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Purpose: In the treatment of cervical cancer, large anatomical deformations, caused by, e.g., tumor shrinkage, bladder and rectum filling changes, organ sliding, and the presence of the brachytherapy (BT) applicator, prohibit the accumulation of external beam radiotherapy (EBRT) and BT dose distributions. This work proposes a structure-wise registration with vector field integration (SW+VF) to map the largely deformed anatomies between EBRT and BT, paving the way for 3D dose accumulation between EBRT and BT. Methods: T2w-MRIs acquired before EBRT and as a part of the MRI-guided BT procedure for 12 cervical cancer patients, along with the manual delineations of the bladder, cervix-uterus, and rectum-sigmoid, were used for this study. A rigid transformation was used to align the bony anatomy in the MRIs. The proposed SW+VF method starts by automatically segmenting features in the area surrounding the delineated organs. Then, each organ and feature pair is registered independently using a feature-based nonrigid registration algorithm developed in-house. Additionally, a background transformation is calculated to account for areas far from all organs and features. In order to obtain one transformation that can be used for dose accumulation, the organ-based, feature-based, and the background transformations are combined into one vector field using a weighted sum, where the contribution of each transformation can be directly controlled by its extent of influence (scope size). The optimal scope sizes for organ-based and feature-based transformations were found by an exhaustive analysis. The anatomical correctness of the mapping was independently validated by measuring the residual distances after transformation for delineated structures inside the cervix-uterus (inner anatomical correctness), and for anatomical landmarks outside the organs in the surrounding region (outer anatomical correctness). The results of the proposed method were compared with the results of the rigid transformation and nonrigid registration of all structures together (AST). Results: The rigid transformation achieved a good global alignment (mean outer anatomical correctness of 4.3 mm) but failed to align the deformed organs (mean inner anatomical correctness of 22.4 mm). Conversely, the AST registration produced a reasonable alignment for the organs (6.3 mm) but not for the surrounding region (16.9 mm). SW+VF registration achieved the best results for both regions (3.5 and 3.4 mm for the inner and outer anatomical correctness, respectively). All differences were significant (p < 0.02, Wilcoxon rank sum test). Additionally, optimization of the scope sizes determined that the method was robust for a large range of scope size values. Conclusions: The novel SW+VF method improved the mapping of large and complex deformations observed between EBRT and BT for cervical cancer patients. Future studies that quantify the mapping error in terms of dose errors are required to test the clinical applicability of dose accumulation by the SW+VF method. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The aim of this study was to systematically analyse the effect of catheter displacements both on target coverage and normal tissue irradiation in fractionated high dose rate (HDR) prostate brachytherapy, using a simulation study, and to define tolerances for catheter displacement ensuring that both target coverage and normal tissue doses remain clinically acceptable. Besides the effect of total implant displacement, also displacements of catheters belonging to selected template rows only were evaluated in terms of target coverage and normal tissue dose, in order to analyse the change in dose distribution as a function of catheter dwell weight and catheter location. Material and methods: Five representative implant geometries, with 17 catheters each, were selected. The clinical treatment plan was compared to treatment plans in which an entire implant displacement in caudal direction over 3, 5, 7 and 10mm was simulated. Besides, treatment plans were simulated considering a displacement of either the central, most ventral or most dorsal catheter rows only, over 5mm caudally. Results: Due to displacement of the entire implant the target coverage drops below the tolerance of 93% for all displacements studied. The effect of displacement of the entire implant on organs at risk strongly depended on the patient anatomy; e.g., for 80% of the implant geometries the V 80 of the rectum exceeded its tolerance for all displacements. The effect of displacement of catheters belonging to selected template rows depended strongly on the relative weight of each catheter row when considering the target coverage and on its location when considering the dose in the organs at risk. Conclusion: This study supports the need for a check of the catheter locations before each fraction and correction of deviations of the catheter position exceeding 3mm. [Copyright &y& Elsevier]

Abstract: Background and purpose: To evaluate the accuracy of on-line planning in an Integrated Brachytherapy Unit (IBU) using dedicated image distortion correction algorithms, correcting the geometric distortion and magnetic distortion separately, and to determine the effect of the reconstruction accuracy on clinical treatment plans in terms of deviations in treatment time and dose. Patients and methods: The reconstruction accuracy has been measured using 20 markers, positioned at well known locations in a QA phantom. Treatment plans of two phantoms representing clinical implant geometries, have been compared with reference plans to determine the effect of the reconstruction accuracy on the treatment plan. Before clinical introduction, treatment plans of three representative patients, based on on-line reconstruction, have been compared with reference plans. Results: The average reconstruction error for 10in. images reduces from −0.6mm (range −2.6 to +1.0mm) to −0.2mm (range −1.2 to +0.6mm) after image distortion correction and for 15in. images from 0.8mm (range −0.5 to +3.0mm) to 0.0mm (range −0.8 to +0.8mm). The error in case of eccentric positioning of the phantom, i.e. 0.8mm (range −1.0 to +3.3mm), reduces to 0.1mm (range −0.5 to +0.9mm). Correction of the image distortions reduces the deviation in the calculated treatment time of maximally 2.7% to less than 0.8% in case of eccentrically positioned clinical phantoms. The deviation in the treatment time or reference dose in the plans based on on-line reconstruction with image distortion correction of the three patient examples is smaller than 0.3%. Conclusions: Accurate on-line implant reconstruction using the IBU localiser and dedicated correction algorithms separating the geometric distortion and the magnetic distortion is possible. The results fulfill the minimum requirements as imposed by the Netherlands Commission on Radiation Dosimetry (NCS) without limitations regarding the usable range of the field of view of the image intensifier. However, the C-arm angle is limited to those angles for which magnetic distortion corrections have been obtained. [Copyright &y& Elsevier]

The purpose of this study is to evaluate anatomy based inverse planning as implemented in PLATO BPS 14.2 for planning of HDR prostate implants. Six patients were analysed. The dose distributions were optimized using geometric optimization followed by graphical optimization (GO), anatomy based inverse planning or standard inverse optimization (SIO), tuned inverse optimization (TIO) and tuned inverse optimization followed by graphical optimization (GOTIO). The mean target coverage was 93±4%, 53±11%, 74±8%, 90±3%, respectively, for GO, SIO, TIO and GOTIO. The conformal index COIN was 0.74±0.02, 0.43±0.15 and 0.77±0.07, respectively, for GO, SIO and GOTIO. Improved dose homogeneity was found when comparing GOTIO with GO. [Copyright &y& Elsevier]

: PurposeA high-dose-rate intraoperative radiotherapy (HDR-IORT) technique for rectum cancer was developed and the technique, local failure, and survival were analyzed.: Methods and materialsAfter the exclusion of metastatic patients, 37 patients were treated with external beam RT, surgery, and HDR-IORT between 1997 and 2000. Primary locally advanced rectum cancer was found in 18 patients and recurrent disease in 19. HDR-IORT was only administered if the resection margins were ≤2 mm. The flexible intraoperative template is a 5-mm-thick pad with 1-cm-spaced parallel catheters. Clips were placed during surgery to define the target area. A dose of 10 Gy was prescribed at a 1 cm depth from the template surface and calculated using standard plans. After treatment, the dose at the clips was calculated using the reconstructed template geometry and the actual treatment dwell times. The median follow-up of surviving patients was 3 years. No patients were lost to follow-up.: ResultsOverall, 12 patients (32%) had local recurrence, 5 (14%) of which were in the HDR-IORT field. The 3-year local failure rate for primary tumors and recurrent tumors was 19% and 52%, respectively (p = 0.0042). The 3-year local failure rate was 37% for negative margins and 26% for positive margins (p = 0.51). A high mean dose at the clip (17.3 Gy) was found. The overall survival was significantly different for primary vs. recurrent tumors, stage, and grade.: ConclusionBecause of the HDR technique, a high dose at the clips was found, with good local control. More out-of-field than in-field failures were seen. The local failure rate was significantly different for primary vs. recurrent disease. [Copyright &y& Elsevier]

HDR intraoperative brachytherapy (IOBT) is applied to locally advanced rectal tumors using a 5 mm thick flexible intraoperative template (FIT). To reduce the procedure time, treatment planning is performed using standard plans that neglect the curvature of the FIT. We have calculated the individual treatment plan, based on the real geometry of the FIT, and the dose at clips placed during surgery. A mean treatment dose of 9.55±0.21 Gy was found for the individual plan, compared to the prescribed 10 Gy (P<0.0001). The mean central dose was 10.03±0.10 Gy in the standard plan and 9.20±0.32 Gy in the individual plan (P<0.0001). The mean dose at the corners of the FIT was 10.3 Gy in the standard plan and ranged between 10.3 and 10.5 Gy in the individual plan. In 63% of the clips, the dose was larger than 15.0 Gy, which is equivalent to a gap between the FIT and the target smaller than 5 mm. In 18% of the clips, the dose was smaller than 13.0 Gy indicating that locally the gap was larger than 5 mm. Clinical practice will have to prove if these small dose deviations influence the clinical outcome. [Copyright &y& Elsevier]

Background and purpose: Brachytherapy is applied in 39 radiotherapy institutions in The Netherlands and Belgium. Each institution has its own quality control (QC) programme to ensure safe and accurate dose delivery to the patient. The main goal of this work is to gain insight into the current practice of QC of brachytherapy in The Netherlands and Belgium and to reduce possible variations in test frequencies and tolerances by formulating a set of minimum QC-requirements.Materials and methods: An extensive questionnaire about QC of brachytherapy was distributed to and completed by the 39 radiotherapy institutions. A separate smaller questionnaire was sent to nine institutions performing intracoronary brachytherapy. The questions were related to safety systems, physical irradiation parameters and total time spent on QC. The results of the questionnaires were compared with recommendations given in international brachytherapy QC reports.Results: The answers to the questionnaires showed large variations in test frequencies and test methods. Furthermore, large variations in time spent on QC exist, which is mainly due to differences in QC-philosophy and differences in the available resources.Conclusions: Based on the results of the questionnaires and the comparison with the international recommendations, a set of minimum requirements for QC of brachytherapy has been formulated. These guidelines will be implemented in the radiotherapy institutions in The Netherlands and Belgium. [Copyright &y& Elsevier]

Background: The steep radiation dose gradients in cervical cancer brachytherapy (BT) necessitate a thorough understanding of the behavior of afterloader source cables or needles in the curved channels of (patient‐tailored) applicators. Purpose: The purpose of this study is to develop and validate computer models to simulate: (1) BT source positions, and (2) insertion forces of needles in curved applicator channels. The methodology presented can be used to improve the knowledge of instrument behavior in current applicators and aid the development of novel (3D‐printed) BT applicators. Methods: For the computer models, BT instruments were discretized in finite elements. Simulations were performed in SPACAR by formulating nodal contact force and motion input models and specifying the instruments' kinematic and dynamic properties. To evaluate the source cable model, simulated source paths in ring applicators were compared with manufacturer‐measured source paths. The impact of discrepancies on the dosimetry was estimated for standard plans. To validate needle models, simulated needle insertion forces in curved channels with varying curvature, torsion, and clearance, were compared with force measurements in dedicated 3D‐printed templates. Results: Comparison of simulated with manufacturer‐measured source positions showed 0.5–1.2 mm median and <2.0 mm maximum differences, in all but one applicator geometry. The resulting maximum relative dose differences at the lateral surface and at 5 mm depth were 5.5% and 4.7%, respectively. Simulated insertion forces for BT needles in curved channels accurately resembled the forces experimentally obtained by including experimental uncertainties in the simulation. Conclusion: The models developed can accurately predict source positions and insertion forces in BT applicators. Insights from these models can aid novel applicator design with improved motion and force transmission of BT instruments, and contribute to the estimation of overall treatment precision. The methodology presented can be extended to study other applicator geometries, flexible instruments, and afterloading systems. [ABSTRACT FROM AUTHOR]

Although MRI-based image guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC) has resulted in favorable outcomes, it can be logistically complex and time consuming compared to 2D image-based brachytherapy, and both physically and emotionally intensive for patients. This prospective study aims to perform time-action and patient experience analyses during IGABT to guide further improvements. LACC patients treated with IGABT were included for the time-action (56 patients) and patient experience (29 patients) analyses. Times per treatment step were reported on a standardized form. For the patient experience analysis, a baseline health status was established with the EQ-5D-5L questionnaire and the perceived pain, anxiety and duration for each treatment step were assessed with the NRS-11. The median total procedure time from arrival until discharge was 530 (IQR: 480–565) minutes. Treatment planning (delineation, reconstruction, optimization) required the most time and took 175 (IQR: 145–195) minutes. Highest perceived pain was reported during applicator removal and treatment planning, anxiety during applicator removal, and duration during image acquisition and treatment planning. Perceived pain, anxiety and duration were correlated. Higher pre-treatment pain and anxiety scores were associated with higher perceived pain, anxiety and duration. This study highlights the complexity, duration and impact on patient experience of the current IGABT workflow. Patient reported pre-treatment pain and anxiety can help identify patients that may benefit from additional support. Research and implementation of measures aiming at shortening the overall procedure duration, which may include logistical, staffing and technological aspects, should be prioritized. [ABSTRACT FROM AUTHOR]

Simple Summary: ThermoBrachyTherapy, a combination therapy where radiation and heat are simultaneously applied using needle-shaped applicators from within the target, is a potentially very effective treatment for prostate cancer. When radiation and thermal therapies are applied, the dose coverage of each treatment is preplanned without considering the combined effect of the two dose distributions. In this study, we propose a method to automatically plan the thermal dose in such a treatment, based on the combined effect with the radiation. Furthermore, we apply the method on 10 patients and compare the treatment to a brachytherapy-only treatment plan. In this way, we show that, with properly optimized ThermoBrachyTherapy, we can provide equivalent combined dose coverages to the prostate, while reducing the dose delivered to critical organs surrounding the prostate, which might translate to reduced toxicity of the treatment. In high-dose-rate brachytherapy (HDR-BT) for prostate cancer treatment, interstitial hyperthermia (IHT) is applied to sensitize the tumor to the radiation (RT) dose, aiming at a more efficient treatment. Simultaneous application of HDR-BT and IHT is anticipated to provide maximum radiosensitization of the tumor. With this rationale, the ThermoBrachyTherapy applicators have been designed and developed, enabling simultaneous irradiation and heating. In this research, we present a method to optimize the three-dimensional temperature distribution for simultaneous HDR-BT and IHT based on the resulting equivalent physical dose (EQDphys) of the combined treatment. First, the temperature resulting from each electrode is precomputed. Then, for a given set of electrode settings and a precomputed radiation dose, the EQDphys is calculated based on the temperature-dependent linear-quadratic model. Finally, the optimum set of electrode settings is found through an optimization algorithm. The method is applied on implant geometries and anatomical data of 10 previously irradiated patients, using reported thermoradiobiological parameters and physical doses. We found that an equal equivalent dose coverage of the target can be achieved with a physical RT dose reduction of 20% together with a significantly lower EQDphys to the organs at risk (p-value < 0.001), even in the least favorable scenarios. As a result, simultaneous ThermoBrachyTherapy could lead to a relevant therapeutic benefit for patients with prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: In High Dose Rate Brachytherapy for prostate cancer there is a need for a new way of increasing cancer cell kill in combination with a stable dose to the organs at risk. In this study, we propose a novel ThermoBrachy applicator that offers the unique ability to apply interstitial hyperthermia while simultaneously serving as an afterloading catheter for high dose rate brachytherapy for prostate cancer. This approach achieves a higher thermal enhancement ratio than in sequential application of radiation and hyperthermia and has the potential to decrease the overall treatment time. Methods: The new applicator uses the principle of capacitively coupled electrodes. We performed a proof of concept experiment to demostrate the feasibility of the proposed applicator. Moreover, we used electromagnetic and thermal simulations to evaluate the power needs and temperature homogeneity in different tissues. Furthermore we investigated whether dynamic phase and amplitude adaptation can be used to improve longitudinal temperature control. Results: Simulations demonstrate that the electrodes achieve good temperature homogeneity in a homogenous phantom when following current applicator spacing guidelines. Furthermore, we demonstrate that by dynamic phase and amplitude adaptation provides a great advancement for further adaptability of the heating pattern. Conclusions: This newly designed ThermoBrachy applicator has the potential to revise the interest in interstitial thermobrachytherapy, since the simultaneous application of radiation and hyperthermia enables maximum thermal enhancement and at maximum efficiency for patient and organization. [ABSTRACT FROM AUTHOR]

Purpose In fractionated high-dose-rate brachytherapy (HDR-BT) for prostate cancer (PCa) with one implant for several fractions, dose delivery relies on reproducibility of catheter positions. However, caudal displacement of implanted catheters does occur between fractions and needs to be corrected. Our protocol prescribes correction of displacements > 3 mm. We investigated whether displacement and its corrections influence acute and late toxicity incidences. Methods and Materials We analyzed 162 PCa patients treated with HDR-BT monotherapy between 2007 and 2013. The implant remained in situ between the 4 fractions. Catheter displacement was assessed before each fraction using lateral X-ray images and corrected if needed. Genitourinary (GU) and gastrointestinal (GI) acute and late toxicities were assessed using clinical record forms and patient self-assessment questionnaires. Results Implant displacement corrections (DC) were needed in 71 patients (43.8%) whereas no DCs were needed in 91 patients (56.2%). No statistically significant differences were seen in acute and late grade ≥ 2 GU and GI toxicity incidences between DC and no DC groups. The maximum displacement nor the number of corrections had any influence on toxicity. Conclusions The occurrence and subsequent correction of implant displacements exceeding 3 mm during fractionated HDR-BT monotherapy for PCa did not lead to increased incidences of acute or late GU and GI toxicity. This indicates that our clinical protocol to correct displacements > 3 mm results in safe treatment regarding organ at risk toxicity. [ABSTRACT FROM AUTHOR]

Background and purpose The use of HDR brachytherapy (HDR-BT) as monotherapy for prostate cancer (PC) is increasing worldwide with good tumour control rates and acceptable toxicity. We report our results on toxicity and quality of life (QoL) after HDR-BT monotherapy for PC patients. Materials and methods 166 low- and intermediate-risk localized PC patients were treated with HDR-BT to a total dose of 38 Gy in four fractions. Genitourinary (GU) and gastrointestinal (GI) toxicities were prospectively assessed using EORTC-RTOG questionnaires and physicians charts. QoL was evaluated using EORTC QLQ-PR25 questionnaires. Results Three months after treatment, acute GU and GI toxicities were reported in 10.8% and 7.2%. Acute toxicity resolved within two months in the majority of patients (61%). Late grade ⩾2 GU and GI toxicity were reported in 19.7% and 3.3% of patients 12 months after HDR-BT. Mean QLQ-PR25 scores showed clinically relevant changes from baseline for urinary symptoms and sexual functioning. With a mean follow-up of 35 months, biochemical failure was observed in 2.4%. Overall survival at 60 months was 93.6% and cancer-specific survival was 100%. Conclusions HDR-BT monotherapy for localized PC showed excellent clinical outcome and acceptable acute and late toxicity. Urinary symptoms and sexual function QoL decreased after treatment. [ABSTRACT FROM AUTHOR]

The combination of interstitial hyperthermia treatment (IHT) with high dose rate brachytherapy (HDR-BT) can improve clinical outcomes since it highly enhances the efficiency of cell kill, especially when applied simultaneously. Therefore, we have developed the ThermoBrachy applicators. To effectively apply optimal targeted IHT, treatment planning is considered essential. However, treatment planning in IHT is rarely applied as it is regarded as difficult to accurately calculate the deposited energy in the tissue in a short enough time for clinical practice. In this study, we investigated various time-efficient methods for fast computation of the electromagnetic (EM) energy deposition resulting from the ThermoBrachy applicators. Initially, we investigated the use of an electro-quasistatic solver. Next, we extended our investigation to the application of geometric simplifications. Furthermore, we investigated the validity of the superpositioning principle, which can enable adaptive treatment plan optimization without the need for continuous recomputation of the EM field. Finally, we evaluated the accuracy of the methods by comparing them to the golden standard Finite-Difference Time-Domain calculation method using gamma-index analysis. The simplifications considerably reduced the computation time needed, improving from >12 h to a few seconds. All investigated methods showed excellent agreement with the golden standard by showing a >99% passing rate with 1%/0.5 mm Dose Difference and Distance-to-Agreement criteria. These results allow the proposed electromagnetic simulation method to be used for fast and accurate adaptive treatment planning. [ABSTRACT FROM AUTHOR]

Purpose: To report clinical outcomes and early and late complications in 264 hormone-naïve patients with low- and intermediate-risk prostate cancer treated with high-dose-rate brachytherapy (HDR-BT) in combination with external-beam radiotherapy (EBRT). Methods and Materials: Between February 2000 and July 2007, 264 patients underwent HDR-BT in combination with EBRT as a treatment for their low- to intermediate-risk prostate cancer. The HDR-BT was performed using ultrasound-based implantation. The total HDR-BT dose was 18 Gy in 3 fractions within 24 h, with a 6-h minimum interval. The EBRT started 2 weeks after HDR-BT and was delivered in 25 fractions of 1.8 Gy to 45 Gy within 5 weeks. Results: After a mean follow-up of 74.5 months, 4 patients (1.5%) showed prostate-specific antigen progression according to the American Society for Radiation Oncology definition and 8 patients (3%) according to the Phoenix definition. A biopsy-proven local recurrence was registered in 1 patient (0.4%), and clinical progression (bone metastases) was documented in 2 patients (0.7%). Seven-year actuarial freedom from biochemical failure was 97%, and 7-year disease-specific survival and overall survival were 100% and 91%, respectively. Toxicities were comparable to other series. Conclusions: Treatment with interstitial HDR-BT plus EBRT shows a low incidence of late complications and a favorable oncologic outcome after 7 years follow-up. [ABSTRACT FROM AUTHOR]

Purpose: To develop and evaluate a method for adding dose distributions of combined external beam radiotherapy (EBRT) and brachytherapy (BT) for oropharyngeal patients. Methods and Materials: Two computed tomography (CT) scans were used for 5 patients: the EBRT CT, used for EBRT planning, and the BT CT, acquired after catheter implantation. For each scan, the salivary glands and the chewing and swallowing muscles were contoured, and a dose distribution was calculated. A nonrigid transformation was obtained by registering the organs’ surfaces. Then the BT dose distribution was mapped onto the EBRT dose distribution by applying the transformation obtained. To account for differences in fractionation, the physical doses were converted to equivalent dose in 2 Gy (EQD 2), and the total dose was found by adding dose voxel by voxel. The robustness of the dose addition was investigated by varying delineations and input parameters of the registration method and by varying the α/β parameter for EQD 2. The effect of the perturbations was quantified using dose–volume histograms (DVH) and gamma analyses (distance-to-agreement/dose-difference = 1 mm/1 Gy). Results: The variations in input parameters and delineations caused only small perturbations in the DVH of the added dose distributions. For most organs the gamma index was low, and it was moderately elevated for organs lying in areas with a steep gradient (median gamma index ≤2.3 for constrictor muscles, ≤0.7 for all other organs). Conclusions: The presented method allows adding dose distributions of combined EBRT and BT for oropharyngeal patients. In general, the method is reliable and robust with respect to uncertainties in organ delineation, perturbations in input parameters of the method, and α/β values. [ABSTRACT FROM AUTHOR]