Development of optimised tissue-equivalent materials for proton therapy.

Objective. In proton therapy there is a need for proton optimised tissue-equivalent materials as existing phantom materials can produce large uncertainties in the determination of absorbed dose and range measurements. The aim of this work is to develop and characterise optimised tissue-equivalent materials for proton therapy.Approach. A mathematical model was developed to enable the formulation of epoxy-resin based tissue-equivalent materials that are optimised for all relevant interactions of protons with matter, as well as photon interactions, which play a role in the acquisition of CT numbers. This model developed formulations for vertebra bone- and skeletal muscle-equivalent plastic materials. The tissue equivalence of these new materials and commercial bone- and muscle-equivalent plastic materials were theoretical compared against biological tissue compositions. The new materials were manufactured and characterised by their mass density, relative stopping power (RSP) measurements, and CT scans to evaluate their tissue-equivalence.Main results. Results showed that existing tissue-equivalent materials can produce large uncertainties in proton therapy dosimetry. In particular commercial bone materials showed to have a relative difference up to 8% for range. On the contrary, the best optimised formulations were shown to mimic their target human tissues within 1%-2% for the mass density and RSP. Furthermore, their CT-predicted RSP agreed within 1%-2% of the experimental RSP, confirming their suitability as clinical phantom materials.Significance. We have developed a tool for the formulation of tissue-equivalent materials optimised for proton dosimetry. Our model has enabled the development of proton optimised tissue-equivalent materials which perform better than existing tissue-equivalent materials. These new materials will enable the advancement of clinical proton phantoms for accurate proton dosimetry.

Animal tissue-based quantitative comparison of dual-energy CT to SPR conversion methods using high-resolution gel dosimetry.

Dual-energy computed tomography (DECT) has been shown to allow for more accurate ion therapy treatment planning by improving the estimation of tissue stopping power ratio (SPR) relative to water, among other tissue properties. In this study, we measured and compared the accuracy of SPR values derived using both dual- and single-energy CT (SECT) based on different published conversion algorithms. For this purpose, a phantom setup containing either fresh animal soft tissue samples (beef, pork) and a water reference or tissue equivalent plastic materials was designed and irradiated in a clinical proton therapy facility. Dosimetric polymer gel was positioned downstream of the samples to obtain a three-dimensional proton range distribution with high spatial resolution. The mean proton range in gel for each tissue relative to the water sample was converted to a SPR value. Additionally, the homogeneous samples were probed with a variable water column encompassed by two ionization chambers to benchmark the SPR accuracy of the gel dosimetry. The SPR values measured with both methods were consistent with a mean deviation of 0.2%, but the gel dosimetry captured range variations up to 5 mm within individual samples.Across all fresh tissue samples the SECT approach yielded significantly greater mean absolute deviations from the SPR deduced using gel range measurements, with an average difference of 1.2%, compared to just 0.3% for the most accurate DECT-based algorithm. These results show a significant advantage of DECT over SECT for stopping power prediction in a realistic setting, and for the first time allow to compare a large set of methods under the same conditions.

Evaluation of the water-equivalence of plastic materials in low- and high-energy clinical proton beams.

The aim of this work was to evaluate the water-equivalence of new trial plastics designed specifically for light-ion beam dosimetry as well as commercially available plastics in clinical proton beams. The water-equivalence of materials was tested by computing a plastic-to-water conversion factor, [Formula: see text]. Trial materials were characterized experimentally in 60 MeV and 226 MeV un-modulated proton beams and the results were compared with Monte Carlo simulations using the FLUKA code. For the high-energy beam, a comparison between the trial plastics and various commercial plastics was also performed using FLUKA and Geant4 Monte Carlo codes. Experimental information was obtained from laterally integrated depth-dose ionization chamber measurements in water, with and without plastic slabs with variable thicknesses in front of the water phantom. Fluence correction factors, [Formula: see text], between water and various materials were also derived using the Monte Carlo method. For the 60 MeV proton beam, [Formula: see text] and [Formula: see text] factors were within 1% from unity for all trial plastics. For the 226 MeV proton beam, experimental [Formula: see text] values deviated from unity by a maximum of about 1% for the three trial plastics and experimental results showed no advantage regarding which of the plastics was the most equivalent to water. Different magnitudes of corrections were found between Geant4 and FLUKA for the various materials due mainly to the use of different nonelastic nuclear data. Nevertheless, for the 226 MeV proton beam, [Formula: see text] correction factors were within 2% from unity for all the materials. Considering the results from the two Monte Carlo codes, PMMA and trial plastic #3 had the smallest [Formula: see text] values, where maximum deviations from unity were 1%, however, PMMA range differed by 16% from that of water. Overall, [Formula: see text] factors were deviating more from unity than [Formula: see text] factors and could amount to a few percent for some materials.

Fluence correction factor for graphite calorimetry in a clinical high-energy carbon-ion beam.

The aim of this work is to develop and adapt a formalism to determine absorbed dose to water from graphite calorimetry measurements in carbon-ion beams. Fluence correction factors, [Formula: see text], needed when using a graphite calorimeter to derive dose to water, were determined in a clinical high-energy carbon-ion beam. Measurements were performed in a 290 MeV/n carbon-ion beam with a field size of 11 × 11 cm2, without modulation. In order to sample the beam, a plane-parallel Roos ionization chamber was chosen for its small collecting volume in comparison with the field size. Experimental information on fluence corrections was obtained from depth-dose measurements in water. This procedure was repeated with graphite plates in front of the water phantom. Fluence corrections were also obtained with Monte Carlo simulations through the implementation of three methods based on (i) the fluence distributions differential in energy, (ii) a ratio of calculated doses in water and graphite at equivalent depths and (iii) simulations of the experimental setup. The [Formula: see text] term increased in depth from 1.00 at the entrance toward 1.02 at a depth near the Bragg peak, and the average difference between experimental and numerical simulations was about 0.13%. Compared to proton beams, there was no reduction of the [Formula: see text] due to alpha particles because the secondary particle spectrum is dominated by projectile fragmentation. By developing a practical dose conversion technique, this work contributes to improving the determination of absolute dose to water from graphite calorimetry in carbon-ion beams.

Theoretical and experimental characterization of novel water-equivalent plastics in clinical high-energy carbon-ion beams.

Water-equivalent plastics are frequently used in dosimetry for experimental simplicity. This work evaluates the water-equivalence of novel water-equivalent plastics specifically designed for light-ion beams, as well as commercially available plastics in a clinical high-energy carbon-ion beam. A plastic- to-water conversion factor [Formula: see text] was established to derive absorbed dose to water in a water phantom from ionization chamber readings performed in a plastic phantom. Three trial plastic materials with varying atomic compositions were produced and experimentally characterized in a high-energy carbon-ion beam. Measurements were performed with a Roos ionization chamber, using a broad un-modulated beam of 11 × 11 cm2, to measure the plastic-to-water conversion factor for the novel materials. The experimental results were compared with Monte Carlo simulations. Commercially available plastics were also simulated for comparison with the plastics tested experimentally, with particular attention to the influence of nuclear interaction cross sections. The measured [Formula: see text] correction increased gradually from 0% at the surface to 0.7% at a depth near the Bragg peak for one of the plastics prepared in this work, while for the other two plastics a maximum correction of 0.8%-1.3% was found. Average differences between experimental and numerical simulations were 0.2%. Monte Carlo results showed that for polyethylene, polystyrene, Rando phantom soft tissue and A-150, the correction increased from 0% to 2.5%-4.0% with depth, while for PMMA it increased to 2%. Water-equivalent plastics such as, Plastic Water, RMI-457, Gammex 457-CTG, WT1 and Virtual Water, gave similar results where maximum corrections were of the order of 2%. Considering the results from Monte Carlo simulations, one of the novel plastics was found to be superior in comparison with the plastic materials currently used in dosimetry, demonstrating that it is feasible to tailor plastic materials to be water-equivalent for carbon ions specifically.

Application of an adapted Fano cavity test for Monte Carlo simulations in the presence of B-fields.

With the advent of MR guided radiotherapy the relevance of Monte Carlo radiation transport simulations in the presence of strong magnetic fields (B-fields) is increasing. While new tests are available to benchmark these simulation algorithms for internal consistency, their application to known codes such as EGSnrc, PENELOPE, and GEANT4 is yet to be provided. In this paper a method is provided to apply the Fano cavity test as a benchmark for a generic implementation of B-field effects in PENELOPE. In addition, it is investigated whether violation of the conditions for the Fano test can partially explain the change in the response of ionization chambers in the presence of strong B-fields. In the present paper it is shown that the condition of isotropy of the secondary particle field (Charged Particle Isotropy, CPI) is an essential requirement to apply the Fano test in the presence of B-fields. Simulations in PENELOPE are performed with (B = 0.0 T) and (B = 1.5 T) for cylindrical cavity geometry. The secondary particle field consists of electrons generated from a mono-energetic source (E = 0.5-4.0 MeV) with a uniform source density and different angular distributions; isotropic, mono-directional, and Compton. In realistic photon fields the secondary radiation field has a non-isotropic angular distribution due to the Compton process. Based on the simulations for the Compton angular distribution (non-CPI), the response change of the cavity model in a uniform radiation field in the presence of B-fields is investigated. For the angular distributions that violate the CPI condition and B = 1.5 T, the deviations from 1 are considerable, which emphasizes the requirement of CPI. For the isotropic angular distributions obeying this requirement, both the results for B = 0.0 T and B = 1.5 T shows deviations from the predictions for E ⩾ 1.5 MeV with values up to 1.0% for E = 4.0 MeV. Nevertheless, due to the high correlation in the deviation for B = 0.0 T and B = 1.5 T, the accuracy of the PENELOPE code for the simulation of the change in detector response in the presence of B-fields is within 0.3%. The effect of the B-field on the detector response for non-isotropic angular distributions suggests that violation of CPI is a major contribution to the response change of ionization chambers in the presence of B-fields.

Correction-less dosimetry of nonstandard photon fields: a new criterion to determine the usability of radiation detectors.

In the IAEA-AAPM dosimetry formalism, detector measurements in general nonstandard conditions are corrected using the factor k(f(clin),f(msr))(Q(clin),Q(msr)). This factor needs to be evaluated on a case-by-case basis which is difficult to accomplish in practice. The present paper aims to provide a method that allows neglecting correction factors for small and composite IMRT fields by first determining a radiation detector's usability in these fields. Detailed models of nine radiation detectors are built: four ionization chambers (NE2571, A12, A1SL, A14), three small field detectors (PTW31018 microLion, PTW60003 natural diamond, PTW60012 unshielded diode) and two near water-equivalent detectors (alanine, W1 scintillating fiber). Using the egs_chamber Monte Carlo code, dose response functions at 6 MV and 25 MV are sampled for each detector and their corresponding volume of water. These functions are then used with a newly derived criterion to evaluate an upper bound ξ(f(ns),f(msr))(Q(ns),Q(msr)) on the variable ε(f(ns),f(msr))(Q(ns),Q(msr)) if no field collimation/modulation occurs over a given perturbation zone. The variable ε(f(ns),f(msr))(Q(ns),Q(msr)) is defined as the absolute value of the relative deviation from unity of a nonstandard field quality correction factor k(f(ns),f(msr))(Q(ns),Q(msr)). Using the same criterion, perturbation zones are evaluated by finding the smallest field size allowed for correction-less dosimetry with a given tolerance ξ(f(ns),f(msr))(Q(ns),Q(msr)). For composite fields, the sensitivity of detectors to the non-uniformity of virtual symmetric collapsed beams over regions of interest specified by the criterion is studied to estimate an upper bound ξ ̃(f(ns),f(ref))(Q(ns),Q) on ε(f(ns),f(ref))(Q(ns),Q) for a given beam flatness. Finally, a newly defined perturbation function is used to minimize the perturbations of the microLion chamber through density compensation. The theoretical criterion shows good agreement with full Monte Carlo simulations of ε(f(ns),f(msr))(Q(ns) Q(msr)). Perturbation zones are shown to be sensitive to both the energy of the beam and the orientation of the detector. The density-compensated microLion shows significantly improved response in both axial and radial orientations in small and composite IMRT fields. Finally, the new Exradin W1 scintillator is shown to have ξ(f(ns),f(msr))(Q(ns),Q(msr)) values under 1% in small fields. The methods presented in this work theoretically show that correction-less dosimetry of nonstandard field can be accomplished by knowing the limit of usability of radiation detectors in these conditions. Potential applications include small field output factor measurements and absolute absorbed dose to water verification in the QA of clinical IMRT fields.

Epitheliotropic lymphoma in a dog.

Despite treatment with steroids, nodular areas of alopecia and erythematous skin lesions persisted in a 9-year-old Irish water spaniel with discoid lupus. Epitheliotropic lymphoma was diagnosed by skin biopsy.

A germline mutation at the extreme 3' end of the APC gene results in a severe desmoid phenotype and is associated with overexpression of beta-catenin in the desmoid tumor.

Desmoid tumors arise sporadically or as part of the extraintestinal manifestations of familial adenomatous polyposis (FAP). In FAP, two distinct clinical presentations of the desmoid phenotype are seen: 1) one or a few desmoid tumors present predominantly in the abdominal wall or the abdomen; 2) a florid proliferation of tumors early in life, mostly near the axial skeleton or extremities. These different phenotypes have been associated with different sites of germline mutations in the adenomatous polyposis coli gene (APC gene). We present a large, French-Canadian kindred with a florid desmoid tumor phenotype caused by a germline mutation at codon 2643-2644 of the APC gene. The phenotype was characterized by the early onset of multiple tumors, arising near the axial skeleton and in proximal extremities. The penetrance of desmoid tumors was near 100% in this kindred. However, the expression of the disease was variable amongst the different affected relatives. Many gene carriers had cutaneous cysts. Polyposis of the colon was rarely observed in the affected individuals and we did not document upper gastro-intestinal polyps. The mutant APC allele did not express a stable truncated protein in vivo. Molecular analysis of the proband's tumor DNA revealed a somatic inactivating mutation of the wild-type allele. Immunohistochemistry on the tumor also demonstrated elevated levels of beta-catenin. The present study demonstrates that this extreme 3' APC mutation is associated with a severely penetrant desmoid phenotype and attenuated polyposis coli. It also suggests the involvement of the beta-catenin pathway in the development of desmoid tumors in FAP. The natural history of the disease is variable between individuals, and surgical interventions have to be timed appropriately due to the frequent recurrences.

Rothmund-Thomson syndrome with osteosarcoma.

Rothmund-Thomson syndrome is a rare genodermatosis that features a progressive, early-onset poikiloderma, a high incidence of juvenile cataracts, stunted growth, and a wide range of skeletal abnormalities. We report the seventh case of osteosarcoma in a patient with Rothmund-Thomson syndrome and review the previous reports describing this association.

Prognostic influence of HSP-27 expression in malignant fibrous histiocytoma: a clinicopathological and immunohistochemical study.

Malignant fibrous histiocytoma is a very aggressive sarcoma. After the tumor has disseminated, chemotherapy is of little influence on the course of the disease because of the resistance to most chemotherapy regimens. We evaluated by immunohistochemistry the prognostic influence of the expression of a member of the stress polypeptides family, the heat-shock protein of 27 KDa (HSP-27). HSP-27 was found to be associated with an aggressive behavior in breast carcinoma and was related to chemoresistance in cell cultures. Forty-three malignant fibrous histiocytomas with no evidence of metastases at the time of diagnosis and resected between 1974 and 1985 were retrieved from the files of the Pathology Department of L'Hôtel-Dieu de Québec hospital. The immunostaining was performed on Bouin-fixed, paraffin-embedded tissue. Regardless of the percentage of positive cells, HSP-27 was expressed in the cytoplasm of 25 (58.1%) cases. HSP-27 expression was associated with a more favorable prognosis, and a significant correlation was observed with overall survival (P less than 0.025) and metastasis-free survival (P less than 0.05). HSP-27 expression was found to be the strongest prognostic factor, and multivariate analysis revealed that it was independent of tumor size, necrosis, and histological subtype. However, in the 13 patients with recurrent disease who underwent chemotherapy, the antigenic expression did not help to predict the treatment response. HSP-27 expression is one of the rare prognostic markers in this tumor type.

[Pathologic study of Morton's neuroma]. / Etude pathologique du névrôme de Morton.

The clinical syndrome of Morton's neuroma [correction of nephroma] was described over a century ago, but its etiopathology remains unknown. Recent studies suggest that it may be induced by compression neuropathy. Histologic changes in digital nerves resected for therapeutic purposes were compared with histologic findings of digital nerves sampled at autopsy of asymptomatic subjects. Results show that approximately one-third of resected "diseased" digital nerves were histologically normal. The authors question the therapeutic approach, which consists of resecting the nerves.

Can in-home hospital care be implemented in Ontario? Implications for public policy.

Two models of in-home hospital care were considered as ways to overcome the current problems plaguing the Home Care Program in Ontario. The hospital-organized home care is an extension of some hospital services into the community, similar to the Verdun Hospital-In-The-Home. The extramural hospital, introduced in New Brunswick, emphasizes the integration of services. These two models were compared to the Ontario Home Care Program to consider feasibility. Clearly defined mandates and the division of services need to be established in addition to an evaluation of cost, the use of services and the impact on health status.

Desmoplastic fibroma of bone. An ultrastructural study.

The ultrastructure of three cases of desmoplastic fibroma of bone is presented. The lesion is principally characterized by myofibroblasts admixed with lesser numbers of fibroblasts and primitive mesenchymal cells. Thus, the cellular composition is similar to that described in a variety of nonneoplastic proliferative processes of soft tissue. It is postulated that the myofibroblastic proliferation develops in response to unknown factors acting on marrow fibroblasts or primitive mesenchymal cells.