Design and characterization of an economical (192)Ir hemi-brain small animal irradiator.

PURPOSE: To describe the design and dosimetric characterization of a simple and economical small animal irradiator. MATERIALS AND METHODS: A high dose rate (HDR) (192)Ir brachytherapy source from a commercially available afterloader was used with a 1.3 cm thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit was equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film measurements. RESULTS: The tungsten collimator provided a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator, and was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam. CONCLUSIONS: Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring steep dose gradients.

Local prostate cancer radiotherapy after prostate-specific antigen progression during primary hormonal therapy.

BACKGROUND: The outcome of patients after radiotherapy (RT) for localized prostate cancer in case of prostate-specific antigen (PSA) progression during primary hormonal therapy (HT) is not well known. METHODS: A group of 27 patients presenting with PSA progression during primary HT for local prostate cancer RT was identified among patients who were treated in the years 2000-2004 either using external-beam RT (EBRT; 70.2 Gy; n=261) or Ir-192 brachytherapy as a boost to EBRT (HDR-BT; 18 Gy + 50.4 Gy; n=71). The median follow-up period after RT was 68 months. RESULTS: Median biochemical recurrence free (BRFS), disease specific (DSS) and overall survival (OS) for patients with PSA progression during primary HT was found to be only 21, 54 and 53 months, respectively, with a 6-year BRFS, DSS and OS of 19%, 41% and 26%. There were no significant differences between different RT concepts (6-year OS of 27% after EBRT and 20% after EBRT with HDR-BT).Considering all 332 patients in multivariate Cox regression analysis, PSA progression during initial HT, Gleason score>6 and patient age were found to be predictive for lower OS (p<0.001). The highest hazard ratio resulted for PSA progression during initial HT (7.2 in comparison to patients without PSA progression during primary HT). PSA progression and a nadir >0.5 ng/ml during initial HT were both significant risk factors for biochemical recurrence. CONCLUSIONS: An unfavourable prognosis after PSA progression during initial HT needs to be considered in the decision process before local prostate radiotherapy. Results from other centres are needed to validate our findings.

A study on the dose distributions in various materials from an Ir-192 HDR brachytherapy source.

Dose distributions of (192)Ir HDR brachytherapy in phantoms simulating water, bone, lung tissue, water-lung and bone-lung interfaces using the Monte Carlo codes EGS4, FLUKA and MCNP4C are reported. Experiments were designed to gather point dose measurements to verify the Monte Carlo results using Gafchromic film, radiophotoluminescent glass dosimeter, solid water, bone, and lung phantom. The results for radial dose functions and anisotropy functions in solid water phantom were consistent with previously reported data (Williamson and Li). The radial dose functions in bone were affected more by depth than those in water. Dose differences between homogeneous solid water phantoms and solid water-lung interfaces ranged from 0.6% to 14.4%. The range between homogeneous bone phantoms and bone-lung interfaces was 4.1% to 15.7%. These results support the understanding in dose distribution differences in water, bone, lung, and their interfaces. Our conclusion is that clinical parameters did not provide dose calculation accuracy for different materials, thus suggesting that dose calculation of HDR treatment planning systems should take into account material density to improve overall treatment quality.

In vivo assessment of catheter positioning accuracy and prolonged irradiation time on liver tolerance dose after single-fraction 192Ir high-dose-rate brachytherapy.

BACKGROUND: To assess brachytherapy catheter positioning accuracy and to evaluate the effects of prolonged irradiation time on the tolerance dose of normal liver parenchyma following single-fraction irradiation with 192Ir. MATERIALS AND METHODS: Fifty patients with 76 malignant liver tumors treated by computed tomography (CT)-guided high-dose-rate brachytherapy (HDR-BT) were included in the study. The prescribed radiation dose was delivered by 1 - 11 catheters with exposure times in the range of 844 - 4432 seconds. Magnetic resonance imaging (MRI) datasets for assessing irradiation effects on normal liver tissue, edema, and hepatocyte dysfunction, obtained 6 and 12 weeks after HDR-BT, were merged with 3D dosimetry data. The isodose of the treatment plan covering the same volume as the irradiation effect was taken as a surrogate for the liver tissue tolerance dose. Catheter positioning accuracy was assessed by calculating the shift between the 3D center coordinates of the irradiation effect volume and the tolerance dose volume for 38 irradiation effects in 30 patients induced by catheters implanted in nearly parallel arrangement. Effects of prolonged irradiation were assessed in areas where the irradiation effect volume and tolerance dose volume did not overlap (mismatch areas) by using a catheter contribution index. This index was calculated for 48 irradiation effects induced by at least two catheters in 44 patients. RESULTS: Positioning accuracy of the brachytherapy catheters was 5-6 mm. The orthogonal and axial shifts between the center coordinates of the irradiation effect volume and the tolerance dose volume in relation to the direction vector of catheter implantation were highly correlated and in first approximation identically in the T1-w and T2-w MRI sequences (p = 0.003 and p < 0.001, respectively), as were the shifts between 6 and 12 weeks examinations (p = 0.001 and p = 0.004, respectively). There was a significant shift of the irradiation effect towards the catheter entry site compared with the planned dose distribution (p < 0.005). Prolonged treatment time increases the normal tissue tolerance dose. Here, the catheter contribution indices indicated a lower tolerance dose of the liver parenchyma in areas with prolonged irradiation (p < 0.005). CONCLUSIONS: Positioning accuracy of brachytherapy catheters is sufficient for clinical practice. Reduced tolerance dose in areas exposed to prolonged irradiation is contradictory to results published in the current literature. Effects of prolonged dose administration on the liver tolerance dose for treatment times of up to 60 minutes per HDR-BT session are not pronounced compared to effects of positioning accuracy of the brachytherapy catheters and are therefore of minor importance in treatment planning.

Numerical dosimetric reconstruction of a radiological accident in South America in April 2009.

A severe irradiation accident involving a victim occurred in April 2009 in South America. The victim has found a (192)Ir source fallen from a gammagraphy device and has put it in the left pocket of his pants. Very quickly, an erythema and a blister appeared on the left leg of the victim involving hospitalisation. Following the request of the IAEA assistance, the Ionizing Radiation Dosimetry Laboratory of IRSN was asked to perform a numerical dosimetric reconstruction. A personalised voxel phantom of the victim has been constructed thanks to the Simulation of External Source Accident with Medical images tool developed by the laboratory, and a calculation of the dose with the MCNPX computer code allowed to determine the boundary of the necrotic dose at 25 Gy. On the basis of these calculations, the physicians have performed exeresis of the necrotic region on the left leg on 4 May 2009. Associated with mesenchymal stem cell injection, the leg of the victim was healthy on December 2009.

Dosimetric optimization of a conical breast brachytherapy applicator for improved skin dose sparing.

PURPOSE: Both the AccuBoost D-shaped and round applicators have been dosimetrically characterized and clinically used to treat patients with breast cancer. While the round applicators provide conformal dose coverage, under certain clinical circumstances the breast skin dose may be higher than preferred. The purpose of this study was to modify the round applicators to minimize skin dose while not substantially affecting dose uniformity within the target volume and reducing the treatment time. METHODS: In order to irradiate the intended volume while sparing critical structures such as the skin, the current round applicator design has been augmented through the addition of an internal truncated cone (i.e., frustum) shield. Monte Carlo methods and clinical constraints were used to design the optimal cone applicator. With the cone applicator now defined as the entire assembly including the surrounding tungsten-alloy shell holding the HDR 192Ir source catheter, the applicator height was reduced to diminish the treatment time while minimizing skin dose. Monte Carlo simulation results were validated using both radiochromic film and ionization chamber measurements based on established techniques. RESULTS: The optimal cone applicators diminished the maximum skin dose by 15%-32% (based on the applicator diameter and breast separation) with the tumor dose reduced by less than 3% for a constant exposure time. Furthermore, reduction in applicator height diminished the treatment time by up to 30%. Radiochromic film and ionization chamber dosimetric results in phantom agreed with Monte Carlo simulation results typically within 3%. Larger differences were outside the treatment volume in low dose regions or associated with differences between the measurement and Monte Carlo simulation environments. CONCLUSIONS: A new radiotherapy treatment device was developed and dosimetrically characterized. This set of applicators significantly reduces the skin dose and treatment time while retaining uniform target dose.

Tracking brachytherapy sources using emission imaging with one flat panel detector.

This work proposes to use the radiation from brachytherapy sources to track their dwell positions in three-dimensional (3D) space. The prototype device uses a single flat panel detector and a BB tray. The BBs are arranged in a defined pattern. The shadow of the BBs on the flat panel is analyzed to derive the 3D coordinates of the illumination source, i.e., the dwell position of the brachytherapy source. A kilovoltage x-ray source located 3.3 m away was used to align the center BB with the center pixel on the flat panel detector. For a test plan of 11 dwell positions, with an Ir-192 high dose rate unit, one projection was taken for each dwell point, and locations of the BB shadows were manually identified on the projection images. The 3D coordinates for the 11 dwell positions were reconstructed based on two BBs. The distances between dwell points were compared with the expected values. The average difference was 0.07 cm with a standard deviation of 0.15 cm. With automated BB shadow recognition in the future, this technique possesses the potential of tracking the 3D trajectory and the dwell times of a brachytherapy source in real time, enabling real time source position verification.

A plesiotherapy technique for the post-operative treatment of skin cancer using Ir192 microSelectron.

We describe a technique of postoperative irradiation of skin cancer using plesiotherapy with Ir192 high dose rate microSelectron afterloading system (Nucletron, Veenendaal, Netherlands). The clinically defined area is drawn on the skin and the flexible 'skin applicator' is then orientated so that the drawn skin area is encompassed within the catheter defined surface. Using a thin pewter wire, the skin drawn area is copied on the air-adjacent surface of the applicator. Ex vivo CT simulation follows. The data are then transferred to the radiotherapy planning computer and the catheters are virtually reconstructed. The isodose curve chosen to prescribe the dose is 3 mm to 5 mm away from the skin surface. Three fractions of 8Gy are scheduled, 1 week apart, delivering a radiobiological equivalent of 48Gy of standard radiotherapy within 2 weeks. Our preliminary experience shows excellent early skin tolerance. The study is ongoing to assess efficacy and late effects.

On the use of HDR 60Co source with the MammoSite radiation therapy system.

This work summarizes Monte Carlo results in order to evaluate the potential of using HDR 60Co sources in accelerated partial breast irradiation (APBI) with the MammoSite applicator. Simulations have been performed using the MCNP5 Monte Carlo Code, in simple geometries comprised of two concentric spheres; the internal consisting of selected concentrations, C, of a radiographic contrast solution in water (Omnipaque 300) to simulate the MammoSite balloon and the external consisting of water to simulate surrounding tissue. The magnitude of the perturbation of delivered dose due to the radiographic contrast medium used in the MammoSite applicator is calculated. At the very close vicinity of the balloon surface, a dose build-up region is observed, which leads to a dose overestimation by the treatment planning system (TPS) which depends on Omnipaque 300 solution concentration (and is in order of 2.3%, 3.0%, and 4.5%, respectively, at 1 mm away from the balloon - water interface, for C=10%, 15%, and 20%). However, dose overestimation by the TPS is minimal for points lying at the prescription distance (d=1 cm) or beyond, for all simulated concentrations and radii of MammoSite balloon. An analytical estimation of the integral dose outside the CTV in the simple geometries simulated shows that dose to the breast for MammoSite applications is expected to be comparable using HDR 60Co and 192Ir sources, and higher than that for 169Yb. The higher enegies of 60Co sources result to approximately twice radiation protection requirements as compared to 169Ir sources. However, they allow for more accurate dosimetry calculation with currently used treatment planning algorithms for 60Co sources, compared to 169Ir.

Response of an implantable MOSFET dosimeter to 192Ir HDR radiation.

New in vivo dosimetry methods would be useful for clinical HDR brachytherapy. An implantable MOSFET Dose Verification System designed by Sicel Technologies, Inc. was examined for use with 192Ir HDR applications. This investigation demonstrated that varying the dose rate from 22 to 84 cGy/min did not change detector response. The detectors exhibited a higher sensitivity to 192Ir energies than 60Co energies. A nonlinear accumulated dose effect was characterized by three third-order polynomials fit to data from detectors placed at three different distances from the source. The detectors were found to have minimal rotational angular dependence. A strong longitudinal angular dependence was found when the detector's copper coil and electronics assembly were aligned between the MOSFETs and incident radiation. This orientation showed a 16% decrease in response relative to other orientations tested.

Toward endobronchial Ir-192 high-dose-rate brachytherapy therapeutic optimization.

A number of patients with lung cancer receive either palliative or curative high-dose-rate (HDR) endobronchial brachytherapy. Up to a third of patients treated with endobronchial HDR die from hemoptysis. Rather than accept hemoptysis as an expected potential consequence of HDR, we have calculated the radial dose distribution for an Ir-192 HDR source, rigorously examined the dose and prescription points recommended by the American Brachytherapy Society (ABS), and performed a radiobiological-based analysis. The radial dose rate of a commercially available Ir-192 source was calculated with a Monte Carlo simulation. Based on the linear quadratic model, the estimated palliative, curative and blood vessel rupture radii from the center of an Ir-192 source were obtained for the ABS recommendations and a series of customized HDR prescriptions. The estimated radius at risk for blood vessel perforation for the ABS recommendations ranges from 7 to 9 mm. An optimized prescription may in some situations reduce this radius to 4 mm. The estimated blood perforation radius is generally smaller than the palliative radius. Optimized and individualized endobronchial HDR prescriptions are currently feasible based on our current understanding of tumor and normal tissue radiobiology. Individualized prescriptions could minimize complications such as fatal hemoptysis without sacrificing efficacy. Fiducial stents, HDR catheter centering or spacers and the use of CT imaging to better assess the relationship between the catheter and blood vessels promise to be useful strategies for increasing the therapeutic index of this treatment modality. Prospective trials employing treatment optimization algorithms are needed.

Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma.

Results of liver transplantation in the treatment of cholangiocarcinoma have been poor as a result of the high incidence of locoregional dissemination and tumor recurrence. This study evaluates the effect of neoadjuvant chemoradiation therapy combined with orthotopic liver transplantation in a carefully selected group of patients with hilar cholangiocarcinoma. Seventeen patients were included in the study. The neoadjuvant protocol included 6,000 cgy biliary brachy-therapy delivered through percutaneous transhepatic catheters and intravenous infusion of 5-fluorouracil (300mg/m2/day) until transplantation. Five of the 17 patients demonstrated tumor progression precluding transplantation. One patient died of sepsis on the waiting list. Eleven patients underwent liver transplantation, a median of 3.4 months (range = 1-26 months) after diagnosis. Five of the 11 (45%) are alive without evidence of tumor recurrence with a median follow up of 7.5 years (range = 2.8-14.5 years). Six deaths occurred in the transplanted patients. Tumor recurrence was responsible for two deaths at 10 and 18months, respectively, after transplantation. Three mortalities resulted from bacterial or fungal peritonitis and sepsis. One patient underwent re-transplantation for chronic rejection and died from graft failure resulting from hepatic artery thrombosis 16 months after diagnosis without evidence of tumor recurrence. Complications of transhepatic catheter placement included bile duct perforation (n = 4) and biliary-portal vein fistula (n = 1). All these patients died of tumor recurrence or sepsis. Cholangiocarcinoma should not be considered an absolute exclusion criteria for orthotopic liver transplantation. Long-term, tumor-free survival was achieved in 45% of the transplanted patients. Complications of biliary catheter placement for brachytherapy were associated with poor outcome.