The potential of low-dose-rate brachytherapy with iodine-125 in the treatment of local recurrences of prostate cancer after primary high-dose-rate monotherapy.

Purpose: The incidence of local prostate cancer recurrences after monotherapy with high-dose-rate brachytherapy (HDR-BT) is low. However, a cumulated number of local recurrences during follow-up is naturally observed in highly specialized oncological centers. This retrospective study aimed to present the treatment of local recurrences after HDR-BT with low-dose-rate brachytherapy (LDR-BT). Material and methods: Nine patients with low- and intermediate-risk prostate cancer with a median age of 71 years (range, 59-82 years) were diagnosed with local recurrences after previous monotherapy HDR-BT, 3 × 10.5 Gy (from 2010 to 2013). Median time to biochemical recurrence was 59 months (range, 21-80 months). All patients received 145 Gy with salvage LDR-BT (iodine-125). Gastrointestinal and urological toxicities were evaluated based on patients' records following CTCAE v. 4.0 and IPSS scales. Results: The median follow-up after salvage treatment was 30 months (range, 17-63 months). Local recurrences (LR) were detected in two cases, and the actuarial 2-year local control was 88%. Biochemical failure was observed in four cases. Distant metastases (DM) were observed in 2 patients. In one patient, both LR and DM were diagnosed simultaneously. Four patients had no relapse of the disease, and a 2-year disease-free survival (DSF) was 58.3%. Before salvage treatment, median IPSS scores were 6.5 points (range, 1-23 points). At the first follow-up visit, after one month, the mean IPSS score was 20 points, and at the last follow-up visit, it was 8 points (range, 1-26 points). One patient had urinary retention after treatment. There was no significant change in IPSS scores before and after the treatment (p = 0.68). Two patients had grade 1 toxicity in the gastrointestinal tract. Conclusions: Salvage LDR-BT for patients with prostate cancer previously treated with HDR-BT monotherapy is characterized by acceptable toxicity, and may result in local disease control.

Superficial high-dose-rate brachytherapy for primary tumors and relapses after surgery in patients with basal cell carcinoma of the head and neck region: results of a retrospective comparative cohort study.

Purpose: The recommended treatments for basal cell carcinoma (BCC) in the head and neck (H&N) region are Mohs surgery, standard surgical excision (SSE), and radiotherapy. According to the literature, local recurrence after surgical treatment in this area is associated with a worse prognosis in case of re-treatment. To our knowledge, there are no reports on high-dose-rate brachytherapy (HDR-BT) for BCC of the H&N region, both in primary lesions and relapses after SSE. This study aimed to fill this gap in the literature. Material and methods: Inclusion criteria were pathologically confirmed BCC, tumor location in the H&N region, treatment performed with superficial HDR-BT, and a minimum follow-up of 12 months. An analysis was performed on a group of 90 patients, in whom a total of 102 tumors were treated. Subsequently, tumors were divided into two sub-groups, including those treated initially, and treated due to local recurrence after previous SSE. Primary treatment group (PrG) included 59 tumors, whereas 43 tumors were included in recurrent group (ReG). Results: Statistical analysis did not reveal any significant differences between the groups in terms of age (p = 0.43), treatment duration (p = 0.17), follow-up time (p = 0.96), sex (p = 0.18), local advancement (p = 0.83), and location (p = 0.68). The estimated 5-year relapse-free survival was 96.4% in the PrG and 94.6% in the ReG group, and the difference was not statistically significant (p = 0.72). In the PrG, skin toxicity was as follows: early G1 - 20.3%, G2 - 28.8%, G3 - 42.4%, G4 - 8.5%; late G1 - 33.9%, G2 - 50.8%, G3 - 1.7%, G4 - 11.9%. Whereas, in the ReG, toxicity was as follows: early G1 - 16.3%, G2 - 41.9%, G3 - 37.2%, G4 - 4.6%; late G1 - 30.2%, G2 - 62.8%, G3 - 4.6%. There were no statistically significant differences in the early nor late toxicity between the groups (p = 0.54, p = 0.16). Conclusions: Superficial HDR-BT is a highly effective treatment for both primary and recurrent BCC of the H&N region, and is associated with acceptable skin toxicity.

Thermal Boost Combined with Interstitial Brachytherapy in Early Breast Cancer Conserving Therapy-Initial Group Long-Term Clinical Results and Late Toxicity.

(1) In breast-conserving therapy (BCT), adjuvant radiation, including tumor bed boost, is mandatory. Safely delivered thermal boost (TB) based on radio-sensitizing interstitial microwave hyperthermia (MWHT) preceding standard high-dose-rate (HDR) brachytherapy (BT) boost has the potential for local control (LC) improvement. The study is to report the long-term results regarding LC, disease-free survival (DFS), overall survival (OS), toxicity, and cosmetic outcome (CO) of HDR-BT boost ± MWHT for early breast cancer (BC) patients treated with BCT. (2) In the years 2006 and 2007, 57 diverse stages and risk (IA-IIIA) BC patients were treated with BCT ± adjuvant chemotherapy followed by 42.5-50.0 Gy whole breast irradiation (WBI) and 10 Gy HDR-BT boost. Overall, 25 patients (group A; 43.9%) had a BT boost, and 32 (group B; 56.1%) had an additional pre-BT single session of interstitial MWHT on a tumor bed. Long-term LC, DFS, OS, CO, and late toxicity were evaluated. (3) Median follow-up was 94.8 months (range 1.1-185.5). LC was 55/57, or 96.5% (1 LR in each group). DFS was 48/57, or 84.2% (4 failures in group A, 5 in B). OS was 46/57, or 80.7% (6 deaths in group A, 5 in B). CO was excellent in 60%, good in 36%, and satisfactory in 4% (A), and in 53.1%, 34.4%, and 9.4% (B), respectively. One poor outcome was noted (B). Late toxicity as tumor bed hardening occurred in 19/57, or 33.3% of patients (9 in A, 10 in B). In one patient, grade 2 telangiectasia occurred (group A). All differences were statistically insignificant. (4) HDR-BT boost ± TB was feasible, well-tolerated, and highly locally effective. LC, DFS, and OS were equally distributed between the groups. Pre-BT MWHT did not increase rare late toxicity.

Personalized Superficial HDR Brachytherapy-Dosimetric Verification of Dose Distribution with Lead Shielding of Critical Organs in the Head and Neck Region.

BACKGROUND: Surface brachytherapy, usually characterized by a high dose gradient, allows the dose to be precisely deposited in the irradiated area while protecting critical organs. When the lesion is located in the nasal or ocular region, the organ of vision must be protected. The aim of this study was to verify the dose distributions near critical organs in the head and neck region during a brachytherapy procedure using lead shielding of the eye. METHODS: Anthropomorphic phantom using 3D-printing technology was prepared. The doses deposited at a point in the lens of the eye and on the surface of the eyelid, directly under the lead shield were calculated and measured using EBT3 radiochromic films. Comparison of doses planned in the treatment planning system using the TG-43 formalism, TG-186 formalism, and measured were also performed. RESULTS: Comparing the planned and calculated doses with TG186 formalism it can be assumed that the use of lead shields is a method for protecting the organ of vision from the adverse effects of ionizing radiation. CONCLUSIONS: The decision to use a lead shield during facial surface brachytherapy procedures should be made on a patient-by-patient basis and based on model-based calculation methods recommended by TG186.

3D printing of individual skin brachytherapy applicator: design, manufacturing, and early clinical results.

Purpose: One of the main challenges in facial region brachytherapy is fixation of vendor-delivered standard applicators. Reproducibility can be maintained; however, there are frequent problems with applicator fitting to the skin surface in pleated regions. Manually prepared individual moulds require technological facilities and highly-trained staff. This article presents 3D-printed applicator preparation for a particular patient skin brachytherapy, using low-cost equipment and free software. We described applicator preparation in a step-by-step workflow. Material and methods: This study demonstrated preparation of a skin brachytherapy applicator for a challenging recurrent tumor located in the nose bridge. During first visit of patient, fiducial markers were placed to enclose treated region. Patient was computed tomography (CT)-scanned, and reconstruction of target volume and surrounding organs at risk (OARs) were performed using treatment planning system (TPS). In TPS on patient's surface, a 1-cm thick bolus was added as a body of applicator. Inside the bolus, source paths were designed, and pre-plan was prepared. Using Beben - DICOM to standard triangle language (STL) software, the body of applicator and source-paths from pre-planning was transformed into an STL file, which was used as a solid definition in 3D printing. Results: The printed applicator fitted very well, and its' placement was quickly consistent regarding placing and securing. CTV was slightly broader in treatment plan (0.34 cm3 vs. 0.31 cm3), and doses given to CTV were lower, except for V150, which was higher for the realized plan (1.15% vs. 1.83%). All reported doses to OARs were lower in the realized plan. Conclusions: A low-cost 3D printer and widely available PLA filaments seem feasible to produce individual contact applicators for skin brachytherapy. Beben - DICOM to STL software and presented workflow appear to be convenient and simple tool.

Thermal Boost to Breast Tumor Bed-New Technique Description, Treatment Application and Example Clinical Results.

(1) Current breast-conserving therapy for breast cancer consists of a combination of many consecutive treatment modalities. The most crucial goal of postoperative treatment is to eradicate potentially relapse-forming residual cancerous cells within the tumor bed. To achieve this, the HDR brachytherapy boost standardly added to external beam radiotherapy was enhanced with an initial thermal boost. This study presents an original thermal boost technique developed in the clinic. (2) A detailed point-by-point description of thermal boost application is presented. Data on proper patient selection, microwave thermal boost planning, and interstitial hyperthermia treatment delivery are supported by relevant figures and schemes. (3) Out of 1134 breast cancer patients who were administered HDR brachytherapy boost in the tumor bed, 262 were also pre-heated interstitially without unexpected complications. The results are supported by two example cases of hyperthermia planning and delivery. (4) Additional breast cancer interstitial thermal boost preceding HDR brachytherapy boost as a part of combined treatment in a unique postoperative setting was feasible, well-tolerated, completed in a reasonable amount of time, and reproducible. A commercially available interstitial hyperthermia system fit and worked well with standard interstitial brachytherapy equipment.

Dosimetric assessment of the impact of low-cost materials used in stereolithography in high-dose-rate brachytherapy.

PURPOSE: 3D printing has become a popular and widely available technique of rapid prototyping. The impact of used materials on the dose distribution has been studied for high energy sources. However, brachytherapy sources emit lower energy photons, and materials used in 3D printing may differ. This study was conducted to analyze the influence of common materials (polylactic acid - PLA and acrylonitrile butadiene styrene - ABS) used in stereolithography. MATERIAL AND METHODS: A 3D-printed phantom was designed, printed, and used to calibrate Gafchromic films. In the next step, a range of 1 mm thick plates of PLA and ABS (from zero to thirty) were inserted between source and detector to measure the impact of studied materials on delivered dose. Measurements were performed using a calibrated radiochromic film and Farmer ionization chamber in water. RESULTS: No statistically significant correlation (p = 0.4854) between the thickness of inserted PLA and the dose delivered to the film was obtained. With ionization chamber, Spearman's rank order test showed a significant correlation (p = 0.00004); however, the correlation was found weak. In case of ABS measurement, a statistically significant (p = 0.0159), yet weak negative correlation was found between the thickness of used material and the dose delivered to the film. On the other hand, a weak statistically significant (p = 0.0212) but positive correlation was found when the dose was measured with Farmer ionization chamber. We find these correlations false, as all measured doses were within the measurement uncertainty range (film ±8.0%, Farmer ±8.8%) from 100% of the prescribed dose. CONCLUSIONS: According to obtained results, with the accuracy of measurement under clinical conditions, the impact of highly filled PLA and ABS printed objects on the dose distribution from an 192Ir source in water can be omitted.

Adjuvant interstitial three-dimensional pulse-dose-rate-brachytherapy for lip squamous cell carcinoma after surgical resection.

PURPOSE: The purpose of this study was to report clinical outcomes of patients treated with pulse-dose-rate brachytherapy (PDR-BT) for lip cancer after insufficient surgery. MATERIAL AND METHODS: Twenty lip cancer patients were treated from January 2012 to September 2016. Primary treatment included surgery with or without reconstruction. All patients were diagnosed with squamous cell carcinoma, most of the tumors were pT1. Brachytherapy procedures were done after post-operative wound healing. Median of three plastic tubes were implanted using a free-hand technique. Two PDR-BT treatments were scheduled for every patient, with the gap of median 13 days. The planned dose was 0.8-1 Gy per pulse to the total dose of 50 Gy from two PDR-BT treatments. Patients were evaluated every 3-6 months. Follow-up time was counted from the last day of treatment to any event or last visit. Early and late toxicities were scored with RTOG scale. RESULTS: Average follow-up was 34.7 months (range, 12.7-67.6). Three- and five-year estimated disease-free survival was 95% and local control was 100%. One patient suffered from regional relapse in the submental region (IA lymph node group). Skin erythema or dry desquamation (grade 1) or wet desquamation (grade 2) was observed in 13 patients (65%) and one patient (5%), respectively. Six patients presented no acute toxicity. Moreover, there were no complications involving lip mucosa. All patients had grade 1 soft tissue fibrosis in the irradiated area, besides that, late toxicity included only skin complications. There were no significant factors associated with late toxicity ≥ grade 2. CONCLUSIONS: PDR-BT in the adjuvant treatment of the lip cancer yields high local control with low toxicity. Even patients with close margins after surgery (< 5 mm) should be considered as candidates for PDR-BT.

Reducing dysphagia with palliative 2D high-dose-rate brachytherapy improves survival in esophageal cancer.

PURPOSE: The goal of this study was to assess the effectiveness of dysphagia relief and overall survival in patients with advanced esophageal cancer treated with palliative high-dose-rate (HDR) brachytherapy (BT) without computed tomography-based planning. MATERIAL AND METHODS: Palliative 2D HDR-BT was used to treat 93 patients with advanced or incurable esophageal cancer in a regional cancer center from October 2010 to December 2016. Before the treatment patients presented the following grades of dysphagia: 0 - 0%, I - 57%, II - 33.3%, III - 6.5%, IV - 3.2%. The planned dose was 22.5 Gy in 3 fractions. The median age of patients was 65 years (45-88). Squamous cell carcinoma was diagnosed in 59.4%, adenocarcinoma in 22.6%, and other histological types of tumors in 6.7% of cases. The histopathological report was unknown in 11.3% of patients. RESULTS: The mean follow-up was 5.0 months (range 1-43). The median tumor length was 72.5 mm. Due to BT dysphagia was significantly decreased: grade 0 - 38.7%, I - 31.2%, II - 20.4%, IV - 1.1% (p < 0.001). Dysphagia relief was achieved in 55% of patients and lasted for a mean time of 4.6 months; stabilization occurred in 31% and deterioration in 14%. The patients with partial or complete dysphagia relief lived longer (5.8 vs. 4.1 months, p = 0.02). The patients with a length of the tumor less than 72.5 mm, histopathologically confirmed adenocarcinoma or after dilatation with a metal stent subsequently to BT had improved overall survival as well (7.1 vs. 3.6; 8.0 vs. 4.1; 6.5 vs. 4.0 months, respectively; p < 0.05). The primary localization and primary grade of dysphagia were not factors that influenced the survival of patients. The logistic regression model did not reveal any predictors for treatment response. CONCLUSIONS: 2D HDR-BT reduces dysphagia and prolongs survival in patients who respond to the treatment. It meets the assumption of palliative treatment for advanced esophageal cancer because of its simplicity and effectiveness.

Quality Assurance Procedures based on Dosimetric, Gamma Analysis as a Fast Reliable Tool for Commissioning Brachytherapy Treatment Planning Systems.

BACKGROUND: Fast and easily repeatable methods for commissioning procedures for brachytherapy (BT) treatment planning systems (TPS) are needed. Radiochromic film dosimetry with gamma analysis is widely used in external beam quality assurance (QA) procedures and planar film dosimetry is also increasingly used for verification of the dose distribution in BT applications. Using the gamma analysis method for comparing calculated and measured dose data could be used for commissioning procedures of the newly developed TG-186 and MBDCA calculation algorithms. The aim of this study was dosimetric verification of the calculation algorithm used in TPS when the CT/MRI ring applicator is used. MATERIALS AND METHODS: Ring applicators with 26 and 30 mm diameters and a 60 mm intra-uterine tube with 60° angle were used for verification. Gafchromic® EBT films were used as dosimetric media. Dose grids, corresponding to each plane (dosimetric film location), were exported from the TPS as a raw data. Gafchromic® films were digitized after irradiation. gamma analysis of the data were performed using the OMNI Pro I'mRT® system, as recommended by the AAPM TG-119 rapport criterion for gamma analysis of 3%, 3 mm and a level of 95%. RESULTS: For the 26 mm and 30 mm rings, the average gamma ranged, respectively, from 0.1 to 0.44 and from 0.1 to 0.27. In both cases, 99% of the measured points corresponded with the calculated data. CONCLUSIONS: This analysis showed excellent agreement between the dose distribution calculated with the TPS and the doses measured by Gafchromic films. This finding confirms the viability of using film dosimetry in BT.

Film based verification of calculation algorithms used for brachytherapy planning-getting ready for upcoming challenges of MBDCA.

PURPOSE: Well-known defect of TG-43 based algorithms used in brachytherapy is a lack of information about interaction cross-sections, which are determined not only by electron density but also by atomic number. TG-186 recommendations with using of MBDCA (model-based dose calculation algorithm), accurate tissues segmentation, and the structure's elemental composition continue to create difficulties in brachytherapy dosimetry. For the clinical use of new algorithms, it is necessary to introduce reliable and repeatable methods of treatment planning systems (TPS) verification. The aim of this study is the verification of calculation algorithm used in TPS for shielded vaginal applicators as well as developing verification procedures for current and further use, based on the film dosimetry method. MATERIAL AND METHODS: Calibration data was collected by separately irradiating 14 sheets of Gafchromic(®) EBT films with the doses from 0.25 Gy to 8.0 Gy using HDR (192)Ir source. Standard vaginal cylinders of three diameters were used in the water phantom. Measurements were performed without any shields and with three shields combination. Gamma analyses were performed using the VeriSoft(®) package. RESULTS: Calibration curve was determined as third-degree polynomial type. For all used diameters of unshielded cylinder and for all shields combinations, Gamma analysis were performed and showed that over 90% of analyzed points meets Gamma criteria (3%, 3 mm). CONCLUSIONS: Gamma analysis showed good agreement between dose distributions calculated using TPS and measured by Gafchromic films, thus showing the viability of using film dosimetry in brachytherapy.

Can we improve the dose distribution for single or multi-lumen breast balloons used for Accelerated Partial Breast Irradiation?

PURPOSE: The aim of the study was to verify dose distribution parameters for multi-lumen, and artificially created single-lumen balloon applicator used for the same patient with two optimization algorithms: inverse planning simulated annealing (IPSA) and dose point optimization with distance option. MATERIAL AND METHODS: Group of 24 patients with multi-lumen balloon applied were investigated. Each patient received 10 fractions of 3.4 Gy (2 fractions daily). For every patient, four treatment plans were prepared. Firstly, for five-lumen balloon optimized with IPSA algorithm and optimization parameters adjusted for each case. Secondly, for the same applicator optimized with dose point optimization and distant option. Two other plans were prepared for single-lumen applicator, created by removing four peripheral lumens, optimized with both algorithms. RESULTS: The highest D95 parameter was obtained for plans optimized with IPSA algorithm, mean value 99.3 percent of prescribed dose, and it was significantly higher than plans optimized with dose point algorithm (mean = 83.50%, p < 0.0001), IPSA single-lumen balloon plan (mean = 83.50%, p = 0.0037) and optimized to dose point single-lumen balloon (mean = 85.51%, p < 0.0001). There were no statistically significant differences concerning maximum doses distributed to skin surface for neither application nor optimization method. Volumes receiving 200% of prescribed dose in PTV were higher for multi-lumen balloon dose point optimized plans (mean = 8.78%), than for other plans (IPSA multi-lumen balloon plan: mean = 7.37%, p < 0.0001, single-lumen IPSA: mean = 7.20%, p < 0.0001, single-lumen dose point: mean = 7.19%, p < 0.0001). CONCLUSIONS: Basing on performed survey, better dose distribution parameters are obtained for patients with multi-lumen balloon applied and optimized using IPSA algorithm with individualized optimization parameters.

Definitive high-dose-rate endobronchial brachytherapy of bronchial stump for lung cancer after surgery.

PURPOSE: The aim of this work was to evaluate outcomes after definitive high-dose-rate endobronchial brachytherapy (HDR-BT) for lung cancer. METHODS AND MATERIAL: We treated 34 patients after surgery for lung cancer, without nodal or distant metastases, with HDR-BT. Two groups were analyzed, one with local recurrence in stump after prior surgery (n = 13) and a second with nonradical primary lobar resection found in histopathologically positive margins (n = 21). There were 27 men and 7 women with a median age of 57.4 years. Twenty-five patients received sole brachytherapy with 4 fractions of 7.5 Gy and 9 received combined treatment consisting of 2 fractions of 6 Gy (HDR-BT) and 50 Gy from external beam radiotherapy. Overall survival time (OS) and overall disease-free survival time (OFS) were compared with prognostic factors. RESULTS: The complete local and radiologic response rate evaluated at the first month after HDR-BT was 73.5% (25/34). The partial response rate was 26.5%. OFS time in total group was 17.4 months; OS was 18.8 months. Differences were found in OS between both groups-primary tumor or recurrence (log-rank test, p = 0.048). Differences were not found according to gender (p = 0.36), clinical stage (p = 0.76), histopathology (p = 0.93), treatment dose (p = 0.45), sole or combined treatment (p = 0.16), or grade of remission in week 4 (p = 0.15). CONCLUSIONS: HDR-BT of a stump recurrence or after nonradical resection leads to a long-term OS rate in patients with localized lung cancer and could be considered curative. We found no correlations between OS and chosen clinical data; adjuvant HDR-BT gave better results.

Quality assurance procedures during commissioning of a treatment planning system as a tool to establish new standards before migration.

PURPOSE: Treatment planning system commissioning is one of the most important parts of the quality assurance system in a working brachytherapy department. Migration to a more sophisticated system is always a step forward for the planning team but careful verification of the workflow and obtained results is mandatory. The question is not only whether the quality and safety of the previous standards can be preserved, but also about the possibility of reaching a higher level. The general objective of this study was to compare and verify calculation algorithms implemented in the treatment planning systems Plato Brachytherapy v.14.3.7 and Oncentra Masterplan (Brachy) V.3.1 SP 3. MATERIAL AND METHODS: In order to revise the optimization algorithms implemented in the compared treatment systems, a series of 20 interstitial breast cancer applications were used. Treatment plans were optimized using geometric optimization with distance option. The parameters V, D90, D100, V100, V150, V200 and DNR were gained for target volume. On the basis of the value of Student's t-test parameters (α = 0.05) plans prepared using optimization algorithms implemented in the two treatment planning systems were compared. RESULTS: For the treatment plans prepared using Oncentra Masterplan a lower value of DNR (p = 0.018) was obtained. Uniformity of the dose distribution does not collide with comparable D90 values for both treatment planning systems (p = 0.109). Dose throughout the target volume (D100) was also proved to be higher in plans prepared using Oncentra Masterplan (p = 0.012). CONCLUSIONS: For interstitial applications Oncentra Masterplan planning system enables one to prepare a more homogeneous dose distribution but also a higher dose in the whole treated volume, while the volume covered with the therapeutic dose does not statistically differ.

HDR and PDR 192Ir source activity control procedures, as the part of the quality assurance system at Brachytherapy Department of Greater Poland Cancer Centre.

PURPOSE: One of the main causes of treatment failures in brachytherapy is incorrect source strength specification in planning system or treatment delivery console. Source strength control is the only scheme to avoid such mistakes. The main aim of this work was to present results of three years of HDR and PDR sources activity control. MATERIAL AND METHODS: Study was based on data from 14 192Ir HDR and PDR sources exchanges. Sources were checked three times: at the exchange day and after one and two months. Measurements were performed twice with thimble chamber (PMMA phantom), and well chamber. The source strength were measured as air - kerma and recalculated to activity. RESULTS: Source activities measured using well chamber and thimble chamber, as well as activities provided by planning system, were presented for PDR and HDR, respectively. Differences between results obtained using each chamber and activities from planning system were presented graphically. The calculated and measured activities differed less than 5%. Wilcoxon test was performed as well, no statistically significant differences were observed among HDR or PDR activities. CONCLUSIONS: Checking of source parameters is one of the most important parts of quality control system in brachytherapy facilities. Well chamber and thimble chamber based dosimetry systems are fast and reliable tools for 192Ir source parameters checking in working brachytherapy department conditions.