanding of physical, chemical and biological mechanisms of both effects is essential to optimize the technical developments and devise clinical trials.
We review the current status of proton FLASH experimental systems, including preclinical physical and biological results. Technological limitations on preclinical investigation of FLASH biological ...mechanisms and determination of clinically relevant parameters are discussed. A review of the biological data reveals no reproduced proton FLASH effect in vitro and a significant in vivo FLASH sparing effect of normal tissue toxicity observed with multiple proton FLASH irradiation systems. Importantly, multiple studies suggest little or no difference in tumor growth delay for proton FLASH when compared to conventional dose rate proton radiation. A discussion follows on future areas of development with a focus on the determination of the optimal parameters for maximizing the therapeutic ratio between tumor and normal tissue response and ultimately clinical translation of proton FLASH radiation.
The reliable prediction of output factors for spread-out proton Bragg peak (SOBP) fields in clinical practice remained unrealized due to a lack of a consistent theoretical framework and the great ...number of variables introduced by the mechanical devices necessary for the production of such fields. These limitations necessitated an almost exclusive reliance on manual calibration for individual fields and empirical, ad hoc, models. We recently reported on a theoretical framework for the prediction of output factors for such fields. In this work, we describe the implementation of this framework in our clinical practice. In our practice, we use a treatment delivery nozzle that uses a limited, and constant, set of mechanical devices to produce SOBP fields over the full extent of clinical penetration depths, or ranges, and modulation widths. This use of a limited set of mechanical devices allows us to unfold the physical effects that affect the output factor. We describe these effects and their incorporation into the theoretical framework. We describe the calibration and protocol for SOBP fields, the effects of apertures and range-compensators and the use of output factors in the treatment planning process.
High-energy proton testing is used for single-event effect (SEE) qualification of electronics to be used in several radiation harsh environments. Given the increasing demand, exploiting the ...capabilities of proton therapy centres for electronics testing may become desirable. In this paper the focus is on the Quirónsalud proton therapy centre, which makes use of a synchrocyclotron to accelerate protons within an energy range of 70-226 MeV. Lower energies can be obtained with degradation. The use of a synchrocyclotron may pose unique challenges for SEE testing, as opposed to the use of a cyclotron, because the time structure of the beam is very complex and very intense instantaneous fluxes are delivered in highly localized areas of the device under test. Independent characterization measurements of the beam time structure and the beam uniformity were performed. SEE testing on some golden chips previously characterized in cyclotron facilities were also accomplished. These showed that the single-event upset (SEU) cross sections measured with this beam are in good agreement with those measured at cyclotrons in the 20-226 MeV proton energy range. As demonstrated by the SEU cross-sections and by the analysis of multiple-cell upsets (MCU), no beam pulse effects are observed that can alter the data collection on the chips despite the very intense instantaneous fluxes. A few limitations were also evidenced when testing with energies below 20 MeV and due to the fixed flux for testing.
Purpose
In ultrahigh dose rate radiotherapy, the FLASH effect can lead to substantially reduced healthy tissue damage without affecting tumor control. Although many studies show promising results, ...the underlying biological mechanisms and the relevant delivery parameters are still largely unknown. It is unclear, particularly for scanned proton therapy, how treatment plans could be optimized to maximally exploit this protective FLASH effect.
Materials and Methods
To investigate the potential of pencil beam scanned proton therapy for FLASH treatments, we present a phenomenological model, which is purely based on experimentally observed phenomena such as potential dose rate and dose thresholds, and which estimates the biologically effective dose during FLASH radiotherapy based on several parameters. We applied this model to a wide variety of patient geometries and proton treatment planning scenarios, including transmission and Bragg peak plans as well as single‐ and multifield plans. Moreover, we performed a sensitivity analysis to estimate the importance of each model parameter.
Results
Our results showed an increased plan‐specific FLASH effect for transmission compared with Bragg peak plans (19.7% vs. 4.0%) and for single‐field compared with multifield plans (14.7% vs. 3.7%), typically at the cost of increased integral dose compared to the clinical reference plan. Similar FLASH magnitudes were found across the different treatment sites, whereas the clinical benefits with respect to the clinical reference plan varied strongly. The sensitivity analysis revealed that the threshold dose as well as the dose per fraction strongly impacted the FLASH effect, whereas the persistence time only marginally affected FLASH. An intermediate dependence of the FLASH effect on the dose rate threshold was found.
Conclusions
Our model provided a quantitative measure of the FLASH effect for various delivery and patient scenarios, supporting previous assumptions about potentially promising planning approaches for FLASH proton therapy. Positive clinical benefits compared to clinical plans were achieved using hypofractionated, single‐field transmission plans. The dose threshold was found to be an important factor, which may require more investigation.
To assess clinical outcome of patients with pacemaker treated with thoracic radiation therapy for T8-T9 paravertebral chloroma. A 92-year-old male patient with chloroma presenting as paravertebral ...painful and compressive (T8-T9) mass was referred for radiotherapy in the Department of Radiation Oncology, Institut Curie. The patient presented with cardiac dysfunction and a permanent pacemaker that had been implanted prior. The decision of Multidisciplinary Meeting was to deliver 30 Gy in 10 fractions for reducing the symptoms and controlling the tumor growth. The patient received a total dose of 30 Gy in 10 fractions using 4-field conformal radiotherapy with 20-MV photons. The dose to pacemaker was 0.1 Gy but a part of the pacing leads was in the irradiation fields. The patient was treated the first time in the presence of his radiation oncologist and an intensive care unit doctor. Moreover, the function of his pacemaker was monitored during the entire radiotherapy course. No change in pacemaker function was observed during any of the radiotherapy fractions. The radiotherapy was very well tolerated without any side effects. The function of the pacemaker was checked before and after the radiotherapy treatment by the cardiologist and no pacemaker dysfunction was observed. Although updated guidelines are needed with acceptable dose criteria for implantable cardiac devices, it is possible to treat patients with these devices and parts encroaching on the radiation field. This case report shows we were able to safely treat our patient through a multidisciplinary approach, monitoring the patient during each step of the treatment.
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