3D Dosimetry Based on LiMgPO4 OSL Silicone Foils: Facilitating the Verification of Eye-Ball Cancer Proton Radiotherapy.

A direct verification of the three-dimensional (3D) proton clinical treatment plan prepared for tumor in the eyeball, using the Eclipse Ocular Proton Planning system (by Varian Medical Systems), has been presented. To achieve this, a prototype of the innovative two-dimensional (2D) circular silicone foils, made of a polymer with the embedded optically stimulated luminescence (OSL) material in powder form (LiMgPO4), and a self-developed optical imaging system, consisting of an illuminating light source and a high-sensitive CCD camera has been applied. A specially designed lifelike eyeball phantom has been used, constructed from 40 flat sheet LMP-based silicone foils stacked and placed together behind a spherical phantom made by polystyrene, all to reflect the curvature of the real eyeball. Two-dimensional OSL signals were captured and further analyzed from each single silicone foil after irradiation using a dedicated patient collimator and a 58.8 MeV modulated proton beam. The reconstructed 3D proton depth dose distribution matches very well with the clinical treatment plan, allowing for the consideration of the new OSL system for further 3D dosimetry applications within the proton radiotherapy area.

Harmonization of proton treatment planning for head and neck cancer using pencil beam scanning: first report of the IPACS collaboration group.

Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer.Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created.Results: For CTV1, the average Dmedian was 59.3 ± 2.4 Gy(RBE) for protons and 58.8 ± 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average Dmedian was 71.2 ± 1.0 Gy(RBE) for protons and 70.6 ± 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D2% for the spinal cord was 25.1 ± 8.5 Gy(RBE) for protons and 47.6 ± 1.4 Gy(RBE) for VMAT. The average D2% for chiasm was 46.5 ± 4.4 Gy(RBE) for protons and 50.8 ± 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams.Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.

Relative biological effectiveness of the 60-MeV therapeutic proton beam at the Institute of Nuclear Physics (IFJ PAN) in Kraków, Poland.

The aim of the study was to determine the relative biological effectiveness (RBE) of a 60-MeV proton radiotherapy beam at the Institute of Nuclear Physics, Polish Academy of Sciences (IFJ PAN) in Kraków, the first one to operate in Poland. RBE was assessed at the surviving fractions (SFs) of 0.01, 0.1, and 0.37, for normal human fibroblasts from three cancer patients. The cells were irradiated near the Bragg peak of the pristine beam and at three depths within a 28.4-mm spread-out Bragg peak (SOBP). Reference radiation was provided by 6-MV X-rays. The mean RBE value at SF = 0.01 for fibroblasts irradiated near the Bragg peak of pristine beam ranged between 1.06 and 1.15. The mean RBE values at SF = 0.01 for these cells exposed at depths of 2, 15, and 27 mm of the SOBP ranged between 0.95-1.00, 0.97-1.02, and 1.05-1.11, respectively. A trend was observed for RBE values to increase with survival level and with depth in the SOBP: at SF = 0.37 and at the depth of 27 mm, RBE values attained their maximum (1.19-1.24). The RBE values estimated at SF = 0.01 using normal human fibroblasts for the 60-MeV proton radiotherapy beam at the IFJ PAN in Kraków are close to values of 1.0 and 1.1, used in clinical practice.

Proteomic analysis of proton beam irradiated human melanoma cells.

Proton beam irradiation is a form of advanced radiotherapy providing superior distributions of a low LET radiation dose relative to that of photon therapy for the treatment of cancer. Even though this clinical treatment has been developing for several decades, the proton radiobiology critical to the optimization of proton radiotherapy is far from being understood. Proteomic changes were analyzed in human melanoma cells treated with a sublethal dose (3 Gy) of proton beam irradiation. The results were compared with untreated cells. Two-dimensional electrophoresis was performed with mass spectrometry to identify the proteins. At the dose of 3 Gy a minimal slowdown in proliferation rate was seen, as well as some DNA damage. After allowing time for damage repair, the proteomic analysis was performed. In total 17 protein levels were found to significantly (more than 1.5 times) change: 4 downregulated and 13 upregulated. Functionally, they represent four categories: (i) DNA repair and RNA regulation (VCP, MVP, STRAP, FAB-2, Lamine A/C, GAPDH), (ii) cell survival and stress response (STRAP, MCM7, Annexin 7, MVP, Caprin-1, PDCD6, VCP, HSP70), (iii) cell metabolism (TIM, GAPDH, VCP), and (iv) cytoskeleton and motility (Moesin, Actinin 4, FAB-2, Vimentin, Annexin 7, Lamine A/C, Lamine B). A substantial decrease (2.3 x) was seen in the level of vimentin, a marker of epithelial to mesenchymal transition and the metastatic properties of melanoma.

Metastasis inhibition after proton beam, ß- and γ-irradiation of melanoma growing in the hamster eye.

Standard ocular tumor treatment includes brachytherapy, as well as proton therapy, particularly for large melanoma tumors. However, the effects of different radiation types on the metastatic spread is not clear. We aimed at comparing ruthenium ((106)Ru, emitting ß electrons) and iodine ((125)I, γ-radiation) brachytherapy and proton beam therapy of melanoma implanted into the hamster eye on development of spontaneous lung metastases. Tumors of Bomirski Hamster Melanoma (BHM) implanted into the anterior chamber of the hamster eye grew aggressively and completely filled the anterior chamber within 8-10 days. Metastases, mainly in the lung, were found in 100% of untreated animals 30 days after enucleation. Tumors were irradiated at a dose of 3-10 Gy with a (106)Ru plaque and at a dose of 6-14 Gy using a (125)I plaque. The protons were accelerated using the AIC-144 isochronous cyclotron operating at 60 MeV. BHM tumors located in the anterior chamber of the eye were irradiated with 10 Gy, for the depth of 3.88 mm. All radiation types caused inhibition of tumor growth by about 10 days. An increase in the number of metastases was observed for 3 Gy of ß-irradiation, whereas at 10 Gy an inhibition of metastasis was found. γ-radiation reduced the metastatic mass at all applied doses, and proton beam therapy at 10 Gy also inhibited the metastastic spread. These results are discussed in the context of recent clinical and molecular data on radiation effects on metastasis.

Proton radiotherapy facility for ocular tumors at the IFJ PAN in Kraków Poland.

The proton radiotherapy facility for the eye melanoma treatment is under development at the Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences (IFJ PAN) in Krakow. The facility uses protons, accelerated by the AIC-144 isochronous cyclotron up to the energy of 60 MeV. The infrastructure and all necessary equipment have been already installed. The paper describes the present status of the facility, gives results of the preliminary beam measurements and shows future perspectives.