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PURPOSE: High-dose-rate (HDR) prostate brachytherapy uses volumetric imaging for treatment planning. Our institution transitioned from computed tomography (CT)-based planning to MRI-based planning with the hypothesis that improved visualization could reduce treatment-related toxicity. This study aimed to compare the patient-reported health-related quality of life (hrQOL) and physician-graded toxicity outcomes of CT-based and MRI-based HDR prostate brachytherapy. METHODS: From 2016 to 2019, 122 patients with low- or intermediate-risk prostate cancer were treated with HDR brachytherapy as monotherapy. Patients underwent CT only or CT and MRI imaging for treatment planning and were grouped per treatment planning imaging modality. Patient-reported hrQOL in the genitourinary (GU), gastrointestinal (GI), and sexual domains was assessed using International Prostate Symptom Score and Expanded Prostate Cancer Index Composite Short Form-26 questionnaires. Baseline characteristics, changes in hrQOL scores, and physician-graded toxicities were compared between groups. RESULTS: The median follow-up was 18 months. Patient-reported GU, GI, and sexual scores worsened after treatment but returned toward baseline over time. The CT cohort had a lower baseline mean International Prostate Symptom Score (5.8 vs. 7.8, p = 0.03). The other patient-reported GU and GI scores did not differ between groups. Overall, sexual scores were similar between the CT and MRI cohorts (p = 0.08) but favored the MRI cohort at later follow-up with a smaller decrease in Expanded Prostate Cancer Index Composite Short Form-26 sexual score from baseline at 18 months (4.9 vs. 19.8, p = 0.05). Maximum physician-graded GU, GI, and sexual toxicity rates of grade ≥2 were 68%, 3%, and 53%, respectively, with no difference between the cohorts (p = 0.31). CONCLUSION: Our study shows that CT- and MRI-based HDR brachytherapy results in similar rates of GU and GI toxicity. MRI-based planning may result in improved erectile function recovery compared with CT-based planning. Published by Elsevier Inc. on behalf of American Brachytherapy Society.

PURPOSE/OBJECTIVE(S) Dual energy (DE) fluoroscopy is being considered for markerless tumor tracking (MTT) of lung tumors. The principal advantage of this technique is that it can be used to remove overlaying bony anatomy, and hence improve the tracking accuracy vs. single energy (SE) fluoroscopy. Previous studies using phantoms have demonstrated the superiority of DE vs. SE imaging for MTT. The goal of this study is to clinically evaluate MTT with fast-kV switching DE imaging on a cohort of SBRT lung cancer patients using the on-board imager (OBI) of a commercial linear accelerator. MATERIALS/METHODS In this Institutional Review Board (IRB)-approved prospective study, DE images were acquired for 10 SBRT lung cancer patients. For each patient, DE images were obtained over 180o arc using fast-kV switching implemented on the OBI of a commercial linear accelerator. This fast-kV switching technique produced x-ray pulses that alternate between programmed tube voltages (i.e., 120 and 60 kVp) at a rate of 15 Hz. Weighted logarithmic subtraction was performed offline on consecutive high-low energy projections to produce soft tissue images. For comparison, SE image sequences were obtained by using the 120 kVp images. Separately, a template was derived from the contoured gross tumor volume (GTV) on the CT simulation scan. A template-based matching algorithm was then used to track target motion on both DE and SE image sequences. Successful matching was defined as any instance in which the algorithm matched the template on the respective fluoroscopic image. Ground truth positions were estimated from both the DE and SE images using Bayesian inference. RESULTS A total of 2278 SE and DE image frames were analyzed. DE imaging resulted in significantly improved tracking vs. SE on 884/2278 (38.8%) of image frames. In those frames, the average tracking error was 1.78 +/- 2.02 mm vs. 2.21 +/- 2.38 mm, for DE vs. SE imaging, respectively (P 0.7 mm. No correlation was observed between tumor volume/location and improved tracking accuracy with DE imaging. Additionally, the fraction of images that could not be tracked with SE was 91/2278 (4.0%). The addition of DE imaging decreased this number to 33/2278 (1.4%) (P < 0.001). CONCLUSION This is the first prospective study to evaluate fast-kV switching DE imaging for MTT in a cohort of SBRT lung cancer patients. This study has demonstrated that by removal of overlapping bony anatomy, DE imaging increases tracking accuracy and decreases the number of images where tracking fails. Future work includes optimization of template parameters to further improve DE tracking accuracy.

The goal of this study is to fully automate the treatment planning and delivery process of hippocampal-sparing whole brain irradiation (HS-WBRT) by combining a RapidPlan (RP) knowledge-based planning model and HyperArc (HA) technology. Additionally, this study compares the dosimetric performance of RapidPlan-HyperArc (RP-HA) treatment plans with RP plans and volumetric modulated arc therapy (VMAT) plans. Ten patients previously treated with HS-WBRT using conventional VMAT were re-planned using RP-HA technique and RP model for HS-WBRT. Treatment plans were generated for 30Gy in 3Gy fractions using 6MV photon beam on a TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, CA) equipped with high definition multileaf collimator (HDMLC). Target coverage, homogeneity index (HI), Paddick Conformity index (CI), dose to organs-at-risk (OARs) provided by the 3 planning modalities were compared, and a paired t-test was performed. Total number of monitor units (MU), effective planning time and beam-on-time time were reported and evaluated for each plan. RP-HA plans achieved on average a 4% increase in D98% of PTV, a 26% improvement in HI, a 2.3% increase in CI, when compared to RP plans. Furthermore, RP-HA plans provided on average 11% decrease in D100% of hippocampi when compared to VMAT plans. All RP-HA plans were generated in less than 30 minutes while RP plans took 40 minutes and VMAT plans required on average 9 hours to complete. Regarding beam-on-time time, it was estimated that RP-HA plans take on average 5 minutes to deliver while RP and VMAT plans require 6.5 and 10 minutes, respectively. RP-HA method provides fully automated planning and delivery for HS-WBRT. The auto-generated plans together with automated treatment delivery allow standardization of plan quality, increased efficiency and ultimately improved patient care.

We investigated skin dose enhancements of brass mesh bolus (BMB) and a recently developed transparent polymer-gel bolus (PGB) for clinically relevant breast treatment delivery techniques. The dose enhancement of the breast surface with BMB and PGB were compared to that of tissue-equivalent bolus. Three breast treatment plans were generated on CT scans of an anthropomorphic chest phantom: tangential step-and-shoot 3D conformal (3DCRT) planned using Field-in-Field (FiF), tangential sliding-window 3DCRT using Electronic Compensator (EC), and volumetric modulated arc therapy (VMAT). All plans were created using 6 MV photons and a prescription dose (Rx) of 180 cGy per fraction. Skin doses of all 3 plans were measured with radiochromic films, separately delivered in triplicate. Each plan was delivered to the phantom without bolus, and then with BMB (1 or 2 layers; 3 or 10 mm tissue-equivalent), PGB, and Superflab (3, 5, and 10 mm tissue-equivalent). Doses were determined by reading the radiochromic films with a flatbed scanner, and analyzing the images using a calibration curve for each specific batch. For all bolus types and plans, surface doses averaged over the 3 measurements were between 88.4% and 107.4% of Rx. Without bolus, average measured skin doses were between 51.2% and 64.2% of Rx. Skin doses with BMB and PGB were comparable to that with tissue-equivalent bolus. Over all 3 treatment delivery techniques, using BMB resulted in average skin doses of 92.8% and 102.1% for 1- and 2 layers, respectively, and using PGB results in average skin doses of 94.8%, 98.2%, and 99.7% for 3, 5, and 10-mm tissue-equivalent, respectively. The average measured skin doses with BMB and PGB agreed within ± 3% compared to the tissue-equivalent thickness bolus. We concluded that BMB and PGB are clinically equivalent in skin dose enhancement for breast treatment as the 3, 5, and 10 mm tissue-equivalent bolus.

Purpose We calculated setup margins for whole breast radiotherapy during voluntary deep‐inspiration breath‐hold (vDIBH) using real‐time surface imaging (SI). Methods and Materials Patients (n = 58) with a 27‐to‐31 split between right‐ and left‐sided cancers were analyzed. Treatment beams were gated using AlignRT by registering the whole breast region‐of‐interest to the surface generated from the simulation CT scan. AlignRT recorded (three‐dimensional) 3D displacements and the beam‐on‐state every 0.3 s. Means and standard deviations of the displacements during vDIBH for each fraction were used to calculate setup margins. Intra‐DIBH stability and the intrafraction reproducibility were estimated from the medians of the 5th to 95th percentile range of the translations in each breath‐hold and fraction, respectively. Results A total of 7269 breath‐holds were detected over 1305 fractions in which a median dose of 200 cGy was delivered. Each fraction was monitored for 5.95 ± 2.44 min. Calculated setup margins were 4.8 mm (A/P), 4.9 mm (S/I), and 6.4 mm (L/R). The intra‐DIBH stability and the intrafraction reproducibility were ≤0.7 mm and ≤2.2 mm, respectively. The isotropic margin according to SI (9.2 mm) was comparable to other institutions’ calculations that relied on x‐ray imaging and/or spirometry for patients with left‐sided cancer (9.8–11.0 mm). Likewise, intra‐DIBH variability and intrafraction reproducibility of breast surface measured with SI agreed with spirometry‐based positioning to within 1.2 and 0.36 mm, respectively. Conclusions We demonstrated that intra‐DIBH variability, intrafraction reproducibility, and setup margins are similar to those reported by peer studies who utilized spirometry‐based positioning.

Purpose: The goal is to develop a stand-alone application, which automatically and consistently computes the coordinates of the dose calculation point recommended by the American Brachytherapy Society (i.e., point A) based solely on the implanted applicator geometry for cervical cancer brachytherapy. Material and methods: The application calculates point A coordinates from the source dwell geometries in the computed tomography (CT) scans, and outputs the 3D coordinates in the left and right directions. The algorithm was tested on 34 CT scans of 7 patients treated with high-dose-rate (HDR) brachytherapy using tandem and ovoid applicators. A single experienced user retrospectively and manually inserted point A into each CT scan, whose coordinates were used as the “gold standard” for all comparisons. The gold standard was subtracted from the automatically calculated points, a second manual placement by the same experienced user, and the clinically used point coordinates inserted by multiple planners. Coordinate differences and corresponding variances were compared using nonparametric tests. Results: Automatically calculated, manually placed, and clinically used points agree with the gold standard to < 1 mm, 1 mm, 2 mm, respectively. When compared to the gold standard, the average and standard deviation of the 3D coordinate differences were 0.35 ± 0.14 mm from automatically calculated points, 0.38 ± 0.21 mm from the second manual placement, and 0.71 ± 0.44 mm from the clinically used point coordinates. Both the mean and standard deviations of the 3D coordinate differences were statistically significantly different from the gold standard, when point A was placed by multiple users (p < 0.05) but not when placed repeatedly by a single user or when calculated automatically. There were no statistical differences in doses, which agree to within 1-2% on average for all three groups. Conclusions: The study demonstrates that the automated algorithm calculates point A coordinates consistently, while reducing inter-user variability. Point placement using the algorithm expedites the planning process and minimizes associated potential human errors.

Reproductive physiology and behavior is mainly regulated by the hypothalamus-pituitary-gonad (HPG) axis, although abnormal thyroid hormone (TH) levels alter HPG axis activity. Seasonally breeding animals, such as green anole lizards (Anolis carolinensis), undergo drastic hormonal and behavioral changes between breeding and non-breeding seasons, with increased sex steroid hormones, larger gonads and increased reproductive behaviors during the breeding compared to non-breeding seasons. Relatively less is known regarding the regulation of gonadal TH in seasonal reproduction. We examined whether the gonadal expression of enzymes involved in TH activation are altered in concert with seasonal reproduction. Type 2 deiodinase (Dio2) mRNA, the TH activating enzyme, was upregulated in breeding compared to non-breeding testes, while type 3 deiodinase (Dio3) mRNA, the TH deactivating enzyme, was upregulated in breeding ovaries. To study the association between the HPG axis and local activation of TH, we manipulated the HPG axis during the non-breeding season by subcutaneously injecting luteinizing hormone (LH) and follicle stimulating hormone (FSH) in male lizards. We found that acute LH and FSH injections induced many aspects of breeding, with increased testes size and testosterone levels. Surprisingly, Dio3 was upregulated in the testes after LH and FSH injections, while Dio2 mRNA levels were unchanged. These results suggest that there might be different roles for local TH activation in developing and maintaining fully mature and functional gonads. Our findings continue to support the role for TH in regulating reproduction.

Purpose We transitioned from a low-dose-rate (LDR) to a high-dose-rate (HDR) prostate brachytherapy program. The objective of this study was to describe our experience developing a prostate HDR program, compare the LDR and HDR dosimetry, and identify the impact of several targeted interventions in the HDR workflow to improve efficiency. Methods and Materials We performed a retrospective cohort study of patients treated with LDR or HDR prostate brachytherapy. We used iodine-125 seeds (145 Gy as monotherapy, and 110 Gy as a boost) and preoperative planning for LDR. For HDR, we used iridium-192 (13.5 Gy × 2 as monotherapy and 15 Gy × 1 as a boost) and computed tomography–based planning. Over the first 18 months, we implemented several targeted interventions into our HDR workflow to improve efficiency. To evaluate the progress of the HDR program, we used linear mixed-effects models to compare LDR and HDR dosimetry and identify changes in the implant procedure and treatment planning durations over time. Results The study cohort consisted of 122 patients (51 who received LDR and 71 HDR). The mean D90 was similar between patients who received LDR and HDR (P = .28). HDR mean V100 and V95 were higher (P < .0001), but mean V200 and V150 were lower (P < .0001). HDR rectum V100 and D1cc were lower (P < .0001). The HDR mean for the implant procedure duration was shorter (54 vs 60 minutes; P = .02). The HDR mean for the treatment planning duration dramatically improved with the implementation of targeted workflow interventions (3.7 hours for the first quartile to 2.0 hours for the final quartile; P < .0001). Conclusions We successfully developed a prostate HDR brachytherapy program at our institution with comparable dosimetry to our historic LDR patients. We identified several targeted interventions that improved the efficiency of treatment planning. Our experience and workflow interventions may help other institutions develop similar HDR programs.

The spatial and temporal tracking performance of a commercially available 3D optical surface imaging system is evaluated for its potential use in frameless stereotactic radiosurgery head tracking applications.Both 3D surface and infrared (IR) marker tracking were performed simultaneously on a head phantom mounted on an xyz motion stage and on four human subjects. To allow spatial and temporal comparison on human subjects, three points were simultaneously monitored, including the upper facial region (3D surface), a dental plate (IR markers), and upper forehead (IR markers).For both static and dynamic phantom studies, the 3D surface tracker was found to have a root mean squared error (RMSE) of approximately 0.30 mm for region-of-interest (ROI) surface sizes greater than 1000 vertex points. Although, the processing period (1/fps) of the 3D surface system was found to linearly increase as a function of the number of ROI vertex points, the tracking accuracy was found to be independent of ROI size provided that the ROI was sufficiently large and contained features for registration. For human subjects, the RMSE between 3D surface tracking and IR marker tracking modalities was 0.22 mm left-right (x-axis), 0.44 mm superior-inferior (y-axis), 0.27 mm anterior-posterior (z-axis), 0.29° pitch (around x-axis), 0.18° roll (around y-axis), and 0.15° yaw (around z-axis).3D surface imaging has the potential to provide submillimeter level head motion tracking. This is provided that a highly accurate camera-to-LINAC frame of reference calibration can be performed and that the reference ROI is of sufficient size and contains suitable surface features for registration.

With the increasing use of external 3D optical tracking cameras to guide modern radiation therapy procedures, it has become vitally important to have an accurate camera to linear accelerator (LINAC) reference frame calibration. To eliminate errors present in current calibration procedures based on the manual hand alignment of a device using the light field crosshairs and in room guidance lasers, a semiautomated quantitative calibration approach requiring only use of an electronic portal imaging device (EPID) was developed.A phantom comprised of seven highly IR reflective plastic BBs was placed on the LINAC treatment couch and imaged with both a 3D stereoscopic IR imager and the on board megavoltage (MV) EPID imager. Having knowledge of the optically determined 3D positions and projected EPID images of the BBs, simulated annealing was used to optimize the location of the BBs in the LINAC frame using four different optimization functions. Singular value decomposition was then used to calculate the transformation matrix between the camera and LINAC reference frames. Results were then compared to a traditional camera calibration method for overall accuracy.Using modeled data, the simulated annealing process was able to determine the actual locations of the BBs with a RMSE of 0.23 mm. Using projection images acquired with an MV imager, the process was able to determine locations of BBs within .26 mm. The results depend on the choice of optimization function.Results show that the method can be used to provide highly accurate spatial registration between an external 3D imaging reference frame and the LINAC frame. The experimental MV imager results, while not as precise as the simulated results, exceed 1 mm accuracy and the current accepted AAPM TG-142 standard of ≤2 mm positioning accuracy.

To establish a new clinical procedure in frameless stereotactic radiosurgery (SRS) for patient setup verification at treatment couch angles as well as for head-motion monitoring during treatment using video-based optical surface imaging (OSI).A video-based three-dimensional (3D) OSI system with three ceiling-mounted camera pods was employed to verify setup at treatment couch angles as well as to monitor head motion during treatment. A noninvasive head immobilization device was utilized, which includes an alpha head mold and a dental mouthpiece with vacuum suction; both were locked to the treatment couch. Cone beam computed tomography (CBCT) was used as the standard for image-guided setup. Orthogonal 2D-kV imaging was applied for setup verification before treatment, between couch rotations, and after treatment at zero couch angle. At various treatment couch angles, OSI setup verification was performed, relative to initial OSI setup verification at zero couch angle after CBCT setup through a coordinate transformation. For motion monitoring, the setup uncertainty was decoupled by taking an on-site surface image as new reference to detect motion-induced misalignment in near real-time (1-2 frames per second). Initial thermal instability baseline of the real-time monitoring was corrected. An anthropomorphous head phantom and a 1D positioning platform were used to assess the OSI accuracy in motion detection in longitudinal and lateral directions. Two hypofractionated (9 Gy x 3 and 6 Gy x 5) frameless stereotactic radiotherapy (SRT) patients as well as two single-fraction (21 and 18 Gy) frameless SRS patients were treated using this frameless procedure. For comparison, 11 conventional frame-based SRS patients were monitored using the OSI to serve as clinical standards. Multiple noncoplanar conformal beams were used for planning both frameless and frame-based SRS with a micromultileaf collimator.The accuracy of the OSI in 1D motion detection was found to be 0.1 mm with uncertainty of +/- 0.1 mm using the head phantom. The OSI registration against simulation computed tomography (CT) external contour was found to be dependent on the CT skin definition with -0.4 mm variation. For frame-based SRS patients, head-motion magnitude was detected to be1.0 mm (0.3 +/- 0.2 mm) and1.0 degree (0.2 degrees +/- 0.2 degrees) for 98% of treatment time, with exception of one patient with head rotation1.5 degrees for 98% of the time. For frameless SRT/SRS patients, similar motion magnitudes were observed with an average of 0.3 +/- 0.2 mm and 0.2 degrees +/- 0.1 degree in ten treatments. For 98% of the time, the motion magnitude was1.1 mm and 1.0 degree. Complex head-motion patterns within 1.0 mm were observed for frameless SRT/SRS patients. The OSI setup verification at treatment couch angles was found to be within 1.0 mm.The OSI system is capable of detecting 0.1 +/- 0.1 mm 1D spatial displacement of a phantom in near real time and useful in head-motion monitoring. This new frameless SRS procedure using the mask-less head-fixation system provides immobilization similar to that of conventional frame-based SRS. Head-motion monitoring using near-real-time surface imaging provides adequate accuracy and is necessary for frameless SRS in case of unexpected head motion that exceeds a set tolerance.

Respiration-induced tumor motion during intensity-modulated radiotherapy (IMRT) of non-small-cell lung cancer (NSCLC) could cause substantial differences between planned and delivered doses. While it has been shown that, for conventionally fractionated IMRT, motion effects average out over the course of many treatments, this might not be true for hypofractionated IMRT (IMHFRT). Numerical simulations were performed for nine NSCLC patients (11 tumors) to evaluate this problem. Dose distributions to the Clinical Target Volume (CTV) and Internal Target Volume (ITV) were retrospectively calculated using the previously-calculated leaf motion files but with the addition of typical periodic motion (i.e. amplitude 0.36-1.26cm, 3-8sec period). A typical IMHFRT prescription of 20Gy x 3 fractions was assumed. For the largest amplitude (1.26 cm), the average +/- standard deviation of the ratio of simulated to planned mean dose, minimum dose, D95 and V95 were 0.98+/-0.01, 0.88 +/- 0.09, 0.94 +/- 0.05 and 0.94 +/- 0.07 for the CTV, and 0.99 +/-0.01, 0.99 +/- 0.03, 0.98 +/- 0.02 and 1.00 +/- 0.01 for the ITV, respectively. There was minimal dependence on period or initial phase. For typical tumor geometries and respiratory amplitudes, changes in target coverage are minimal but can be significant for larger amplitudes, faster beam delivery, more highly-modulated fields, and smaller field margins.

We present production measurements of the charged hadrons {pi}{sup {+-}}, K{sup {+-}} and p/{bar p} in e{sup +}e{sup -} interactions at the Z{sup 0} pole. The excellent particle identification capability of the SLC Large Detector (SLD) at the Stanford Linear Collider (SLC) are used. In addition to studies over a wide momentum range in hadronic Z{sup 0} events of all five flavors, we have made the most precise measurements in light (uds), c and b flavor events separately. Unambiguous flavor dependencies have been observed, and the results have been compared with the predictions of several QCD fragmentation models. We have also exploited the unique feature of electron beam polarization in our experiment to compare hadron production separately in quark and antiquark jets. Direct evidence that higher momentum hadrons are more likely to contain the primary quark and antiquark is seen, with precision sufficient to provide new model tests. Finally, we have studied hard gluon jets in detail. We have confirmed that gluon jets have a higher multiplicity of softer particles than light quark jets, and found this enhancement to be the same for {pi}{sup {+-}}, K{sup {+-}} and p/{bar p} at the few percent level at all momenta. Any overallmore » difference in the hadron fractions is limited to 0.018 at the 95% confidence level, indicating that there are no differences at the hadronization stage in jet formation between gluons and quarks.« less

We present measurements of identified charged hadron production over a wide momentum range using the SLD Cherenkov Ring Imaging Detector. In addition to studying particle production in flavor-inclusive Z{sup 0} decays, we compare the production in decays into light, c and b flavor events. We also examine particle production in gluon jets with that in light quark jets. The jet flavors are selected by using displaced vertex information.