Customized 3D-printed molds for high dose-rate brachytherapy in facial skin cancer: First clinical experience.

BACKGROUND AND OBJECTIVE: Radiotherapy of elderly, frail patients with facial skin cancer in proximity to critical organs is challenging. This is the first report on clinical experience with facial skin cancer treated by individualized 3D-printer-based mold high-dose-rate (HDR) brachytherapy (BT). PATIENTS AND METHODS: Fifteen patients not eligible for radical surgery or definitive external beam radiotherapy (EBRT) were treated with 3D-printer-based mold HDR-BT. Patient selection and treatment were in accordance with multidisciplinary tumor board recommendations. Clinical response, toxicity and cosmesis were analyzed. RESULTS: Median age was 77 years. Histology revealed squamous cell carcinoma in seven, basal cell carcinoma in five, melanoma in situ in one, Lentigo maligna in one, and melanoma in one patient, respectively. Median prescription dose was 39 Gy delivered in once-daily fractions of 3 Gy. After a median follow-up of 12.2 months, local recurrence was observed in one patient with melanoma in situ. Apart from one grade 4 cataract, no other > grade 2 late toxicity was documented. CONCLUSIONS: HDR-BT with 3D-printer-based molds for facial skin cancer is a well-tolerated and safe treatment option for elderly, frail patients not eligible for radical surgery or definitive EBRT due to functional inoperability or tumor location.

Image-guided high-dose-rate brachytherapy for rectal cancer: technical note and first clinical experience on an organ-preserving approach.

PURPOSE: As the population ages, the incidence of rectal cancer among elderly patients is rising. Due to the risk of perioperative morbidity and mortality, alternative nonoperative treatment options have been explored in elderly and frail patients who are clinically inoperable or refuse surgery. METHODS: Here we present technical considerations and first clinical experience after treating a cohort of six rectal cancer patients (T1­3, N0­1, M0; UICC stage I-IIIB) with definitive external-beam radiation therapy (EBRT) followed by image-guided, endorectal high-dose-rate brachytherapy (HDR-BT). Patients were treated with 10-13â€¯× 3 Gy EBRT followed by HDR-BT delivering 12-18 Gy in two or three fractions. Tumor response was evaluated using endoscopy and magnetic resonance imaging of the pelvis. RESULTS: Median age was 84 years. All patients completed EBRT and HDR-BT without any high-grade toxicity (> grade 2). One patient experienced rectal bleeding (grade 2) after 10 weeks. Four patients (67%) demonstrated clinical complete response (cCR) or near cCR, there was one partial response, and one residual tumor and hepatic metastasis 8 weeks after HDR-BT. The median follow-up time for all six patients is 42 weeks (range 8-60 weeks). Sustained cCR without evidence of local regrowth has been achieved in all four patients with initial (n)cCR to date. CONCLUSION: Primary EBRT combined with HDR-BT is feasible and well tolerated with promising response rates in elderly and frail rectal cancer patients. The concept could be an integral part of a highly individualized and selective nonoperative treatment offered to patients who are not suitable for or refuse surgery.

Effects of iodinated contrast agent on HU-based dose calculation and dose delivered in iridium-192 high-dose-rate brachytherapy.

PURPOSE: This study compares the effect of iodinated contrast agent on Hounsfield unit (HU)-based TG-186 dose calculation vs. delivered dose for high-dose-rate (HDR) iridium-192 brachytherapy using a phantom model. MATERIAL AND METHODS: A reservoir filled with a diluted contrast agent was placed inside a water phantom. A single steel needle applicator was centrally positioned inside the reservoir. Computed tomography (CT) datasets of five different contrast agent dilutions (25 to 300 mg/ml iodine concentration) were acquired, and dose calculations were performed with TG-186 ACE dose calculation formalism of Oncentra®Brachy (Elekta). The dose was measured with a PinPoint® ionization chamber (PTW) inside the contrast agent. ACE calculated and measured data were compared. RESULTS: For the different contrast agent dilutions, averaged Hounsfield units from 453 ±21 to 2623 ±221 were obtained. Electron densities derived from CT data were significantly higher than corresponding electron densities calculated from chemical compositions. Consequently, the measured dose was higher than corresponding HU-based calculated dose. Relative deviation ranged from 2.5% to 7% per 10 mm penetration depth, depending on contrast agent concentration. CONCLUSIONS: The application of HU-based TG-186 dose formalisms in the presence of high-Z contrast agent bulks overestimates electron densities. Consequently, HU-based dose calculations result in a higher delivered dose than expected from the treatment planning system.

Individualized mould-based high-dose-rate brachytherapy for perinasal skin tumors: technique evaluation from a dosimetric point of view.

PURPOSE: Dosimetric treatment planning evaluations concerning patient-adapted moulds for iridium-192 high-dose-rate brachytherapy are presented in this report. MATERIAL AND METHODS: Six patients with perinasal skin tumors were treated with individual moulds made of biocompatible epithetic materials with embedded plastic applicators. Treatment plans were optimized with regard to clinical requirements, and dose was calculated using standard water-based TG-43 formalism. In addition, retrospective material-dependent collapsed cone calculations according to TG-186 protocol were evaluated to quantify the limitations of TG-43 protocol for this superficial brachytherapy technique. RESULTS: The dose-volume parameters D90, V100, and V150 of the planning target volumes (PTVs) for TG-43 dose calculations yielded 92.2% to 102.5%, 75.1% to 93.1%, and 7.4% to 41.7% of the prescribed dose, respectively. The max- imum overall dose to the ipsilateral eyeball as the most affected organ at risk (OAR) varied between 8.9 and 36.4 Gy. TG-186 calculations with Hounsfield unit-based density allocation resulted in down by -6.4%, -16.7%, and -30.0% lower average D90, V100, and V150 of the PTVs, with respect to the TG-43 data. The corresponding calculated OAR doses were also lower. The model-based TG-186 dose calculations have considered reduced backscattering due to environmental air as well as the dose-to-medium influenced by the mould materials and tissue composition. The median PTV dose was robust within 0.5% for simulated variations of mould material densities in the range of 1.0 g/cm3 to 1.26 g/cm3 up to 7 mm total mould thickness. CONCLUSIONS: HDR contact BT with individual moulds is a safe modality for routine treatment of perinasal skin tumors. The technique provides good target coverage and OARs' protection, while being robust against small variances in mould material density. Model-based dose calculations (TG-186) should complement TG-43 dose calculations for verification purpose and quality improvement.

HDR brachytherapy with individual epithetic molds for facial skin cancer: techniques and first clinical experience.

BACKGROUND: Facial skin cancer lesions in close proximity to critical organs require further development of radiotherapeutic techniques for highly conformal treatment, especially when treating elderly frail patients. We report on our treatment technique and first clinical experience for patients with perinasal/periorbital skin cancer treated with individualized epithetic mold high-dose-rate brachytherapy (BRT). METHODS: From January 2019, patients with complex shaped or unfavorably located skin cancer not eligible for surgery or external beam radiotherapy (RT) were screened for mold-based BRT. Six patients were identified. Toxicity and clinical response were documented during therapy and posttreatment follow-up. RESULTS: Median patient age was 80 years (74-92 years). Median prescription dose was 42 Gy (range, 33-44 Gy) delivered in once-daily fractions of 3 or 4 Gy. Two patients had treatment interruptions caused by acute conjunctivitis grade 2 and a nontreatment-related cardiac event, respectively. At a median follow-up of 335 days (96-628 days), no ≥ grade 2 late toxicity was documented with all patients showing complete clinical response. CONCLUSIONS: High-dose-rate BRT with individualized epithetic molds for perinasal/periorbital skin cancer is a well-tolerated and safe treatment option for patients not eligible for primary surgery or definitive external beam RT because of comorbidities or tumor location.

Interstitial multicatheter HDR-brachytherapy as accelerated partial breast irradiation after second breast-conserving surgery for locally recurrent breast cancer.

Our aim was to evaluate the efficacy and toxicity of interstitial multicatheter high dose rate brachytherapy (imHDR-BRT) as accelerated partial breast irradiation (APBI) after second breast-conserving surgery (BCS) in patients with ipsilateral breast tumor recurrence (IBTR). Between January 2010 and December 2019, 20 patients with IBTR who refused salvage mastectomy (sMT) were treated with second BCS and post-operative imHDR-BRT as APBI. All patients had undergone primary BCS followed by adjuvant external beam radiotherapy. Median imHDR-BRT dose was 32 Gy delivered in twice-daily fractions of 4 Gy. Five-year IBTR-free survival, distant metastasis-free survival (DMFS), overall survival (OS) as well as toxicity and cosmesis were evaluated in the present retrospective analysis. Median age at recurrence and median time from the first diagnosis to IBTR was 65.1 years and 12.2 years, respectively. After a median follow-up of 69.9 months, two patients developed a second local recurrence resulting in 5-year IBTR free-survival of 86.8%. Five-year DMFS and 5-year OS were 84.6% and 92.3%, respectively. Grade 1-2 fibrosis was noted in 60% of the patients with no grade 3 or higher toxicity. Two (10%) cases of asymptomatic fat necrosis were documented. Cosmetic outcome was classified as excellent in 6 (37.5%), good in 6 (37.5%), fair in 3 (18.75%) and poor in 1 (6.25%) patient, respectively. We conclude that imHDR-BRT as APBI re-irradiation is effective and safe for IBTR and should be considered in appropriately selected patients.

Real-world dosimetric comparison between CyberKnife SBRT and HDR brachytherapy for the treatment of prostate cancer.

PURPOSE: High-dose-rate (HDR) brachytherapy (BRT) and stereotactic body radiotherapy (SBRT) are currently the two treatment options for definitive radiotherapy of prostate cancer, employing extreme hypofractionation. There are only very few studies comparing their dosimetry, all using computed tomography for treatment planning. We present here a real-word dosimetric comparison between SBRT and ultrasound-based virtual HDR-BRT, with both imaging modalities coming from the same patient. METHODS AND MATERIALS: Patients with prostate cancer on a prospective trial evaluating the toxicity of robotic-based SBRT were treated to a total dose of 35 Gy in 5 fractions. Fifteen patients were included in this analysis. During ultrasound-based fiducial implantation, a three-dimensional data set as in real HDR-BRT procedure was acquired. Virtual HDR-BRT plans were generated and various organs at risk and prostate dosimetric parameters were evaluated. RESULTS: Concerning prostate, SBRT achieved significant higher D98, V35 Gy, and V37.5 Gy coverage, whereas virtual HDR-BRT achieved significant higher intratumoral doses reflected in the V42 Gy and V52.5 Gy. Rectal Dmax, V36 Gy, and V29 Gy were significantly lower for HDR-BRT with no difference as for V18 Gy. SBRT was significantly inferior regarding bladder dosimetry (Dmax, V36 Gy, V18 Gy), whereas urethra Dmax and V44 Gy where significantly higher at the expense of HDR-BRT. CONCLUSIONS: HDR-BRT is superior regarding rectum and bladder dosimetry, with SBRT being superior relative to urethra dosimetry. A randomized study is warranted to define the best extreme hypofractionated modality.

Matched-pair dosimetric comparison of cardiac radiation exposure between deep-inspiration breath-hold whole-breast radiation therapy with Active Breathing Coordinator and interstitial multicatheter high-dose-rate brachytherapy as accelerated partial breast irradiation in adjuvant treatment of left-sided breast cancer after breast-conserving surgery.

BACKGROUND AND PURPOSE: To compare dosimetrically the radiation exposure to heart, left ventricle (LV), and left anterior descending artery (LAD) between whole-breast radiotherapy (WBRT) with Active Breathing Coordinator (ABC; ABC-WBRT) and interstitial multicatheter high-dose-rate (HDR) brachytherapy as accelerated partial breast irradiation (ABPI; imHDR-APBI) for left-sided breast cancer (BCA) after breast-conserving surgery (BCS). MATERIALS AND METHODS: Between January 2016 and December 2019, 32 and 20 patients were treated with ABC-WBRT (63 Gy/2.25 Gy) and imHDR-APBI (32 Gy/4 Gy), respectively. Among them a matched-pair analysis was performed according to tumor location (clock position) before BCS as well as planning target volume of imHDR-APBI and boost volume of ABC-WBRT. This yielded 17 pairs of patients for whom dosimetric parameters for heart, LV, and LAD were evaluated. The Mann-Whitney test was used for comparison after adjusting for equivalent dose in 2­Gy fractions (EQD2). In addition, a second analysis of ABC-WBRT to 40.05 Gy in 15 fractions was performed in order to account for the EQD2 difference between the 63-Gy ABC-WBRT and the imHDR-APBI protocol. RESULTS: Tumor location for the 17 pairs of patients relative to breast quadrant was as follows: upper outer 8, lower outer 5, upper inner 3, and lower inner 1. There was no difference regarding mean heart dose (MHD) and V5, whereas D25%, D45%, V10, and V25 significantly favored imHDR-APBI. Likewise, mean dose- and V5-LV did not differ, while Dmax- and V23-LV were significantly higher for ABC-WBRT. For LAD, Dmax, D25%, and V30 significantly favored imHDR-APBI without differences for mean dose and V40. When comparing imHDR-APBI with the 40.05 Gy ABC-WBRT schedule, MHD and mean dose LV were significantly lower in favor of ABC-WBRT. CONCLUSION: ABC-WBRT and imHDR-APBI yield similar low heart and LV exposure for left-sided BCA after BCS, whereas LAD can be better spared with imHDR-APBI.

New possibilities for volumetric-modulated arc therapy using the Agility™ 160-leaf multileaf collimator.

PURPOSE: This study compares the quality of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans optimized for an Elekta Agility(TM) (Elekta, Stockholm, Sweden) multileaf collimator (MLC; leaf width 5 mm) and an Elekta MLCi2 (leaf width 10 mm) for complex target volumes (anal, AC; head and neck, H&N and prostate cancer, PC). PATIENTS AND METHODS: For plan comparisons, 15 patients who had been treated with IMRT or VMAT using the MLCi2 were selected. For each patient, a retrospective treatment plan using the MLCi2 for the technique not applied was created, as were treatment plans for both techniques using the Agility(TM) MLC. Dose-volume histograms (DHVs) for planning target volumes (PTVs) and organs at risk (OARs) were compared. Further parameters relating to dose conformity, dose homogeneity and mean dose (Dmean) to the PTV, compliance with the intended OAR dose criteria and overall dose to normal tissue were analyzed. Verification measurements were performed and optimization and treatment times were compared. RESULTS: Compared to the MLCi2 plans, the Agility(TM) IMRT and VMAT plans show better or equivalent results in terms of PTV dose conformity and homogeneity. Compliance with the intended OAR dose criteria does not differ according to technique or MLC type. Slight differences are shown for dose distributions in OARs and normal tissue. Verification measurements show that all plans fulfill the acceptance criteria of a minimum of 95 % matched dose points for the 3 %/3 mm γ criterion. Optimization times for the VMAT plans increase compared to the IMRT plans, whereas treatment times decrease. CONCLUSION: With the MLCi2, treatment of complex target volumes with VMAT was only possible with compromises in terms of target coverage. Using the Agility(TM) MLC, even complex target volumes can be treated with VMAT without compromising target coverage or resulting in higher exposure of OARs or normal tissue.

Field study of age-differentiated strain for assembly line workers in the automotive industry.

A field study in an automotive supply industry company was conducted to explore age-differentiated strain of assembly line workers. Subjective and objective data from 23 female workers aged between 27 and 57 years were collected at the workplace belt buckle assembly during morning shifts. Subjects with medication or chronic diseases affecting heart rate and breath rate were excluded. For subjective data generation different questionnaires were used. Before the Work Ability Index and the Munich Chronotype Questionnaire were completed by the subjects. Short questionnaires (strain-ratings, NASA-TLX) directly at begin and end of the work were used for obtaining shift-related data. During the whole shift (6 a.m. - 2.45 p.m.) bodily functions were logged with a wireless chest strap. In addition, the motion of the hand-arm-system was recorded for 30 times, 3 minutes each after a fixed time-schedule. First results show that younger subjects need significant less time for assembly (mean = 14.940 s) compared to older subjects (mean = 17.040 s; t(472.026) = -9.278 , p < 0.01).

Simple proposal for dosimetry with an Elekta iViewGT™ electronic portal imaging device (EPID) using commercial software modules.

BACKGROUND: An electronic portal imaging device (EPID) is used to control for patient setup and positioning during fractionated radiotherapy. Due to the rising complexity and conformity of irradiation techniques, the demand for an accurate verification of the dose delivered to the patient has also increased. The purpose of this study was to investigate a simple guidance for dosimetry with an Elekta iViewGT™ EPID using commercial software modules. MATERIAL AND METHODS: EPID measurements were performed using an Elekta iViewGT™ EPID on a linear accelerator with 6 MV x-ray beam. The EPID signal was studied for reproducibility, as well as characteristics as a function of dose, dose rate, and field size. A series of experiments, comparing the response of the flat panel imager and ionization chamber measurements of dose, determine the parameters for the calibration model. EPID measurements were also compared with calculations of the treatment planning system. RESULTS: We found a stable response of the EPID signal over a period of 14 months. It showed nonlinearity depending on dose up to 6.8%. There were low oscillations up to 1.2% depending on dose rate. For all fields, the calibrated flat panel profiles match the measured and calculated dose profiles with maximum deviation of 2-3% for the in-field region. In the high gradient areas, higher differences up to 6% were found. CONCLUSIONS: The gamma evaluation indicates good correlation between predicted and acquired EPID images. The EPID-based pretreatment IMRT verification method will help to improve the quality assurance procedure.

Silicon diodes as an alternative to diamond detectors for depth dose curves and profile measurements of photon and electron radiation.

BACKGROUND: Depth dose curves and lateral dose profiles should correspond to relative dose to water in any measured point, what can be more or less satisfied with different detectors. Diamond as detector material has similar dosimetric properties like water. Silicon diodes and ionization chambers are also commonly used to acquire dose profiles. MATERIAL AND METHODS: The authors compared dose profiles measured in an MP3 water phantom with a diamond detector 60003, unshielded and shielded silicon diodes 60008 and 60012 and a 0.125-cm(3) thimble chamber 233642 (PTW, Freiburg, Germany) for 6- and 25-MV photons. Electron beams of 6, 12 and 18 MeV were investigated with the diamond detector, the unshielded diode and a Markus chamber 23343. RESULTS: The unshielded diode revealed relative dose differences at the water surface below +10% for 6-MV and +4% for 25-MV photons compared to the diamond data. These values decreased to less than 1% within the first millimeters of water depth. The shielded diode was only required to obtain correct data of the fall-off zones for photon beams larger than 10 x 10 cm(2) because of important contributions of low-energy scattered photons. For electron radiation the largest relative dose difference of -2% was observed with the unshielded silicon diode for 6 MeV within the build-up zone. Spatial resolutions were always best with the small voluminous silicon diodes. CONCLUSION: Relative dose profiles obtained with the two silicon diodes have the same degree of accuracy as with the diamond detector.

In vivo dosimetry with semiconducting diodes for dose verification in total-body irradiation. A 10-year experience.

BACKGROUND AND PURPOSE: For total-body irradiation (TBI) using the translation method, dose distribution cannot be computed with computer-assisted three-dimensional planning systems. Therefore, dose distribution has to be primarily estimated based on CT scans (beam-zone method) which is followed by in vivo measurements to ascertain a homogeneous dose delivery. The aim of this study was to clinically establish semiconductor probes as a simple and fast method to obtain an online verification of the dose at relevant points. PATIENTS AND METHODS: In 110 consecutively irradiated TBI patients (12.6 Gy, 2 x 1.8 Gy/day), six semiconductor probes were attached to the body surface at dose-relevant points (eye/head, neck, lung, navel). The mid-body point of the abdomen was defined as dose reference point. The speed of translation was optimized to definitively reach the prescribed dose in this point. Based on the entrance and exit doses, the mid-body doses at the other points were computed. The dose homogeneity in the entire target volume was determined comparing all measured data with the dose at the reference point. RESULTS: After calibration of the semiconductor probes under treatment conditions the dose in selected points and the dose homogeneity in the target volume could be quantitatively specified. In the TBI patients, conformity of calculated and measured doses in the given points was achieved with small deviations of adequate accuracy. The data of 80% of the patients are within an uncertainty of +/- 5%. CONCLUSION: During TBI using the translation method, dose distribution and dose homogeneity can be easily controlled in selected points by means of semiconductor probes. Semiconductor probes are recommended for further use in the physical evaluation of TBI.

[Certification of an in-house manufactured translational couch unit for total body irradiation in accordance with the medical devices act]. / Zertifizierung einer Translationsliege zur Ganzkörperbestrahlung aus In-Haus-Herstellung gemäss dem Medizinproduktegesetz.

UNLABELLED: A new translational couch unit with extended potentials of dose optimization by variable velocity and a comfortable user interface with integrated patient administration was developed at the university clinic of Regensburg. MATERIALS AND METHODS: The concept and construction were elaborated in legal accordance with the in-house manufacture conditions mentioned in the German Medical Devices Act. In particular we have implemented a concept of functional safety based on a controller unit, an independent monitoring unit and self-testing procedures. Redundant safety relevant hard- and software components are continuously checked against each other. In case of any malfunction the translation movement and the linear accelerator are stopped. Gap-free continuation of the treatment will be possible after elimination of the cause of the interrupt. RESULTS AND CONCLUSION: After the testing of the implemented functional safety features including the risk assessment and management, electrical safety, electromagnetic compatibility by accredited technical experts the translational couch system complies with the requirements of the Medical Devices Act and can be operated in terms of in-house application. The presented certification procedure can motivate other radiation departments to develop own systems for in-house usage.

[Verification and application of the voxel-based Monte Carlo (VMC++) electron dose module of Oncentra MasterPlan]. / Verifikation und Anwendungen des voxelbasierten Monte-Carlo-(VMC++-)Elektronen-Dosismoduls von Oncentra MasterPlan.

UNLABELLED: PURPOSE, MATERIAL AND METHODS: The dose calculation accuracy of the voxel-based Monte Carlo (VMC++) electron dose module of Oncentra MasterPlan (Nucletron B.V., Veenendaal, The Netherlands) was verified by measurements in homogeneous water phantoms. RESULTS: Measured and calculated dose maxima on the central beam axis (calculations with 10,000-20,000 incident electron histories per cm(2)) agree well using standard applicator configurations as well as individually shaped inserts. Profile scans with higher electron energies (>/= 15 MeV) reveal differences up to 5% especially in the penumbra region. Depth dose curves agree best in the vicinity of maximum depths. In the buildup region energy-dependent differences up to 5% in both directions could be observed. In the decay region of depth dose curves calculated doses were up to 10% higher than measured values. CONCLUSION: Good VMC++ accuracy combined with moderate computing times of 1-15 min per beam satisfy all clinical needs. VMC++ allows, for the first time, accurate routine dose evaluations of radiation therapy with electrons. Adequate positioning of the dose reference point is essential. Even small displacements may significantly influence the calculation of monitor units.

Anion diffusion in Y- and N-doped ZrO2.

Effective single particle potentials governing the motion of O2 and N3- anions have been determined by single crystal neutron diffraction at high temperatures for three samples of ZrO2 doped with different amounts of Y and N. Diffusion jumps take place directly to vacant nearest neighbour anion sites through the edges of the surrounding cation tetrahedra along (100)-directions. Activation enthalpies of migration for O (1.09 eV) and N (1.99 eV) are in good agreement with values obtained from tracer diffusion measurements (M. Kilo, C. Argirusis, G. Borchardt and R. A. Jackson, Phys. Chem. Chem. Phys., 2003, 5, 2219 and M. Kilo, M. A. Taylor, C. Argirusis, G. Borchardt, M. Lerch, O. Kaitasov and B. Lesage, Phys. Chem. Chem. Phys., 2004, 6, 3645). The diffusion process is facilitated by local short range order and anharmonic thermal vibrations. It is therefore advocated that the interactions with the phonons have to be taken into account in the description of the diffusion process.