[Report on current status of Hungarian radiotherapy]. / A magyar sugárterápia jelenlegi helyzetének bemutatása.

The purpose of the study is to report the status of Hungarian radiotherapy (RT). In the 13 centers 84 radiation oncologists, 19 residents, 66 physicists and 231 radiotherapy technologists work, and 40 megavoltage units (38 linear accelerators, 2 cobalt units) are in use. HDR afterloader is available in all and CT-simulator in all but one centers. In 2017 33,024 patients received RT, 22,236 were irradiated with MV beams, 1,406 with BT and 9,382 with orthovoltage X-ray. Main indications for BT were gynecological tumors (75%), HDR prostate implants were performed in 3 centers. Due to the recent infrastructural developments the number of patients receiving modern RT increased, but in order to fulfil the international recommendations additional linear accelerators have to be installed along with the replacement of the out of date equipment. From professional point of view further developments are warranted in Budapest.

[Initial experience with image-guided and intensity-modulated postoperative radiotherapy of gynecological cancer]. / Nõgyógyászati tumorok képvezérelt, intenzitásmodulált adjuváns sugárkezelésével szerzett kezdeti tapasztalataink.

Our goal was to determine the extent of the CTV-PTV margin. Accuracy of patient setup was checked with daily CBCT. Two radiation oncologists performed the image matching independently. The CTV-PTV margin was calculated with the van Herk formula. The treatment plans were created with the Varian Eclipse v11 planning system, and the treatments were carried out with a Varian TrueBeam accelerator by using RapidArc technique with two full arcs. Dose constraints on the target volume and organs at risk recommended by international bodies were applied. Conformity number (CN) for PTV, V45 and V50 for organs at risk were used to assess and compare the treatment plans of RapidArc and 3D-KRT (conformal radiotherapy) techniques. The average CTV-PTV margins with or without IGRT were 0.67 cm vs. 1.53 cm, 0.66 cm vs. 1.25 cm and 0.34 cm vs. 0.98 cm in vertical, longitudinal and lateral directions, respectively. In case of daily on-line CBCT verification 0.5 cm margin can be used.

[Investigating the clinical applicability of EBT2 self-developing films]. / Az EBT2 önhívó filmek sugárterápiás klinikai alkalmazhatóságának vizsgálata.

The purpose of the study was to investigate the physical properties of the EBT2 radiochromic films and define the conditions of its clinical applicability. We irradiated the films with different treatment techniques 3D conformal (3DCRT), intensity-modulated (IMRT) and stereotactic body radiotherapy with arc therapy (SBRT), and then compared the data with the dose distribution exported from the treatment planning system (Eclipse). Two film analysis softwares were investigated for the comparison: PTW Mephysto and FilmQA Pro. The comparisons of dose distributions were performed with gamma analysis, and the gamma criterion was 3%, 3mm, and 2%, 2mm. The gamma analysis results by the two programs were the following, (PTW/FilmQA Pro) with 3%, 3mm gamma criterion: 3DCRT (95,5/100%), IMRT (97/99,9%), SBRT (99,7/100%). In case of 2%, 2mm the results were: 3DCRT (87,1/98,9%), IMRT (92/98,5%), SBRT (96,7/97,9%). Based on the results it can be stated that during proper use, the features of the scanner do not affect the results. Both evaluation softwares are suitable for calibrating and evaluating films, moreover, performing the gamma analysis. The EBT2 film is suitable for the two-dimensional controlling of radiation therapy plans.

Evaluation of ¹77Lu-EDTMP in Dogs with Spontaneous Tumor Involving Bone: Pharmacokinetics, Dosimetry and Therapeutic Efficacy.

177Lu-EDTMP is currently being investigated as a potential agent for providing palliative care to the patients suffering from bone pain due to metastatic skeletal carcinoma. The present article describes the evaluation of 177Lu-EDTMP complex in four different canine patients with different types of primary and metastatic skeletal lesions with respect to its pharmacokinetic properties, dosimetry and therapeutic efficacy. The dogs were treated with a dose of ~44.4 MBq (1.2 mCi) per kg body weight of 177Lu-EDTMP, synthesized in-house with high radiochemical purity (98.8 ± 0.4 %) and excellent in vitro stability. The radiopharmaceutical showed favourable pharmacokinetic properties, such as, preferential accumulation at skeletal lesion sites and fast clearance from blood and other non-target organs through urinary route. The administered dose of the radiopharmacutical showed excellent therapeutic efficacy in case of a dog suffering from skeletal metastasis originating from primary tumor elsewhere. On the other hand, two of the remaining three patients with primary bone cancer showed stable disease intially with palliative effect. The fourth patient having metal implant induced osteosarcoma with severe limb oedema did not show any response to the treatment.

[Status report of Hungarian radiotherapy based on treatment data, available infrastucture, and human resources]. / A magyar sugárterápia helyzete a betegellátási adatok, a rendelkezésre álló infrastruktúra és emberi eroforrás tükrében.

The purpose of the study is to report the status of Hungarian radiotherapy (RT) based on the assessment of treatment data in years 2012 to 2014, available infrastructure, and RT staffing. Between December 2014 and January 2015, a RT questionnaire including 3 parts (1. treatment data; 2. infrastructure; 3. staffing) was sent out to all Hungarian RT centers (n=12). All RT centers responded to all questions of the survey. 1. Treatment data: In 2014, 33,162 patients were treated with RT: 31,678 (95.5%) with teletherapy, and 1484 (4.5%) with brachytherapy (BT). Between 2012 and 2014, the number of patients treated with radiotherapy increased with 6.6%, but the number of BT patients decreased by 11%. Forty-two percent of all patients were treated in the two centers of the capital: 9235 patients (28%) at the National Institute of Oncology (NIO), and 4812 (14%) at the Municipial Oncoradiology Center (MOC). Out of the patients treated on megavoltage RT units (n=22,239), only 901 (4%) were treated with intensity-modulated RT (IMRT), and 2018 (9%) with image-guided RT (IGRT). In 2014, 52% of all BT treatments were performed in Budapest: NIO - 539 patients (36%); MOC - 239 patients (16%); and BT was not available in 3 RT centers. Prostate I-125 seed implants and interstitial breast BT was utilized in one, prostate HDR BT in two, and head&neck implants in three centers. 2. Infrastructure: Including ongoing development projects funded by the European Union, by the end of year 2015, 39 megavoltage teletherapy units, and 12 HDR BT units will be in use in 13 available Hungarian RT centers. 3. Staffing: Actually, 92 radiation oncologists (RO), 29 RT residents, 61 medical physicists, and 229 radiation therapy technologists are working in 12 RT centers. There are 23 vacant positions (including 11 RO positions) available at the Hungarian RT centers. According to the professional minimal requirements and WHO guidelines, the implementation of 11 new linear accelerators, and 1 BT units are needed in Hungary. Further resources for the development and upgrade of RT infrastructure and capacity should be allocated to RT centers in Budapest. Brachytherapy and modern teletherapy (e.g. IMRT and IGRT) are underutilized in Hungary compared to other European countries. Implementation of continuous education and practical training programs in leading Hungarian and international RT centers are suggested in an effort to a wider implementation of modern RT techniques in Hungarian RT centers.

Thulium-170-labeled microparticles for local radiotherapy: preliminary studies.

The present article describes the preparation, characterization, and biological evaluation of Thulium-170 ((170)Tm) [T1/2 = 128.4 days; Eßmax = 968 keV; Eγ = 84 keV (3.26%)] labeled tin oxide microparticles for its possible use in radiation synovectomy (RSV) of medium-sized joints. (170)Tm was produced by irradiation of natural thulium oxide target. 170Tm-labeled microparticles were synthesized with high yield and radionuclidic purity (> 99%) along with excellent in vitro stability by following a simple process. Particle sizes and morphology of the radiolabeled particles were examined by light microscope, dynamic light scattering, and transmission electron microscope and found to be of stable spherical morphology within the range of 1.4-3.2 µm. The preparation was injected into the knee joints of healthy Beagle dogs intraarticularly for biological studies. Serial whole-body and regional images were taken by single-photon-emission computed tomography (SPECT) and SPECT-CT cameras up to 9 months postadministration, which showed very low leakage (< 8% of I.D.) of the instilled particles. The majority of leaked radiocolloid particles were found in inguinal lymph nodes during the 9 months of follow-up. All the animals tolerated the treatment well; the compound did not show any possible radiotoxicological effect. These preliminary studies showed that 170Tm-labeled microparticles could be a promising nontoxic and effective radiopharmaceutical for RSV applications or later local antitumor therapy.

Verification of quality parameters for portal images in radiotherapy.

BACKGROUND: The purpose of the study was to verify different values of quality parameters of portal images in radiotherapy. MATERIALS AND METHODS: We investigated image qualities of different field verification systems. Four EPIDs (Siemens OptiVue500aSi(®), Siemens BeamView Plus(®), Elekta iView(®) and Varian PortalVision™) were investigated with the PTW EPID QC PHANTOM(®) and compared with two portal film systems (Kodak X-OMAT(®) cassette with Kodak X-OMAT V(®) film and Kodak EC-L Lightweight(®) cassette with Kodak Portal Localisation ReadyPack(®) film). RESULTS: A comparison of the f50 and f25 values of the modulation transfer functions (MTFs) belonging to each of the systems revealed that the amorphous silicon EPIDs provided a slightly better high contrast resolution than the Kodak Portal Localisation ReadyPack(®) film with the EC-L Lightweight(®) cassette. The Kodak X-OMAT V(®) film gave a poor low contrast resolution: from the existing 27 holes only 9 were detectable. CONCLUSIONS: On the base of physical characteristics, measured in this work, the authors suggest the use of amorphous-silicon EPIDs producing the best image quality. Parameters of the EPIDs with scanning liquid ionisation chamber (SLIC) were very stable. The disadvantage of older versions of EPIDs like SLIC and VEPID is a poor DICOM implementation, and the modulation transfer function (MTF) values (f50 and f25) are less than that of aSi detectors.

Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent.

INTRODUCTION: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low beta- energy, (177)Lu [T(1/2)=6.73 days, E(beta max)=497 keV, E(gamma)=113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of (177)Lu-EDTMP to collect preclinical data for starting human clinical trials. METHODS: (177)Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of (177)Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. RESULTS: (177)Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. CONCLUSION: The protracted effective half-life of (177)Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing (177)Lu does not alter its biological behaviour as a specific bone-seeking tracer. Species-specific pharmacokinetic behavior differences were observed. Toxicity studies in dogs did not show any biological adverse effects. The studies demonstrate that (177)Lu-EDTMP is a promising radiopharmaceutical that can be further evaluated for establishing as a radiopharmaceutical for human use.

[Quality control of computed tomography scanners from the viewpoint of radiotherapy planning in Hungary]. / Computertomográfiás készülékek minôségellenôrzése a besugárzástervezés szempontjai alapján (Magyarországi helyzetelemzés).

The aim of this publication is to review the requirements necessary for using computed tomography (CT) for radiotherapy treatment planning. The equipments were tested with different CT phantoms. The authors made several measurements for checking the CT number, the quality and the mechanical parameters of CT tables. The CT numbers measured on the equipments of different manufacturers were in quite good agreement with the IAEA requirements. The geometric distortions of CT images are negligible, while the mechanical parameters of CT tables show considerable variety. A quality assurance - quality control protocol is recommended to implement in a safe workflow.

Concomitant radiochemotherapy of cervical cancer: is it justified to reduce the dosage of cisplatin?

PURPOSE: To review the experiences regarding the therapeutic response and side effects of concomitant radiochemotherapy of cervical cancer carried out with different cisplatin doses. PATIENTS AND METHODS: At the Municipal Center for Oncoradiology, Budapest, Hungary, 92 patients with cervical cancer were treated with concomitant radiochemotherapy in the period between July 2002 and March 2007. The total dose of high-energy external radiation (megavoltage) treatment was 50.4 Gy with a fraction dose of 1.8 Gy on the small pelvis. Before irradiation, cisplatin 40 mg/m(2), 30 mg/m(2), or 20 mg/m(2) was administered once a week. RESULTS: In 17 cases, the cisplatin dose was 30 mg/m(2); during radiochemotherapy the number of cisplatin treatments was equal to or more than four in 14 patients (82%). After administering 40 mg/m(2) cisplatin to 64 patients, chemotherapy in four or more treatments could only be applied in 37 cases (58%). Eleven patients received cisplatin at the dose of 20 mg/m(2); in ten (91%) of them, the number of treatments was four or more. By comparing the side effects, it can be stated that hematologic side effects (mostly leukopenia) grade 3 occurred in 12% of the patients receiving cisplatin 30 mg/m(2), and grade G3-4 in 16% of the 40-mg/m(2) cisplatin group. For cisplatin 30 mg/m(2), 82% of hematologic side effects were in the G1 range. There was no significant difference between the 20- and 30-mg/m(2) regimens. As for the gastrointestinal toxicity, similar side effects grade 1 were detected, which occurred in 58% and 38% of the patients receiving 30 mg/m(2) and 40 mg/m(2), respectively. CONCLUSION: On the basis of a detailed analysis, the correlation between the number of treatments, the therapeutic and the side effects could be verified. In the course of dose reduction, there was no significant difference when comparing the results of therapy, however, the quality of life was better if cisplatin 30 mg/m(2) was administered instead of 40 mg/m(2). If cisplatin 20 mg/m(2) was given, the results were significantly worse. On the basis of the own results, it can be stated that the optimal weekly dose of cisplatin is 30 mg/m(2).

Quality Control of Portal Imaging with PTW EPID QC PHANTOM.

PURPOSE: Quality assurance (QA) and quality control (QC) of different electronic portal imaging devices (EPID) and portal images with the PTW EPID QC PHANTOM. MATERIAL AND METHODS: Characteristic properties of images of different file formats were measured on Siemens OptiVue500aSi, Siemens BeamView Plus, Elekta iView, and Varian PortalVision and analyzed with the epidSoft 2.0 program in four radiation therapy centers. The portal images were taken with Kodak X-OMAT V and the Kodak Portal Localisation ReadyPack films and evaluated with the same program. RESULTS: The optimal exposition both for EPIDs and portal films of different kind was determined. For double exposition, the 2+1 MU values can be recommended in the case of Siemens OptiVue500aSi Elekta iView and Kodak Portal Localisation ReadyPack films, while for Siemens BeamView Plus, Varian PortalVision and Kodak X-OMAT V film 7+7 MU is recommended. CONCLUSION: The PTW EPID QC PHANTOM can be used not only for amorphous silicon EPIDs but also for images taken with a video-based system or by using an ionization chamber matrix or for portal film. For analysis of QC tests, a standardized format (used at the acceptance test) should be applied, as the results are dependent on the file format used.

Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs.

The purpose of this study was to determine the absorption, distribution and excretion of (99m)technetium-labeled, high-molecular-weight hyaluronan (((99m)Tc-HA) and (99m)technetium pertechnetate ((99m)Tc-P) after single dose, oral administration to Wistar rats and Beagle dogs. A pilot study utilized (99m)Tc-HA alone, and a second confirmatory study compared uptake of labeled (99m)Tc-HA with (99m)Tc-P. Urinary and fecal excretion after (99m)Tc-HA ingestion by rats showed 86.7-95.6% of radioactivity was recovered, almost all in feces. All tissues examined showed incorporation of radioactivity from (99m)Tc-HA starting at 15 min and persisting for 48 h, in a pattern significantly different from (99m)Tc-P. Whole-body scintigraphs and close-ups of the ventral chest region showed nonalimentary radioactivity from (99m)Tc-HA concentrated in joints, vertebrae and salivary glands four hours after administration. Autoradiography of skin, bone and joint tissue pieces after 24 h showed incorporation of radioactivity from (99m)Tc-HA, but not from (99m)Tc-P. Conversely, absorption, distribution and excretion of (99m)Tc was completely different from (99m)Tc-HA, showing an expected pattern of rapid absorption and excretion in urine, with accumulation in thyroid glands, stomach, kidney and bladder. This report presents the first evidence for uptake and distribution to connective tissues of orally administered, high-molecular-weight HA.

Interaction of FliS flagellar chaperone with flagellin.

Premature polymerization of flagellin (FliC), the main component of flagellar filaments, is prevented by the FliS chaperone in the cytosol. Interaction of FliS with flagellin was characterized by isothermal titration calorimetry producing an association constant of 1.9x10(7) M-1 and a binding stoichiometry of 1:1. Experiments with truncated FliC fragments demonstrated that the C-terminal disordered region of flagellin is essential for FliS binding. As revealed by thermal unfolding experiments, FliS does not function as an antifolding factor keeping flagellin in a secretion-competent conformation. Instead, FliS binding facilitates the formation of alpha-helical secondary structure in the chaperone binding region of flagellin.

Preliminary studies with 188rhenium-tin colloid for radiation synovectomy: preparation, size determination, in-vivo distribution, effect and dosimetry studies.

BACKGROUND: Generator-produced beta-emitting radionuclides such as (188)Re are gaining in importance for radiosynoviorthesis because of their availability on a regular basis. MATERIAL AND METHODS: We prepared a (188)Re-tin colloid in a reaction carried out either at 100 degrees C or at room temperature (RT). The size of the colloid particles was measured with a laser lightscattering method, and their biodistribution, dosimetric aspects and therapeutic effects were studied in an antigen-induced arthritis (AIA) model in rabbits. (188)Re-tin colloid solution was injected intra-articularly into the knee joints of rabbits with AIA and imaging studies were performed. Blood samples were collected post injection for estimation of the blood residence time. We also injected 2 intact rabbits in the same manner with (188)Re perrhenate solution in order to observe its effects and distribution in the body. All the treated rabbit knees were subjected to histopathology. RESULTS: The colloid particle size distribution was different after preparation at the different reaction temperatures, with a more suitable mean of 4.53 micro m in the RT preparation. The dose delivered to the synovial surface was between 3.51 and 4.21 Gy and that to the bone surface was between 0.70 and 0.84 Gy. Histopathologic examination revealed the development of fibrous connective tissue in the AIA knees 4 weeks after treatment, but not in the control group. CONCLUSIONS: The (188)Re-tin colloid preparation used in this study was suitable for radiation synovectomy application. It requires modifications in the preparation protocol so as to increase the labeling efficiency in correlation with an appropriate particle size.

Sentinel lymph node detection in canine oncological patients.

BACKGROUND: Sentinel lymph node detection was investigated in dogs with spontaneously occurring tumours. MATERIAL AND METHODS: In this pilot study, 24 client-owned spontaneously tumorous dogs presented for sentinel lymph node detection. A multiple method was used with a nuclear medicine technique (injection of 99mTc human serum albumin colloid) with scintigraphy and intraoperative guidance, and blue dye injection. RESULTS: Of the 35 lymph nodes histologically demonstrated to contain metastases, 34 (97%) were found by radioguided surgery, which means that one would have been missed in the intraoperative localisation process; 31 nodes (89%) were clearly visualised in the gamma camera images; only 27 (77%) were blue-stained by vital dye; a mere 8 lymph nodes (23%) were enlarged and therefore easily detectable by palpation. CONCLUSIONS: Data obtained from the harmless application of the sentinel node concept are useful for the radiopharmaceutist. The sentinel lymph node concept is well applicable in the veterinary clinic.