30 years of ocular proton therapy, the Nice view.

PURPOSE: Radiotherapy with protons (PT) is a standard treatment of ocular tumors. It achieves excellent tumor control, limited toxicities, and the preservation of important functional outcomes, such as vision. Although PT may appear as one homogenous technique, it can be performed using dedicated ocular passive scattering PT or, increasingly, Pencil Beam Scanning (PBS), both with various degrees of patient-oriented customization. MATERAIAL AND METHODS: MEDICYC PT facility of Nice are detailed with respect to their technical, dosimetric, microdosimetric and radiobiological, patient and tumor-customization process of PT planning and delivery that are key. 6684 patients have been treated for ocular tumors (1991-2020). Machine characteristics (accelerator, beam line, beam monitoring) allow efficient proton extraction, high dose rate, sharp lateral and distal penumbrae, and limited stray radiation in comparison to beam energy reduction and subsequent straggling with high-energy PBS PT. Patient preparation before PT includes customized setup and image-guidance, CT-based planning, and ocular PT software modelling of the patient eye with integration of beam modifiers. Clinical reports have shown excellent tumor control rates (∼95%), vision preservation and limited toxicity rates (papillopathy, retinopathy, neovascular glaucoma, dry eye, madarosis, cataract). RESULTS: Although demanding, dedicated ocular PT has proven its efficiency in achieving excellent tumor control, OAR sparing and patient radioprotection. It is therefore worth adaptations of the equipments and practice. CONCLUSIONS: Some of these adaptations can be transferred to other PT centers and should be acknowledeged when using non-PT options.

Ocular proton therapy, pencil beam scanning high energy proton therapy or stereotactic radiotherapy for uveal melanoma; an in silico study.

PURPOSE: In radiotherapy, the dose and volumes of the irradiated normal tissues is correlated to the complication rate. We assessed the performances of low-energy proton therapy (ocular PT) with eye-dedicated equipment, high energy PT with pencil-beam scanning (PBS) or CyberKnifeR  -based stereotactic irradiation (SBRT). MATERIAL AND METHODS: CT-based comparative dose distribution between external beam radiotherapy techniques was assessed using an anthropomorphic head phantom. The prescribed dose was 60Gy_RBE in 4 fractions to a typical posterior pole uveal melanoma. Clinically relevant structures were delineated, and doses were calculated using radiotherapy treatment planning softwares and measured using Gafchromic dosimetry films inserted at the ocular level. RESULTS: Precision was significantly better with ocular PT than both PBS or SBRT in terms of beam penumbra (80%-20%: laterally 1.4 vs. ≥10mm, distally 0.8 vs. ≥2.5mm). Ocular PT duration was shorter, allowing eye gating and lid sparing more easily. Tumor was excellent with all modalities, but ocular PT resulted in more homogenous and conformal dose compared to PBS or SBRT. The maximal dose to ocular/orbital structures at risk was smaller and often null with ocular PT compared to other modalities. Mean dose to ocular/orbital structures was also lower with ocular PT. Structures like the lids and lacrimal punctum could be preserved with ocular PT using gaze orientation and lid retractors, which is easier to implement clinically than with the other modalities. The dose to distant organs was null with ocular PT and PBS, in contrast to SBRT. CONCLUSIONS: ocular PT showed significantly improved beam penumbra, shorter treatment delivery time, better dose homogeneity, and reduced maximal/mean doses to critical ocular structures compared with other current external beam radiation modalities. Similar comparisons may be warranted for other tumor presentations.

A 60 MeV proton beam-line dedicated to research and development programs.

A new proton beam-line dedicated to R&D programs has been developed at CentreAntoine Lacassagne (CAL), in Nice (France), in collaboration with the Centrenational d'études spatiales (CNES). This is the second beam-line of the MEDICYC 65 MeV cyclotron that is currently in operation, the first being the clinical 'eye-line' used for ocular proton therapy. The R&D beam-line is proposed with two configurations, the first producing a Gaussian narrow beam of a few mm width, the second a 100 mm diameter flat beam with a homogeneity better than ±3%. The energy range is (20 - ∼60) MeV, where the exact upper limit depends on the beam configuration being used. The energy spread of the non-degraded beam is (0.3 ± 0.1) MeV. A beam current between 10 pA and 10 µA can be produced with a stability better than 0.2% above 100 pA, and 2% below. The beam can be monitored online at a precision better than 5% in the flux range 1E5 (1E6) - 1E9 (1E10) p/cm2/s for a flat (Gaussian) configuration, although work is in progress to extend this range. Targeted applications for the R&D beam-line are instrumentation research, radiation tolerance tests of components and radiobiology.

Experimental demonstration of accurate Bragg peak localization with ionoacoustic tandem phase detection (iTPD).

Accurate knowledge of the exact stopping location of ions inside the patient would allow full exploitation of their ballistic properties for patient treatment. The localized energy deposition of a pulsed particle beam induces a rapid temperature increase of the irradiated volume and leads to the emission of ionoacoustic (IA) waves. Detecting the time-of-flight (ToF) of the IA wave allows inferring information on the Bragg peak location and can henceforth be used forin-vivorange verification. A challenge for IA is the poor signal-to-noise ratio at clinically relevant doses and viable machines. We present a frequency-based measurement technique, labeled as ionoacoustic tandem phase detection (iTPD) utilizing lock-in amplifiers. The phase shift of the IA signal to a reference signal is measured to derive theToF. Experimental IA measurements with a 3.5 MHz lead zirconate titanate (PZT) transducer and lock-in amplifiers were performed in water using 22 MeV proton bursts. A digital iTPD was performedin-silicoat clinical dose levels on experimental data obtained from a clinical facility and secondly, on simulations emulating a heterogeneous geometry. For the experimental setup using 22 MeV protons, a localization accuracy and precision obtained through iTPD deviates from a time-based reference analysis by less than 15µm. Several methodological aspects were investigated experimentally in systematic manner. Lastly, iTPD was evaluatedin-silicofor clinical beam energies indicating that iTPD is in reach of sub-mm accuracy for fractionated doses < 5 Gy. iTPD can be used to accurately measure theToFof IA signals online via its phase shift in frequency domain. An application of iTPD to the clinical scenario using a single pulsed beam is feasible but requires further development to reach <1 Gy detection capabilities.

Three-dimensional MRI-based treatment planning approach for non-invasive ocular proton therapy.

PURPOSE: To develop a high-resolution three-dimensional (3D) magnetic resonance imaging (MRI)-based treatment planning approach for uveal melanomas (UM) in proton therapy. MATERIALS/METHODS: For eight patients with UM, a segmentation of the gross tumor volume (GTV) and organs-at-risk (OARs) was performed on T1- and T2-weighted 7 Tesla MRI image data to reconstruct the patient MR-eye. An extended contour was defined with a 2.5-mm isotropic margin derived from the GTV. A broad beam algorithm, which we have called πDose, was implemented to calculate relative proton absorbed doses to the ipsilateral OARs. Clinically favorable gazing angles of the treated eye were assessed by calculating a global weighted-sum objective function, which set penalties for OARs and extreme gazing angles. An optimizer, which we have named OPT'im-Eye-Tool, was developed to tune the parameters of the functions for sparing critical-OARs. RESULTS: In total, 441 gazing angles were simulated for every patient. Target coverage including margins was achieved in all the cases (V95%  > 95%). Over the whole gazing angles solutions space, maximum dose (Dmax ) to the optic nerve and the macula, and mean doses (Dmean ) to the lens, the ciliary body and the sclera were calculated. A forward optimization was applied by OPT'im-Eye-Tool in three different prioritizations: iso-weighted, optic nerve prioritized, and macula prioritized. In each, the function values were depicted in a selection tool to select the optimal gazing angle(s). For example, patient 4 had a T2 equatorial tumor. The optimization applied for the straight gazing angle resulted in objective function values of 0.46 (iso-weighted situation), 0.90 (optic nerve prioritization) and 0.08 (macula prioritization) demonstrating the impact of that angle in different clinical approaches. CONCLUSIONS: The feasibility and suitability of a 3D MRI-based treatment planning approach have been successfully tested on a cohort of eight patients diagnosed with UM. Moreover, a gaze-angle trade-off dose optimization with respect to OARs sparing has been developed. Further validation of the whole treatment process is the next step in the goal to achieve both a non-invasive and a personalized proton therapy treatment.

Beam characterization and feasibility study for a small animal irradiation platform at clinical proton therapy facilities.

A deeper understanding of biological mechanisms to promote more efficient treatment strategies in proton therapy demands advances in preclinical radiation research. However this is often limited by insufficient availability of adequate infrastructures for precision image guided small animal proton irradiation. The project SIRMIO aims at filling this gap by developing a portable image-guided research platform for small animal irradiation, to be used at clinical facilities and allowing for a precision similar to a clinical treatment, when scaled down to the small animal size. This work investigates the achievable dosimetric properties of different lowest energy clinical proton therapy beams, manipulated by a dedicated portable beamline including active focusing after initial beam energy degradation and collimation. By measuring the lateral beam size in air close to the beam nozzle exit and the laterally integrated depth dose in water, an analytical beam model based on the beam parameters of the clinical beam at the Rinecker Proton Therapy Center was created for the lowest available clinical beam energy. The same approach was then applied to estimate the lowest energy beam model of different proton therapy facilities, Paul Scherrer Institute, Centre Antoine Lacassagne, Trento Proton Therapy Centre and the Danish Centre for Particle Therapy, based on their available beam commissioning data. This comparison indicated similar beam properties for all investigated sites, with emittance values of a few tens of mm·mrad. Finally, starting from these beam models, we simulated propagation through a novel beamline designed to manipulate the beam energy and size for precise small animal irradiation, and evaluated the resulting dosimetric properties in water. For all investigated initial clinical beams, similar dosimetric results suitable for small animal irradiation were found. This work supports the feasibility of the proposed SIRMIO beamline, promising suitable beam characteristics to allow for precise preclinical irradiation at clinical treatment facilities.

Imaging issues specific to hadrontherapy (proton, carbon, helium therapy and other charged particles) for radiotherapy planning, setup, dose monitoring and tissue response assessment.

Imaging is critical to each step of precision radiation therapy, i.e. planning, setup, delivery and assessment of response. Hadrontherapy can be considered to deliver more precise dose distribution that may better spare normal tissues from intermediate low doses of radiation. In addition, hadrontherapy using high linear energy transfer ions may also be used for dose escalation on biological target volumes defined by functional imaging. However, the physical characteristics of hadrontherapy also make it more demanding in terms of imaging accuracy and image-based dose calculation. Some of the developments needed in imaging are specific to hadrontherapy. The current review addresses current status of imaging in proton therapy and the drawbacks of photon-based imaging for hadrons. It also addresses requirements in hadrontherapy planning with respect to multimodal imaging for proper target and organ at risk definition as well as to target putative radioresistant areas such as hypoxic ones, and with respect to dose calculation using dual energy CT, MR-proton therapy, proton radiography. Imaging modalities, such as those used in photon-based radiotherapy (intensity modulated and stereotactic radiotherapy), are somewhat already implemented or should be reaching "routine" hadrontherapy (at least proton therapy) practice in planning, repositioning and response evaluation optimizable within the next five years. Online monitoring imaging by PET, as currently developed for hadrontherapy, is already available. Its spatiotemporal limits restrict its use but similar to prompt gamma detection, represents an area of active research for the next 5 to 10 years. Because of the more demanding and specific dose deposit characteristics, developments image-guided hadrontherapy, such as specific proton imaging using tomography or ionoacoustics, as well as delivery with MR-proton therapy, may take another 10 years to reach the clinics in specific applications. Other aspects are briefly described such as range monitoring. Finally, the potential of imaging normal tissue changes and challenges to assess tumour response are discussed.

[Measurement of out-of-field dose to the uterus during proton therapy of the head and neck]. / Mesure de la dose délivrée hors champ à l'utérus lors d'un traitement ORL par protons.

The decision to irradiate during pregnancy is based on a risk benefit compromise of two kinds: maternal risk and fetal risk. The aim of this work is to determine the foetal risk, and uterine dose measurement in proton therapy. Foetal exposure during treatment is linked to two sources: the treatment phase, and the repositioning phase. An Alderson-Rando anthropomorphic ghost (170cm, 74kg) was positioned on the table in the treatment position. A tissue-equivalent proportional counter (TEPC), adapted to the analysis of complex radiation fields (neutron and photonics), was used to determine the irradiation related to the treatment phase. An AT1123 radiation survey meter was used to measure photons generated by X-ray radiation. I dosimetry was proposed using radio-photoluminescent dosimeters, allowing for a daily check of the dose received in the uterus. The treatment phase produces higher uterine doses than the positioning phase, but these remain very low. The equivalent dose received in the uterus for the entire treatment is estimated at 840 µSv. Using a methodology for measuring the out-of-field dose with pencil beam scanning proton therapy, the foetal dose in the first trimester was well below the acceptance dose of 100 mGy determined by the International Commission on Radiological Protection.

Experimental characterisation of a proton kernel model for pencil beam scanning techniques.

The aim of this work is to perform Monte Carlo simulations of a proton pencil beam scanning machine, characterise the low-dose envelope of scanned proton beams and assess the differences between various approximations for nozzle geometry. Measurements and Monte Carlo simulations were carried out in order to describe the dose distribution of a proton pencil beam in water for energies between 100 and 220 MeV. Dose distributions were simulated by using a Geant4 Monte Carlo platform (TOPAS), and were measured in water using a two-dimensional ion chamber array detector. The beam source in air was adjusted for each configuration. Double Gaussian parameterisation was proposed for definition of the beam source model in order to improve simulations starting at the nozzle exit. Absolute dose distributions and field size factors were measured and compared with simulations. The influence of the high-density components present in the treatment nozzle was also investigated by analysis of proton phase spaces at the nozzle exit. An excellent agreement was observed between experimental dose distributions and simulations for energies higher than 160 MeV. However, minor differences were observed between 100 and 160 MeV, suggesting poorer modelling of the beam when the full treatment head was not taken into account. We found that the first ionisation chamber was the main cause of the tail component observed for low proton beam energies. In this work, various parameterisations of proton sources were proposed, thereby allowing reproduction of the low-dose envelope of proton beams and excellent agreement with measured data.

[Proton therapy for head and neck squamous cell carcinomas: From physics to clinic]. / Protonthérapie des carcinomes épidermoïdes des voies aérodigestives supérieures : de la physique à la clinique.

Intensity-modulated radiation therapy (IMRT) is presently the recommended technique for the treatment of locally advanced head and neck carcinomas. Proton therapy would allow to reduce the volume of irradiated normal tissue and, thus, to decrease the risk of late dysphagia, xerostomia, dysgeusia and hypothyroidism. An exhaustive research was performed with the search engine PubMed by focusing on the papers about the physical difficulties that slow down use of proton therapy for head and neck carcinomas. Range uncertainties in proton therapy (±3 %) paradoxically limit the use of the steep dose gradient in distality. Calibration uncertainties can be important in the treatment of head and neck cancer in the presence of materials of uncertain stoichiometric composition (such as with metal implants, dental filling, etc.) and complex heterogeneities. Dental management for example may be different with IMRT or proton therapy. Some uncertainties can be somewhat minimized at the time of optimization. Inter- and intrafractional variations and uncertainties in Hounsfield units/stopping power can be integrated in a robust optimization process. Additional changes in patient's anatomy (tumour shrinkage, changes in skin folds in the beam patch, large weight loss or gain) require rescanning. Dosimetric and small clinical studies comparing photon and proton therapy have well shown the interest of proton therapy for head and neck cancers. Intensity-modulated proton therapy is a promising treatment as it can reduce the substantial toxicity burden of patients with head and neck squamous cell carcinoma compared to IMRT. Robust optimization will allow to perform an optimal treatment and to use proton therapy in current clinical practice.

Effects of proton versus photon irradiation on (lymph)angiogenic, inflammatory, proliferative and anti-tumor immune responses in head and neck squamous cell carcinoma.

The proximity of organs at risk makes the treatment of head and neck squamous cell carcinoma (HNSCC) challenging by standard radiotherapy. The higher precision in tumor targeting of proton (P) therapy could promote it as the treatment of choice for HNSCC. Besides the physical advantage in dose deposition, few is known about the biological impact of P versus photons (X) in this setting. To investigate the comparative biological effects of P versus X radiation in HNSCC cells, we assessed the relative biological effectiveness (RBE), viability, proliferation and mRNA levels for genes involved in (lymph)angiogenesis, inflammation, proliferation and anti-tumor immunity. These parameters, particularly VEGF-C protein levels and regulations, were documented in freshly irradiated and/or long-term surviving cells receiving low/high-dose, single (SI)/multiple (MI) irradiations with P/X. The RBE was found to be 1.1 Key (lymph)angiogenesis and inflammation genes were downregulated (except for vegf-c) after P and upregulated after X irradiation in MI surviving cells, demonstrating a more favorable profile after P irradiation. Both irradiation types stimulated vegf-c promoter activity in a NF-κB-dependent transcriptional regulation manner, but at a lesser extent after P, as compared to X irradiation, which correlated with mRNA and protein levels. The cells surviving to MI by P or X generated tumors with higher volume, anarchic architecture and increased density of blood vessels. Increased lymphangiogenesis and a transcriptomic analysis in favor of a more aggressive phenotype were observed in tumors generated with X-irradiated cells. Increased detection of lymphatic vessels in relapsed tumors from patients receiving X radiotherapy was consistent with these findings. This study provides new data about the biological advantage of P, as compared to X irradiation. In addition to its physical advantage in dose deposition, P irradiation may help to improve treatment approaches for HNSCC.

[Indications and results for protontherapy in cancer treatments]. / Indications et résultats de la protonthérapie dans le traitement des cancers.

Purpose was to summarize results for proton therapy in cancer treatment. A systematic review has been done by selecting studies on the website www.pubmed.com (Medline) and using the following keywords: proton therapy, radiation therapy, cancer, chordoma, chondrosarcoma, uveal melanoma, retinoblastoma, meningioma, glioma, neurinoma, pituitary adenoma, medulloblastoma, ependymoma, craniopharyngioma and nasal cavity. There are several retrospective studies reporting results for proton therapy in cancer treatments in the following indications: ocular tumors, nasal tumors, skull-based tumors, pediatric tumors. There is no prospective study except one phase II trial in medulloblastoma. The use of proton therapy for these indications is due to dosimetric advantages offering better tumor coverage and organ at risk sparing in comparison with photon therapy. Clinical results are historically at least as efficient as photon therapy with a better toxicity profile in pediatric tumors (cognitive and endocrine functions, radiation-induced cancer) and a better tumoral control in tumors of the nasal cavity. Clinical advantages of proton therapy counterbalance its cost especially in pediatric tumors. Proton therapy could be used in other types of cancer. Proton therapy showed good outcome in ocular, nasal tumors, pediatric, skull-based and paraspinal tumors. Because of some dosimetric advantages, proton therapy could be proposed for other indications in cancer treatments.

Influence of beam incidence and irradiation parameters on stray neutron doses to healthy organs of pediatric patients treated for an intracranial tumor with passive scattering proton therapy.

PURPOSE: In scattering proton therapy, the beam incidence, i.e. the patient's orientation with respect to the beam axis, can significantly influence stray neutron doses although it is almost not documented in the literature. METHODS: MCNPX calculations were carried out to estimate stray neutron doses to 25 healthy organs of a 10-year-old female phantom treated for an intracranial tumor. Two beam incidences were considered in this article, namely a superior (SUP) field and a right lateral (RLAT) field. For both fields, a parametric study was performed varying proton beam energy, modulation width, collimator aperture and thickness, compensator thickness and air gap size. RESULTS: Using a standard beam line configuration for a craniopharyngioma treatment, neutron absorbed doses per therapeutic dose of 63µGyGy(-1) and 149µGyGy(-1) were found at the heart for the SUP and the RLAT fields, respectively. This dose discrepancy was explained by the different patient's orientations leading to changes in the distance between organs and the final collimator where external neutrons are mainly produced. Moreover, investigations on neutron spectral fluence at the heart showed that the number of neutrons was 2.5times higher for the RLAT field compared against the SUP field. Finally, the influence of some irradiation parameters on neutron doses was found to be different according to the beam incidence. CONCLUSION: Beam incidence was thus found to induce large variations in stray neutron doses, proving that this parameter could be optimized to enhance the radiation protection of the patient.

Tumour Response in Uveal Melanomas Treated with Proton Beam Therapy.

AIMS: Post-proton therapy surveillance of uveal melanomas relies on decreased thickness on repeat ultrasound B every 6 months for 2 years and yearly thereafter. Earlier pseudoprogression, a phenomenon described in other tumour types within the first months of irradiation, can also be observed in uveal melanomas and may lead to inappropriate enucleation. The Collaborative Ocular Melanoma Study (COMS) has defined ultrasound criteria to identify tumour progression after brachytherapy. We aimed to determine the reliability of ultrasound as a means to measure tumour height after proton therapy and predict local relapse. MATERIALS AND METHODS: All 1992-2012 consecutive patients with at least three ultrasound B measurements during follow-up were included. RESULTS: There were 55 local relapses of 886 patients (6.2%). Ultrasound B reliability was highest at 24 months, with specificity higher than 95% starting at 18 months. CONCLUSION: Before 18 months post-proton therapy, the risk of falsely concluding in favour of a relapse exceeds 5% and should prompt repeat measurements 3 and 6 months later but should not prompt enucleation without further clinical assessment.

[Operative therapy and irradiation of conjunctival melanoma]. / Operative Therapie und Bestrahlung konjunktivaler Melanome.

BACKGROUND: Radiotherapy of conjunctival melanoma has gained in importance in recent years compared to less invasive therapeutic approaches. This is due to the high recurrence rates achieved by omitting adjuvant therapy and to the increasing availability of suitable radiotherapeutic methods, so that tumors formerly not amenable to organ-preserving therapy can now be treated. OBJECTIVE: This article presents the current radiotherapeutic options for conjunctival melanoma. The aim is to describe the diagnostic and therapeutic strategies and the course of therapy of malignant conjunctival melanoma. It is the authors' intention to justify the necessity of the adjuvant therapy of conjunctival melanoma and to emphasize the need for interdisciplinary cooperation during the course of tumor therapy. METHODS: The article is based on results published in the literature as well as on data collected and experience gained in our centre.

[Proton imaging applications for proton therapy: state of the art]. / Imagerie protonique pour la protonthérapie : état de l'art.

Proton therapy allows a highly precise tumour volume irradiation with a low dose delivered to the healthy tissues. The steep dose gradients observed and the high treatment conformity require a precise knowledge of the proton range in matter and the target volume position relative to the beam. Thus, proton imaging allows an improvement of the treatment accuracy, and thereby, in treatment quality. Initially suggested in 1963, radiographic imaging with proton is still not used in clinical routine. The principal difficulty is the lack of spatial resolution, induced by the multiple Coulomb scattering of protons with nuclei. Moreover, its realization for all clinical locations requires relatively high energies that are previously not considered for clinical routine. Abandoned for some time in favor of X-ray technologies, research into new imaging methods using protons is back in the news because of the increase of proton radiation therapy centers in the world. This article exhibits a non-exhaustive state of the art in proton imaging.

Management of choroidal metastases.

BACKGROUND: Choroidal metastases (CM) are the most common malignant intraocular lesion observed in up to 4-12% of necropsy series of patients with solid cancer. The spectrum of presentations varies from prevalent CM in disseminated cancer to isolated CM. CM are responsible for visual deterioration. Depending on the primary cancer, estimated life expectancy, overall cancer presentation and ocular symptoms, the management of CM varies widely. We address the multidisciplinary management of CM and technical aspects of radiotherapy. MATERIAL AND METHODS: A systematic review of literature was performed from 1974 to 2014. RESULTS: Choroidal metastases occur preferentially in breast and lung carcinomas but are reported in all cancer types. The standard treatment remains external beam radiotherapy, applying 30Gy in 10 fractions or 40Gy in 20 fractions. The reported complete response and improved visual acuity rates are 80% and 57% to 89%, respectively. Some chemotherapy or new targeted therapy regimens yield promising CM response rates. DISCUSSION: Radiation therapy consistently shows rapid symptom alleviation, yield excellent local control and functional outcomes. However, there are only few reports on late toxicities after 6months given the unfavorable prognostic of CM patients. Selected patients may live more than two years, underlying the need to better assess mean and long term outcomes. Some authors have favored exclusive systemic strategies with omission of irradiation. The current literature suffers from the scarcity of prospective trials. Duration of tumor response following systemic therapy is rarely reported but appears less favorable as compared to radiotherapy. Systemic treatments may be proposed for pauci-symptomatic CM in a polymetastatic context while radiation therapy remains necessary in symptomatic CM either upfront or as an alternating treatment. Focalized radiation like brachytherapy and proton therapy may be proposed for isolated CM with long disease-free interval between primary and CM, as these techniques have the potential to yield better tumor and functional outcomes in patients with long life expectancy.

Optimum reduction of the dynamo threshold by a ferromagnetic layer located in the flow.

We consider a fluid dynamo model generated by the flow on both sides of a moving layer. The magnetic permeability of the layer is larger than that of the flow. We show that there exists an optimum value of magnetic permeability for which the critical magnetic Reynolds number for dynamo onset is smaller than for a nonmagnetic material and also smaller than for a layer of infinite magnetic permeability. We present a mechanism that provides an explanation for recent experimental results. A similar effect occurs when the electrical conductivity of the layer is large.

Monte Carlo modeling of proton therapy installations: a global experimental method to validate secondary neutron dose calculations.

Monte Carlo calculations are increasingly used to assess stray radiation dose to healthy organs of proton therapy patients and estimate the risk of secondary cancer. Among the secondary particles, neutrons are of primary concern due to their high relative biological effectiveness. The validation of Monte Carlo simulations for out-of-field neutron doses remains however a major challenge to the community. Therefore this work focused on developing a global experimental approach to test the reliability of the MCNPX models of two proton therapy installations operating at 75 and 178 MeV for ocular and intracranial tumor treatments, respectively. The method consists of comparing Monte Carlo calculations against experimental measurements of: (a) neutron spectrometry inside the treatment room, (b) neutron ambient dose equivalent at several points within the treatment room, (c) secondary organ-specific neutron doses inside the Rando-Alderson anthropomorphic phantom. Results have proven that Monte Carlo models correctly reproduce secondary neutrons within the two proton therapy treatment rooms. Sensitive differences between experimental measurements and simulations were nonetheless observed especially with the highest beam energy. The study demonstrated the need for improved measurement tools, especially at the high neutron energy range, and more accurate physical models and cross sections within the Monte Carlo code to correctly assess secondary neutron doses in proton therapy applications.