The effect of vaginal cylinder inhomogeneity on the HDR brachytherapy dose calculations using Monte Carlo simulations.

PURPOSE: To analytically assess the heterogeneity effect of vaginal cylinders (VC) made of high-density plastics on dose calculations, considering the prescription point (surface or 5 mm beyond the surface), and benchmark the accuracy of a commercial model-based dose calculation (MBDC) algorithm using Monte Carlo (MC) simulations. METHODS AND MATERIALS: The GEANT4 MC code was used to simulate a commercial 192 Ir HDR source and VC, with diameters ranging from 20 to 35 mm, inside a virtual water phantom. Standard plans were generated from a commercial treatment planning system [TPS-BrachyVision ACUROS (BV)] optimized for a treatment length of 5 cm through two dose calculation approaches: (1) assuming all the environment as water (i.e., Dw,w-MC & Dw,w-TG43 ) and (2) accounting for the heterogeneity of VC applicators (i.e., Dw,w-App-MC & Dw,w-App-MBDC ). The compared isodose lines, and dose & energy difference maps were extracted for analysis. In addition, the dose difference on the peripheral surface, along the applicator and at middle of treatment length, as well as apical tip was evaluated. RESULTS: The Dw,w-App-MC results indicated that the VC heterogeneity can cause a dose reduction of (up to) % 6.8 on average (for all sizes) on the peripheral surface, translating to 1 mm shrinkage of the isodose lines compared to Dw,w-MC . In addition, the results denoted that BV overestimates the dose on the peripheral surface and apical tip of about 3.7% and 17.9%, respectively, (i.e., Dw,w-App-MBDC vs Dw,w-App-MC ) when prescribing to the surface. However, the difference between the two were negligible at the prescription point when prescribing to 5 mm beyond the surface. CONCLUSION: The VCs' heterogeneity could cause dose reduction when prescribing dose to the surface of the applicator, and hence increases the level of uncertainty. Thus, reviewing the TG43 results, in addition to ACUROS, becomes prudent, when evaluating the surface coverage at the apex.

Monte Carlo dosimetry of a novel Yttrium-90 disc source for episcleral brachytherapy.

PURPOSE: To calculate the dose distribution using Monte Carlo simulations for a novel high-dose-rate Yttrium-90 (Y-90) disc source recently developed for episcleral brachytherapy and provide a lookup table for treatment planning. METHODS: Monte Carlo simulations were performed to calculate the in-water dose distribution of the Y-90 disc source using the "GATE", a software based on the "Geant4" Monte Carlo simulation toolkit developed by the international OpenGATE collaboration. The geometry of this novel beta source, its capsule, and the surrounding water medium were accurately modeled in the simulation input files. The standard Y-90 element beta spectrum from ICRU 72 was used, and the physics processes for beta and photon interactions with matters were all included. The dose distribution of this Y-90 disc source was measured in a separate study using Gafchromic EBT-3 films and the results were reported elsewhere. To match the setup of the experiment, a Gafchromic EBT-3 film was also included in the simulation geometry. The simulated dose profiles were exported from the 3D dose distribution results and compared with the measured dose profiles. Transverse dose profiles at different distances from the seed surface were also obtained to study the lateral coverage of the source. RESULTS: The measured percent depth dose (PDD) curves along the central axis perpendicular to the surface of the Y-90 disc were constructed from the experimental and simulated data, and normalized to the reference point at 1 mm from the source capsule. Both PDD curves agreed well up to 4 mm from the source surface (maximum difference ± 10%) but deviated from each other beyond 4 mm. The deviation might be caused by the increased measurement uncertainty in the low-dose region. The dose rate at the reference point calculated from the Monte Carlo simulation was 1.09 cGy/mCi-s and agreed very well with the measured dose rate of 1.05 cGy/mCi-s. If the 80% isodose line is selected as the lateral coverage, the lateral dose coverage is maximal (∼4.5 mm) at the plane next to the source surface, and gradually decreases with the increasing distance, approaching 3.5 mm when the plane is 5 mm from the 6-mm diameter source surface. CONCLUSION: Monte Carlo simulations were successfully performed to confirm the measured PDD curve of the novel Y-90 disc source. This simulation work laid a solid foundation for characterizing the full dosimetry parameters of this source for episcleral brachytherapy applications.

Quantitative study on dose distribution of Freiburg flap for keloid high-dose-rate brachytherapy based on MatriXX.

PURPOSE: To quantify the dose distribution effect of insufficient scattering conditions in keloid HDR brachytherapy with Freiburg fFlap (FF) applicator. MATERIALS AND METHODS: A phantom composed of FF applicator, MatriXX and solid water slices was designed and scanned for treatment planning. Bolus with different thicknesses were covered to offer different scatter conditions. Planar dose distributions were measured by MatriXX. The maximum value (Max), average value (Avg) and γ passing rate (3 mm/3%) were evaluated by the software MyQA Platform. RESULTS: The maximum and average doses measured by MatriXX were lower than the calculated values. The difference increased as field size decreased. The Max value, found at 0.86 cm level in the two tube case, was -20.0%, and the avg value was -11.9%. All the γ values were less than 95%. This difference gradually decreased with increasing bolus thickness and the γ values were significantly improved. CONCLUSION: MatriXX could be used for dose verification of HDR brachytherapy with an FF applicator. When the FF applicator was applied for keloid, insufficient scattering conditions would cause an insufficient target dose. This difference could be reduced by covering the bolus with different thicknesses on the applicator. The smaller the field, the thicker the bolus required.

High levels of health-related quality of life five years after curative treatment of prostate cancer with HDR-brachytherapy and external beam radiation.

BACKGROUND AND PURPOSE: The aim of this cross-sectional study was to investigate long-term health-related quality of life (HRQoL) in men with prostate cancer treated 2002-2008 with external beam radiotherapy (EBRT) combined with high dose-rate brachytherapy (HDRBT), Cohort A, and to compare these data with age-adjusted normative data. In addition, differences in HRQoL following adjustments of the brachytherapy technique in 2001 were investigated by comparing Cohort A with men treated at the same clinic from 1998-2000, Cohort B. METHODS AND MATERIAL: Cohort A: 1495 men treated with EBRT 2 Gy to 50 Gy and 2 fractions of 10 Gy HDRBT at a single centre, 2002-2008, still alive at five years. As part of routine follow-up, the patients responded to the EORTC QLQ-C30 and PR-25 questionnaires. Cohort B: HRQoL data was retrieved from an earlier study from the original article. RESULTS: In Cohort A, 1046 (70%) men completed the questionnaires at five years, median age 66 years. In general, HRQoL mean scores were high and similar to Swedish age-matched normative data. Concerning disease-specific HRQoL, low levels of bowel and urinary problems were reported, in contrast to a substantial effect on sexual functioning. 'No' or 'A little' problems with faecal incontinence and urinary incontinence were reported by 98% and 93% of patients, respectively. The corresponding figure for sexual functioning was 39%. A difference in the frequency of nocturia in favour of Cohort A was the only statistically significant difference between Cohort A and B found in general and disease-specific HRQOL (p = 0.03), despite modifications in the brachytherapy procedure introduced in 2001. CONCLUSION: Long-term general HRQoL was rated high and comparable to an aged-matched reference population five years after treatment with combined radiotherapy. Disease-specific HRQoL was still affected, foremost in the sexual domain.

Evaluating dosimetric accuracy of the 6 MV calibration on EBT3 film in the use of Ir-192 high dose rate brachytherapy.

PURPOSE: To evaluate the dosimetric accuracy of EBT3 film calibrated with a 6 MV beam for high dose rate brachytherapy and propose a novel method for direct film calibration with an Ir-192 source. METHODS: The 6 MV calibration was performed in water on a linear accelerator (linac). The Ir-192 calibration was accomplished by irradiating the film wrapped around a cylinder applicator with an Ir-192 source. All films were scanned 1-day post-irradiation to acquire calibration curves for all three (red, blue, and green) channels. The Ir-192 calibration films were also used for single-dose comparison. Moreover, an independent test film under a H.A.M. applicator was irradiated and the 2D dose distribution was obtained separately for each calibration using the red channel data. Gamma analysis and point-by-point profile comparison were performed to evaluate the performance of both calibrations. The uncertainty budget for each calibration system was analyzed. RESULTS: The red channel had the best performance for both calibration systems in the single-dose comparison. We found a significant 4.89% difference from the reference for doses <250 cGy using the 6 MV calibration, while the difference was only 0.87% for doses >600 cGy. Gamma analysis of the 2D dose distribution showed the Ir-192 calibration had a higher passing rate of 91.9% for the 1 mm/2% criterion, compared to 83.5% for the 6 MV calibration. Most failing points were in the low-dose region (<200 cGy). The point-by-point profile comparison reported a discrepancy of 2%-3.6% between the Ir-192 and 6 MV calibrations in this low-dose region. The linac- and Ir-192-based dosimetry systems had an uncertainty of 4.1% (k = 2) and 5.66% (k = 2), respectively. CONCLUSIONS: Direct calibration of EBT3 films with an Ir-192 source is feasible and reliable, while the dosimetric accuracy of 6 MV calibration depends on the dose range. The Ir-192 calibration should be used when the measurement dose range is below 250 cGy.

3D in vivo dosimetry of HDR gynecological brachytherapy using micro silica bead TLDs.

PURPOSE: This study aimed to evaluate the feasibility of defining an in vivo dosimetry (IVD) protocol as a patient-specific quality assurance (PSQA) using the bead thermoluminescent dosimeters (TLDs) for point and 3D IVD during brachytherapy (BT) of gynecological (GYN) cancer using 60 Co high-dose-rate (HDR) source. METHODS: The 3D in vivo absorbed dose verification within the rectum and bladder as organs-at-risk was performed by bead TLDs for 30 GYN cancer patients. For rectal wall dosimetry, 80 TLDs were placed in axial arrangements around a rectal tube covered with a layer of gel. Ten beads were placed inside the Foley catheter to get the bladder-absorbed dose. Beads TLDs were localized and defined as control points in the treatment planning system (TPS) using CT images of the patients. Patients were planned and treated using the routine BT protocol. The experimentally obtained absorbed dose map of the rectal wall and the point dose of the bladder were compared to the TPSs predicted absorbed dose at these control points. RESULTS: Relative difference between TPS and TLDs results were -8.3% ± 19.5% and -7.2% ± 14.6% (1SD) for rectum- and bladder-absorbed dose, respectively. Gamma analysis was used to compare the calculated with the measured absorbed dose maps. Mean gamma passing rates of 84.1%, 90.8%, and 92.5% using the criteria of 3%/2 mm, 3%/3 mm, and 4%/2 mm were obtained, respectively. Eventually, a "considering level" of at least 85% as pass rate with 4%/2-mm criteria was recommended. CONCLUSIONS: A 3D IVD protocol employing bead TLDs was presented to measure absorbed doses delivered to the rectum and bladder during GYN HDR-BT as a reliable PSQA method. 3D rectal absorbed dose measurements were performed. Differences between experimentally measured and planned absorbed dose maps were presented in the form of a gamma index, which may be used as a warning for corrective action.

High rate of local control and cure at 10 years after treatment of prostate cancer with external beam radiotherapy and high-dose-rate brachytherapy: a single centre experience.

BACKGROUND AND PURPOSE: To analyse the cumulative incidence of any failure (AF), prostate cancer-specific failure (PCSF), any death (AD), prostate cancer-specific death (PCSD), and local control in 2387 men with prostate cancer (PC), consecutively treated with combined high-dose-rate brachytherapy (HDRBT) and external beam radiotherapy (EBRT) from 1998 to 2010. MATERIAL AND METHODS: A retrospective, single-institution study of men with localised PC. The mean age was 66 years and 54.7% had high-risk PC according to the Cambridge prognostic group (CPG) classification. The treatment was delivered as EBRT (2 Gy × 25) and HDRBT (10 Gy × 2) with combined androgen blockade (CAB). The median follow-up was 10.2 years. RESULTS: The cumulative incidence of PCSD at 10 years was 5% [CI 95% 0.04-0.06]. The 10 years PCSD per risk group were: low (L) 0.4%, intermediate favourable (IF) 1%, intermediate unfavourable (IU) 4.3%, high-risk favourable (HF) 5.8%, and high-risk unfavourable (HU) 13.9%. The PCSF rate at 10 years was 16.5% [CI 95% 0.15-0.18]. The PCSF per risk group at 10 years were: L 2.5%, IF 5.5%, IU 15.9%, HF 15.6%, and HU 38.99%. PCSF occurred in 399 men, of whom 15% were found to have local failure. The estimated frequency of local failure in the entire cohort was 1.2%. CONCLUSIONS: HDRBT combined with EBRT is an effective treatment with long-term overall survival and excellent local control for patients with PC. The low rate of local recurrence among men with relapse suggests that these patients were micro metastasised at time of treatment, which calls for improved methods to detect disseminated disease.

Dose reduction in HDR brachytherapy of esophageal cancer using gold and gold alloy plaques: a Monte Carlo study.

In this work, the use of gold and gold alloy plaques is proposed for the first time, to reduce the dose to healthy organs in brachytherapy with Ir-192 sources. For dose simulations in tumour and healthy tissue, the MCNPX Monte Carlo code was used. The radiation source implemented in those simulations was benchmarked with well-known TG-43 criteria of dose rate constant, air-kerma strength, radial dose function, and 2D anisotropy function. For various arrangements of iridium sources and plaques of gold and gold alloy of various thicknesses, the dose distributions in an esophagus tumour and in surrounding healthy organs were simulated. The results showed that while the dose to the tumour is not much affected by the presence of gold plaques with a thickness of 3.5 mm in an optimized 192Ir sources' configuration, a relative reduction in average organ dose of 64%, 65%, 73%, 67%, and 35% was observed, for esophagus, thyroid, heart, stomach, and liver, respectively. Moreover, it was found that a gold plaque leads to smaller doses to healthy organs than a gold alloy plaque. It is concluded that gold plaques can be used to improve the treatment of esophageal cancer by HDR brachytherapy and to protect surrounding non-target organs.

MRI-TRUS registration methodology for TRUS-guided HDR prostate brachytherapy.

PURPOSE: High-dose-rate (HDR) prostate brachytherapy is an established technique for whole-gland treatment. For transrectal ultrasound (TRUS)-guided HDR prostate brachytherapy, image fusion with a magnetic resonance image (MRI) can be performed to make use of its soft-tissue contrast. The MIM treatment planning system has recently introduced image registration specifically for HDR prostate brachytherapy and has incorporated a Predictive Fusion workflow, which allows clinicians to attempt to compensate for differences in patient positioning between imaging modalities. In this study, we investigate the accuracy of the MIM algorithms for MRI-TRUS fusion, including the Predictive Fusion workflow. MATERIALS AND METHODS: A radiation oncologist contoured the prostate gland on both TRUS and MRI. Four registration methodologies to fuse the MRI and the TRUS images were considered: rigid registration (RR), contour-based (CB) deformable registration, Predictive Fusion followed by RR (pfRR), and Predictive Fusion followed by CB deformable registration (pfCB). Registrations were compared using the mean distance to agreement and the Dice similarity coefficient for the prostate as contoured on TRUS and the registered MRI prostate contour. RESULTS: Twenty patients treated with HDR prostate brachytherapy at our center were included in this retrospective evaluation. For the cohort, mean distance to agreement was 2.1 ± 0.8 mm, 0.60 ± 0.08 mm, 2.0 ± 0.5 mm, and 0.59 ± 0.06 mm for RR, CB, pfRR, and pfCB, respectively. Dice similarity coefficients were 0.80 ± 0.05, 0.93 ± 0.02, 0.81 ± 0.03, and 0.93 ± 0.01 for RR, CB, pfRR, and pfCB, respectively. The inclusion of the Predictive Fusion workflow did not significantly improve the quality of the registration. CONCLUSIONS: The CB deformable registration algorithm in the MIM treatment planning system yielded the best geometric registration indices. MIM offers a commercial platform allowing for easier access and integration into clinical departments with the potential to play an integral role in future focal therapy applications for prostate cancer.

The clinical impact of removing rectal gas on high-dose-rate brachytherapy dose distributions for gynecologic cancers.

PURPOSE: To evaluate the impact of gas removal on bladder and rectal doses during intracavitary and interstitial high-dose-rate brachytherapy (HDRB) for gynecologic cancers. MATERIAL AND METHODS: Fifteen patients treated with definitive external beam radiation followed by HDRB for gynecologic cancers for a total of 21 fractions, presented with a significant amount of rectal gas at initial CT imaging (CTGAS ) after implantation. The gas was removed via rectal tubing followed by subsequent scan acquisition (CTCLINICAL ), which was used for planning and treatment delivery. To assess the effect of gas removal on dosimetry, both bladder and rectum volumes were recontoured on CTGAS . In order to evaluate the clinical impact on the total Equivalent-Dose-in-2Gy-fraction (EQD2 ), each fraction was also replanned to maintain clinically delivered target coverage (HRCTV D90). EQD2 D2cm3 for bladder and rectum were compared between plans. The Wilcoxon signed rank test was performed to evaluate statistically significant differences for all comparisons (P < 0.05). RESULTS: Mean rectum and bladder Dmax , D0.1cm3 , D1cm3 , D2cm3 , and D5cm3 were significantly different between CTGAS and CTCLINICAL . The mean percent increases on CTGAS for bladder were 12.3, 8.4, 9.9, 10.2, and 9.5% respectively and for rectum were 27.0, 19.6, 18.1, 18.5, and 19.4%, respectively. After replanning with CTGAS to maintain HRCTV D90 EQD2 , bladder and rectum EQD2 D2 cm3 resulted in significantly higher doses. The mean EQD2 D2 cm3 difference was 2.4 and 4.1 Gy for bladder and rectum, revealing a higher impact of gas removal on rectal DVH. CONCLUSION: Rectal gas removal resulted in statistically significant differences for both bladder and rectum. The resulting larger EQD2 D2 cm3 for bladder and rectum demonstrates that if patients were treated without removing gas, target coverage would need to be sacrificed to satisfy the rectum constraints and prevent toxicities. Therefore, this study demonstrates the importance of gas removal for gynecologic HDRB patients.

Sensitivity of dose-volume indices to computation settings in high-dose-rate prostate brachytherapy treatment plan evaluation.

PURPOSE: To investigate the variation in computed dose-volume (DV) indices for high-dose-rate (HDR) prostate brachytherapy that can result from typical differences in computation settings in treatment planning systems (TPSs). METHODS: Five factors were taken into account: number of dose-calculation points, radioactive source description, interpolation between delineated contours, intersections between delineated organ contours, and organ shape at the top and bottom contour using either full or partial slice thickness. Using in-house developed software, the DV indices of the treatment plans of 26 patients were calculated with different settings, and compared to a baseline setting that closely followed the default settings of the TPS used in our medical center. Studied organs were prostate and seminal vesicles, denoted as targets, and bladder, rectum, and urethra, denoted as organs at risk (OARs), which were delineated on MRI scans with a 3.3 mm slice thickness. RESULTS: When sampling a fixed number of points in each organ, in order to achieve a width of the 95% confidence interval over all patients of the DV indices of 1% or less, only 32,000 points had to be sampled per target, but 256,000 points had to be sampled per OAR. For the remaining factors, DV indices changed up to 0.4% for rectum, 1.3% for urethra, and 2.6% for prostate. DV indices of the bladder changed especially if the high-dose-region was (partly) located at the most caudal contour, up to 8.5%, and DV indices of the vesicles changed especially if there were few delineated contours, up to 9.8%, both due to the use of full slice thickness for the top and bottom contour. CONCLUSIONS: The values of DV indices used in prostate HDR brachytherapy treatment planning are influenced by the computation settings in a TPS, especially at the most caudal part of the bladder, as well as in the seminal vesicles.

Improved prostate delineation in prostate HDR brachytherapy with TRUS-CT deformable registration technology: A pilot study with MRI validation.

Accurate prostate delineation is essential to ensure proper target coverage and normal-tissue sparing in prostate HDR brachytherapy. We have developed a prostate HDR brachytherapy technology that integrates intraoperative TRUS-based prostate contour into HDR treatment planning through TRUS-CT deformable registration (TCDR) to improve prostate contour accuracy. In a perspective study of 16 patients, we investigated the clinical feasibility as well as the performance of this TCDR-based HDR approach. We compared the performance of the TCDR-based approach with the conventional CT-based HDR in terms of prostate contour accuracy using MRI as the gold standard. For all patients, the average Dice prostate volume overlap was 91.1 ± 2.3% between the TCDR-based and the MRI-defined prostate volumes. In a subset of eight patients, inter and intro-observer reliability study was conducted among three experienced physicians (two radiation oncologists and one radiologist) for the TCDR-based HDR approach. Overall, a 10 to 40% improvement in prostate volume accuracy can be achieved with the TCDR-based approach as compared with the conventional CT-based prostate volumes. The TCDR-based prostate volumes match closely to the MRI-defined prostate volumes for all 3 observers (mean volume difference: 0.5 ± 7.2%, 1.8 ± 7.2%, and 3.5 ± 5.1%); while CT-based contours overestimated prostate volumes by 10.9 ± 28.7%, 13.7 ± 20.1%, and 44.7 ± 32.1%. This study has shown that the TCDR-based HDR brachytherapy is clinically feasible and can significantly improve prostate contour accuracy over the conventional CT-based prostate contour. We also demonstrated the reliability of the TCDR-based prostate delineation. This TCDR-based HDR approach has the potential to enable accurate dose planning and delivery, and potentially enhance prostate HDR treatment outcome.

Electromagnetic tracking (EMT) technology for improved treatment quality assurance in interstitial brachytherapy.

Electromagnetic Tracking (EMT) is a novel technique for error detection and quality assurance (QA) in interstitial high dose rate brachytherapy (HDR-iBT). The purpose of this study is to provide a concept for data acquisition developed as part of a clinical evaluation study on the use of EMT during interstitial treatment of breast cancer patients. The stability, accuracy, and precision of EMT-determined dwell positions were quantified. Dwell position reconstruction based on EMT was investigated on CT table, HDR table and PDR bed to examine the influence on precision and accuracy in a typical clinical workflow. All investigations were performed using a precise PMMA phantom. The track of catheters inserted in that phantom was measured by manually inserting a 5 degree of freedom (DoF) sensor while recording the position of three 6DoF fiducial sensors on the phantom surface to correct motion influences. From the corrected data, dwell positions were reconstructed along the catheter's track. The accuracy of the EMT-determined dwell positions was quantified by the residual distances to reference dwell positions after using a rigid registration. Precision and accuracy were investigated for different phantom-table and sensor-field generator (FG) distances. The measured precision of the EMT-determined dwell positions was ≤ 0.28 mm (95th percentile). Stability tests showed a drift of 0.03 mm in the first 20 min of use. Sudden shaking of the FG or (large) metallic objects close to the FG degrade the precision. The accuracy with respect to the reference dwell positions was on all clinical tables < 1 mm at 200 mm FG distance and 120 mm phantom-table distance. Phantom measurements showed that EMT-determined localization of dwell positions in HDR-iBT is stable, precise, and sufficiently accurate for clinical assessment. The presented method may be viable for clinical applications in HDR-iBT, like implant definition, error detection or quantification of uncertainties. Further clinical investigations are needed.

Evaluating the performance of TG-43 protocol in esophageal HDR brachytherapy viewpoint to trachea inhomogeneity.

AIM: The aim of this study is to evaluate the effect of air within trachea on dose calculations of esophageal HDR brachytherapy treatment planning. BACKGROUND: Dose calculations in esophageal HDR brachytherapy treatment planning systems are greatly based on TG-43 protocol which in all materials are considered to be water equivalent. MATERIALS AND METHODS: A cylindrical PMMA phantom with a tube in the center (neck equivalent phantom) accompanied by Flexitron HDR brachytherapy system was used in this study. Brachytherapy applicators with various diameters were placed inside the esophageal tube and EDR2 film was used for dosimetry. The absorbed dose by reference point of esophageal HDR brachytherapy and anterior wall of trachea were measured and compared with those calculated by Flexiplan treatment planning system. RESULTS: Based on the performed statistical analysis (t-test) with 95% confidence level (t-value >1.96), there was a meaningful difference between the results of film dosimetry and treatment planning at all of the points understudy. CONCLUSION: The meaningful difference between the results of film dosimetry and treatment planning indicates that the trachea inhomogeneity has a considerable effect on dose calculations of Flexiplan treatment planning software featuring the TG-43 dose calculation algorithm. This mismatch can affect the accuracy of performed treatment plan and irradiation.

The influence of smoking on radiation-induced bystander signal production in esophageal cancer patients.

The relevance of radiation-induced bystander effects in humans is unclear. Much of the existing data relate to cell lines but the effect of bystander signals in complex human tissues is unclear. A phase II clinical study was untaken, where blood sera from 60 patients along with 15 cancer-free volunteers were used to detect whether measurable bystander factor(s) could be found in the blood following high dose rate (HDR) brachytherapy. Overall, there was no significant change in bystander signal production (measured in a human keratinocyte reporter system) before and after one treatment fraction of HDR brachytherapy (p>0.05). Further assessment of patient characteristics and environmental modifiable factors including smoking were also analyzed. Similar to previously published data, samples taken from smokers produced weaker signals compared to non-smokers (p<0.05). Although the number of non-smoking subjects was low, there was a clear decrease in cloning efficiency observed in keratinocyte cultures for these patients that requires further study. This study found that samples taken from smokers do not produce bystander signals, whereas samples taken from non-smokers can produce such signals following HDR brachytherapy. These findings highlight the importance of studying the interactions of multiple stressors including environmental modifiers with radiation, since some factors such as smoking may elicit protection in tumor cells which could counteract the effectiveness of radiation therapy.

Evaluation of tolerance and toxicity of high-dose-rate brachytherapy boost combined with interstitial hyperthermia for prostate cancer.

Purpose The aim of this retrospective study was to evaluate the tolerance and early as well as late toxicity of high dose rate brachytherapy (HDRBT) boost combined with interstitial hyperthermia (IHT) in patients treated for prostate cancer. Material and methods Between January 2011 and June 2013 76 patients diagnosed with prostate cancer received treatment consisting of external beam radiotherapy (EBRT), followed by a HDRBT boost combined with IHT. IHT was performed before each brachytherapy fraction. Results The median follow-up time was 26.3 months (range 7-43 months). Early genitourinary (GU) grade 1 and 2 toxicities were common, but only two patients (2.6%) experienced acute urinary retention requiring temporary catheterisation (grade 2 toxicity). No grade 3 or 4 genitourinary or gastrointestinal toxicities were observed. In the group analysed, 59 of 76 patients had follow-up times longer than 18 months. The incidence of grade 2 late toxicity in the group studied did not exceed 23.7%. There were no late grade 2 or higher complications from the gastrointestinal tract. Conclusions The tolerance of HDRBT boost combined with IHT is good. The profile and the percentage of early and late complications are acceptable.

Prostate Specific Antigen (PSA) as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT) in Combination with Additional External Beam Radiation Therapy (EBRT) for High Risk Prostate Cancer.

High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer (PCa). Seventy-nine male patients (median age 71 years, range 50 to 79) with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval) with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA) value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index), Gleason score, D'Amico risk classification for PCa, digital rectal examination (DRE), PSA value after one/three/five year(s) follow-up (FU), time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis (p = 0.009), PSA on date of first HDR-BT (p = 0.033), and PSA on date of first follow-up after one year (p = 0.025) have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities.

Dosimetric analysis of Co-60 source based high dose rate (HDR) brachytherapy: A case series of ten patients with carcinoma of the uterine cervix.

AIM: To analyse the dosimetric parameters of Co-60 based high dose rate (HDR) brachytherapy plans for patients of carcinoma uterine cervix. BACKGROUND: Co-60 high dose rate (HDR) brachytherapy unit has been introduced in past few years and is gaining importance owing to its long half life, economical benefits and comparable clinical outcome compared to Ir-192 HDR brachytherapy. MATERIALS AND METHODS: A study was conducted on ten patients with locally advanced carcinoma of the uterine cervix (Ca Cx). Computed tomography (CT) images were taken after three channel applicator insertions. The planning for 7 Gray per fraction (7 Gy/#) was done for Co-60 HDR brachytherapy unit following the American Brachytherapy Society (ABS) guidelines. All the patients were treated with 3# with one week interval between fractions. RESULTS: The mean dose to high risk clinical target volumes (HRCTV) for D90 (dose to 90% volume) was found to be 102.05% (Standard Deviation (SD): 3.07). The mean D2cc (dose to 2 cubic centimeter volume) of the bladder, rectum and sigmoid were found to be 15.9 Gy (SD: 0.58), 11.5 Gy (SD: 0.91) and 4.1 Gy (SD: 1.52), respectively. CONCLUSION: The target coverage and doses to organs at risk (OARs) were achieved as per the ABS guidelines. Hence, it can be concluded that the Co-60 HDR brachytherapy unit is a good choice especially for the centers with a small number of brachytherapy procedures as no frequent source replacement is required like in an Ir-192 HDR unit.

Correlation between the changes in the EPIC QOL scores and the dose-volume histogram parameters in high-dose-rate brachytherapy combined with hypofractionated external beam radiation therapy for prostate cancer.

OBJECTIVE: To evaluate the correlations between the changes in the quality-of-life scores and the dose-volume histogram parameters in patients receiving high-dose-rate brachytherapy combined with hypofractionated external beam radiation therapy for localized prostate cancer. METHODS: Among the patients who were treated with high-dose-rate brachytherapy (18 Gy in two fractions) combined with hypofractionated external beam radiation therapy (45 Gy in 15 fractions), the data of 118 consecutive patients followed up for >24 months were prospectively analyzed. The disease-specific quality of life was assessed using the expanded prostate cancer index composite, and the acute genitourinary toxicities were graded based on the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer Toxicity criteria. RESULTS: The median follow-up duration was 58 months (42-84 months). Thirteen patients (11%) developed Grade 2 or more severe acute genitourinary toxicities. The score for the general urinary domain of the expanded prostate cancer index composite quality-of-life scores dropped significantly at 1 month after high-dose-rate brachytherapy, and then returned to the baseline level by 3 months. Among the dose-volume histogram parameters, the reduction of the expanded prostate cancer index composite quality-of-life scores for the general urinary domain and its subscales at 12 months after high-dose-rate brachytherapy was significantly greater in the patients for whom the V150 or urethral D10 was within the upper 20% of the range than in those in whom the values of these dosimetric parameters were within the lower 20% of the range. CONCLUSION: The high-dose area of the prostate gland (V150) or urethra (D10) might influence the quality-of-life scores for the urinary domain and its subscales over the long term.

A Monte Carlo study on dose distribution evaluation of Flexisource (192)Ir brachytherapy source.

AIM: The aim of this study is to evaluate the dose distribution of the Flexisource (192)Ir source. BACKGROUND: Dosimetric evaluation of brachytherapy sources is recommended by task group number 43 (TG. 43) of American Association of Physicists in Medicine (AAPM). MATERIALS AND METHODS: MCNPX code was used to simulate Flexisource (192)Ir source. Dose rate constant and radial dose function were obtained for water and soft tissue phantoms and compared with previous data on this source. Furthermore, dose rate along the transverse axis was obtained by simulation of the Flexisource and a point source and the obtained data were compared with those from Flexiplan treatment planning system (TPS). RESULTS: The values of dose rate constant obtained for water and soft tissue phantoms were equal to 1.108 and 1.106, respectively. The values of the radial dose function are listed in the form of tabulated data. The values of dose rate (cGy/s) obtained are shown in the form of tabulated data and figures. The maximum difference between TPS and Monte Carlo (MC) dose rate values was 11% in a water phantom at 6.0 cm from the source. CONCLUSION: Based on dosimetric parameter comparisons with values previously published, the accuracy of our simulation of Flexisource (192)Ir was verified. The results of dose rate constant and radial dose function in water and soft tissue phantoms were the same for Flexisource and point sources. For Flexisource (192)Ir source, the results of TPS calculations in a water phantom were in agreement with the simulations within the calculation uncertainties. Furthermore, the results from the TPS calculation for Flexisource and MC calculation for a point source were practically equal within the calculation uncertainties.