Outcome of intraoperative brachytherapy as a salvage treatment for locally recurrent rectal cancer.

BACKGROUND: Locally advanced recurrent rectal cancer (RRC) requires a multimodal approach. Intraoperative high-dose-rate brachytherapy (HDR-BT) may reduce the risk of local recurrence. However, the optimal therapeutic regimen remains unclear. The aim of this retrospective monocentric study was to evaluate the toxicity of HDR-BT after resection of RRC. METHODS: Between 2018 and 2022, 17 patients with RRC received resection and HDR-BT. HDR-BT was delivered alone or as an anticipated boost with a median dose of 13 Gy (range 10-13 Gy) using an 192iridium microSelectron HDR remote afterloader (Elekta AB, Stockholm, Sweden). All participants were followed for assessment of acute and late adverse events using the Common Terminology Criteria for Adverse Events version 5.0 and the modified Late Effects in Normal Tissues criteria (subjective, objective, management, and analytic; LENT-SOMA) at 3­ to 6­month intervals. RESULTS: A total of 17 patients were treated by HDR-BT with median dose of 13 Gy (range 10-13 Gy). Most patients (47%) had an RRC tumor stage of cT3­4 N0. At the time of RRC diagnosis, 7 patients (41.2%) had visceral metastases (hepatic, pulmonary, or peritoneal) in the sense of oligometastatic disease. The median interval between primary tumor resection and diagnosis of RRC was 17 months (range 1-65 months). In addition to HDR-BT, 2 patients received long-course chemoradiotherapy (CRT; up to 50.4 Gy in 1.8-Gy fractions) and 2 patients received short-course CRT up to 36 Gy in 2­Gy fractions. For concomitant CRT, all patients received 5­fluorouracil (5-FU) or capecitabine. Median follow-up was 13 months (range 1-54). The most common acute grade 1-2 toxicities were pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and lymphedema in 2 patients (11.8%). Chronic toxicities were similar: grade 1-2 pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and incontinence in 2 patients (11.8%). No patient experienced a grade ≥3 event. CONCLUSION: Reirradiation using HDR-BT is well tolerated with low toxicity. An individualized multimodality approach using HDR-BT in the oligometastatic setting should be evaluated in prospective multi-institutional studies.

Intraoperative radiotherapy boost as part of breast-conservation therapy for breast cancer: a single-institution retrospective analysis.

BACKGROUND: There are currently no data from randomized controlled trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost as part of a breast-conservation approach for breast cancer. This study retrospectively reviewed the safety and efficacy of IORT as a boost treatment at a tertiary cancer center. METHODS: From 2015 to 2019, patients underwent breast-conserving surgery with axillary lymph node staging and a single dose of 20 Gy IORT with 50-kV photons, followed by whole-breast irradiation (WBI) and adjuvant systemic therapy (if applicable). Patients were followed for assessment of acute and late toxicities (using the Common Terminology Criteria for Adverse Events version 5.0) at 3-6-month intervals. Outcomes included ipsilateral (IBTR) and contralateral breast progression-free survival (CBE), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: Median follow-up for the 214 patients was 28 (range 2-59) months. Most patients had T1 disease (n = 124) and were clinically node negative. Only few patients had high-grade and/or triple-negative disease. The vast majority of patients underwent sentinel node biopsy, and 32 (15%) required re-resection for initially positive margins. Finally, all tumor bed margins were clear. Nine (4.2%) and 48 (22.4%) patients underwent neoadjuvant and adjuvant chemotherapy, respectively. WBI was predominantly performed as conventionally fractionated WBI (n = 187, 87.4%), and the median time from BCS to WBI was 54.5 days. IORT was delivered with a single dose of 20 Gy. The median WBI dose was 50 Gy (range 29.4-50.4 Gy). No patients experienced grade 4 events; acute grade 3 toxicities were limited to 17 (8%) cases of radiation dermatitis. Postoperative toxicities were mild. After WBI only one case of late grade ≥ 2 events was reported. There were two recurrences in the tumor bed and one contralateral breast event. CONCLUSION: This investigation provides additional preliminary data supporting the using of IORT in the boost setting and corroborates the existing literature. These encouraging results should be prospectively validated by the eventual publication of randomized studies such as TARGIT­B.

Biological imaging for individualized therapy in radiation oncology: part I physical and technical aspects.

Recently, there has been an increase in the imaging modalities available for radiotherapy planning and radiotherapy prognostic outcome: dual energy computed tomography (CT), dynamic contrast enhanced CT, dynamic contrast enhanced magnetic resonance imaging (MRI), diffusion-weighted MRI, positron emission tomography-CT, dynamic contrast enhanced ultrasound, MR spectroscopy and positron emission tomography-MR. These techniques enable more precise gross tumor volume definition than CT alone and moreover allow subvolumes within the gross tumor volume to be defined which may be given a boost dose or an individual voxelized dose prescription may be derived. With increased plan complexity care must be taken to immobilize the patient in an accurate and reproducible manner. Moreover the physical and technical limitations of the entire treatment planning chain need to be well characterized and understood, interdisciplinary collaboration ameliorated (physicians and physicists within nuclear medicine, radiology and radiotherapy) and image protocols standardized.

Biological imaging for individualized therapy in radiation oncology: part II medical and clinical aspects.

Positron emission tomography and multiparametric MRI provide crucial information concerning tumor extent and normal tissue anatomy. Moreover, they are able to visualize biological characteristics of the tumor, which can be considered in the radiation treatment planning and monitoring. In this review we discuss the impact of biological imaging positron emission tomography and multiparametric MRI for radiation oncology, based on the data of the literature and on the experience of our own institution in this field.

Evaluation of RADIANCE Monte Carlo algorithm for treatment planning in electron based Intraoperative Radiotherapy (IOERT).

PURPOSE: To perform experimental as well as independent Monte Carlo (MC) evaluation of the MC algorithm implemented in RADIANCE version 4.0.8, a dedicated treatment planning system (TPS) for 3D electron dose calculations in intraoperative radiation therapy (IOERT). METHODS AND MATERIALS: The MOBETRON 2000 (IntraOp Medical Corporation, Sunnyvale, CA) IOERT accelerator was employed. PDD and profiles for five cylindrical plastic applicators with 50-90 mm diameter and 0°, 30° beveling were measured in a water phantom, at nominal energies of 6, 9 and 12 MeV. Additional PDD measurements were performed for all the energies without applicator. MC modeling of the MOBETRON was performed with the user code BEAMnrc and egs_chamber of the MC simulation toolkit EGSnrc. The generated phase space files of the two 0°-bevel applicators (50 mm, 80 mm) and three energies in both RADIANCE and BEAMnrc, were used to determine PDD and profiles in various set-ups of virtual water phantoms with air and bone inhomogeneities. 3D dose distributions were also calculated in image data sets of an anthropomorphic tissue-equivalent pelvis phantom. Image acquisitions were realized with a CT scanner (Philips Big Bore CT, Netherlands). Gamma analysis was applied to quantify the deviations of the RADIANCE calculations to the measurements and EGSnrc calculations. Gamma criteria normalized to the global maximum were investigated between 2%, 2 mm and 3%, 3 mm. RESULTS: RADIANCE MC calculations satisfied the gamma criteria of 3%, 3 mm with a tolerance limit of 85% passing rate compared to in- water phantom measurements, except for the dose profiles of the 30° beveled applicators. Mismatches lay in surface doses, in umbra regions and in the beveled end of the 30° applicators. A very good agreement to the EGSnrc calculations in heterogeneous media was observed. Deviations were more pronounced for the larger applicator diameter and higher electron energy. In 3D dose comparisons in the anthropomorphic phantom, gamma passing rates were higher than 96 % for both simulated applicators. CONCLUSIONS: RADIANCE MC algorithm agrees within 3%, 3 mm criteria with in-water phantom measurements and EGSnrc MC dose distributions in heterogeneous media for 0°-bevel applicators. The user should be aware of missing scattering components and the 30° beveled applicators should be used with attention.

The value of a multimodal approach combining radical surgery and intraoperative radiotherapy in the recurrence treatment of gynecological malignancies - analysis of a large patient cohort in a tertiary care center.

BACKGROUND: Recurrent and locally advanced gynecological malignancies have a poor prognosis. In particularly, pelvic local recurrence after previous radiotherapy and/or positive resection margins during surgical treatment for recurrent disease result in low survival rates. Consequently, locoregional control is of utmost importance in this cohort of patients. The aim of this study was to analyze treatment outcomes and determine prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for recurrent and locally advanced gynecological malignancies. METHODS: 40 patients who underwent surgical treatment and IORT between 2010 and 2022 were eligible for inclusion. The median follow-up time was 22 months. The outcomes measured were locoregional control (LRC), overall survival (OS), and survival without distant metastases (DMFS). The Cox proportional hazards model was used for univariate and multivariate analysis to assess the impact of patient variables and treatment factors on the endpoints mentioned. The following variables were analyzed: age at surgical treatment and IORT and initial diagnosis (< 65 vs. ≥65 years, each), disease-free interval (DFI) between initial diagnosis and first recurrence, DFI to surgical treatment and IORT, grading, histology, IORT dose (≤ 13 vs. >13 Gy) and technique (high dose radiotherapy (HDR) vs. IORT using electrons, (IOERT)). Survival curves were generated using the Kaplan-Meier method. RESULTS: The mean IORT dose was 13.8 Gy (range 10-18 Gy). Cervical carcinoma was most frequently found in 27.5% of patients followed by endometrial carcinoma and vulvar carcinoma in 25% respectively. The final histopathologic results after surgery with IORT showed no residual tumour in 24 patients (60%), microscopic residual disease in 5 patients (12.5%), resection status could not be evaluated in three patients (7.5%) and the resection status was unknown in eight patients (20%). Subsequently, 27.5% of patients also received adjuvant radiotherapy of the local recurrence bed. However, after IORT, 65% of the women suffered a recurrence. Of these, the recurrences were localized: in-field 32.5%, out-of-field 22.5% and margin-of-field 12.5%. The 3- and 5-year OS was 69% and 55% respectively. The 3- and 5-year LRC was 56% respectively. The 3- and 5-year DMFS was 66% and 49%. Whereas the comparison between groups by IORT dose level (≤ 13 vs. >13 Gy) showed a non-significant trend in favor of the higher dose only for OS (p = 0.094), but not in LRC and DMFS (p > 0.05). OS and DMFS, but not LRC, differed significantly between the HDR-IORT and IOERT groups (p = 0.06 and p = 0.03,) in favor of the HDR-IORT technique. For HDR-IORT technique a trend towards superior OS and LRC was observed in the univariate analysis: HR 3.76, CI 95%: 0.95-14.881, p = 0.059 and HR 2.165 CI 95%: 0.916-5.114, p = 0.078 CONCLUSIONS: The survival rate for pelvic recurrence in gynecological malignancies remains poor and comparable with historical data from the last two decades. Particularly HDR-IORT, appears to provide a long-term oncological benefit in carefully selected patients.

Determination of the dose rate around a HDR 192Ir brachytherapy source with the microDiamond and the microSilicon detector.

PURPOSE: To employ the microDiamond and the microSilicon detector (mDD and mSD, both PTW-Freiburg, Germany) to determine the dose rate around a HDR 192Ir brachytherapy source (model mHDR-v2r, Elekta AB, Sweden). METHODS: The detectors were calibrated with a 60Co beam at the PTW Calibration Laboratory. Measurements around the 192Ir source were performed inside a PTW MP3 water phantom. The detectors were placed at selected points of measurement at radial distances r, ranging from 0.5 to 10 cm, keeping the polar angle θ = 90°. Additional measurements were performed with the mSD at fixed distances r = 1, 3 and 5 cm, with θ varying from 0 to 150°, 0 to 166°, and 0 to 168°, respectively. The corresponding mDD readings were already available from a previous work (Rossi et al., 2020). The beam quality correction factor of both detectors, as well as a phantom effect correction factor to account for the difference between the experimental geometry and that assumed in the TG-43 formalism, were determined using the Monte Carlo (MC) toolkit EGSnrc. The beam quality correction factor was factorized into energy dependence and volume-averaging correction factors. Using the abovementioned MC-based factors, the dose rate to water at the different points of measurement in TG-43 conditions was obtained from the measured readings, and was compared to the dose rate calculated according to the TG-43 formalism. RESULTS: The beam quality correction factor was considerably closer to unity for the mDD than for the mSD. The energy dependence of the mDD showed a very weak radial dependence, similar to the previous findings showing a weak angular dependence as well (Rossi et al., 2020). Conversely, the energy dependence of the mSD decreased significantly with increasing distances, and also showed a considerably more pronounced angular dependence, especially for the smallest angles. The volume-averaging showed a similar radial dependence for both detectors: the correction had a maximal impact at 0.5 cm and then approached unity for larger distances, as expected. Concerning the angular dependence, the correction for the mSD was also similar to the one previously determined for the mDD (Rossi et al., 2020): a maximal impact was observed at θ = 0°, with values tending to unity for larger angles. In general, the volume-averaging was less pronounced for the mSD due to the smaller sensitive volume radius. After the application of the MC-based factors, differences between mDD dose rate measurements and TG-43 dose rate calculations ranged from -2.6% to +4.3%, with an absolute average difference of 1.0%. For the mSD, the differences ranged from -3.1% to +5.2%, with an absolute average difference of 1.0%. For both detectors, all differences but one were within the combined uncertainty (k = 2). The differences of the mSD from the mDD ranged from -3.9% to +2.6%, with the vast majority of them being within the combined uncertainty (k = 2). For θ ≠ 0°, the mDD was able to provide sufficiently accurate results even without the application of the MC-based beam quality correction factor, with differences to the TG-43 dose rate calculations from -1.9% to +3.4%, always within the combined uncertainty (k = 2). CONCLUSION: The mDD and the mSD showed consistent results and appear to be well suitable for measuring the dose rate around HDR 192Ir brachytherapy sources. MC characterization of the detectors response is needed to determine the beam quality correction factor and to account for energy dependence and/or volume-averaging, especially for the mSD. Our findings support the employment of the mDD and mSD for source QA, TPS verification and TG-43 parameters determination.

Comparison of intraoperative radiotherapy as a boost vs. simultaneously integrated boosts after breast-conserving therapy for breast cancer.

Background: Currently, there are no data from randomized trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost in women at high risk of local recurrence. The aim of this retrospective analysis was to compare the toxicity and oncological outcome of IORT or simultaneous integrated boost (SIB) with conventional external beam radiotherapy (WBI) after breast conserving surgery (BCS). Methods: Between 2009 and 2019, patients were treated with a single dose of 20 Gy IORT with 50 kV photons, followed by WBI 50 Gy in 25 or 40.05 in 15 fractions or WBI 50 Gy with SIB up to 58.80-61.60 Gy in 25-28 fractions. Toxicity was compared after propensity score matching. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Results: A 1:1 propensity-score matching resulted in an IORT + WBI and SIB + WBI cohort of 60 patients, respectively. The median follow-up for IORT + WBI was 43.5 vs. 32 months in the SIB + WBI cohort. Most women had a pT1c tumor: IORT group 33 (55%) vs. 31 (51.7%) SIB group (p = 0.972). The luminal-B immunophenotype was most frequently diagnosed in the IORT group 43 (71.6%) vs. 35 (58.3%) in the SIB group (p = 0.283). The most reported acute adverse event in both groups was radiodermatitis. In the IORT cohort, radiodermatitis was grade 1: 23 (38.3%), grade 2: 26 (43.3%), and grade 3: 6 (10%) vs. SIB cohort grade 1: 3 (5.1%), grade 2: 21 (35%), and grade 3: 7 (11.6%) without a meaningful difference (p = 0.309). Fatigue occurred more frequently in the IORT group (grade 1: 21.7% vs. 6.7%; p = 0.041). In addition, intramammary lymphedema grade 1 occurred significantly more often in the IORT group (11.7% vs. 1.7%; p = 0.026). Both groups showed comparable late toxicity. The 3- and 5-year local control (LC) rates were each 98% in the SIB group vs. 98% and 93% in the IORT group (LS: log rank p = 0.717). Conclusion: Tumor bed boost using IORT and SIB techniques after BCS shows excellent local control and comparable late toxicity, while IORT application exhibits a moderate increase in acute toxicity. These data should be validated by the expected publication of the prospective randomized TARGIT-B study.

Methods for monitor-unit-preserving adaptation of intensity modulated arc therapy techniques to the daily target-A simple comparison.

PURPOSE: For fast adaptation of step and shoot intensity modulated radiotherapy (IMRT) plans, monitor units (MU)-preserving methods which modify only the segment shapes have been proposed in the literature. In this work, two such adaptation methods are applied to intensity modulated arc therapy (IMAT) and their results are compared to that of a newly optimized IMAT plan. METHODS: In a simplified cylindrically symmetric model, the organ at risk (OAR) is surrounded by the planning target volume (PTV). For the initial plan, a steep dose gradient is produced by variants of double arc (IMAT) plans. To simulate situations which require adaptation, the OAR radius and the inner PTV radius have been varied. One adaptation method (Warp) is based on a mesh spanned over structures identified within the beam's eye view (BEV). Changes to the structure projections warp the mesh. For the adaptation, the segment shapes are fixed to the mesh. The other method (2-Step) uses geometrical 3D information from the computed tomography (CT). For comparison, the objective function representing the dose to the PTV as well as the mean and the maximum dose to the OAR is used. RESULTS: For the narrow segments that compensate the underdosage in the PTV areas proximate to the OAR, the Warp method suggests contrary adaptation rules compared to the 2-Step method. In contrast to Warp, the 2-Step method approximates the behavior of a newly optimized plan and leads to better dose homogeneity in the clinical target volume (CTV) and the PTV, whilst simultaneously sparing the OAR. CONCLUSIONS: For minor changes associated with less steep dose gradients, both Warp and 2-Step methods are suitable. However, the 2-Step method should be preferred for more challenging cases, where steep dose gradients between the OAR and the concave PTV are needed. For considerable interfractional reductions of the gap between the OAR and the PTV, where especially steep dose gradients have to be generated, MU-preserving adaptation techniques are not adequate. In this case, narrower segments in the initial plan can be used to facilitate the adaptation. Otherwise, non-MU-preserving adaptation methods have to be applied. Further work is needed to include clinical cases with more complex geometries and expand the methods to IMRT techniques.

PSMA-PET- and MRI-Based Focal Dose Escalated Radiation Therapy of Primary Prostate Cancer: Planned Safety Analysis of a Nonrandomized 2-Armed Phase 2 Trial (ARO2020-01).

PURPOSE: The bicentric HypoFocal phase 2 trial investigates the implementation of molecular imaging with positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET) into modern focal dose-escalation radiation therapy (RT) concepts in 2 nonrandomized arms. We present the planned safety analysis after 6 months of follow-up. MATERIALS AND METHODS: Intermediate- and high-risk localized primary prostate cancer patients staged with multiparametric magnet resonance tomography and PSMA-PET were either treated with focal dose-escalated moderately hypofractionated RT (arm A) or single fraction high-dose-rate brachytherapy followed by external beam RT (arm B). PSMA-PET was used in addition to primary prostate cancer to define the intraprostatic gross tumor volume. Gastrointestinal and genitourinary toxicities were assessed according to Common Toxicity Criteria for Adverse Events (version 5.0) criteria. International Prostate Symptom Score was measured and quality of life assessed with European Organisation for Research and Treatment of Cancer questionnaires QLQ-PR25/-PR30. We enrolled 25 patients in each study arm. RESULTS: The implementation of PET-information led to large median volumes for dose escalation: 10.2 mL in arm A and 6.8 mL in Arm B. RT dose-escalation was feasible in all patients of arm A with up to 75 Gy (20 fractions) and in 23 patients with up to 19 Gy (1 fraction) in arm B. Toxicities, International Prostate Symptom Scores, and European Organisation for Research and Treatment of Cancer quality of life scores were not significantly different between baselines and 6 months follow-up in both arms. No grade 3 toxicities were observed at 6 months follow-up. CONCLUSIONS: This is the first prospective data supporting the feasibility of PSMA-PET-implementation into definitive focal dose-escalated RT. Patients maintained a good quality of life and a low toxicity profile after 6 months of follow-up.

Fast intensity-modulated arc therapy based on 2-step beam segmentationa.

PURPOSE: Single or few are intensity-modulated arc therapy (IMAT) is intended to be a time saving irradiation method, potentially replacing classical intensity-modulated radiotherapy (IMRT). The aim of this work was to evaluate the quality of different IMAT methods with the potential of fast delivery, which also has the possibility of adapting to the daily shape of the target volume. METHODS: A planning study was performed. Novel double and triple IMAT techniques based on the geometrical analysis of the target organ at risk geometry (2-step IMAT) were evaluated. They were compared to step and shoot IMRT reference plans generated using direct machine parameter optimization (DMPO). Volumetric arc (VMAT) plans from commercial preclinical software (SMARTARC) were used as an additional benchmark to classify the quality of the novel techniques. Four cases with concave planning target volumes (PTV) with one dominating organ at risk (OAR), viz., the PTV/OAR combination of the ESTRO Quasimodo phantom, breast/lung, spine metastasis/ spinal cord, and prostate/rectum, were used for the study. The composite objective value (COV) and other parameters representing the plan quality were studied. RESULTS: The novel 2-step IMAT techniques with geometry based segment definition were as good as or better than DMPO and were superior to the SMARTARC VMAT techniques. For the spine metastasis, the quality measured by the COV differed only by 3%, whereas the COV of the 2-step IMAT for the other three cases decreased by a factor of 1.4-2.4 with respect to the reference plans. CONCLUSIONS: Rotational techniques based on geometrical analysis of the optimization problem (2-step IMAT) provide similar or better plan quality than DMPO or the research version of SMARTARC VMAT variants. The results justify pursuing the goal of fast IMAT adaptation based on 2-step IMAT techniques.

Suitability of the microDiamond detector for experimental determination of the anisotropy function of High Dose Rate 192 Ir brachytherapy sources.

PURPOSE: To investigate the suitability of the microDiamond detector (mDD) type 60019 (PTW-Freiburg, Germany) to measure the anisotropy function F(r,θ) of High Dose Rate (HDR) 192 Ir brachytherapy sources. METHODS: The HDR 192 Ir brachytherapy source, model mHDR-v2r (Elekta AB, Sweden), was placed inside a water tank within a 4F plastic needle. Four mDDs (mDD1, mDD2, mDD3, and mDD4) were investigated. Each mDD was placed laterally with respect to the source, and measurements were performed at radial distances r = 1 cm, 3 and 5 cm, and polar angles θ from 0° to 168°. The Monte Carlo (MC) system EGSnrc was used to simulate the measurements and to calculate phantom effect, energy dependence and volume-averaging correction factors. F(r,θ) was determined according to TG-43 formalism from the detector reading corrected with the MC-based factors and compared to the consensus anisotropy function CON F(r,θ). RESULTS: At 1 cm, the differences between measurements and MC simulations ranged from -0.8% to +0.8% for θ = 0° and from -2.1% to + 2.3% for θ ≠ 0°. At 3 and 5 cm, the differences ranged from +1.4% to +3.9% for θ = 0°, and from -0.4% to +2.9% for θ ≠ 0°. All differences were within the uncertainties (k = 2). At small angles, the phantom effect correction was up to -1.9%. This effect was mainly caused by the air between source and needle tip. The energy correction was angle-independent everywhere. For small angles at 1 cm, the volume-averaging correction was up to -2.9% and became less important for larger angles and distances. The differences of the measured F(r,θ) corrected with the MC-based factors to CON F(r,θ) ranged from -1.0% to +3.4% for mDD1, -2.2% to +4.2% for mDD2, -2.5% to +4.0% for mDD3, and -2.6% to +3.4% for mDD4. All differences were within the uncertainties (k = 2) except one at (3 cm, 0°). For all the mDDs, F(r,0°) was always higher than CON F(r,0°), with average differences of +3.1% (1 cm), +3.6% (3 cm), and +1.9% (5 cm). The inter-detector variability was within 2.9% (1 cm), 1.8% (3 cm), and 3.4% (5 cm). CONCLUSIONS: A reproducible method and experimental setup were presented for measuring and validating F(r,θ) of an HDR 192 Ir brachytherapy source in a water phantom using the mDD. The phantom effect and the volume-averaging need to be taken into account, especially for the smaller distances and angles. Good agreement to CON F(r,θ) was obtained. The discrepancies at (1 cm, 0°), accurately predicted by the MC results, may suggest a reconsideration of CON F(r,θ), at least for this position. The slight overestimations at (3 cm,0°) and (5 cm,0°), both in comparison to CON F(r,θ) and MC results, may be due to an underestimation of the air volume between source and needle tip, dark current, intrinsic over-response of the mDDs, or radiation-induced charge imbalance in the detector's components. The results indicate that the mDD is a valuable tool for measurements with HDR 192 Ir brachytherapy sources and support its employment for the determination and validation of TG-43 parameters of such sources.

Investigating the role of constrained CVT and CVT in HIPO inverse planning for HDR brachytherapy of prostate cancer.

PURPOSE: The purpose of this study is to investigate the role of the centroidal Voronoi tessellation (CVT) and constrained CVT (CCVT) in inverse planning in combination with the Hybrid Inverse Planning Optimization (HIPO) algorithm in HDR brachytherapy of prostate cancer. HIPO implemented in Oncentra© Prostate treatment planning system, is used for three-dimensional (3D)-ultrasound-based intraoperative treatment planning in high dose rate brachytherapy. HIPO utilizes a hybrid iterative process to determine the most appropriate placement of a given number of catheters to fulfil predefined dose-volume constraints. The main goals of the current investigation were to identify a way of improving the performance of HIPO inverse planning; accelerating the HIPO, and to evaluate the effect of the two CVT-based initialization methods on the dose distribution in the sub-region of prostate that is not accessible by catheters, when trying to avoid perforation of urethra. METHODS: We implemented the CVT algorithm to generate initial catheter configurations before the initialization of the HIPO algorithm. We introduced the CCVT algorithm to improve the dose distribution to the sub-volume of prostate within the bounding box of the urethra contours including its upper vertical extension (U-P). For the evaluation, we considered a total of 15 3D ultrasound-based HDRBT prostate implants. Execution time and treatment plan quality were evaluated based on the dose-volume histograms of prostate (PTV), its sub-volume U-P, and organs at risk (OARs). Furthermore, the conformity index COIN, the homogeneity index HI and the complication-free tumor control probability (P+ ) were used for our treatment plan comparisons. Finally, the plans with the recommended HIPO execution mode were compared to the clinically used intraoperative pre-plans. RESULTS: The plan quality achieved with CCVT-based HIPO initialization was superior to the default HIPO initialization method. Focusing on the U-P sub-region of the prostate, the CCVT method resulted in a significant improvement of all dosimetric indices compared to the default HIPO, when both were executed in the adaptive mode. For that recommended HIPO execution mode, and for U-P, CCVT demonstrated in general higher dosimetric indices than CVT. Additionally, the execution time of CCVT initialized HIPO was lower compared to both alternative initialization methods. This is also valid for the values of the aggregate objective function with the differences to the default initialization method being highly significant. Paired non-parametric statistical tests (Wilcoxon signed-rank) showed a significant improvement of dose-volume indices, COIN and P+ for the plans generated by the CCVT-based catheter configuration initialization in HIPO compared to the default HIPO initialization process. Furthermore, in ten out of 15 cases, the CCVT-based HIPO plans fulfilled all the clinical dose-volume constraints in a single trial without any need for further catheter position adaption. CONCLUSION: HIPO with CCVT-based initialization demonstrates better performance regarding the aggregate objective function and convergence when compared to the CVT-based and default catheter configuration initialization methods. This improved performance of HIPO inverse planning is clearly not at the cost of the dosimetric and radiobiologically evaluated plan quality. We recommend the use of the CCVT method for HIPO initialization especially in the adaptive planning mode.

Monte Carlo and experimental high dose rate 192Ir brachytherapy dosimetry with microDiamond detectors.

The purpose of this study was to investigate the suitability of the microDiamond detector (mDD) type 60019 (PTW-Freiburg, Germany) for radial dose function measurements with High Dose Rate (HDR) 192Ir brachytherapy sources. An HDR 192Ir source model mHDR v2r (Nucletron BV, an Elekta company, The Netherlands) was placed at the centre of a MP3 water phantom (PTW-Freiburg, Germany) within a 4F needle. Three mDDs were employed to measure the radial dose function of the source by acquiring profiles along the source transverse axis. Meanwhile, the experimental setup was simulated using the Monte Carlo (MC) code MCNP6.1™ (Los Alamos National Laboratory, USA) to calculate phantom-size, absorbed-dose energy dependence and volume averaging correction factors. After applying the correction factors, the radial dose function gL(r) for the line source approximation was calculated as defined in the TG-43 formalism at radial distances from 0.5cm to 10cm and compared to the consensus gL(r) (ESTRO and AAPM). The percentage differences to the consensus gL(r) for all the three mDDs were from -2.3% to +1.4% for distances r≤5cm and -6.2% to +2.6% for larger distances. These results indicate the suitability of the mDD for HDR brachytherapy measurements when all required corrections are applied.

[In-phantom dosimetric measurements as quality control for brachytherapy: System check and constancy check]. / Messungen im Festkörperphantom als Qualitätskontrolle in der Brachytherapie - Systemprüfung und Konstanzprüfung.

In brachytherapy dosimetric measurements are difficult due to the inherent dose-inhomogenieties. Typically in routine clincal practice only the nominal dose rate is determined for computer controlled afterloading systems. The region of interest lies close to the source when measuring the spatial dose distribution. In this region small errors in the postioning of the detector, and its finite size, lead to large measurement uncertainties that exacerbate the routine dosimetric control of the system in the clinic. The size of the measurement chamber, its energy dependence, and the directional dependence of the measurement apparatus are the factors which have a significant influence on dosimetry. Although ionisation chambers are relatively large, they are employed since similar chambers are commonly found on clincal brachytherapy units. The dose is determined using DIN 6800 [11] since DIN 6809-2 [12], which deals with dosimetry in brachytherapy, is antiquated and is currently in the process of revision. Further information regarding dosimetry for brachytherapy can be found in textbooks [1] and [2]. The measurements for this work were performed with a HDR (High-Dose-Rate) (192)Ir source, type mHDR V2, and a Microselectron Afterloader V2 both from Nucletron/Elekta. In this work two dosimetric procedures are presented which, despite the aforemention difficulties, should assist in performing checks of the proper operation of the system. The first is a system check that measures the dose distribution along a line and is to be performed when first bringing the afterloader into operation, or after significant changes to the system. The other is a dosimetric constancy check, which with little effort can be performed monhtly or weekly. It simultaneously verifies the positioning of the source at two positions, the functionality of the system clock and the automatic re-calculation of the source activity.

Correction factors kE and kQ for LiF-TLDs for dosimetry in megavoltage electron and photon beams.

For the determination of absorbed dose to water D,using thermolumeniscence (TL) probes in a beam different from that used for calibration, correction factors for radiation type and radiation quality kE and kQ are needed. Values for kE and kQ for two different shapes of LiF probes (rods and disks) were obtained for high-energy photon and electron beams. The relation between the absorbed dose to the medium (water) D, measured by ion-chambers according to DIN 6800-2, 2008 and TL-probes having a (60)Co-calibration factor, leads for each shape and each batch of LiF probes to correction factors for radiation type and radiation quality kE and kQ.. The influence of the shape on the correction factor of the probes amounts in our experiment up to 2%. Therefore, it is recommended that the correction factors kE and kQ for rods and disks should be checked for each batch of LiF-detectors.

Visualization of data in radiotherapy using web services for optimization of workflow.

BACKGROUND: Every day a large amount of data is produced within a radiotherapy department. Although this data is available in one form or other within the centralised systems, it is often not in the form which is of interest to the departmental staff. This work presents a flexible browser based reporting and visualization system for clinical and scientific use, not currently found in commercially available software such as MOSAIQ(TM) or ARIA(TM). Moreover, the majority of user merely wish to retrieve data and not record and/or modify data. Thus the idea was conceived, to present the user with all relevant information in a simple and effective manner in the form of web-services. Due to the widespread availability of the internet, most people can master the use of a web-browser. Ultimately the aim is to optimize clinical procedures, enhance transparency and improve revenue. METHODS: Our working group (BAS) examined many internal procedures, to find out whether relevant information suitable for our purposes lay therein. After the results were collated, it was necessary to select an effective software platform. After a more detailed analysis of all data, it became clear that the implementation of web-services was appropriate. In our institute several such web-based information services had already been developed over the last few years, with which we gained invaluable experience. Moreover, we strived for high acceptance amongst staff members. RESULTS: By employing web-services, we attained high effectiveness, transparency and efficient information processing for the user. Furthermore, we achieved an almost maintenance-free and low support system. The aim of the project, making web-based information available to the user from the departmental system MOSAIQ, physician letter system MEDATEC(R) and the central finding server MiraPlus (laboratory, pathology and radiology) were implemented without restrictions. CONCLUSION: Due to widespread use of web-based technology the training effort was effectively nil, since practically every member of staff can master the use of a web-browser. Moreover, we have achieved high acceptance amongst staff members and have improved our effectiveness resulting in a considerable time saving. The many MOSAIQ-specific parts of the system can be readily used by departments which use MOSAIQ as the departmental system.

Towards automated on-line adaptation of 2-Step IMRT plans: QUASIMODO phantom and prostate cancer cases.

BACKGROUND: The standard clinical protocol of image-guided IMRT for prostate carcinoma introduces isocenter relocation to restore the conformity of the multi-leaf collimator (MLC) segments to the target as seen in the cone-beam CT on the day of treatment. The large interfractional deformations of the clinical target volume (CTV) still require introduction of safety margins which leads to undesirably high rectum toxicity. Here we present further results from the 2-Step IMRT method which generates adaptable prostate IMRT plans using Beam Eye View (BEV) and 3D information. METHODS: Intermediate/high-risk prostate carcinoma cases are treated using Simultaneous Integrated Boost at the Universitätsklinkum Würzburg (UKW). Based on the planning CT a CTV is defined as the prostate and the base of seminal vesicles. The CTV is expanded by 10 mm resulting in the PTV; the posterior margin is limited to 7 mm. The Boost is obtained by expanding the CTV by 5 mm, overlap with rectum is not allowed. Prescription doses to PTV and Boost are 60.1 and 74 Gy respectively given in 33 fractions.We analyse the geometry of the structures of interest (SOIs): PTV, Boost, and rectum, and generate 2-Step IMRT plans to deliver three fluence steps: conformal to the target SOIs (S0), sparing the rectum (S1), and narrow segments compensating the underdosage in the target SOIs due to the rectum sparing (S2). The width of S2 segments is calculated for every MLC leaf pair based on the target and rectum geometry in the corresponding CT layer to have best target coverage. The resulting segments are then fed into the DMPO optimizer of the Pinnacle treatment planning system for weight optimization and fine-tuning of the form, prior to final dose calculation using the collapsed cone algorithm.We adapt 2-Step IMRT plans to changed geometry whilst simultaneously preserving the number of initially planned Monitor Units (MU). The adaptation adds three further steps to the previous isocenter relocation: 1) 2-Step generation for the geometry of the day using the relocated isocenter, MU transfer from the planning geometry; 2) Adaptation of the widths of S2 segments to the geometry of the day; 3) Imitation of DMPO fine-tuning for the geometry of the day. RESULTS AND CONCLUSION: We have performed automated 2-Step IMRT adaptation for ten prostate adaptation cases. The adapted plans show statistically significant improvement of the target coverage and of the rectum sparing compared to those plans in which only the isocenter is relocated. The 2-Step IMRT method may become a core of the automated adaptive radiation therapy system at our department.

Fast IMRT by increasing the beam number and reducing the number of segments.

PURPOSE: The purpose of this work is to develop fast deliverable step and shoot IMRT technique. A reduction in the number of segments should theoretically be possible, whilst simultaneously maintaining plan quality, provided that the reduction is accompanied by an increased number of gantry angles. A benefit of this method is that the segment shaping could be performed during gantry motion, thereby reducing the delivery time. The aim was to find classes of such solutions whose plan quality can compete with conventional IMRT. MATERIALS/METHODS: A planning study was performed. Step and shoot IMRT plans were created using direct machine parameter optimization (DMPO) as a reference. DMPO plans were compared to an IMRT variant having only one segment per angle ("2-Step Fast"). 2-Step Fast is based on a geometrical analysis of the topology of the planning target volume (PTV) and the organs at risk (OAR). A prostate/rectum case, spine metastasis/spinal cord, breast/lung and an artificial PTV/OAR combination of the ESTRO-Quasimodo phantom were used for the study. The composite objective value (COV), a quality score, and plan delivery time were compared. The delivery time for the DMPO reference plan and the 2-Step Fast IMRT technique was measured and calculated for two different linacs, a twelve year old Siemens Primus™ ("old" linac) and two Elekta Synergy™ "S" linacs ("new" linacs). RESULTS: 2-Step Fast had comparable or better quality than the reference DMPO plan. The number of segments was smaller than for the reference plan, the number of gantry angles was between 23 and 34. For the modern linac the delivery time was always smaller than that for the reference plan. The calculated (measured) values showed a mean delivery time reduction of 21% (21%) for the new linac, and of 7% (3%) for the old linac compared to the respective DMPO reference plans. For the old linac, the data handling time per beam was the limiting factor for the treatment time reduction. CONCLUSIONS: 2-Step Fast plans are suited to reduce the delivery time, especially if the data handling time per beam is short. The plan quality can be retained or even increased for fewer segments provided more gantry angles are used.

Remarks on reporting and recording consistent with the ICRU reference dose.

BACKGROUND: ICRU 50/62 provides a framework to facilitate the reporting of external beam radiotherapy treatments from different institutions. A predominant role is played by points that represent "the PTV dose". However, for new techniques like Intensity Modulated Radiotherapy (IMRT) - especially step and shoot IMRT - it is difficult to define a point whose dose can be called "characteristic" of the PTV dose distribution. Therefore different volume based methods of reporting of the prescribed dose are in use worldwide. Several of them were compared regarding their usability for IMRT and compatibility with the ICRU Reference Point dose for conformal radiotherapy (CRT) in this study. METHODS: The dose distributions of 45 arbitrarily chosen volumes treated by CRT plans and 57 volumes treated by IMRT plans were used for comparison. Some of the IMRT methods distinguish the planning target volume (PTV) and its central part PTVx (PTV minus a margin region of x mm). The reporting of dose prescriptions based on mean and median doses together with the dose to 95% of the considered volume (D95) were compared with each other and in respect of a prescription report with the aid of one or several possible ICRU Reference Points. The correlation between all methods was determined using the standard deviation of the ratio of all possible pairs of prescription reports. In addition the effects of boluses and the characteristics of simultaneous integrated boosts (SIB) were examined. RESULTS: Two types of methods result in a high degree of consistency with the hitherto valid ICRU dose reporting concept: the median dose of the PTV and the mean dose to the central part of the PTV (PTVx). The latter is similar to the CTV, if no nested PTVs are used and no patient model surfaces are involved. A reporting of dose prescription using the CTV mean dose tends to overestimate the plateau doses of the lower dose plateaus of SIB plans. PTVx provides the possibility to approach biological effects using the standard deviation of the dose within this volume. CONCLUSION: The authors advocate reporting the PTV median dose or preferably the mean dose of the central dose plateau PTVx as a potential replacement or successor of the ICRU Reference Dose - both usable for CRT and IMRT.