Intraoperative HDR Brachytherapy: Present and Future

Radiotherapy is one of the most effective modalities in cancer treatment, and can be applied either by external beam radiotherapy or by brachytherapy. Brachytherapy is a treatment modality in which tumors are irradiated by positioning radioactive sources very close to or in the tumor volume. The use of (fractionated) HDR and PDR brachytherapy has increased dramatically. In chapter 2 the techniques and results of fractionated HDR and PDR brachytherapy for head and neck cancer are presented. HDR/PDR brachytherapy is usually performed with single stepping source afterloaders, containing a small Iridium-192 source, enabling optimization of the dose distribution by optimization of the dwell times over all dwell positions in the implant. In chapter 3 the effects of geometric optimization on the dose distribution of interstitial volume implants have been studied in terms of the irradia¬ted volume, the dose uniformity, and the choice of the reference dose. The results of anatomy based inverse planning in HDR prostate implants are evaluated in chapter 4. An Integrated Brachytherapy Unit (IBU), i.e. a shielded operating room with an HDR afterloader and a dedicated brachytherapy localiser, connected to a treatment planning computer, was established at the Erasmus MC – Daniel Den Hoed Cancer Center. This set-up enables integration of the entire brachy¬therapy procedure, i.e. implantation, implant reconstruction, dose planning and delivery in a single session. In chapter 5 the reconstruction accuracy of this dedicated localiser has been evaluated by simulations and by measurements using phantoms representing clinical relevant implant geometries. When converting to on-line planning by importing the fluoroscopy images directly in the planning computer the image distortions present in fluoroscopy images should be eliminated. In chapter 6, the accuracy of on-line planning in the IBU using dedicated image distortion correction algorithms has been evaluated. The availability of an HDR afterloader in the IBU enables the use of intraoperative brachytherapy (IOBT). IOBT is applied 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. In chapter 7 we have calculated the individual treatment plan, based on the real geometry of the FIT, and the dose at clips placed during surgery, of 32 patients with locally advanced rectal tumors treated this way. In chapter 8 the technique and results, in terms of local failure and survival, of IOBT for patients with locally advanced or recurrent rectal cancer are discussed. A taskgroup on quality assurance (QA) of brachytherapy systems of the Netherlands Commission on Radiation Dosimetry was established to develop nation wide accepted guidelines for QA in brachytherapy. The taskgroup investigated the accuracy of brachytherapy treatments in 33 radiotherapy institutions in The Netherlands and Belgium, by determining the accuracy of implant reconstruction and dose delivery (chapter 9). In chapter 10 the practice of brachytherapy QA in The Netherlands and Belgium was evaluated and compared with international recommendations. The determination of the reference air kerma rate for Iridium-192 sources and the related uncertainty are discussed in chapter 11. In chapter 12 the presented set-up for HDR (intraoperative) brachytherapy is discussed in some more detail and future perspectives are presented

Surface Pressure of Ovalbumin and Pepsin Films

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

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 ·106 J·m-3 as 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 ·106 J·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.</p

Determination of the accuracy of implant reconstruction and dose delivery in brachytherapy in The Netherlands and Belgium

Purpose: To gain insight into the accuracy of brachytherapy treatments, the accuracy of implant reconstruction and dose delivery was investigated in 33 radiotherapy institutions in The Netherlands and Belgium. Materials and methods: The accuracy of the implant reconstruction method was determined using a cubic phantom containing 25 spheres at well-known positions. Reconstruction measurements were obtained on 41 brachytherapy localizers, 33 of which were simulators. The reconstructed distances between the spheres were compared with the true distances. The accuracy of the dose delivery was determined for high dose rate (HDR), pulsed dose rate (PDR) and low dose rate (LDR) afterloading systems using a polymethyl methacrylate cylindrical phantom containing a NE 2571 ionization chamber in its centre. The institutions were asked to deliver a prescribed dose at the centre of the phantom. The measured dose was compared with the prescribed dose. Results: The average reconstruction accuracy was -0.07 mm (±0.4 mm, 1 SD) for 41 localizers. The average deviation of the measured dose from the prescribed dose was +0.9% (±1.3%, 1 SD) for 21 HDR afterloading systems, +1.0% (±2.3%, 1 SD) for 12 PDR afterloaders, and +1.8% (±2.5%, 1 SD) for 15 LDR afterloaders. Conclusions: This comparison showed a good accuracy of brachytherapy implant reconstruction and dose delivery in The Netherlands and Belgium

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

BackgroundAccelerated 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.MethodsIn 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 50years with a histologically proven non-lobular breast carcinoma and/or ductal carcinoma in situ (DCIS), tumor size 3cm, 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, 4-10cc of biodegradable hyaluronic acid (Barrigel, Palette Life Sciences, Santa Barbara, CA, USA or Restylane SubQ (R), Galderma Benelux, Breda, the Netherlands) is injected directly under the skin using ultrasound guidance to create an extra 0.5-1cm space between the treatment volume and the skin. The primary outcome is the rate of telangiectasia at twoyears, 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 twoyears. 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.DiscussionIn 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 registrationNetherlands Trial Register, NTR6549. Registered on 27 June 2017