Gamma camera calibrations for the Italian multicentre study for lesion dosimetry in 223Ra therapy of bone metastases.

PURPOSE: The aim was to calibrate gamma cameras in the framework of the Italian multicentre study for lesion dosimetry in 223Ra therapy of bone metastases. Equipments of several manufacturers and different models were used. METHODS: Eleven gamma cameras (3/8- and 5/8-inch crystal) were used, acquiring planar static images with double-peak (82 and 154keV, 20% wide) and MEGP collimator. The sensitivity was measured in air, varying source-detector distance and source size. Transmission curves were measured, calculating the parameters used for attenuation/scatter correction with the pseudo-extrapolation number method, and assessing their variations with the source size. RESULTS: Values of the calibration factor (geometric mean of both detector sensitivities) ranged from 41.1 to 113.9cps/MBq. For the smallest source (diameter of 3.5cm), the calibration factor decrease ranged from -30% to -4%, highlighting the importance of partial volume effects according to the equipment involved. The sensitivity variation with the source-detector distance, with respect to the 15cm-value, reached 10% (in absolute value) in the range 5-30cm, but fixing the distance between the two heads, the calibration factor variation with the distance from the midline was within 3.6%. Appreciable variation of the transmission curves with the source size were observed, examining the results obtained with six gamma cameras. CONCLUSION: Assessments of sensitivity and transmission curve variations with source size should be regularly implemented in calibration procedures. The results of this study represent a useful compendium to check the obtained calibrations for dosimetric purposes.

H2AX phosphorylation level in peripheral blood mononuclear cells as an event-free survival predictor for bladder cancer.

Bladder cancer (BC) has a typical aetiology characterized by a multistep carcinogenesis due to environmental exposures, genetic susceptibility, and their interaction. Several lines of evidence suggest that DNA repair plays a role in the development and progression of BC. In particular, the study of individual susceptibility to DNA double strand breaks (DSBs) may provide valuable information on BC risk, and help to identify those patients at high-risk of either recurrence or progression of the disease, possibly personalizing both surveillance and treatment. Among the different DSB markers, the most well characterized is phosphorylation of the histone H2AX (γ-H2AX). We assessed any potential role of γ-H2AX as a molecular biomarker in a case-control study (146 cases and 146 controls) to identify individuals with increased BC risk and at high-risk of disease recurrence or progression. We investigated γ-H2AX levels in peripheral blood mononuclear cells before and after their exposure to ionizing radiation (IR). We did not find any significant difference among cases and controls. However, we observed a significant association between γ-H2AX basal levels and risk of disease recurrence or progression. In particular, both BC patients as a whole and the subgroup of non-muscle invasive BC (NMIBC) with high basal H2AX phosphorylation levels had a decreased risk of recurrence or progression (for all BC HR 0.70, 95%CI 0.52-0.94, P = 0.02; for NMIBC HR 0.68, 95%CI 0.50-0.92, P = 0.01), suggesting a protective effect of basal DSB signaling. Our data suggest that γ-H2AX can be considered as a potential molecular biomarker to identify patients with a higher risk of BC recurrence. © 2015 Wiley Periodicals, Inc.

Implementation of a program for quality assurance on leaf positioning accuracy using Gafchromic(®) RTQA2 films.

In radiotherapy treatments the correct dose delivery to the target volume and the consequent conservation of healthy tissues is affected by multileaf collimator (MLC) leaf positioning accuracy and reproducibility, mostly in intensity-modulated radiation therapy (IMRT): For this reason a quality assurance (QA) program is necessary to ensure the best treatment possible to each patient. The aim of this study is the implementation of a method using Gafchromic(®) RTQA 2 films to perform routine QA on the MLC, both for qualitative and quantitative analysis. A flatbed document scanner (Epson 10000XL) was used in conjunction with radiochromic detector; a scanning protocol was firstly defined to improve readout accuracy. RTQA2 films were irradiated with 6 MV X-rays at different dose levels to obtain calibration curve. To evaluate the leaf positioning accuracy in different conditions, a rhomboidal shape and a field consisting in three rectangular segments were selected. The images quantitative analysis was handled with a program developed in MATLAB to evaluate the differences between expected and measured leaves positions. The reproducibility and global uncertainty of the method were estimated to be equal to 0.5% and 0.6 mm, respectively. Moreover, a qualitative test was performed: A garden picket fence field, consisting in multiple segments 2 × 22 cm(2), was realized setting known leaves shifts to test the method sensitivity. The picket fence test shows that the method is able to detect displacements equal to 1 mm. The results suggest that Gafchromic(®) RTQA2 films represent a reliable tool to perform MLC routine QA.

Volumetric and positional changes of planning target volumes and organs at risk using computed tomography imaging during intensity-modulated radiation therapy for head-neck cancer: an "old" adaptive radiation therapy approach.

PURPOSE: This study aimed to assess, in a department of radiation oncology not equipped with in-room imaging systems, volumetric and positional changes of planning target volumes (PTVs) and organs at risk in head and neck (H&N) cancer patients treated with intensity-modulated radiation therapy (IMRT), using consecutive off-board computed tomography (CT) imaging. Dosimetric aspects were not investigated. MATERIALS AND METHODS: Ten patients with H&N cancer underwent CT re-scanning at 3, 5, and 7 weeks. Positional changes of the PTVs and parotid glands as distances relative to the virtual isocentre were determined. The parotids glands (PGs) were re-delineated on each CT set and volume differences were computed. Anterior-posterior (AP) and latero-lateral (LL) displacements for the spinal cord at C1 and C6 level were calculated. Changes in patient body contours were evaluated by comparing the volumes within the external skin outline. RESULTS: Apart from two patients requiring re-planning due to substantial weight loss, our results evidenced no significant shifts of PTVs and PGs. PG volume decreased with a trend in volume reduction for the ipsilateral parotid. No significant shift of spinal cord at C1 and C6 level was detected, in either the AP or LL direction. The collected data demonstrated a trend in external skin contour volume loss. CONCLUSIONS: Our preliminary results reflect the literature data and indicate that an off-line adaptive RT approach is appropriate in clinical practice.

A case of primary mediastinal Ewing's sarcoma / primitive neuroectodermal tumor presenting with initial compression of superior vena cava.

Ewing's sarcomas and peripheral primitive neuroectodermal tumors (ES/PNETs) are high grade malignant neoplasms. These malignancies are characterized by a chromosome 22 rearrangement, arise from bone or soft tissue, predominantly affect children and young adults, and are grouped in the Ewing family of tumors. Multimodality treatment programs are the treatment of choice. Primary localization of ES/PNET in the mediastinum is extremely rare. We describe a case of ES/PNET presenting as a mediastinal mass with tracheal compression and initial signs of superior vena cava in a 66-year-old woman.

Dosimetric predictors of radiation-induced lung injury in stereotactic body radiation therapy.

MATERIALS AND METHODS: The aim was to retrospectively investigate correlations between potential predictive parameters and the occurrence of radiation-induced lung injury in patients with primary or secondary lung tumours treated with stereotactic body radiation therapy (SBRT). Sixty patients (63 tumours) underwent SBRT, with a dose of 45 Gy in 3 fractions over 5 days or 26 Gy in single fraction. The following parameters were tested for correlation with Radiation Therapy Oncology Group (RTOG) lung toxicity score: planning target volume (PTV), tumour location, primary vs. metastatic tumour, and Mean Lung Dose (in 2 Gy fractions, MLD2). Normal Tissue Complication Probability (NTCP) values were then estimated. RESULTS: The median follow-up time was 30.9 months (range 6.7-56.7). RTOG grade 0-1 toxicity was observed in 54/63 (85.7%) and grade 2-3 in 9/63 (14.3%) cases. Mean values of MLD(2) for RTOG grade 0-1 and 2-3 were respectively 11.2 Gy (95% Confidence Interval (CI) 10.1-12.3 Gy) and 20.3 Gy (95% CI 16.6-23.9 Gy). NTCP mean values for RTOG grade 0-1 and 2-3 were respectively 4% (95% CI 2-5.9%) and 37% (95% CI 11.6-62.3%). Univariate analysis, performed with t-Student test, showed a statistically significant difference between MLD(2) values in the two groups (t=5.93 and p < or = 0.001). Logistic regression analysis showed a good correlation between MLD(2) and toxicity scores 2-3 (p=0.008, odds ratio 1.5). From logistic regression relationship between the observed rates of grade 2-3 and MLD(2), a D(50)=19.8 Gy and a gamma50= 2.2 were obtained. From the sigmoid-shaped dose-response relationship between NTCP and MLD(2), a D(50)=22.4 Gy and gamma(50)= 2.2 were derived. DISCUSSION: MLD(2) is strongly associated to the risk of lung injury. Higher NTCP values are associated with a higher risk, but when comparing the expected to the observed toxicity rate, NTCP seems to underestimate the risk.

Absolute and relative dose measurements with Gafchromic EBT film for high energy electron beams with different doses per pulse.

The authors have evaluated the accuracy, in absolute and relative dose measurements, of the Gafchromic EBT film in pulsed high-energy electron beams. Typically, the electron beams used in radiotherapy have a dose-per-pulse value of less than 0.1 mGy/pulse. However, very high dose-per-pulse electron beams are employed in certain linear accelerators dedicated to intraoperatory radiation therapy (IORT). In this study, the absorbed dose measurements with Gafchromic EBT in both low (less than 0.3 mGy per pulse) and high (30 and 70 mGy per pulse) dose-per-pulse electron beams were compared with ferrous sulfate chemical Fricke dosimetry (operated by the Italian Primary Standard Dosimetry Laboratory), a method independent of the dose per pulse. A summary of Gafchromic EBT in relative and absolute beam output determination is reported. This study demonstrates the independence of Gafchromic EBT absorption as a function of dose per pulse at different dose levels. A good agreement (within 3%) was found with Fricke dosimeters for plane-base IORT applicators. Comparison with a diode detector is presented for relative dose measurements, showing acceptable agreement both in the steep dose falloff zone and in the homogeneous dose region. This work also provides experimental values for recombination correction factor (Ksat) of a Roos (plane parallel) ionization chamber calculated on the basis of theoretical models for charge recombination.

Clinical use of EBT model Gafchromic film in radiotherapy.

The Gafchromic EBT was recently introduced in film dosimetry for external beam therapy (EBT). The high spatial resolution, weak energy dependence, and near-tissue equivalence of EBT films make them suitable for measurement of dose distributions in radiotherapy, especially intensity-modulated radiation therapy (IMRT). Starting with a sensitometric curve and dose uncertainty relative to the flatbed scanner, the goal of this study was to find an efficient method of correcting for light scattering, and to compare dose distribution supplied by Gafchromic EBT with the distribution obtained with a 2D ion-chamber detector system. Light scattering was analyzed for different levels of dose, and was found to depend on the red-scale value as well as the position of the pixel on the scanner. Many "uniform" films were exposed at different levels of dose to create a two-dimensional matrix correction to take this effect into account. The dose distribution obtained for three clinical beams (10 x 10, 15 x 15 cm open fields and 12 x 12 cm wedge 60 degrees field) were in agreement with those supplied by the 2D array. Gamma index <1 (using 5 mm distance and 5% dose as constraints) for the three fields considered was reached in an average of 98% of the points.

Prostate brachytherapy with iodine-125 seeds: radiation protection issues.

AIMS AND BACKGROUND: Brachytherapy for prostate cancer by means of permanently implanted 125I sources is a well established procedure. An increasing number of patients all over the world are treated with this modality. When the technique was introduced at our institution, radiation protection issues relative to this technique were investigated in order to comply with international recommendations and national regulations. Particular attention was paid to the need for patient shielding after discharge from hospital. METHODS: The effective and equivalent doses to personnel related to implantation, the effective dose to patient relatives as computed by a developed algorithm, the air kerma strength values for the radioactive sources certified by the manufacturer compared with those measured by a well chamber, and the effectiveness of lead gloves in shielding the hands were evaluated. RESULTS: The effective dose to the bodies of personnel protected by a lead apron proved to be negligible. The mean equivalent doses to the physician's hands was 420 microSv for one implant; the technician's hands received 65 microSv. The mean air kerma rate measured at the anterior skin surface of the patient who had received an implant was 55 microGy/h (range, 10-115) and was negligible with lead protection. The measured and certified air kerma strength for125I seeds in RAPID Strand corresponded within a margin of +/- 5%. The measured attenuation by lead gloves in operative conditions was about 80%. We also defined the recommendations to be given to the patient at discharge. CONCLUSIONS: The exposure risks related to brachytherapy with 125I to operators and public are limited. However, alternation of operators should be considered to minimize exposure. Patient-related measurements should verify the dose rate around the patient to evaluate the need for shielding and to define appropriate radiation protection recommendations.