A Systematic Comparison of Dose Distributions Delivered in 125I Plaque Brachytherapy and Proton Radiation Therapy for Ocular Melanoma.

PURPOSE: To characterize dose distributions with 125I plaque brachytherapy compared with proton radiation therapy for ocular melanoma for relevant clinical scenarios, based on tumor base diameter (d), apical height (h), and location. METHODS AND MATERIALS: Plaque and proton treatment plans were created for 4 groups of cases: (1) REF: 39 instances of reference midsize circular-base tumor (d = 12 mm, h = 5 mm), in locations varying by retinal clock hours and distance to fovea, optic disc, and corneal limbus; (2) SUP: 25 superiorly located; (3) TEMP: 25 temporal; and (4) NAS: 25 nasally located tumors that were a fixed distance from the fovea but varying in d (6-18 mm) and h (3-11 mm). For both modalities, 111 unique scenarios were characterized in terms of the distance to points of interest, doses delivered to fovea, optic disc, optic nerve at 3 mm posterior to the disc (ON@3mm), lens, and retina. Comparative statistical evaluation was performed with the Mann-Whitney U test. RESULTS: Superior dose distributions favored plaque for sparing of (1) fovea in large (d + h ≥ 21 mm) NAS tumors; (2) ON@3mm in REF cases located ≤4 disc diameters from disc, and in NAS overall. Protons achieved superior dose sparing of (1) fovea and optic disc in REF, SUP, and TEMP; (2) ON@3mm in REF >4 disc diameters from disc, and in SUP and TEMP; and (3) the lens center overall and lens periphery in REF ≤6 mm from the corneal limbus, and in TEMP with h = 3 mm. Although protons could completely spare sections of the retina, plaque dose was more target conformal in the high-dose range (50% and 90% of prescription dose). CONCLUSIONS: Although comparison between plaque and proton therapy is not straightforward because of the disparity in dose rate, prescriptions, applicators, and delivery techniques, it is possible to identify distinctions between dose distributions, which could help inform decisions by providers and patients.

Personalized Radiation Attenuating Materials for Gastrointestinal Mucosal Protection.

Cancer patients undergoing therapeutic radiation routinely develop injury of the adjacent gastrointestinal (GI) tract mucosa due to treatment. To reduce radiation dose to critical GI structures including the rectum and oral mucosa, 3D-printed GI radioprotective devices composed of high-Z materials are generated from patient CT scans. In a radiation proctitis rat model, a significant reduction in crypt injury is demonstrated with the device compared to without (p < 0.0087). Optimal device placement for radiation attenuation is further confirmed in a swine model. Dosimetric modeling in oral cavity cancer patients demonstrates a 30% radiation dose reduction to the normal buccal mucosa and a 15.2% dose reduction in the rectum for prostate cancer patients with the radioprotectant material in place compared to without. Finally, it is found that the rectal radioprotectant device is more cost-effective compared to a hydrogel rectal spacer. Taken together, these data suggest that personalized radioprotectant devices may be used to reduce GI tissue injury in cancer patients undergoing therapeutic radiation.

Technical Note: Scintillation markers for real-time visual source tracking during skin high dose rate brachytherapy.

BACKGROUND: Treatment misadministration during high dose rate (HDR) brachytherapy is mainly caused due to gross errors in incorrect manual entry of catheter length and manual connection of hardware. The probability of these errors increases with increasing complexity of a surface applicator. A simple, real-time visual verification method was developed using a scintillator to enhance quality assurance (QA) measures for HDR surface brachytherapy and thus reduce manual errors and improve patient safety. MATERIALS AND METHODS: Scintillation markers were fabricated from cerium-doped lutetium yttrium orthosilicate (LYSO) embedded in a polymer compound to form 5-mm diameter markers. To verify catheter-transfer tube connections, markers were attached to each channel of a Freiburg flap and irradiated with an 192 Ir source. To determine if the source reached the edge of a target, markers were placed along the periphery. The HDR source was visually tracked by following the illumination from the markers. The response of the markers was also verified in the presence of thermoplastic material overlaid on the Freiburg applicator. RESULTS: Scintillation markers emitted intense blue visible light upon irradiation when the HDR source was beneath the marker, verifying the source's presence in the correct catheter. The signal was clearly visible even when the marker was placed on top of the thermoplastic material covering the Freiburg Flap. Crosstalk from adjacent catheters was <50% of the maximum light intensity. CONCLUSION: Scintillation markers and paint were developed to successfully meet the challenge of visually tracking of HDR source during brachytherapy by surface applicators. This direct visualization of source allows real-time catheter verification during treatment, and correct superficial target coverage, thus preventing a medical event. It can easily be integrated into pre-existing QA program.

Custom-made micro applicators for high-dose-rate brachytherapy treatment of chronic psoriasis.

PURPOSE: In this study, we present the treatment of the psoriatic nail beds of patients refractory to standard therapies using high-dose-rate (HDR) brachytherapy. The custom-made micro applicators (CMMA) were designed and constructed for radiation dose delivery to small curvy targets with complicated topology. The role of the HDR brachytherapy treatment was to stimulate the T cells for an increased immune response. MATERIAL AND METHODS: The patient diagnosed with psoriatic nail beds refractory to standard therapies received monthly subunguinal injections that caused significant pain and discomfort in both hands. The clinical target was defined as the length from the fingertip to the distal interphalangeal joint. For the accurate and reproducible setup in the multi-fractional treatment delivery, the CMMAs were designed. Five needles were embedded into the dense plastic mesh and covered with 5 mm bolus material for each micro applicator. Five CMMAs were designed, resulting in the usage of 25 catheters in total. RESULTS: The prescription dose was planned to the depth of the anterior surface of the distal phalanx, allowing for the sparing of the surrounding tissue. The total number of the active dwell positions was 145 with step size of 5 mm. The total treatment time was 115 seconds with a 7.36 Ci activity of the 192Ir source. The treatment resulted in good pain control. The patient did not require further injections to the nail bed. After this initial treatment, additional two patients with similar symptoms received HDR brachytherapy. The treatment outcome was favorable in all cases. CONCLUSIONS: The first HDR brachytherapy treatment of psoriasis of the nail bed is presented. The initial experience revealed that brachytherapy treatment was well-tolerated and resulted in adequate control of the disease. A larger cohort of patients will be required for additional conclusions related to the long-term clinical benefits.

Characterization of efficacy and toxicity after high-dose pelvic reirradiation with palliative intent for genitourinary second malignant neoplasms or local recurrences after full-dose radiation therapy in the pelvis: A high-volume cancer center experience.

PURPOSE: The use of large-field external beam reirradiation (re-RT) after pelvic radiation therapy (RT) for genitourinary (GU) cancers has not been reported. We report the results of such treatment in patients with either symptomatic GU second malignant neoplasms or locally recurrent pelvic tumors after initial RT for whom surgery or further systemic therapy was not an option. METHODS AND MATERIALS: The records of 28 consecutive patients with advanced, bulky GU malignancies treated with high-dose, large-field re-RT with palliative intent between 2008 and 2014 were retrospectively reviewed. Descriptive outcome analyses focused on toxicities and symptom control, and responses were evaluated by 2 independent observers. RESULTS: Twenty-seven male patients (96%) were included. Median initial external beam RT dose was 64 Gy (range, 30-75.6 Gy). The median time between initial RT and re-RT was 9.5 years (range, 0.2-32 years). At the time of re-RT, there were 16 local recurrences and 12 second malignant neoplasms together comprising 16 bladder, 10 prostate, 1 ureteral, and 1 penile cancer. Indications for re-RT were pain and bleeding/hemorrhage. The median equivalent sphere diameter planning target volume for re-RT was 8.6 cm (range, 4.7-16.3 cm). Given the severity of the symptoms and the bulk of the disease at the time of re-RT, a higher dose of RT was administered. The median re-RT dose was 50 Gy (range, 27.5-66 Gy). For patients who received <60 Gy, hypofractionation of 250 cGy was used. The median cumulative dose was 113.9 Gy (range, 81.5-132.8 Gy). Re-RT was well tolerated with no Radiation Therapy Oncology Group grade 3-4 toxicities. Twenty-four patients (92%) had complete resolution of symptoms, and relief was durable in 67% of patients. The median overall survival was 5.8 months (range, 0.3-38.9 months). Of those patients who are still alive, 100% remain free of initial symptoms. CONCLUSION: This small series suggests that aggressive re-RT of inoperable and symptomatic GU malignancies that is undertaken with meticulous treatment planning is well tolerated and provides excellent, durable relief without undue short-term toxicity. Validation in a larger prospective cohort is required.

The value of systematic contouring of the bowel for treatment plan optimization in image-guided cervical cancer high-dose-rate brachytherapy.

PURPOSE: To investigate the dose-volume histogram metrics and optimization results of the contoured bowel in cervical cancer brachytherapy. METHODS AND MATERIALS: Treatment plans of cervical cancer patients treated with image-guided high dose rate were retrospectively analyzed with institutional review board approval. In addition to the clinical target volume, rectum, bladder, and sigmoid, the bowel was contoured at the time of planning (Group 1) or at the time of this analysis (Group 2). RESULTS: Thirty-two patients treated with 145 insertions were included. Before optimization, mean ± 1 standard deviation overall bowel minimum dose to the most irradiated 2 cm3 volume of an organ (D2cc) was 67.8 Gyα/ß3 ± 13.7 Gyα/ß3 (Group 1: 72.6 ± 13.2 Gyα/ß3; Group 2: 57.3 ± 8.0 Gyα/ß3). Before optimization, one patient in Group 1 presented a bowel D2cc metric exceeding 100 Gyα/ß3. After optimization, bowel D2cc mean ± 1 standard deviation was 59.4 ± 6.7 Gyα/ß3 (Group 1: 61.4 ± 6.0 Gyα/ß3, p < 0.001; Group 2: 55.2 ± 6.5 Gyα/ß3, p = 0.026). CONCLUSIONS: Given the potentially high doses and the benefit of optimization in reducing dose to the organs at risk, we recommend consideration of systematic contouring of the bowel when bowel is present in the pelvis.

Clinical implementation of a novel applicator in high-dose-rate brachytherapy treatment of esophageal cancer.

PURPOSE: In this study, we present the clinical implementation of a novel transoral balloon centering esophageal applicator (BCEA) and the initial clinical experience in high-dose-rate (HDR) brachytherapy treatment of esophageal cancer, using this applicator. MATERIAL AND METHODS: Acceptance testing and commissioning of the BCEA were performed prior to clinical use. Full performance testing was conducted including measurements of the dimensions and the catheter diameter, evaluation of the inflatable balloon consistency, visibility of the radio-opaque markers, congruence of the markers, absolute and relative accuracy of the HDR source in the applicator using the radiochromic film and source position simulator, visibility and digitization of the applicator on the computed tomography (CT) images under the clinical conditions, and reproducibility of the offset. Clinical placement of the applicator, treatment planning, treatment delivery, and patient's response to the treatment were elaborated as well. RESULTS: The experiments showed sub-millimeter accuracy in the source positioning with distal position at 1270 mm. The digitization (catheter reconstruction) was uncomplicated due to the good visibility of markers. The treatment planning resulted in a favorable dose distribution. This finding was pronounced for the treatment of the curvy anatomy of the lesion due to the improved repeatability and consistency of the delivered fractional dose to the patient, since the radioactive source was placed centrally within the lumen with respect to the clinical target due to the five inflatable balloons. CONCLUSIONS: The consistency of the BCEA positioning resulted in the possibility to deliver optimized non-uniform dose along the catheter, which resulted in an increase of the dose to the cancerous tissue and lower doses to healthy tissue. A larger number of patients and long-term follow-up will be required to investigate if the delivered optimized treatment can lead to improved clinical outcomes.

Redesign of process map to increase efficiency: Reducing procedure time in cervical cancer brachytherapy.

PURPOSE: To increase intraprocedural efficiency in the use of clinical resources and to decrease planning time for cervical cancer brachytherapy treatments through redesign of the procedure's process map. METHODS AND MATERIALS: A multidisciplinary team identified all tasks and associated resources involved in cervical cancer brachytherapy in our institution and arranged them in a process map. A redesign of the treatment planning component of the process map was conducted with the goal of minimizing planning time. Planning time was measured on 20 consecutive insertions, of which 10 were performed with standard procedures and 10 with the redesigned process map, and results were compared. Statistical significance (p < 0.05) was measured with a two-tailed t test. RESULTS: Twelve tasks involved in cervical cancer brachytherapy treatments were identified. The process map showed that in standard procedures, the treatment planning tasks were performed sequentially. The process map was redesigned to specify that contouring and some planning tasks are performed concomitantly. Some quality assurance tasks were reorganized to minimize adverse effects of a possible error on procedure time. Test dry runs followed by live implementation confirmed the applicability of the new process map to clinical conditions. A 29% reduction in planning time (p < 0.01) was observed with the introduction of the redesigned process map. CONCLUSIONS: A process map for cervical cancer brachytherapy was generated. The treatment planning component of the process map was redesigned, resulting in a 29% decrease in planning time and a streamlining of the quality assurance process.

Independent brachytherapy plan verification software: improving efficacy and efficiency.

BACKGROUND AND PURPOSE: To compare the pre-treatment brachytherapy plan verification by a physicist assisted by custom plan verification software (SAV) with those performed manually (MV). MATERIALS AND METHODS: All HDR brachytherapy plans used for treatment in 2013, verified using either SAV or MV, were retrospectively reviewed. Error rate (number of errors/number of plans) was measured and verification time calculated. All HDR brachytherapy safety events recorded between 2010 and 2013 were identified. The rate of patient-related safety events (number of events/number of fractions treated) and the impact of SAV on the underlying errors were assessed. RESULTS: Three/106 errors (2.8%) were found in the SAV group and 24/273 (8.8%) in the MV group (p=0.046). The mean ±1 standard deviation plan verification time was 8.4±4.0min for SAV and 11.6±5.3 for MV (p=0.006). Seven safety events out of 4729 fractions delivered (0.15%) were identified. Four events (57%) were associated with plan verification and could have been detected by SAV. CONCLUSIONS: We found a safety event rate in HDR brachytherapy of 0.15%. SAV significantly reduced the number of undetected errors in HDR treatment plans compared to MV, and reduced the time required for plan verification.

A phenomenological kV beam model for cone-beam imaging.

A phenomenological kV beam model was developed to address attenuation and scatter in radiographic images for the purpose of cone-beam imaging. Characterization of a kV beam in terms of the minimal number of parameters and calculation of attenuation and scatter in radiographs of scanned objects are the main applications of this model. Model parameters are derived from radiographs of homogeneous solid water phantoms for various depths and field sizes. The response of the cone-beam detector to kV beams is factorized into different contributions such as output factor, tissue-air ratio and off-axis ratio, with each contribution having an analytical representation. The formulas which are used to characterize the beam model in uniform phantoms are then extended to arbitrary objects using the concept of the water-equivalent pathlength. A weighted sum of three Gaussians in each direction models the dose deposition kernel. Detector response arising from the first Gaussian term can be interpreted as the primary signal while the second and third Gaussians constitute short- and long-range scatter. The model is then applied to predict the primary and scatter signals for arbitrary objects. A technique of scatter removal from the measured radiographs is investigated. The model accurately predicts detector response of varying-thickness phantoms such as multi-step and cylindrical phantoms. The scatter contributes over 90% to the total signal for 20 cm thick phantoms. The calculated scatter-to-primary ratio as a function of spatial coordinates agrees with Monte Carlo studies reported in the literature. Water-equivalent thickness related to primary and scatter contributions calculated from an analysis of radiographs results in an improved calibration technique suitable for CB-CT reconstruction. The kV beam model and the associated theoretical formulations can be utilized to characterize any kV beam line; however, for the specific study the OBI system (Varian) was used to obtain experimental radiographs.

Evaluation of MatriXX for IMRT and VMAT dose verifications in peripheral dose regions.

PURPOSE: MatriXX is a two-dimensional ion chamber array designed for IMRT/VMAT (RapidArc, IMAT, etc.) dose verifications. Its dosimetric properties have been characterized for megavoltage beams in a number of studies; however, to the best of the authors' knowledge, there is still a lack of an investigation into its performance in the peripheral or low dose regions. In this work, the authors have carried out a systematic study on this issue. METHODS: The authors compare the performance of MatriXX with a cylindrical ion chamber in solid water phantoms in the peripheral dose regions. The comparisons are performed for a number of typical irradiation conditions that involve different gantry and/or MLC motions, field sizes, and distances to the target including static gantry/open fields, static gantry/sweeping MLC gap (mimicking an IMRT delivery), dynamic gantry/oscillating sweeping MLC gap (mimicking a VMAT delivery), as well as clinical IMRT and VMAT plans. RESULTS: MatriXX, when used according to the manufacturer's recommendations, is found to disagree with an ion chamber in peripheral dose regions. This disagreement has been attributed to four types of MatriXX errors, namely, positive bias, over-response to scattered doses, round-off error, and angular dependence, all of which contribute to dose inaccuracies in the peripheral regions. The positive bias, which is independent of the dose level, is cumulative when MatriXX operates in the movie mode. The accumulation is proportional to the number of movie frames (snaps) when the sampling time is greater than 500 ms and is proportional to the overall movie time for a sampling time shorter than 500 ms. This behavior suggests multiple sources of the bias. MatriXX is also found to over-respond to peripheral doses by about 2.0% for the regions investigated in this work (3-15 cm from the field edge), where phantom scatter and collimator scatter dominate. Round-off error is determined to be due to insufficient precision in conversion of the raw signals to MatriXX software data for low doses. Angular dependence is defined as the dose response of MatriXX at different gantry angles. Up to 8% difference in detector response has been observed between 0 degree and 180 degrees. Possible sources of these errors are discussed and a correction method is suggested. With corrections, MatriXX shows good agreement with the ion chamber in all cases involving different gantry and/or MLC dynamics, as well as the clinical plans. For both primary and peripheral doses, MatriXX shows dose linearity down to 2 cGy with an accuracy of within 1% of the local dose. CONCLUSIONS: The performance of MatriXX has been systematically evaluated in the peripheral dose regions. Major sources of error associated with MatriXX are identified and a correction method is suggested. This method has been successfully tested using both experimental and clinical plans. In all cases, good agreements between MatriXX and an ion chamber are achieved after corrections. The authors conclude that with proper corrections, MatriXX can be reliably used for peripheral dose measurements within the ranges studied.

An oscillating sweeping gap test for VMAT quality assurance.

The objective of this study was to develop an oscillating sweeping gap test for volumetric modulated arc therapy (VMAT) quality assurance (QA). A novel test was designed and used to simultaneously determine uncertainties associated with linac performance, dose calculation and dosimetric MLC parameters during VMAT delivery. Delivered doses were measured with Matrixx, ionization chamber A12 and EDR2 films, and compared to calculations from the treatment planning system (TPS) Eclipse. A new gantry and MLC motion pattern, called here 'oscillating sweeping gap', is developed as an extension of the standard sweeping gap MLC pattern developed for IMRT QA. Specifically, in the oscillating sweeping gap test, a uniform MLC gap is moving repeatedly back and forth across the field at a constant speed during a full rotation of the gantry. The dose distribution generated by the combined gantry and MLC motion pattern is designed to be quasi-uniform within a cylindrical target volume with a sharp penumbra. The test design allows for an easy detection of dose errors as deviations from the uniform background. MLC gap sizes, gantry and MLC speeds and monitor units (MU) are selected according to a formula determining the magnitude of dose delivered to the target. Both measured and calculated dose distributions were analyzed as a function of the number of control points in the TPS, MLC gap size and magnitude of the gantry angle error. Dose calculation errors due to the insufficient number of control points in the gantry and MLC motion pattern appear as streak artifacts. The magnitude of these artifacts is increasing with the decreased number of control points, and with the decreased MLC gap size. The spatial distribution of dose errors due to the gantry angle errors (unsteady rocking motion) appears as high-frequency noise for higher wobble frequencies and as large hot/cold spots for lower wobble frequencies. The actual MLC leaf position as a function of time (or the gantry angle), determined from the Matrixx snaps (dose images measured per time interval) of the moving gap and compared to the ideal leaf positions, reveal discrepancies in agreement with theoretical calculations. The MLC parameters determined for VMAT with the oscillating sweeping gap test, their uncertainties and the associated dose errors are similar to those determined for IMRT with the standard sweeping gap test. The oscillating sweeping gap test has been developed for the gantry and MLC QA. Applications include commissioning of the planning system for VMAT and performing routine linac QA. The test is sensitive to several errors in dose calculation and delivery.

Angular dose dependence of Matrixx TM and its calibration.

One of the applications of MatriXX (IBA Dosimetry) is experimental verification of dose for IMRT, VMAT, and tomotherapy. For cumulative plan verification, dose is delivered for all the treatment gantry angles to a stationary detector. Experimental calibration of MatriXX detector recommended by the manufacturer involves only AP calibration fields and does not address angular dependency of MatriXX. Angular dependency may introduce dose bias in cumulative plan verification if not corrected. For this reason, we characterized angular dependency of MatriXX and developed a method for its calibration. We found relatively large discrepancies in responses to posterior vs. anterior fields for four MatriXX (Evolution series) detectors (up to 11%), and relatively large variability of responses as a function of gantry angle in the gantry angle ranges of 91 degrees-110 degrees and 269 degrees-260 degrees. With our calibration method, the bias due to angular dependency is effectively removed in experimental verification of IMRT and VMAT plans.