A comprehensive quality assurance protocol for electromagnetic tracking in brachytherapy.

BACKGROUND: Electromagnetic tracking (EMT) systems have proven to be a valuable source of information regarding the location and geometry of applicators in patients undergoing brachytherapy (BT). As an important element of an enhanced and individualized pre-treatment verification, EMT can play a pivotal role in detecting treatment errors and uncertainties to increase patient safety. PURPOSE: The purpose of this study is two-fold: to design, develop and test a dedicated measurement protocol for the use of EMT-enabled afterloaders in BT and to collect and compare the data acquired from three different radiation oncology centers in different clinical environments. METHODS: A novel quality assurance (QA) phantom composed of a scaffold with supports to fix the field generator, different BT applicators, and reference sensors (sensor verification tools) was used to assess the precision (jitter error) and accuracy (relative distance errors and target registration error) of the EMT sensor integrated into an afterloader prototype. Measurements were repeated in different environments where EMT measurements are likely to be performed, namely an electromagnetically clean laboratory, a BT suite, an operating room, and, if available, a CT suite and an MRI suite dedicated to BT. RESULTS: The mean positional jitter was consistently under 0.1 mm across all measurement points, with a slight trend of increased jitter at greater distances from the field generator. The mean variability of sensor positioning in the tested tandem and ring gynecological applicator was also below 0.1 mm. The tracking accuracy close to the center of the measurement volume was higher than at its edges. The relative distance error at the center was 0.2-0.3 mm with maximum values reaching 1.2-1.8 mm, but up to 5.5 mm for measurement points close to the edges. In general, similar accuracy results were obtained in the clinical environments and in all investigated institutions (median distance error 0.1-0.4 mm, maximum error 1.0-2.0 mm), however, errors were found to be larger in the CT suite (median distance error up to 1.0 mm, maximum error up to 3.6 mm). CONCLUSION: The presented quality assessment protocol for EMT systems in BT has demonstrated that EMT offers a high-accuracy determination of the applicator/implant geometry even in clinical environments. In addition to that, it has provided valuable insights into the performance of EMT-enabled afterloaders across different radiation oncology centers.

Time-action and patient experience analyses of locally advanced cervical cancer brachytherapy.

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Multibody dynamic modeling of the behavior of flexible instruments used in cervical cancer brachytherapy.

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.

Narrowing the difference in dose delivery for IOERT and IOBT for locally advanced and locally recurrent rectal cancer.

Purpose: Intra-operative radiotherapy (IORT) has been used as a tool to provide a high-dose radiation boost to a limited volume of patients with fixed tumors with a likelihood of microscopically involved resection margins, in order to improve local control. Two main techniques to deliver IORT include high-dose-rate (HDR) brachytherapy, termed 'intra-operative brachytherapy' (IOBT), and electrons, termed 'intra-operative electron radiotherapy' (IOERT), both having very different dose distributions. A recent paper described an improved local recurrence-free survival favoring IOBT over IOERT for patients with locally advanced or recurrent rectal cancer and microscopically irradical resections. Although several factors may have contributed to this result, an important difference between the two techniques was the higher surface dose delivered by IOBT. This article described an adaptation of IOERT technique to achieve a comparable surface dose as dose delivered by IOBT. Material and methods: Two steps were taken to increase the surface dose for IOERT: 1. Introducing a bolus to achieve a maximum dose on the surface, and 2. Re-normalizing to allow for the same prescribed dose at reference depth. Conclusions: We describe and propose an adaptation of IOERT technique to increase surface dose, decreasing the differences between these two techniques, with the aim of further improving local control. In addition, an alternative method of dose prescription is suggested, to consider improved comparison with other techniques in the future.

A Novel Framework for the Optimization of Simultaneous ThermoBrachyTherapy.

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.

Simultaneous ThermoBrachytherapy: Electromagnetic Simulation Methods for Fast and Accurate Adaptive Treatment Planning.

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.

Design of the novel ThermoBrachy applicators enabling simultaneous interstitial hyperthermia and high dose rate brachytherapy.

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.

An anthropomorphic deformable phantom of the vaginal wall and cavity.

Brachytherapy is a common treatment in cervical, uterine and vaginal cancer management. The technique is characterised by rapid developments in the fields of medical imaging, dosimetry planning and personalised medical device design. To reduce unnecessary burden on patients, assessments and training of these technologies should preferable be done using high-fidelity physical phantoms. In this study, anthropomorphic deformable phantoms of the vaginal wall and cavity were developed for image-guided adaptive brachytherapy, in which vaginal wall biomechanics were mimicked. Phantoms were produced from both silicone and polyvinyl alcohol materials. Material characterisations were performed with uniaxial tensile tests, via which Young's moduli and toughness were quantified. In addition, the contrast between adjacent phantom layers was quantified in magnetic resonance images. The results showed that stress-strain curves of the silicone phantoms were within the range of those found in healthy human vaginal wall tissues. Sample preconditioning had a large effect on Young's moduli, which ranged between 2.13 and 6.94 MPa in silicone. Toughness was a more robust and accurate metric for biomechanical matching, and ranged between 0.23 and 0.28 ·106J·m-3as a result of preconditioning. The polyvinyl alcohol phantoms were not stiff or tough enough, with a Young's modulus of 0.16 MPa and toughness of 0.02 ·106J·m-3. All materials used could be clearly delineated in magnetic resonance images, although the MRI sequence did affect layer contrast. In conclusion, we developed anthropomorphic deformable phantoms that mimic vaginal wall tissue and are well visible in magnetic resonance images. These phantoms will be used to evaluate the properties and to optimise the development and use of personalised brachytherapy applicators.

Intraoperative Electron Beam Radiation Therapy (IOERT) Versus High-Dose-Rate Intraoperative Brachytherapy (HDR-IORT) in Patients With an R1 Resection for Locally Advanced or Locally Recurrent Rectal Cancer.

PURPOSE: Intraoperative radiation therapy (IORT), delivered by intraoperative electron beam radiation therapy (IOERT) or high-dose-rate intraoperative brachytherapy (HDR-IORT), may reduce the local recurrence rate in patients with locally advanced and locally recurrent rectal cancer (LARC and LRRC, respectively). The aim of this study was to compare the oncological outcomes between both IORT modalities in patients with LARC or LRRC who underwent a microscopic irradical (R1) resection. METHODS: All consecutive patients who received IORT because of an R1 resection of LARC or LRRC between 2000 and 2016 in two tertiary referral centers were included. In LARC, a resection margin of ≤2 mm was considered R1. A resection margin of 0 mm was considered R1 in LRRC. RESULTS: In total, 215 patients with LARC were included, of whom 151 (70%) received IOERT and 64 (30%) received HDR-IORT; in addition, 158 patients with LRRC were included, of whom 112 (71%) received IOERT and 46 (29%) received HDR-IORT. After multivariable analyses, the overall survival was not significantly different between the two IORT modalities. The local recurrence-free survival was significantly longer in patients treated with HDR-IORT, both in LARC (hazard ratio [HR], 0.496; 95% CI, 0.253-0.973; P = .041) and LRRC (HR, 0.567; 95% CI, 0.349-0.920; P = .021). In patients with LARC, major postoperative complications were similar for both IORT modalities (IOERT, 30%; HDR-IORT, 27%), whereas in patients with LRRC, the incidence of major postoperative complications was higher after HDR-IORT (IOERT, 26%; HDR-IORT, 46%). CONCLUSIONS: This study showed a significantly better local recurrence-free survival in favor of HDR-IORT in patients with an R1 resection for LARC or LRRC. Optimization of the IOERT technique seems warranted.

Accuracy of dwell position detection with a combined electromagnetic tracking brachytherapy system for treatment verification in pelvic brachytherapy.

BACKGROUND AND PURPOSE: To investigate the accuracy of dwell position detection with a combined electromagnetic tracking (EMT) brachytherapy (BT) system for treatment verification, by quantifying positional errors due to EM field interference in typical pelvic BT clinical settings. MATERIALS AND METHODS: Dedicated prostate and cervix BT phantoms were imaged with CT. For the cervix phantom, the Utrecht applicator + interstitial catheters were used. The implants were reconstructed and treatment plans were created with 270/65 dwell positions for the prostate/cervix phantom. Next, EMT experiments were performed in clinical BT settings using a prototype of a combined EMT/BT system. We quantified positional errors due to EM field interference from surrounding equipment by comparing planned and EMT-measured dwell positions. The mean residual error between planned and EMT-measured dwell positions was calculated in the prostate interstitial catheters and in the whole cervix implant including the applicator. For the cervix phantom, the analysis was repeated for only the interstitial catheters. RESULTS: Mean residual errors of less than 0.5/0.4 mm in the prostate/cervix catheters were found. For the whole cervix implant including the applicator, large deviations up to 2.4 mm were found. Compared to the interference free set-up, the CT and patient bed environments showed larger residual errors in the interstitial catheters, but residual errors remained <1 mm in all cases. CONCLUSION: Dwell position detection with the combined system in interstitial catheters is sufficiently accurate to perform EMT-based treatment verification. The effect of EM interference from the surrounding equipment was limited.

Fast and fully-automated multi-criterial treatment planning for adaptive HDR brachytherapy for locally advanced cervical cancer.

PURPOSE: To develop and evaluate a fast, automated multi-criterial treatment planning approach for adaptive high-dose-rate (HDR) intracavitary + interstitial brachytherapy (BT) for locally advanced cervical cancer. METHODS AND MATERIALS: Twenty-two previously delivered single fraction MRI-based HDR treatment plans (SFclin) were used to guide training of our in-house system for multi-criterial autoplanning, aiming for an autoplan quality superior to the training plans, while respecting the clinically desired "pear-shaped" dose distribution. Next, the configured algorithm was used to automatically generate treatment plans for 63 other fractions (SFauto). The SFauto plans were compared to the corresponding SFclin plans in blind pairwise comparisons by an expert clinician. Then, the effect of adaptive autoplanning on total treatment (TT) plans (external beam + 3 BT fractions) was evaluated for 16 patients by simulating the clinically applied adaptive strategy to generate TTauto plans and compare them with the corresponding clinical treatments (TTclin). RESULTS: In the blind comparisons, all SFauto plans were considered clinically acceptable. In 62/63 comparisons, SFauto plans were considered at least as good as, or better than the corresponding SFclin. The average optimization time for autoplanning was 20.5 ± 19.2 s (range 4.4-106.4 s) per plan. In 14 of 16 TTauto plans, the desired total dose of 90 Gy (EQD2) was obtained, compared to only 9 in the corresponding TTclin, while autoplanning also decreased bladder and rectum doses. CONCLUSIONS: Fast, fully-automated multi-criterial treatment planning for adaptive HDR-BT for locally advanced cervical cancer is feasible. Autoplans were superior to corresponding clinical plans.

Fast automated multi-criteria planning for HDR brachytherapy explored for prostate cancer.

We developed a fast and fully-automated, multi-criteria treatment planning workflow for high dose rate brachytherapy (HDR-BT). In this workflow, the patient-CT with catheter reconstructions and dwell positions are imported from the clinical TPS into a novel system for automated dwell time optimisation. The optimised dwell times are then imported into the clinical TPS. The aims of automation were (1) planner-independent, enhanced plan quality, (2) short optimisation times. Our in-house developed system for fully automated, multi-criteria external beam radiotherapy (EBRT) treatment planning (Erasmus-iCycle) was adapted for optimisation of HDR-BT dose distributions. The investigations were performed with planning CT scans with catheter reconstructions and delineations of twenty-five low- and intermediate-risk prostate cancer patients who were previously treated in our center with [Formula: see text] Gy HDR-BT. Automatically generated plans (autoplans) were compared to the corresponding clinical plans. All evaluations were performed in the clinical TPS. The requested 95% tumour coverage was obtained for all autoplans, while this was only observed in 23/25 clinical plans. All autoplans showed a consistent reduction of the [Formula: see text] for the highest prioritised OAR, the urethra. The average and maximum reductions were 6.3%-point and 12.1%-point of the prescribed dose, respectively. In addition, conformality of the autoplans was higher. The autoplans had slightly smaller delivery times. Autoplanning took on average 4.6 s, including computation of the dose kernels.

Subcutaneous spacer injection to reduce skin toxicity in breast brachytherapy: A pilot study on mastectomy specimens.

PURPOSE: Accelerated partial breast irradiation is a treatment option for selected patients with early-stage breast cancer. Some accelerated partial breast irradiation techniques lead to skin toxicity with the skin dose as a main risk factor. Biodegradable spacers are effective and safe in prostate brachytherapy to protect the rectum. We hypothesize that a subcutaneous spacer injection reduces the skin dose in breast brachytherapy. METHODS AND MATERIALS: Ultrasound-guided spacer injections, either hyaluronic acid (HA) or iodined polyethylene glycol (PEG), were performed on fresh mastectomy specimens. Success was defined as a spacer thickness of ≥5 mm in the high-dose skin area. Usability was scored using the system usability scale. Pre and postinjection CT scans were used to generate low-dose-rate seed brachytherapy treatment plans after defining a clinical target volume. Maximum dose to small skin volumes (D0.2cc) and existence of hotspots (isodose ≥90% on 1 cm2 of skin) were calculated as skin toxicity indicators. RESULTS: We collected 22 mastectomy specimens; half had HA and half had PEG injection. Intervention success was 100% for HA and 90.9% for PEG (p = NS). Hydrodissection was feasible in 81.8% with HA and 63.6% with PEG. Median system usability scale score was 97.5 for HA and 82.5 for PEG (p < 0.001). Mean D0.2cc was 80.8 Gy without spacer and 53.7 Gy with spacer (p < 0.001). Skin hotspots were present in 40.9% without spacer but none with spacer (p < 0.001). CONCLUSIONS: A spacer injection in mastectomy specimens is feasible. An extra 5 mm space is always achieved, thereby potentially reducing the skin dose dramatically in low-dose-rate seed breast brachytherapy.

A randomized controlled trial testing a hyaluronic acid spacer injection for skin toxicity reduction of brachytherapy accelerated partial breast irradiation (APBI): a study protocol.

BACKGROUND: Accelerated partial breast irradiation (APBI) is a treatment option for selected early stage breast cancer patients. Some APBI techniques lead to skin toxicity with the skin dose as main risk factor. We hypothesize that a spacer injected between the skin and target volume reduces the skin dose and subsequent toxicity in permanent breast seed implant (PBSI) patients. METHODS: In this parallel-group, single-center, randomized controlled trial, the effect of a subcutaneous spacer injection on skin toxicity among patients treated with PBSI is tested. Eligibility for participation is derived from international guidelines for suitable patients for partial breast radiotherapy, e.g. women aged ≥ 50 years with a histologically proven non-lobular breast carcinoma and/or ductal carcinoma in situ (DCIS), tumor size ≤ 3 cm, node-negative, and PBSI technically feasible. Among exclusion criteria are neoadjuvant chemotherapy, lymphovascular invasion, and allergy for hyaluronic acid. For the patients allocated to receive spacer, after the PBSI procedure, 4-10 cc of biodegradable hyaluronic acid (Barrigel™, Palette Life Sciences, Santa Barbara, CA, USA or Restylane SubQ®, Galderma Benelux, Breda, the Netherlands) is injected directly under the skin using ultrasound guidance to create an extra 0.5-1 cm space between the treatment volume and the skin. The primary outcome is the rate of telangiectasia at two years, blindly assessed using Bentzen's 4-point scale. Secondary outcomes include: local recurrence; disease-free and overall survival rates; adverse events (pain, redness, skin/subcutaneous induration, radiation dermatitis, pigmentation, surgical site infection); skin dose; cosmetic and functional results; and health-related quality of life. A Fisher's exact test will be used to test differences between groups on the primary outcome. Previous studies found 22.4% telangiectasia at two years. We expect the use of a spacer could reduce the occurrence of telangiectasia to 7.7%. A sample size of 230 patients will allow for a 10% lost to follow-up rate. DISCUSSION: In this study, the effect of a subcutaneous spacer injection on the skin dose, late skin toxicity, and cosmetic outcome is tested in patients treated with PBSI in the setting of breast-conserving therapy. Our results will be relevant for most forms of breast brachytherapy as well as robotic radiosurgery, as skin spacers could protect the skin with these other techniques. TRIAL REGISTRATION: Netherlands Trial Register, NTR6549 . Registered on 27 June 2017.

Fractionated high-dose-rate brachytherapy as monotherapy in prostate cancer: Does implant displacement and its correction influence acute and late toxicity?

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.

Toxicity and quality of life after high-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer.

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 38Gy 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.

Improving anatomical mapping of complexly deformed anatomy for external beam radiotherapy and brachytherapy dose accumulation in cervical cancer.

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.

MR guided applicator reconstruction for brachytherapy of cervical cancer using the novel titanium Rotterdam applicator.

A novel model of the titanium Rotterdam tandem and ovoid applicator is presented. As titanium produces artefacts in MR images, an MR sequence was sought and optimised for visualisation and accurate applicator reconstruction. The mean inter-observer (8 observers) variability for four patients was only 0.7 mm (maximum 1.7 mm).

Stereotactic body radiotherapy with a focal boost to the MRI-visible tumor as monotherapy for low- and intermediate-risk prostate cancer: early results.

BACKGROUND: There is growing evidence that prostate cancer (PC) cells are more sensitive to high fraction dose in hypofractionation schemes. High-dose-rate (HDR) brachytherapy as monotherapy is established to be a good treatment option for PC using extremely hypofractionated schemes. This hypofractionation can also be achieved with stereotactic body radiotherapy (SBRT). We report results on toxicity, PSA response, and quality of life (QOL) in patients treated with SBRT for favorable-risk PC. METHODS: Over the last 4 years, 50 hormone-naïve patients with low- and intermediate-risk PC were treated with SBRT to a total dose of 38 Gy delivered in four daily fractions of 9.5 Gy. An integrated boost to 11 Gy per fraction was applied to the dominant lesion if visible on MRI. Toxicity and QoL was assessed prospectively using validated questionnaires. RESULTS: Median follow-up was 23 months. The 2-year actuarial biochemical control rate was 100%. Median PSA nadir was 0.6 ng/ml. Median International Prostate Symptoms Score (IPSS) was 9/35 before treatment, with a median increase of 4 at 3 months and remaining stable at 13/35 thereafter. The EORTC/RTOG toxicity scales showed grade 2 and 3 gastrointestinal (GI) acute toxicity in 12% and 2%, respectively. The late grade 2 GI toxicity was 3% during 24 months FU. Genitourinary (GU) grade 2, 3 toxicity was seen in 15%, 8%, in the acute phase and 10%, 6% at 24 months, respectively. The urinary, bowel and sexual domains of the EORTC-PR25 scales recovered over time, showing no significant changes at 24 months post-treatment. CONCLUSIONS: SBRT to 38 Gy in 4 daily fractions for low- and intermediate-risk PC patients is feasible with low acute and late genitourinary and gastrointestinal toxicity. Longer follow-up preferably within randomized studies, is required to compare these results with standard fractionation schemes.

Local control in advanced cancer of the nasopharynx: is a boost dose by endocavitary brachytherapy of prognostic significance?

PURPOSE: To analyze whether local tumor control in advanced nasopharyngeal cancer (NPC) can be optimized by boosting the primary dose by endocavitary brachytherapy (EBT). METHODS AND MATERIALS: To study the role of EBT, three data sets on NPC, that is, the "Vienna", "Rotterdam," and "Amsterdam" series, with a total number of 411 advanced NPC patients, were available. The Rotterdam series consisted of 72 patients (34 T1,2N+ and 38 T3,4N0,+) and were treated with neoadjuvant chemotherapy followed by external beam radiotherapy (dose 70/2Gy). After 70/2Gy, a boost was applied by EBT (in case of T1,2N+) or stereotactic radiation (in case of T3,4 tumors). The Amsterdam (Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute) series consisted of 76 patients (40 T1,2N+ and 36 T3,4N0,+) and were irradiated to a dose of 70/2Gy with concomitant chemotherapy. No second boost by EBT was applied. RESULTS: In the case of T1,2N+ tumors, the local relapse rate (LRR) was significantly smaller if a boost was applied, that is, 0% (0/34, EBT boost) vs. 14% (14/102, no EBT boost) (p=0.023). For the T3,4 tumors, an LRR of 10% (4/38, EBT or stereotactic radiation boost) vs. 15% (17/111, no boost) was found (p=0.463). CONCLUSIONS: In the case of advanced NPC (T1,2N+ vs. T3,4N+,0), for early T-stages (T1,2N+), an EBT boost seems an excellent way to deliver highly conformal high doses of radiation to the nasopharynx, with high local control rates. For advanced T-stages (T3,4N+,0), the reduction in LRR (10% vs. 15%) was not significant (p=0.463).