Polyethylene glycol-fused allografts produce rapid behavioral recovery after ablation of sciatic nerve segments.

Restoration of neuronal functions by outgrowths regenerating at ∼1 mm/day from the proximal stumps of severed peripheral nerves takes many weeks or months, if it occurs at all, especially after ablation of nerve segments. Distal segments of severed axons typically degenerate in 1-3 days. This study shows that Wallerian degeneration can be prevented or retarded, and lost behavioral function can be restored, following ablation of 0.5-1-cm segments of rat sciatic nerves in host animals. This is achieved by using 0.8-1.1-cm microsutured donor allografts treated with bioengineered solutions varying in ionic and polyethylene glycol (PEG) concentrations (modified PEG-fusion procedure), being careful not to stretch any portion of donor or host sciatic nerves. The data show that PEG fusion permanently restores axonal continuity within minutes, as initially assessed by action potential conduction and intracellular diffusion of dye. Behavioral functions mediated by the sciatic nerve are largely restored within 2-4 weeks, as measured by the sciatic functional index. Increased restoration of sciatic behavioral functions after ablating 0.5-1-cm segments is associated with greater numbers of viable myelinated axons within and distal to PEG-fused allografts. Many such viable myelinated axons are almost certainly spared from Wallerian degeneration by PEG fusion. PEG fusion of donor allografts may produce a paradigm shift in the treatment of peripheral nerve injuries.

A portable primary-standard level graphite calorimeter for absolute dosimetry in clinical pencil beam scanning proton beams.

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry.Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm-2depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in60Co applying the recommendations in the IAEA TRS-398 CoP.Main results.The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k= 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k= 1) for proton beams).Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.

Dosimetric comparison of four high performance techniques for irradiation of breast cancer patients.

PURPOSE: The use of IMRT for the treatment of breast cancer has been growing considerably in our institution since 2009. Alternatively, helical tomotherapy (HT) using a field width of 2.5 and 5cm (HT_FW_5), volumetric-modulated arc therapy (VMAT), or proton therapy with pencil-beam scanning (PT-PBS) have also been used to reduce treatment duration or optimize organ-at-risk (OAR) sparing. The purpose of this study was to compare the 4 treatment modalities available at our site. PATIENTS AND METHODS: We studied 10 patients treated for breast cancer with lymph node involvement. The prescribed dose was 51.8Gy to the breast with a simultaneous integrated boost up to 63Gy, and 50.4Gy to lymph nodes in 28 fractions. The CTV was delineated according to ESTRO Guidelines. Dosimetric planning in routine clinical practice was performed using HT_FW_2.5. The approved clinical plan was compared to the 3 other plans. Dosimetric goals for PTV coverage were D95%≥95% and D2%≤107% of the prescribed dose. Mean and maximum doses to OAR were recorded. RESULTS: HT_FW_5 and VMAT plans ensure equivalent or even better PTV coverage compared to the initial clinically approved plan but at the cost of poorer OAR sparing. PT_PBS plans showed that an excellent PTV coverage can be maintained with significantly lower doses to OAR. CONCLUSION: HT_FW_5 and VMAT plans allow a significant reduction of treatment duration and can be a good alternative to HT_FW_2.5 for specific populations. HT_FW_2.5 could be chosen for patients at higher risk of side effects. In addition, PT_PBS should be considered in the near future as it has been shown to have a major potential benefit to lower the risk of side effects with the same level of PTV coverage.

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.

[French national evaluation for helicoidal tomotherapy: description of indications, dose constraints and set-up margins]. / Evaluation nationale de la tomothérapie hélicoïdale: description des indications, des contraintes de dose et des seuils de repositionnement.

After a request for proposal initiated by National Institute against cancer (INCa) in 2005, three French centers in France started tomotherapy in the first semester of 2007. A national policy of evaluation was performed to study the feasibility of this innovative technique and to compare the interest of helicoidal tomotherapy with other modalities of conformal therapy. Common protocols have been designed to facilitate this evaluation. Description of dose, IMRT levels and constraints are achieved according to each selected indication as: sarcoma, head and neck tumors, lung cancer, mesothelioma, bone metastases, anal carcinoma and craniospinal irradiation.

[Helical tomotherapy: general methodology for clinical and dosimetric evaluation (national French project)]. / Questions d'actualité: schéma général d'élaboration des protocoles de tomothérapie hélicoïdale pour chaque localisation.

The methodology and choice of criteria and indexes used for a common evaluation of helical tomotherapy by 3 French centres are described. After a selection of clinical indications and definition of the general purpose are successively described the criteria and index selected for: 1) description of volumes and adaptation for on board imaging; 2) dose prescription and constraints related to IMRT; 3) intercomparaison of volumes and doses and potential dosimetric gain with this new equipment.

Analytical linear energy transfer model including secondary particles: calculations along the central axis of the proton pencil beam.

In proton therapy, the relative biological effectiveness (RBE) depends on various types of parameters such as linear energy transfer (LET). An analytical model for LET calculation exists (Wilkens' model), but secondary particles are not included in this model. In the present study, we propose a correction factor, L sec, for Wilkens' model in order to take into account the LET contributions of certain secondary particles. This study includes secondary protons and deuterons, since the effects of these two types of particles can be described by the same RBE-LET relationship. L sec was evaluated by Monte Carlo (MC) simulations using the GATE/GEANT4 platform and was defined by the ratio of the LET d distributions of all protons and deuterons and only primary protons. This method was applied to the innovative Pencil Beam Scanning (PBS) delivery systems and L sec was evaluated along the beam axis. This correction factor indicates the high contribution of secondary particles in the entrance region, with L sec values higher than 1.6 for a 220 MeV clinical pencil beam. MC simulations showed the impact of pencil beam parameters, such as mean initial energy, spot size, and depth in water, on L sec. The variation of L sec with these different parameters was integrated in a polynomial function of the L sec factor in order to obtain a model universally applicable to all PBS delivery systems. The validity of this correction factor applied to Wilkens' model was verified along the beam axis of various pencil beams in comparison with MC simulations. A good agreement was obtained between the corrected analytical model and the MC calculations, with mean-LET deviations along the beam axis less than 0.05 keV µm(-1). These results demonstrate the efficacy of our new correction of the existing LET model in order to take into account secondary protons and deuterons along the pencil beam axis.

[Prevention of radio-induced cancers]. / Prévention des cancers radio-induits.

The article deals with the prevention of cancers only directly related to therapeutic radiation which are distinguished from "secondary cancer". The consideration of the risk of radiation-induced cancers after radiation therapy, although it is fortunately rare events, has become indispensable today. With a review of the literature, are detailed the various involved parameters. The age of the irradiated patient is one of the main parameters. The impact of the dose is also discussed based on the model used, and based on clinical data. Other parameters defining a radiation treatment are discussed one after the other: field with the example of Hodgkin's disease, the type of radiation and the participation of secondary neutrons, spreading and splitting. All these parameters are discussed according to each organ whose sensitivity is different. The article concludes with a list of recommendations to reduce the risk of radio-induced cancers. Even with the advent of conformal radiotherapy, intensity modulation, the modulated volume arctherapy, and the development of specific machinery for the extra-cranial stereotactic, the radiation therapist must consider this risk and use of reasonable and justified control imaging. Although they constitute a small percentage of cancers that occur secondarily after a first malignant tumor, radiation-induced cancers, can not and must not be concealed or ignored and justify regular monitoring over the long term, precisely adapted on the described parameters.

Dosimetric characteristics of four PTW microDiamond detectors in high-energy proton beams.

Small diamond detectors are useful for the dosimetry of high-energy proton beams. However, linear energy transfer (LET) dependence has been observed in the literature with such solid state detectors. A novel synthetic diamond detector has recently become commercially available from the manufacturer PTW-Freiburg (PTW microDiamond type 60019). This study was designed to thoroughly characterize four microDiamond detectors in clinical proton beams, in order to investigate their response and their reproducibility in high LET regions. Very good dosimetric characteristics were observed for two of them, with good stability of their response (deviation less than 0.4% after a pre-irradiation dose of approximately 12 Gy), good repeatability (coefficient of variation of 0.06%) and a sensitivity of approximately 0.85 nC Gy(-1). A negligible dose rate dependence was also observed for these two microDiamonds with a deviation of the sensitivity less than 0.7% with respect to the one measured at the reference dose rate of 2.17 Gy min(-1), in the investigated dose rate range from 1.01 Gy min(-1) to 5.52 Gy min(-1). Lateral dose profile measurements showed the high spatial resolution of the microDiamond oriented with its stem perpendicular to the beam axis and with its small sensitive thickness of about 1 µm in the scanning profile direction. Finally, no significant LET dependence was found with these two diamond dosimeters in comparison to a reference ionization chamber (model IBA PPC05). These good results were in accordance to the literature. However, this study showed also a non reproducibility between the devices in terms of stability, sensitivity and LET dependence, since the two other microDiamonds characterized in this work showed different dosimetric characteristics making them not suitable for proton beam dosimetry with a maximum difference of the peak-to-plateau ratio of 6.7% relative to the reference ionization chamber in a clinical 138 MeV proton beam.

The sliding slit test for dynamic IMRT: a useful tool for adjustment of MLC related parameters.

For treatments with dynamic intensity modulated radiotherapy (IMRT), the adjustment of multileaf collimator (MLC) parameters affecting both the optimization algorithm and dose distributions is crucial. The main parameters characterizing the MLC are the transmission (T) and the dosimetric leaf separation (DLS). The aim of this study is twofold: a methodology based on the 'sliding slit' test is proposed to determine (T, DLS) combinations inducing the best conformity between calculations and measurements. Secondly, the effects of the MLC adjustment on measured dose and on optimization are presented for different configurations as the chair test and for the patient dosimetric quality control (DQC). Tests were performed with a Varian 23EX linac operated at 20 MV and equipped with a 120 leaf Millenium dynamic collimator. The treatment planning system was CadPlan/Helios (version 6.3.6). Results demonstrated that the sliding width (SW) strongly depends on the (T, DLS) combinations, and the measured dose is a linear function of the SW. Different (T, DLS) combinations induced a good agreement between calculations and measurements. The influence of the MLC calibration was found to be particularly important on the 'sliding slit' test (11.8% for a gap change of 0.8 mm) but not so much on the chair test and on the DQC. To detect small variations in leaf adjustment and to ensure consistency between calculation and actual dose delivered to patients, a daily check called IMRT MU check is proposed.

[Chordomas of the base of the skull and upper cervical spine. 100 patients irradiated by a 3D conformal technique combining photon and proton beams]. / Les chordomes de la base du crâne et du rachis cervical haut. A propos d'une série de 100 patients irradiés selon une technique conformationnelle 3D par une association de faisceaux de photons et de protons.

OBJECTIVE: To define prognostic factors for local control and survival in 100 consecutive patients treated by fractionated photon and proton radiation for chordoma of the skull base and upper cervical spine. PATIENTS AND METHODS: Between December 1995 and August 2002, 100 patients (median age: 53 years, range: 8-85, M/F sex-ratio: 3/2), were treated by a combination of high-energy photons and protons. The proton component was delivered by the 201 MeV proton beam of the Centre de Protonthérapie d'Orsay (CPO). The median total dose delivered to the gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (range: 60-71). A complete surgery, incomplete surgery or a biopsy was performed before the radiotherapy in 16, 75 and 9 cases, respectively. RESULTS: With a median follow-up of 31 months (range: 1-87), 25 tumours failed locally. The 2 and 4-year local control rates were 86.3% (+/-3.9%) and 53.8% (+/-7.5%), respectively. According to multivariate analysis, less than 95% of the tumour volume encompassed by the 95% isodose line (P=0.048; RR: 3.4 IC95% [1.01-11.8]) and a minimal dose less than 56 CGE (p=0.042; RR: 2.3 IC95% [1.03-5.2]) were independent prognostic factors of local control. Ten patients died. The 2 and 5-year overall survival rates were 94.3% (+/-2.5%) and 80.5% (+/-7.2%). According to multivariate analysis, a controlled tumour (P=0.005; RR: 21 IC95% [2.2-200]) was the lonely independent favourable prognostic factor for overall survival. CONCLUSION: In chordomas of the skull base and upper cervical spine treated by surgical resection followed by high-dose photon and proton irradiation, local control is mainly dependent on the quality of radiation, especially dose-uniformity within the gross tumour volume. Special attention must be paid to minimise underdosed areas due to the close proximity of critical structures and possibly escalate dose-constraints to tumour targets in future studies, in view of the low toxicity observed to date.

Use of gEUD for predicting ear and pituitary gland damage following proton and photon radiation therapy.

OBJECTIVE: To determine the relationship between the dose to the inner ear or pituitary gland and radiation-induced late effects of skull base radiation therapy. METHODS: 140 patients treated between 2000 and 2008 were considered for this study. Hearing loss and endocrine dysfunction were retrospectively reviewed on pre- and post-radiation therapy audiometry or endocrine assessments. Two normal tissue complication probability (NTCP) models were considered (Lyman-Kutcher-Burman and log-logistic) whose parameters were fitted to patient data using receiver operating characteristics and maximum likelihood analysis. The method provided an estimation of the parameters of a generalized equivalent uniform dose (gEUD)-based NTCP after conversion of dose-volume histograms to equivalent doses. RESULTS: All 140 patients had a minimum follow up of 26 months. 26% and 44% of patients experienced mild hearing loss and endocrine dysfunction, respectively. The fitted values for TD50 and γ50 ranged from 53.6 to 60.7 Gy and from 1.9 to 2.9 for the inner ear and were equal to 60.6 Gy and 4.9 for the pituitary gland, respectively. All models were ranked equal according to Akaike's information criterion. CONCLUSION: Mean dose and gEUD may be used as predictive factors for late ear and pituitary gland late complications after skull base proton and photon radiation therapy. ADVANCES IN KNOWLEDGE: In this study, we have reported mean dose effects and dose-response relationship of small organs at risk (partial volumes of the inner ear and pituitary gland), which could be useful to define optimal dose constraints resulting in an improved therapeutic ratio.

An experimental approach to the design of a scattering system for a proton therapy beam line dedicated to ophthalmological applications.

PURPOSE: The development of a scattering system for a proton therapy beam line dedicated to ophthalmological applications. METHODS AND MATERIALS: A protontherapy beam line has been developed for the treatment of uveal melanoma at the Orsay synchrocyclotron. The original 200 MeV proton beam is degraded to 76 MeV and the final beam characteristics (range, modulation, flatness, collimation) are obtained with beam modifiers in the treatment room. A passive scattering system is used to obtain a uniform dose distribution in the beam cross-section throughout 30 mm in diameter, with minimal losses in energy and dose rate. We have used an experimental approach for the scattering study. RESULTS: An elliptical ring shaped from 0.1-mm thick lead is the solution we have adopted for the scattering system. For a modulated beam, a flatness of 1% is obtained on transverse profiles. The energy loss introduced by this scatterer is only 0.5 MeV, with no appreciable change in the range over the treatment field. For an unmodulated beam, 21% of intensity is lost when the scatterer is used. The distal and the lateral dose fall-off (90-10%) for a modulated beam are 2.6 mm. These last values are independent of the range and the modulation currently used for the ophthalmic applications. CONCLUSION: A specific passive scattering system can be adapted to a particular beam emittance. A systematic experimental approach can easily be undertaken to obtain the scatterer adapted for small irradiation fields in proton therapy.

Proton dosimetry comparison involving ionometry and calorimetry.

A comparison of the absorbed dose to tissue determined by various ionization chambers, Faraday cups, and an A-150 plastic calorimeter was performed in the 200 MeV proton beam of Orsay, France. Four European proton-therapy centers (Clatterbridge, UK, Louvain la Neuve, Belgium, and Nice and Orsay, France) participated in the comparison. An agreement of better than 1% was observed in the absorbed dose to A-150 measured with the different chambers of the participating groups. The mean ratio of the absorbed dose to A-150 determined with the calorimeter to that determined by the different ionization chambers in the different irradiation conditions was found to be 0.952 +/- 0.007 [1 standard deviation (SD)] according to the code of practice used by all the participating centers, based on Janni's tables of stopping powers and a value of 35.2 J/Coulomb for (W(air)/e)p. A better agreement in the mean ratio calorimeter/chamber, 0.985 +/- 0.007 (1 SD) is observed when using the proton stopping power ratio values recently published by the International Commission on Radiation Units and Measurements in Report no. 49. The mean ratio of these doses determined in accordance with the American Association of Physicists in Medicine protocol and using the new recommended stopping power tables becomes 1.002 +/- 0.007 (1 SD). Two Faraday cups agree in measured charge to within 0.8%; however, the calculation of dose is underestimated by up to 17%; compared with ion chamber measurements and seems to be very sensitive to measurement conditions, particularly to the distance to the collimator.

Combination of photon and proton radiation therapy for chordomas and chondrosarcomas of the skull base: the Centre de Protonthérapie D'Orsay experience.

PURPOSE: Prospective analysis of local tumor control, survival, and treatment complications in 44 consecutive patients treated with fractionated photon and proton radiation for a chordoma or chondrosarcoma of the skull base. METHODS AND MATERIALS: Between December 1995 and December 1998, 45 patients with a median age of 55 years (14-85) were treated using a 201-MeV proton beam at the Centre de Protonthérapie d'Orsay, 34 for a chordoma and 11 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two-thirds of the total dose and protons one-third. The median total dose delivered within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70). RESULTS: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively, and 3-year overall survival rates were 91% and 90%, respectively. Eight patients (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four patients died of tumor and 2 others of intercurrent disease. In univariate analysis, young age at time of radiotherapy influenced local control positively (p < 0.03), but not in multivariate analysis. Only 2 patients presented Grade 3 or 4 complications. CONCLUSION: In skull-base chordomas and chondrosarcomas, the combination of photons with a proton boost of one-third the total dose offers an excellent chance of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.

A simple method for 3D lesion reconstruction from two projected angiographic images: implementation to a stereotactic radiotherapy treatment planning system.

INTRODUCTION: The most used imaging modality for diagnosis and localisation of arteriovenous malformations (AVMs) treated with stereotactic radiotherapy is angiography. The fact that the angiographic images are projected images imposes the need of the 3D reconstruction of the lesion. This, together with the 3D head anatomy from CT images could provide all the necessary information for stereotactic treatment planning. We have developed a method to combine the complementary information provided by angiography and 2D computerized tomography, matching the reconstructed AVM structure with the reconstructed head of the patient. MATERIALS AND METHODS: The ISIS treatment planning system, developed at Institute Curie, has been used for image acquisition, stereotactic localisation and 3D visualisation. A series of CT slices are introduced in the system as well as two orthogonal angiographic projected images of the lesion. A simple computer program has been developed for the 3D reconstruction of the lesion and for the superposition of the target contour on the CT slices of the head. RESULTS AND CONCLUSIONS: In our approach we consider that the reconstruction can be made if the AVM is approximated with a number of adjacent ellipses. We assessed the method comparing the values of the reconstructed and the actual volumes of the target using linear regression analysis. For treatment planning purposes we overlapped the reconstructed AVM on the CT slices of the head. The above feature is to our knowledge a feature that the majority of the commercial stereotactic radiotherapy treatment planning system could not provide. The implementation of the method into ISIS TPS shows that we can reliably approximate and visualize the target volume.

A preliminary comparative treatment planning study for radiotherapy of age-related maculopathy.

PURPOSE: We present a comparative planning of different approaches for external radiotherapy in age-related maculopathies. MATERIALS AND METHODS: Calculated dose distributions and dose-volume histograms for (a) bilateral irradiation with 6 MV photons, (b) a single lateral-oblique beam using either photons, electrons or protons and (c) an anterior circular proton beam. RESULTS: For lateral photon or electron beams the dose to the lens is usually lower than 10% of the dose to the macula. The entrance doses for bilateral photon beams are about 50% which increase up to 100% at the orbital bone. About 5 mm of optic nerves are irradiated at the maximal dose while the optic chiasma is spared. A single photon beam gives 50% of the dose to the fellow eye. The electron beam spares the fellow eye but gives a rather inhomogeneous dose to the target volume. For a lateral proton beam, 4 mm of optic nerve receives 90% of the dose, the skin dose is at least 70% of the dose to the macula and the lens and the fellow eye are spared. An anterior proton beam gives 90% of the dose to 1 mm of optic nerve and the 50% isodose approaches the periphery of the lens. CONCLUSION: Doses to the critical structures can be dramatically diminished for all the techniques by reducing the beam size, but only if very precise set-up techniques are used. Proton beams are an attractive solution, but the impact of such a choice on the use of proton facilities and on the national health system should be carefully evaluated, as well as the risk of radio-induced secondary neoplasias.

Proton dosimetry intercomparison based on the ICRU report 59 protocol.

BACKGROUND AND PURPOSE: A new protocol for calibration of proton beams was established by the ICRU in report 59 on proton dosimetry. In this paper we report the results of an international proton dosimetry intercomparison, which was held at Loma Linda University Medical Center. The goals of the intercomparison were, first, to estimate the level of consistency in absorbed dose delivered to patients if proton beams at various clinics were calibrated with the new ICRU protocol, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration factors. MATERIALS AND METHODS: Eleven institutions participated in the intercomparison. Measurements were performed in a polystyrene phantom at a depth of 10.27 cm water equivalent thickness in a 6-cm modulated proton beam with an accelerator energy of 155 MeV and an incident energy of approximately 135 MeV. Most participants used ionization chambers calibrated in terms of exposure or air kerma. Four ionization chambers had 60Co-based calibration in terms of absorbed dose-to-water. Two chambers were calibrated in a 60Co beam at the NIST both in terms of air kerma and absorbed dose-to-water to provide a comparison of ionization chambers with different calibrations. RESULTS: The intercomparison showed that use of the ICRU report 59 protocol would result in absorbed doses being delivered to patients at their participating institutions to within +/-0.9% (one standard deviation). The maximum difference between doses determined by the participants was found to be 2.9%. Differences between proton doses derived from the measurements with ionization chambers with N(K)-, or N(W) - calibration type depended on chamber type. CONCLUSIONS: Using ionization chambers with 60Co calibration factors traceable to standard laboratories and the ICRU report 59 protocol, a distribution of stated proton absorbed dose is achieved with a difference less than 3%. The ICRU protocol should be adopted for clinical proton beam calibration. A comparison of proton doses derived from measurements with different chambers indicates that the difference in results cannot be explained only by differences in 60Co calibration factors.

Effectiveness of protons and argon ions in initiating lipid peroxidation in low-density lipoproteins.

In this study, human low-density lipoprotein (LDL) vesicles were irradiated with 73 MeV protons (LET of 1 keV/microm) and 11.4 MeV/nucleon argon ions (LET of 1.52 MeV/pm) and the effectiveness of charged particles in initiating peroxidation of LDLs was investigated. The LDL suspension (6 g/l) was exposed to protons and to argon ions in a dose range of 24 Gy to 2.4 kGy. Irradiations were carried out at the synchrocyclotron at the CPO and at the UNILAC of the GSI. After irradiation three chemical assays were used to study the progression of peroxidation of LDLs: the formation of conjugated dienes, the formation of thiobarbituric acid-reactive substances (TBARS) and the increase in the relative electrophoretic mobility of the LDLs. The results were compared with those obtained after gamma irradiation. For protons the yields of the peroxidation products were 10 times lower than after gamma irradiation. However, for doses below 200 Gy, protons appeared to be more effective than gamma rays in damaging the protein moiety, as deduced from the observed increase in the relative electrophoretic mobility of the LDLs. The irradiation with argon ions led to a negligible formation of peroxidation products, but an increase in the relative electrophoretic mobility of the LDLs was observed. The results are indicative of a lower yield of lipid peroxidation after irradiation with high-LET particles. In contrast, protons and argon ions appear to be more effective in inducing bulk protein and phospholipid damage than gamma rays.

A model for the lateral penumbra in water of a 200-MeV proton beam devoted to clinical applications.

An experimental approach for modeling the lateral penumbra of a proton beam has been investigated. Measurements were made with a silicon diode in a water tank. Several geometrical configurations (phantom position, collimator-to-surface distance, collimator diameter, bolus thickness, air gap, etc.) and beam characteristics (range, modulation, etc.) have been studied. The results show that the lateral penumbra is almost independent of the beam modulation and the diameter of the collimator. The use of scaled variables for depth and penumbra allows us to represent the increase in penumbra with depth for any configuration with a second order polynomial function, provided that the penumbra at the entrance of the medium and at the depth of the range are known.