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Purpose: Craniospinal irradiation (CSI) has greatly increased survival rates for patients with a diagnosis of medulloblastoma and other primitive neuroectodermal tumors. However, as it includes exposure of a large volume of healthy tissue to unwanted doses, there is a strong concern about the complications of the treatment, especially for the children. To estimate the risk of second cancers and other unwanted effects, out-of-field dose assessment is necessary. The purpose of this study is to evaluate and compare out-of-field doses in pediatric CSI treatment using conventional and advanced photon radiotherapy (RT) and advanced proton therapy. To our knowledge, it is the first such comparison based on in-phantom measurements. Additionally, for out-of-field doses during photon RT in this and other studies, comparisons were made using analytical modeling. Methods: In order to describe the out-of-field doses absorbed in a pediatric patient during actual clinical treatment, an anthropomorphic phantom which mimics the 10-year-old child was used. Photon 3D-conformal radiotherapy (3D-CRT) and two advanced, highly conformal techniques: photon volumetric modulated arc therapy (VMAT) and active pencil beam scanning (PBS) proton radiotherapy were used for CSI treatment. Radiophotoluminescent (RPL) and poly-allyl-diglycol-carbonate (PADC) nuclear track detectors were used for photon and neutron dosimetry in the phantom, respectively. Out-of-field doses from neutrons were expressed in terms of dose equivalent. A two-Gaussian model was implemented for out-of-field doses during photon RT. Results: The mean VMAT photon doses per target dose to all organs in this study were under 50% of the target dose (i.e., < 500 mGy/Gy), while the mean 3D-CRT photon dose to oesophagus, gall bladder and thyroid, exceeded that value. However, for 3D-CRT, better sparing was achieved for eyes and lungs. The mean PBS photon doses for all organs were up to 3 orders of magnitude lower compared to VMAT and 3D-CRT and exceeded 10 mGy/Gy only for the oesophagus, intestine and lungs. The mean neutron dose equivalent during PBS for 8 organs of interest (thyroid, breasts, lungs, liver, stomach, gall bladder, bladder, prostate) ranged from 1.2 mSv/Gy for bladder to 23.1 mSv/Gy for breasts. Comparison of out-of-field doses in this and other phantom studies found in the literature showed that a simple and fast two-Gaussian model for out-of-field doses as a function of distance from the field edge can be applied in a CSI using photon RT techniques. Conclusions: PBS is the most promising technique for out-of-field dose reduction in comparison to photon techniques. Among photon techniques, VMAT is a preferred choice for most of out-of-field organs and especially for the thyroid, while doses for eyes, breasts and lungs, are lower for 3D-CRT. For organs outside the field edge, a simple analytical model can be helpful for clinicians involved in treatment planning using photon RT but also for retrospective data analysis for cancer risk estimates and epidemiology in general.

Nano-sized radiosensitizers can be used to increase the effectiveness of radiation-based anticancer therapies. In this study, bimetallic, ~30 nm palladium-platinum nanoparticles (PdPt NPs) with different nanostructures (random nano-alloy NPs and ordered core-shell NPs) were prepared. Scanning transmission electron microscopy (STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS), zeta potential measurements, and nanoparticle tracking analysis (NTA) were used to provide the physicochemical characteristics of PdPt NPs. Then, PdPt NPs were added to the cultures of colon cancer cells and normal colon epithelium cells in individually established non-toxic concentrations and irradiated with the non-harmful dose of X-rays/protons. Cell viability before and after PdPt NPs-(non) assisted X-ray/proton irradiation was evaluated by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Flow cytometry was used to assess cell apoptosis. The results showed that PdPt NPs significantly enhanced the effect of irradiation on cancer cells. It was noticed that nano-alloy PdPt NPs possess better radiosensitizing properties compared to PtPd core-shell NPs, and the combined effect against cancer cells was c.a. 10% stronger for X-ray than for proton irradiation. Thus, the radio-enhancing features of differently structured PdPt NPs indicate their potential application for the improvement of the effectiveness of radiation-based anticancer therapies.

In this paper, we investigate the use of a positron emission tomography (PET) system to monitor the proton therapy. The monitoring procedure is based on the comparison between the ${ \beta }+$ activity generated in the irradiated volume during the treatment, with the ${ \beta }+$ activity distribution obtained with Monte Carlo (MC) simulation. The dedicated PET system is a dual head detection system; each head is composed of nine scintillating LYSO crystal matrices read out independently with a custom modularized acquisition system. Our experimental data were acquired at the Cyclotron Centre Bronowice, Institute Nuclear Physics in Krakow, Poland, and were simulated with the FLUKA MC code. Homogeneous and heterogeneous plastic phantoms were irradiated with monoenergetic 130 MeV protons. The capabilities of our PET system to distinguish different irradiated materials were investigated, and the proton pencil-beams were used as probes. Our focus was to analyze the activity width and the total activity event number in several cases. Irradiations were performed using either single pencil-beams one at a time, or two pencil-beams during the same data taking. The comparison of 1-D activity profile for experimental data and MC simulation were always in good agreement showing that, the treatment quality assessment in proton therapy can be based on ${ \beta }+$ activity measurements.

Enhancing the effectiveness of colorectal cancer treatment is highly desirable. Radiation-based anticancer therapy&mdash, such as proton therapy (PT)&mdash, can be used to shrink tumors before subsequent surgical intervention, therefore, improving the effectiveness of this treatment is crucial. The addition of noble metal nanoparticles (NPs), acting as radiosensitizers, increases the PT therapeutic effect. Thus, in this paper, the effect of novel, gold&ndash, platinum nanocauliflowers (AuPt NCs) on PT efficiency is determined. For this purpose, crystalline, 66-nm fancy shaped, bimetallic AuPt NCs were synthesized using green chemistry method. Then, physicochemical characterization of the obtained AuPt NCs by transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersive X-ray spectroscopy (EDS), and UV-Vis spectra measurements was carried out. Fully characterized AuPt NCs were placed into a cell culture of colon cancer cell lines (HCT116, SW480, and SW620) and a normal colon cell line (FHC) and subsequently subjected to proton irradiation with a total dose of 15 Gy. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) test, performed after 18-h incubation of the irradiated cell culture with AuPt NCs, showed a significant reduction in cancer cell viability compared to normal cells. Thus, the radio-enhancing features of AuPt NCs indicate their potential application for the improvement in effectiveness of anticancer proton therapy.

Purpose To evaluate the effect on charge collection in the ionization chamber (IC) in proton pencil beam scanning (PBS), where the local dose-rate may exceed the dose rates encountered in conventional MV therapy by up to 3 orders of magnitude. Methods We measured values of the ion recombination (ks) and polarity (kpol) correction factors in water, for a plane–parallel Markus TM23343 IC, using the cyclotron-based Proteus-235 therapy system with an active proton PBS of energies 30-230 MeV. Values of ks were determined from extrapolation of the saturation curve and the Two-Voltage Method (TVM), for planar fields. We compared our experimental results with those obtained from theoretical calculations. The PBS dose rates were estimated by combining direct IC measurements with results of simulations performed using the FLUKA MC code. Values of ks were also determined by the TVM for uniformly irradiated volumes over different ranges and modulation depths of the proton PBS, with or without range shifter. Results By measuring charge collection efficiency versus applied IC voltage, we confirmed that, with respect to ion recombination, our PBS proton beam represents a continuous beam. For a given chamber parameter, e.g. nominal voltage, the value of ks depends on the energy and the dose rate of the proton PBS, reaching c. 0.5% for the TVM, at the dose rate of 13.4 Gy/s. For uniformly irradiated regular volumes the ks value was significantly smaller, within 0.2% or 0.3% for irradiations with or without range shifter, respectively. Within measurement uncertainty, the average value of kpol, for the Markus TM23343 IC, was close to unity over the whole investigated range of clinical proton beam energies. Conclusion While no polarity effect was observed for the Markus TM23343 IC in our pencil scanning proton beam system, the effect of volume recombination cannot be ignored. This article is protected by copyright. All rights reserved.

Proton radiotherapy requires precise knowledge of the volumetric dose distribution. In proton beam delivery systems, based on narrow pencil beams, a contribution from small doses in low-intensity regions, consisting mainly of scattered protons, may have not negligible influence on total dose delivered to patient. Insufficient information about dose profile can cause underestimation of dose and potential delivery of inflated dose during hadrontherapy treatment. Presented work aims to verify applicability of diamond detectors, produced by Chemical Vapor Deposition method, for therapeutic proton beam profilometry at large fields. This requires the capability of measuring the core of the beam intensity profile (wide dynamic range) as well as its lateral spread (very high sensitivity) with a single device.

Gafchromic EBT3 films are applied in proton radiotherapy for 2D dose mapping because they demonstrate spatial resolution well below 1 mm. However, the film response must be corrected in order to reach the accuracy of dose measurements required for the clinical use. The in-house developed AnalyseGafchromic software allows to analyze and correct the measured response using triple channel dose calibration, statistical scan-to-scan fluctuations as well as experimentally determined dose and LET dependence. Finally, the optimized protocol for evaluation of response of Gafchromic EBT3 films was applied to determine 30 × 40 cm2 dose profiles of the scanning therapy unit at the Cyclotron Centre Bronowice, CCB in Krakow, Poland.

Purpose Radiotherapy is one of essential methods of treatment for medulloblastoma – a primitive neuroectodermal tumor growing in cerebellum. Proton craniospinal irradiations are recommended because of sparing of intermediate-to-low-dose to healthy tissues and reduction of side effects, including secondary cancers. Two laterally opposed cranial fields and several posterior spine fields are usually used for irradiation in medulloblastoma as well in conventional radiotherapy as in proton one. In this field configuration a potential dose inhomogeneity at the field junctions can appear. We have investigated the dose homogeneity in the junction areas using Gafchromic films and alanine detectors. Methods A clinical plan for an anthropomorphic phantom of a 5-year-old child have been prepared. There were two opposed lateral brain fields and 2 posterior spine fields. Therefore two field junctions were investigated. Then the phantom was equipped with alanine detectors and Gafchromic films at chosen positions mainly in junction areas and irradiated. Alanine doses were assessed using proton beam calibration (5–20 Gy). The calibration curve was designed upon developed protocol based on ISO/WD 15566.1 document. Alanine doses were then compared with doses in the treatment plan. Gafchromic films were analyzed using in-house developed AnalyseGafchromic software allowing to calculate dose based on triple channel calibration and apply corrections on scanner spatial inhomogeneity and scan-to-scan instability. Finally, the measured 2D dose distributions were compared with dose planes exported from TPS (Treatment Planning System) using gamma index analysis. Results The compatibility of alanine doses and TPS doses was at the level of 1%. For all the dose planes measured with Gafchromic passing rates of gamma index test (3%/3 mm) was higher than 95%. Conclusions Patients with medulloblastoma may benefit greatly from proton radiotherapy, however the main condition for a successful treatment is a careful and accurate field junctions, where all the uncertainties of beam model in TPS, CT calibration curve and Patient Positioning may affect the dose delivered to the patient. We have proved that Gafchromic films and alanine detectors can be successfully used for complex system check for ability to irradiate the target with sufficient accuracy.