Inter-observer effects in needle reconstruction for temporary prostate brachytherapy: Dosimetric implications and adaptive CBCT-TRUS registration solutions.

PURPOSE: To investigate geometric and dosimetric inter-observer variability in needle reconstruction for temporary prostate brachytherapy. To assess the potential of registrations between transrectal ultrasound (TRUS) and cone-beam computed tomography (CBCT) to support implant reconstructions. METHODS AND MATERIALS: The needles implanted in 28 patients were reconstructed on TRUS by three physicists. Corresponding geometric deviations and associated dosimetric variations to prostate and organs at risk (urethra, bladder, rectum) were analyzed. To account for the found inter-observer variability, various approaches (template-based, probe-based, marker-based) for registrations of CBCT to TRUS were investigated regarding the respective needle transfer accuracy in a phantom study. Three patient cases were examined to assess registration accuracy in-vivo. RESULTS: Geometric inter-observer deviations >1 mm and >3 mm were found for 34.9% and 3.5% of all needles, respectively. Prostate dose coverage (changes up to 7.2%) and urethra dose (partly exceeding given dose constraints) were most affected by associated dosimetric changes. Marker-based and probe-based registrations resulted in the phantom study in high mean needle transfer accuracies of 0.73 mm and 0.12 mm, respectively. In the patient cases, the marker-based approach was the superior technique for CBCT-TRUS fusions. CONCLUSION: Inter-observer variability in needle reconstruction can substantially affect dosimetry for individual patients. Especially marker-based CBCT-TRUS registrations can help to ensure accurate reconstructions for improved treatment planning.

Investigating the impact of breast positioning control on physical treatment parameters in multi-catheter breast brachytherapy.

PURPOSE: To assess the effects of a workflow for reproducible patient and breast positioning on implant stability during high-dose-rate multi-catheter breast brachytherapy. METHODS: Thirty patients were treated with our new positioning control workflow. Implant stability was evaluated based on a comparison of planning-CTs to control-CTs acquired halfway through the treatment. To assess geometric stability, button-button distance variations as well as Euclidean dwell position deviations were evaluated. The latter were also quantified within various separated regions within the breast to investigate the location-dependency of implant alterations. Furthermore, dosimetric variations to target volume and organs at risk (ribs, skin) as well as isodose volume changes were analyzed. Results were compared to a previously treated cohort of 100 patients. RESULTS: With the introduced workflow, the patient fraction affected by button-button distance variations > 5 mm and by dwell position deviations > 7 mm were reduced from 37% to 10% and from 30% to 6.6%, respectively. Implant stability improved the most in the lateral to medial breast regions. Only small stability enhancements were observed regarding target volume dosimetry, but the stability of organ at risk exposure became substantially higher. D0.2ccm skin dose variations > 12.4% and D0.1ccm rib dose variations > 6.7% were reduced from 11% to 0% and from 16% to 3.3% of all patients, respectively. CONCLUSION: Breast positioning control improved geometric and dosimetric implant stability for individual patients, and thus enhanced physical plan validity in these cases.

Development and clinical implementation of a digital system for risk assessments for radiation therapy.

Before introducing new treatment techniques, an investigation of hazards due to unintentional radiation exposures is a reasonable activity for proactively increasing patient safety. As dedicated software is scarce, we developed a tool for risk assessment to design a quality management program based on best practice methods, i.e., process mapping, failure modes and effects analysis and fault tree analysis. Implemented as a web database application, a single dataset was used to describe the treatment process and its failure modes. The design of the system and dataset allowed failure modes to be represented both visually as fault trees and in a tabular form. Following the commissioning of the software for our department, previously conducted risk assessments were migrated to the new system after being fully re-assessed which revealed a shift in risk priorities. Furthermore, a weighting factor was investigated to bring risk levels of the migrated assessments into perspective. The compensation did not affect high priorities but did re-prioritize in the midrange of the ranking. We conclude that the tool is suitable to conduct multiple risk assessments and concomitantly keep track of the overall quality management activities.

Seed-displacements in the immediate post-implant phase in permanent prostate brachytherapy.

PURPOSE: To investigate differences in seed-displacements between the immediate post-implant phase (day 0-1) and the time to post-plan computed tomography (CT) (day 1-30) in seed prostate brachytherapy. MATERIALS AND METHODS: Seed positions were identified on the intra-operatively created ultrasound-based treatment plan (day 0) and CT scans of day 1 and 30 for 33 patients. The day 1 (30) seed arrangement was registered onto the day 0 (1) arrangement using a seed-only approach. Based on a 1:1 assignment of seeds via the Kuhn-Munkres algorithm, seed-displacements were analyzed. Displacements were evaluated depending on strand-length and anatomical implant location. Resulting dosimetric effects were calculated. RESULTS: Seed-displacements in the immediate post-implant phase (median displacements: 3.8 ± 3.6 mm) were stronger than in the time to post-plan CT (2.1 ± 2.6 mm) and enhanced along the superior-inferior direction. From day 0 to 1, strands containing one (7.3 ± 5.4 mm) or two (8.1 ± 5.8 mm) seeds showed larger displacements than strands of higher lengths (up to 4.2 ± 7.0 mm), whereas no length-dependency was found to day 30. Seeds implanted in base and apex tended to move towards the prostate midzone during both time periods. D90 (dose that 90% of prostate receives) was with variations of 2 ± 15 Gy more stable from day 1 to 30 than in the immediate post-implant phase (-18 ± 11 Gy). CONCLUSION: Seed-displacements in the immediate post-implant phase was enhanced compared to day 1-30. This may result from uncertainties in the gold-standard ultrasound-based treatment planning and implantation. Adaptive implantation workflows appear useful for ensuring high implant stability from the beginning.

On the implant stability in adaptive multi-catheter breast brachytherapy: Establishment of a decision-tree for treatment re-planning.

BACKGROUND AND PURPOSE: To assess implant stability and identify causes of implant variations during high-dose-rate multi-catheter breast brachytherapy. MATERIALS AND METHODS: Planning-CTs were compared to control-CTs acquired halfway through the treatment for 100 patients. For assessing geometric stability, Fréchet-distance and button-to-button distance changes of all catheters as well as variations of Euclidean distances and convex hulls of all dwell positions were determined. The CTs were inspected to identify the causes of geometric changes. Dosimetric effects were evaluated by target volume transfers and re-contouring of organs at risk. The dose non-uniformity ratio (DNR), 100% and 150% isodose volumes (V100 and V150), coverage index (CI), and organ doses were calculated. Correlations between the examined geometric and dosimetric parameters were assessed. RESULTS: Fréchet-distance and dwell position deviations >2.5 mm as well as button-to-button distance changes >5 mm were detected for 5%, 2%, and 6.3% of catheters, but for 32, 17, and 37 patients, respectively. Variations occurred enhanced in the lateral breast and close to the ribs, e.g. due to different arm positions. Only small dosimetric effects with median DNR, V100, and CI variations of -0.01 ± 0.02, (-0.5 ± 1.3)ccm, and (-1.4 ± 1.8)% were observed in general. Skin dose exceeded recommended levels for 12 of 100 patients. Various correlations between geometric and dosimetric implant stability were found, based on which decision-tree regarding treatment re-planning was established. CONCLUSION: Multi-catheter breast brachytherapy shows a high implant stability in general, but considering skin dose changes is important. To increase implant stability for individual patients, we plan to investigate patient immobilization aids during treatments.

End-to-end testing for stereotactic radiotherapy including the development of a Multi-Modality phantom.

PURPOSE: A new insert for a commercially available end-to-end test phantom was designed and in-house manufactured by 3D printing. Subsequently, the insert was tested for different stereotactic radiation therapy workflows (SRS, SBRT, FSRT, and Multimet) also in comparison to the original insert. MATERIAL AND METHODS: Workflows contained imaging (MR, CT), treatment planning, positioning, and irradiation. Positioning accuracy was evaluated for non-coplanar x-ray, kV- and MV-CBCT systems, as well as surface guided radiation therapy. Dosimetric accuracy of the irradiation was measured with an ionization chamber at four different linear accelerators including dynamic tumor tracking for SBRT. RESULTS: CT parameters of the insert were within the specification. For MR images, the new insert allowed quantitative analysis of the MR distortion. Positioning accuracy of the phantom with the new insert using the imaging systems of the different linacs was < 1 mm/degree also for MV-CBCT and a non-coplanar imaging system which caused > 3 mm deviation with the original insert. Deviation of point dose values was <3% for SRS, FSRT, and SBRT for both inserts. For the Multimet plans deviations exceeded 10% because the ionization chamber was not positioned in each metastasis, but in the center of phantom and treatment plan. CONCLUSION: The in-house manufactured insert performed well in all steps of four stereotactic treatment end-to-end tests. Advantages over the commercially available alternative were seen for quantitative analysis of deformation correction in MR images, applicability for non-coplanar x-ray imaging, and dynamic tumor tracking.

Automating implant reconstruction in interstitial brachytherapy of the breast: A hybrid approach combining electromagnetic tracking and image segmentation.

BACKGROUND AND PURPOSE: To develop a method for automatic reconstruction of catheter implants in interstitial brachytherapy (iBT) of the breast by means of electromagnetic tracking (EMT) with the goal of making treatment planning as time-effective and accurate as possible. MATERIALS AND METHODS: The implant geometry of 64 patients was recorded using an afterloader prototype with EMT functionality immediately after the planning CT. EMT data were transferred to the CT image space by rigidly registering the catheter fixation buttons as landmarks. To further improve reconstruction accuracy, the EMT reconstruction points were used as starting points to define small regions of interest (ROI) in the CT image. Within these ROIs, the catheter track was segmented in the CT using image processing operations such as thresholding and blob detection, thus refining the reconstruction. The perpendicular distance between the refined EMT implant reconstruction points and the manually reconstructed catheters by an experienced treatment planner was calculated as a measure of their geometric agreement. RESULTS: Geometrically, the refined EMT based implant reconstruction shows excellent agreement with the manual reconstruction. The median distance across all patients is 0.25 mm and the 95th percentile is 1 mm. Refinement takes approximately 0.5 s per reconstruction point and typically does not exceed 3 min per implant at no user interaction. CONCLUSION: The refined EMT based implant reconstruction proved to be extremely accurate and fast compared to manual reconstruction. The presented procedure can in principle be easily transferred to clinical routine and therefore has enormous potential to provide significant time savings in iBT treatment planning whilst improving reconstruction accuracy.

Permanent LDR prostate brachytherapy: Comprehensive characterization of seed-dynamics within the prostate on a seed-only level.

PURPOSE: Seed brachytherapy is a well-established treatment modality for prostate cancer. However, there is still a lack of profound characterizations of seed motions within the prostate. We assessed these dynamics between day 0 and day 30 of brachytherapy. METHODS: We considered 45 patients with 2408 implanted seeds, and performed a 1:1 assignment between their positions on post-plan CT (nominal day 30) and intraoperative ultrasound (day 0). Geometric seed arrangement changes were measured for each patient and the entire collective. The impact of seed strand-lengths and implant regions was investigated. Correlations with patient characteristics were evaluated. We determined corresponding dosimetric effects by calculating common dose metrics. RESULTS: We found a median seed displacement of 4.3 mm [interquartile range: 3.1-6.9 mm], occurring preferentially in superior-inferior direction. Single and double strands moved significantly stronger than strands of higher lengths. Seed dynamics was more pronounced in base (5.6 mm [3.7-10.7 mm]) and apex (6.5 mm [4.1-15.0 mm]) than in the mid-gland (3.8 mm [2.7-5.0 mm]), and less pronounced in peripheral (4.3 mm [3.0-6.7 mm]) than in urethra-near (5.5 mm [3.5-10.7 mm]) regions. Correlations of seed dynamics with prostate volume changes and the number of implanted seeds and needles were found. D90 (dose that 90% of the prostate receives) varied by a median of 3 Gy [-6 to 15 Gy] between treatment plan and post-plan, but >40 Gy for individual patients. CONCLUSIONS: Reducing seed dynamics is important to ensure a high treatment quality. For this, strands containing ≥3 seeds may be useful, implantations in base-, apex-, and urethra-near zone should be avoided, and the number of needles and seeds may be minimized where possible.

Brachytherapy focal dose escalation using ultrasound based tissue characterization by patients with non-metastatic prostate cancer: Five-year results from single-center phase 2 trial.

PURPOSE: This prospective trial investigates side effects and efficacy of focal dose escalation with brachytherapy for patients with prostate cancer. METHODS AND MATERIALS: In the Phase II, monocentric prospective trial 101 patients with low-/intermediate- and high-risk prostate cancer were enrolled between 2011 and 2013. Patients received either PDR-/HDR-brachytherapy alone with 86-90 Gy (EQD2, α/ß = 3 Gy) or PDR-/HDR-brachytherapy as boost after external beam radiation therapy up to a total dose of 91-96 Gy (EQD2, α/ß = 3 Gy). Taking place brachytherapy all patients received the simultaneous integrated focal boost to the intra-prostatic tumor lesions visible in computer-aided ultrasonography (HistoScanning™) - up to a total dose of 108-119 Gy (EQD2, α/ß = 3 Gy). The primary endpoint was toxicity. Secondary endpoints were cumulative freedom from local recurrence, PSA-free survival, distant metastases-free survival, and overall survival. This trial is registered with ClinicalTrials.gov, number NCT01409876. RESULTS: Median follow-up was 65 months. Late toxicity was generally low with only four patients scoring urinary grade 3 toxicity (4/101, 4%). Occurrence of any grade of late rectal toxicities was very low. We did not register any grade ≥2 of late rectal toxicities. The cumulative 5 years local recurrence rate (LRR) for all patients was 1%. Five years- biochemical disease-free survival estimates according Kaplan-Meier were 98,1% and 81,3% for low-/intermediate-risk and high-risk patients, respectively. Five years metastases-free survival estimates according Kaplan-Meier were 98,0% and 83,3% for all patients, low-/intermediate-risk and high-risk patients, respectively. CONCLUSIONS: The 5 years-results from this Phase II Trial show that focal dose escalation with computer-aided ultrasonography and brachytherapy for patients with non-metastatic prostate cancer is safe and effective.

First clinical experience with a novel, mobile cone-beam CT system for treatment quality assurance in brachytherapy.

BACKGROUND AND PURPOSE: On-site cone-beam computed tomography (CBCT) has gained in importance in adaptive brachytherapy during recent years. Besides treatment planning, there is increased need particularly for image-guidance during interventional procedures and for image-guided treatment quality assurance (QA). For this purpose, an innovative CBCT device was rolled out at our hospital as the first site worldwide. We present the first clinical images and experiences. MATERIALS AND METHODS: The novel CBCT system is constructed of a 121 cm diameter ring gantry, and features a 43.2â€¯× 43.2 cm2 flat-panel detector, wireless remote-control via tablet-PC, and battery-powered maneuverability. Within the first months of clinical operation, we performed CBCT-based treatment QA for a total of 26 patients (8 with breast, 16 with cervix, and 2 with vaginal cancer). CBCT scans were analyzed regarding potential movements of implanted applicators in-situ during the brachytherapy course. RESULTS: With the presented device, treatment QA was feasible for the majority of patients. The CBCT scans of breast patients showed sufficient contrast between implanted catheters and tissue. For gynecologic patients, a distinct visualization of applicators was achieved in general. However, reasonable differentiations of organic soft tissues were not feasible. CONCLUSION: The CBCT system allowed basic treatment QA measures for breast and gynecologic patients. For image-guidance during interventional brachytherapy procedures, the current image quality is not adequate. Substantial performance enhancements are required for intraoperative image-guidance.

Risk analysis for radiotherapy at the Universitätsklinikum Erlangen.

PURPOSE: Risk analysis is required by various laws and regulations in Germany and has an impact on each department of a large clinic. We provide an overview of the relevant laws and regulations in Germany and present the technical and organizational experience of introducing risk analysis in the Department of Radiation Oncology at the Universitätsklinikum Erlangen. METHODS: Risk analysis was performed with an in-house developed extension of our intranet platform and ticketing system. Risks were classified according to occurrence and severity, each on a 5-level scale resulting into a risk matrix. An interdisciplinary team of six experienced members formed the core meeting weekly. RESULTS: A total of 38 risks and 50 measures have been identified in 41 1h-meetings corresponding to approx. 260 working hours. Risk was distributed 8/20/13 to the categories critical (n=8), monitoring (n=20), and conditionally acceptable (n=13). Risk analysis has been evaluated before and after introducing measures. CONCLUSION: The risk analysis method introduced has been successfully used in routine operations for over a year. Risk analysis takes time and effort. However, because experts from different disciplines meet each other every week, the overall workflow of the radiation oncology department can be improved efficiently and continuously.

Dosimetry, Optimization and FMEA of Total Skin Electron Irradiation (TSEI).

PURPOSE: Total Skin Electron Irradiation (TSEI) is a method for treating malignant cutaneous T-cell lymphomas. This work aims to implement and optimize the total skin technique established at Strahlenklinik Erlangen, Germany on two new linear accelerators and to quantify the risks using failure mode and effects (FMEA) analysis. MATERIAL AND METHODS: TSEI is performed at a VersaHD accelerator (Elekta, Stockholm) with 6MeV in the "high dose rate mode" HDRE and a nominal field size of 40×40cm2. To reach the entire skin surface, the patients perform 6 different body positions at a distance of 330cm behind an acrylic scatter plate, with two overlapping irradiation fields being radiated at 2 gantry angles per position. The irradiation technique was commissioned according to the recommendation of AAPM report 23. With the help of a reference profile at 270°, 2 gantry angles were calculated, which in total resulted in an optimal dose distribution. This was metrologically verified with ion-chamber measurements in the patient's longitudinal axis. The influence of the shape of the acrylic scatter plate and the distance between the acrylic scatter plate and patient was determined by measurements. The dose homogeneity was verified using an anthropomorphic disc phantom equipped with GafChromic films. The workflows and failure modes of the total skin technique were described in a process map and subsequently quantified with a FMEA analysis. RESULTS: An optimal dose distribution is achieved at a distance of SSD=330cm, using the gantry angles 289° and 251°. The previously used segmented acrylic scatter plate was replaced by a flat plate (200×120×0.5cm3), which is placed at a distance of 50cm in front of the patient. The densitometric evaluation of the GafChromic films in the anthropomorphic disc phantom revealed an expected dose distribution of 3Gy at a depth of up to 1.5cm below the skin surface, with a homogeneity of ±10% over the phantom's longitudinal axis. By FMEA a maximum risk priority number of 30 was determined. CONCLUSION: Based on the calculations and measurements performed on the new accelerators as well as the risk analysis, we concluded that total skin therapy can be implemented clinically.

Long-term results of a protocol-based ultrasound-guided salvage brachytherapy as re-irradiation for local recurrent prostate cancer.

BACKGROUND AND PURPOSE: To assess the long-term results of protocol-based ultrasound-guided salvage pulsed-dose rate brachytherapy in locally recurrent prostate cancer following previous radiation therapy. MATERIALS AND METHODS: A total of 82 patients (median age 69 years) with locally recurrent prostate cancer after previous external beam radiation therapy (43/82, 52.4%), prostatectomy and adjuvant radiation therapy (24/82, 29.3%) or brachytherapy (15/82, 18.3%) were treated with sole salvage interstitial pulsed-dose rate brachytherapy (PDR-BT). The treatment regimen consisted of two PDR-BT sections with 30 Gy (single pulse dose 0.6 Gy/h, 24 h per day) each up to a total reference dose of 60 Gy (EQD2 = 71.5 Gy-eq). The endpoints of the present analysis are cumulative local recurrence-rate, PSA-free survival, overall survival and the treatment-associated late toxicity according to the "Common Toxicity Criteria" with a median follow-up of 49 months (range, 12-129 months). RESULTS: The 5-y. overall cumulative local recurrence rate was 17.7% with no significant differences between low, intermediate and high-risk groups. Differences in PSA-free survival were marginally non-significant, at 67.3%, 70.4% and 63.8% for low, intermediate and high risk group, respectively. No grade 3 gastrointestinal late side effects have been observed. The most common late side effect was urinary incontinence grade 1-3 and urinary frequency/urgency grade 1-3 in 18.3% (15/82) and 17.1% (14/82) of patients, respectively. CONCLUSION: PDR salvage brachytherapy in local recurrent previously irradiated prostate cancer is efficient with low late toxicity. Salvage-brachytherapy represents a valuable therapeutic option for the treatment of previously irradiated locally recurrent prostate cancer.

Is adaptive treatment planning in multi-catheter interstitial breast brachytherapy necessary?

PURPOSE: For 55 patients treated with interstitial multi-catheter breast brachytherapy the need for adaptive treatment planning was assessed. METHODS AND MATERIALS: For all patients a treatment planning computed tomography (CT) and a follow-up CT were acquired and used for the retrospective evaluation. Keeping dwell time and dwell positions constant, the treatment plan assessed directly after catheter implantation was compared to the situation 48 h after implantation. Both manual catheter reconstructions, based on the planning and follow-up CT, were rigid registered to each other and the resulting deviations analyzed, like the difference between corresponding dwell positions (ΔDP) or the discrete Fréchet distance. Further, the dosimetric changes, e.g., coverage index (ΔCI), conformal index (ΔCOIN) and dose non-uniformity ratio (ΔDNR) were considered for a deformed planning target volume (PTV) and the rigid warped PTV structure. The PTV was deformed according to the vector field estimated between the two acquired CTs. RESULTS: Over all patients with rigid aligned CTs a mean ΔDP, ΔCI, ΔCOIN and ΔDNR were determined to 2.41 ±â€¯1.73 mm, 3.10 ±â€¯3.17%, 0.009 ±â€¯0.007 and 0.036 ±â€¯0.040, respectively. Considering the deformed PTV ΔCI was estimated to 5.05 ±â€¯4.14%. CONCLUSION: In conclusion, in 4% of the cases re-planning would have been beneficial to ensure the planned dose delivery. Large PTV changes or large DP deviations were found to be the main reasons for dosimetric variations.

Estimation of inter-fractional variations in interstitial multi-catheter breast brachytherapy using a hybrid treatment delivery system.

PURPOSE: Irradiation of the tumor bed using interstitial multi-catheter brachytherapy is one of the treatment options for breast cancer patients. In order to ensure the planned dose delivery an advanced quality intervention method using an electromagnetic tracking (EMT) system is presented. The system is used to assess inter-fractional variations within the framework of a patient study. METHODS AND MATERIALS: Until now 41 patients were included in the study for the evaluation and overall 355 EMT measurements were performed. The catheter traces are measured automatically and sequentially using an afterloader prototype (Flexitron, Elekta, Veenendaal, The Netherlands) equipped with an EMT sensor. The implant geometry is tracked directly after implantation, after CT imaging and after each irradiation fraction. The acquired data is rigidly registered to the catheter traces defined in the treatment plan and the dwell positions (DP) are reconstructed. DPs defined in treatment planning serve as reference. Breathing motion was corrected and recorded using three reference 6DoF sensors placed on the patients' skin. The Euclidean distance between the planned and reconstructed DPs provides information about possible inter-fractional deviations. Further, the influence of various factors on the occurrence of large deviations was investigated, like the patients' age, the length of the catheter, the breast volume, etc. RESULTS: Over all patient measurements a median Euclidean distance of 2.19 mm was determined between the reconstructed DPs and the reference DPs. The median deviation combining all datasets was minimal (1.67 mm) at the measurement directly after CT imaging. The deviations between the different fractions have a median distance of 2.31 mm which could be improved to 2.05 mm by adapting the treatment plan according to the follow-up CT. No correlation between the distance to the skin, ribs, mammilla or the breast volume and the occurrences of large deviations was found. The largest deviations were determined in the upper inner quadrant of the breast. CONCLUSION: The afterloader prototype could be well integrated into the clinical routine and is beneficial for ensuring the quality of the brachytherapy. Overall, a small median DP deviation, lower than the used step size of 2.5 mm, was detected.

Impact of inter- and intra-observer variabilities of catheter reconstruction on multi-catheter interstitial brachytherapy of breast cancer patients.

PURPOSE: The aim of this study was to evaluate inter- and intra-observer variabilities of catheter reconstruction and its dosimetric impact for multi-catheter interstitial breast cancer patients. METHODS AND MATERIALS: In order to evaluate inter-observer variabilities (IOV) three medical physicists reconstructed the catheter traces of 13 patients. These manual reconstructions were further compared to the automatic reconstruction algorithm integrated into the planning system and one on purpose imprecise manual reconstruction. For intra-observer variabilities (IAV) repeated reconstructions of two physicists were compared for 13 patients. In total 426 catheters were considered. Keeping dwell times, dwell positions, the optimization and the normalization relative points constant the geometrical deviations between the corresponding dwell positions of the reference data set and the investigated reconstructions were evaluated. Also, the effect on the quality indices, such as coverage index (CI), dose non-uniformity ratio (DNR) or conformal index (COIN), and the exposure of the organs at risk were analyzed. RESULTS: Over all patients and all different catheter reconstructions considered for IOV a mean deviation between the corresponding dwell positions of 0.60 ±â€¯0.35 mm was detected. The first observer had a mean deviation of 0.54 ±â€¯0.32 mm, whereas the second observer yielded a mean deviation of 0.58 ±â€¯0.37 mm. The length of the catheter traces varied in the mean by 0.51 ±â€¯0.45 mm. The mean relative deviation of the CI, DNR, COIN, mean heart dose and mean lung dose varied by 0.27 ±â€¯0.31%, 0.0027 ±â€¯0.0025, 0.0036 ±â€¯0.0033, 0.024 ±â€¯0.019%, 0.05 ±â€¯0.11%, respectively. The skin dose (D0.2ccm) changed in the maximum 8.52%. On average IAV reached a deviation between the corresponding dwell positions of 0.49 ±â€¯0.30 mm. IOVs and IAVs proved to be significantly different (Wilcoxon's test p < 0.01). CONCLUSIONS: The study proved that a repeated reconstruction of the catheter traces does not lead to large geometrical deviations or to a significant change in the dose exposure. But the lack of ground truth makes the estimation of the quality of the reconstruction challenging. A precise reconstruction mapping the reality is a necessity for the planned dose delivery. With all considered reconstruction techniques reliable quality indices for the target and the organs at risk could be obtained.

Introduction of a hybrid treatment delivery system used for quality assurance in multi-catheter interstitial brachytherapy.

Multi-catheter interstitial brachytherapy (iBT) is a treatment option for breast cancer patients after breast conserving surgery. Typically, only a few additional quality interventions after the first irradiation have been introduced to ensure the planned treatment delivery. Therefore, the purpose of this study is to show the possibilities of an electromagnetic tracking (EMT) system integrated into the afterloader for quality assurance (QA) in high-dose rate (HDR) iBT of patients with breast cancer. The hybrid afterloader system equipped with an electromagnetic sensor was used for all phantom and patient measurements. Phantom measurements were conducted to estimate the quality of different evaluation schemes. After a coherent point drift registration of the EMT traces to the reconstructed catheters based on computed tomograms the dwell positions (DP) were defined. Different fitting and interpolation methods were analyzed for the reconstruction of DPs. All estimated DPs were compared to the DPs defined in treatment planning. Until now, the implant geometry of 20 patients treated with HDR brachytherapy was acquired and explored. Regarding the reconstruction techniques, both fitting and interpolation were able to detect manually introduced shifts and swaps. Nonetheless, interpolation showed superior results (RMSE = 1.27 mm), whereas fitting seemed to be more stable to distortion and motion. The EMT system proved to be beneficial for QA in brachytherapy and furthermore, clinical feasibility was proven.

ESTRO-ACROP guideline: Interstitial multi-catheter breast brachytherapy as Accelerated Partial Breast Irradiation alone or as boost - GEC-ESTRO Breast Cancer Working Group practical recommendations.

PURPOSE: This consensus statement from the Breast Cancer Working Group of Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO) aims at generating practical guidelines for multi-catheter image-guided brachytherapy in the conservative management of breast cancer patients used for either Accelerated Partial Breast Irradiation (APBI) or for a breast boost. METHODS: Recent advances in techniques of multi-catheter brachytherapy were summarized and all the relevant literature was reviewed by a panel of experts. Panel members of the GEC-ESTRO experts participated in a series of conferences, supplemented their clinical experience, were surveyed to determine their current practices and patterns, performed a literature review, and formulated recommendations for implementing APBI with multi-catheter brachytherapy, focusing on treatment planning issues, catheter insertion, dosimetry and quality assurance. This document was reviewed and approved by the full panel, the GEC-ESTRO executive board and by the ACROP (Advisory Committee on Radiation Oncology Practice). RESULTS: Three-dimensional (3D) treatment planning, catheter insertion techniques, dosimetry and methods of quality assurance for APBI and boost with multi-catheter image-guided brachytherapy after breast conserving surgery are described. Detailed recommendations for daily practice including dose constraints are given. CONCLUSIONS: Recent standards and guidelines for the use of APBI with different multi-catheter image-guided brachytherapy techniques have been defined. Different techniques are used to insert the catheters. Guidelines are mandatory to assure precise catheter insertion for coverage of the target volume and to guarantee high-quality dosimetry. The same rules apply for brachytherapy based boost irradiation for breast cancer after whole breast irradiation as well as for partial breast re-irradiation.

Hypofractionated Irradiation Has Immune Stimulatory Potential and Induces a Timely Restricted Infiltration of Immune Cells in Colon Cancer Tumors.

In addition to locally controlling the tumor, hypofractionated radiotherapy (RT) particularly aims to activate immune cells in the RT-modified microenvironment. Therefore, we examined whether hypofractionated RT can activate dendritic cells (DCs), induce immune cell infiltration in tumors, and how the chronology of immune cell migration into tumors occurs to gain knowledge for future definition of radiation breaks and inclusion of immunotherapy. Colorectal cancer treatments offer only limited survival benefit, and immunobiological principles for additional therapies need to be explored with preclinical models. The impact of hypofractionated RT on CT26 colon cancer tumor cell death, migration of DCs toward supernatants (SN) of tumor cells, and activation of DCs by SN were analyzed. The subcutaneous tumor of a BALB/c-CT26 mouse model was locally irradiated with 2 × 5 Gy, the tumor volume was monitored, and the infiltration of immune cells in the tumor was determined by flow cytometry daily. Hypofractionated RT induced a mixture of apoptotic and necrotic CT26 cells, which is known to be in particular immunogenic. DCs that migrated toward SN of CT26 cells particularly upregulated the activation markers CD80 and CD86 when in contact with SN of irradiated tumor cells. After hypofractionated RT, the tumor outgrowth was significantly retarded and in the irradiated tumors an increased infiltration of macrophages (CD11bhigh/F4-80+) and DCs (MHC-II+), but only between day 5 and 10 after the first irradiation, takes place. While CD4+ T cells migrated into non-irradiated and irradiated tumors, CD8+ T cells were only found in tumors that had been irradiated and they were highly increased at day 8 after the first irradiation. Myeloid-derived suppressor cells and regulatory T cells show regular turnover in irradiated and non-irradiated tumors. Tumor cell-specific anti-IgM antibodies were enhanced in the serum of animals with irradiated tumors. We conclude that hypofractionated RT suffices to activate DCs and to induce infiltration of innate and adaptive immune cells into solid colorectal tumors. However, the presence of immune cells in the tumor which are beneficial for antitumor immune responses is timely restricted. These findings should be considered when innovative multimodal tumor treatment protocols of distinct RT with immune therapies are designed and clinically implemented.

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.