Rapid multi-catheter segmentation for magnetic resonance image-guided catheter-based interventions.

BACKGROUND: Magnetic resonance imaging (MRI) is the gold standard for delineating cancerous lesions in soft tissue. Catheter-based interventions require the accurate placement of multiple long, flexible catheters at the target site. The manual segmentation of catheters in MR images is a challenging and time-consuming task. There is a need for automated catheter segmentation to improve the efficiency of MR-guided procedures. PURPOSE: To develop and assess a machine learning algorithm for the detection of multiple catheters in magnetic resonance images used during catheter-based interventions. METHODS: In this work, a 3D U-Net was trained to retrospectively segment catheters in scans acquired during clinical MR-guided high dose rate (HDR) prostate brachytherapy cases. To assess confidence in segmentation, multiple AI models were trained. On clinical test cases, average segmentation results were used to plan the brachytherapy delivery. Dosimetric parameters were compared to the original clinical plan. Data was obtained from 35 patients who underwent HDR prostate brachytherapy for focal disease with a total of 214 image volumes. 185 image volumes from 30 patients were used for training using a five-fold cross validation split to divide the data for training and validation. To generate confidence measures of segmentation accuracy, five trained models were generated. The remaining five patients (29 volumes) were used to test the performance of the trained model by comparison to manual segmentations of three independent observers and assessment of dosimetric impact on the final clinical brachytherapy plans. RESULTS: The network successfully identified 95% of catheters in the test set at a rate of 0.89 s per volume. The multi-model method identified the small number of cases where AI segmentation of individual catheters was poor, flagging the need for user input. AI-based segmentation performed as well as segmentations by independent observers. Plan dosimetry using AI-segmented catheters was comparable to the original plan. CONCLUSION: The vast majority of catheters were accurately identified by AI segmentation, with minimal impact on plan outcomes. The use of multiple AI models provided confidence in the segmentation accuracy and identified catheter segmentations that required further manual assessment. Real-time AI catheter segmentation can be used during MR-guided insertions to assess deflections and for rapid planning of prostate brachytherapy.

Investigation of cyanine-based infrared dyes as calibrants in radiochromic films.

BACKGROUND: Radiochromic material such as lithium pentacosa-10,12-diynoate (LiPCDA) has been suggested as the radiation-sensitive material for real-time in vivo fiber-optic dosimetry. In this configuration, micron-thick radiochromic coating would measure the absorbed dose, where a major challenge is the uncertainty in the active material thickness, necessitating calibration. A homogeneously incorporated inert infrared (IR) dye, which must also be stable in ambient conditions and against radiolysis, can be added to the radiochromic film to enable optical calibration. PURPOSE: This study investigates four commercial cyanine-based dyes (IR-783, IR-806, IR-868, and IR-880) for use as an optical calibrant in fiber-optic radiochromic dosimeters. METHODS: All dyes were dissolved in water to confirm solubility. IR-783 and IR-806 were dissolved in 10% w/w gelatin solution and coated onto a polyester substrate, which were then sandwiched between two layers of adhesives forming IR-783 and IR-806 films. A second batch of IR dyes in gelatin incorporated the LiPCDA, and was coated onto substrate and sandwiched between adhesive to form IR dye + LiPCDA films. The absorbance spectra of the films were measured periodically (176 and 102 days for IR-dye films, and IR dye + LiPCDA, respectively). The average percentage absorbance, normalized to day 1, was fit to either a single or a double exponential decay model to calculate the spectral stability lifetime (τ1 , τ2 ). Films were irradiated using a 6 MV LINAC beam with a standard setup of 100 source to axis distance (SAD), 10 cm × 10 cm field size and 1.5 cm depth. The change in absorbance of the IR-dye + LiPCDA films were measured after they were irradiated to 1, 2, 5, 10, and 20 Gy at 3 Gy/min. RESULTS: Only IR-783 and IR-806 were sufficiently water soluble. In gelatin matrix, these dyes demonstrated a decrease in absorbance with time for IR-783 and IR-806 dyes, with IR-783 films having an average τ1  = 73 ± 7 days and IR-806 films τ1  = 7 ± 3 days. When combined with LiPCDA, IR-806 degraded, losing its original peak at ∼820 nm. Similarly, IR-783, combined with LiPCDA, showed signs of degradation; however, its original absorbance peak was still observed at ∼800 nm. In the IR-783 + LiPCDA films, the IR-783 dye had a τ = 4 ± 1 days, an order of magnitude faster than the IR-783 with no LiPCDA films. When exposed to x-ray irradiation, the IR-783 dye in the IR-783 + LiPCDA films showed no change in absorbance with increasing absorbed dose. In contrast, the LiPCDA in the films responded as expected, increasing in optical density with increased absorbed dose. CONCLUSIONS: IR-783 and IR-806 dyes were observed to degrade over time following exponential decay curves. IR-806 could not be combined with the LiPCDA without degrading. The combination of IR-783 with LiPCDA demonstrated single exponential decay behavior at a comparatively faster rate than films that did not have LiPCDA. IR-783 was insensitive to ionizing radiation and thus may be suitable for thickness correction, but an alternative manufacturing procedure may need to be developed.

Artificial intelligence applications in brachytherapy: A literature review.

PURPOSE: Artificial intelligence (AI) has the potential to simplify and optimize various steps of the brachytherapy workflow, and this literature review aims to provide an overview of the work done in this field. METHODS AND MATERIALS: We conducted a literature search in June 2022 on PubMed, Embase, and Cochrane for papers that proposed AI applications in brachytherapy. RESULTS: A total of 80 papers satisfied inclusion/exclusion criteria. These papers were categorized as follows: segmentation (24), registration and image processing (6), preplanning (13), dose prediction and treatment planning (11), applicator/catheter/needle reconstruction (16), and quality assurance (10). AI techniques ranged from classical models such as support vector machines and decision tree-based learning to newer techniques such as U-Net and deep reinforcement learning, and were applied to facilitate small steps of a process (e.g., optimizing applicator selection) or even automate the entire step of the workflow (e.g., end-to-end preplanning). Many of these algorithms demonstrated human-level performance and offer significant improvements in speed. CONCLUSIONS: AI has potential to augment, automate, and/or accelerate many steps of the brachytherapy workflow. We recommend that future studies adhere to standard reporting guidelines. We also stress the importance of using larger sample sizes and reporting results using clinically interpretable measures.

Comparing dosimetry of locally advanced cervical cancer patients treated with 3 versus 4 fractions of MRI-guided brachytherapy.

PURPOSE: To demonstrate the feasibility of treating cervical cancer patients with MRI-guided brachytherapy (MRgBT) using 24 Gy in 3 fractions (F) versus a standard, more resource-intensive regimen of 28 Gy in 4F, and its ability to meet EMBRACE II planning aims. METHODS AND MATERIALS: A retrospective review of 224 patients with FIGO Stage IB-IVA cervical cancer treated with 28 Gy/4F (n = 91) and 24 Gy/3F (n = 133) MRgBT between 2016-2021 was conducted. Multivariable linear regression models were fitted to compare dosimetric parameters between the two groups, adjusting for CTVHR and T stage. RESULTS: Most patients had squamous cell carcinoma, T2b disease, and were treated with intracavitary applicator plus interstitial needles (96%). The 28 Gy/4F group had higher CTVHR (median 28 vs. 26 cm3, p = 0.04), CTVIR D98% (mean 65.5 vs. 64.5 Gy, p = 0.03), rectum D2cm3 (mean 61.7 vs. 59.2 Gy, p = 0.04) and bladder D2cm3 (81.3 vs. 77.9 Gy, p = 0.03). There were no significant differences in the proportion of patients meeting the EMBRACE II OAR dose constraints and planning aims, except fewer patients treated with 28 Gy/4F met rectum D2cm3 < 65 Gy (73 vs. 85%, p = 0.027) and ICRU rectovaginal point < 65 Gy (65 vs. 84%, p = 0.005). CONCLUSIONS: Cervical cancer patients treated with 24 Gy/3F MRgBT had comparable target doses and lower OAR doses compared to those treated with 28 Gy/4F. A less-resource intense fractionation schedule of 24 Gy/3F is an alternative to 28 Gy/4F in cervix MRgBT.

Corrigendum: MRI-guided focal or integrated boost high dose rate brachytherapy for recurrent prostate cancer.

[This corrects the article DOI: 10.3389/fonc.2022.971344.].

MRI-guided focal or integrated boost high dose rate brachytherapy for recurrent prostate cancer.

Background and purpose: Locally recurrent prostate cancer after radiotherapy merits an effective salvage strategy that mitigates the risk of adverse events. We report outcomes of a cohort enrolled across two institutions investigating MRI-guided tumor-targeted salvage high dose rate brachytherapy (HDR-BT). Materials and methods: Analysis of a prospective cohort of 88 patients treated across two institutions with MRI-guided salvage HDR-BT to visible local recurrence after radiotherapy (RT). Tumor target dose ranged from 22-26 Gy, using either an integrated boost (ibBT) or focal technique (fBT), delivered in two implants over a median of 7 days. Outcome metrics included cancer control and toxicity (CTCAE). Quality of life (QoL-EPIC) was analyzed in a subset. Results: At a median follow-up of 35 months (6 -134), 3 and 5-year failure-free survival (FFS) outcomes were 67% and 49%, respectively. At 5 years, fBT was associated with a 17% cumulative incidence of local failure (LF) outside the GTV (vs. 7.8% ibBT, p=0.14), while LF within the GTV occurred in 13% (vs. 16% ibBT, p=0.81). Predictors of LF outside fBT volumes included pre-salvage PSA>7 ng/mL (p=0.03) and interval since RT less than 5 years (p=0.04). No attributable grade 3 events occurred, and ibBT was associated with a higher rate of grade 2 toxicity (p<0.001), and trend towards a larger reduction in QoL sexual domain score (p=0.07), compared to fBT. Conclusion: A tumor-targeted HDR-BT salvage approach achieved favorable cancer control outcomes. While a fBT was associated with less toxicity, it may be best suited to a subgroup with lower PSA at later recurrence. Tumor targeted dose escalation may be warranted.

Role of water in the crystal structure of LiPCDA monomer and the radiotherapy dose response of EBT-3 film.

PURPOSE: Radiochromic material used in recent commercial films has been suggested as a candidate for in vivo dosimetry because of its dose sensitivity, real-time response, and atomic composition. It was observed that its sensitive material, lithium pentacosa-10,12-diynoate (LiPCDA), can have two distinct forms, with main absorbance peaks at ∼635 and ∼674 nm. The spectrum of the latter is similar to that of pentacosa-10,12-diynoic acid (PCDA) used in the commercial predecessor, obtained through desiccation of the commercial film. Water was suggested to be a part of the crystal structure and thus its presence or absence would affect dosimetric parameters. The objective of this study is to: (a) investigate how desiccated commercial films compared to the native form in terms of macroscopic crystal structure, dose-response, signal linearity, and post-exposure kinetics; (b) demonstrate proof-of-concept that the two versions can be combined into one optical dosimeter and measured simultaneously. METHODS: Commercial radiochromic film, EBT-3, was desiccated for 10 days at 45°C. Using a 6 MV LINAC beam and standard setup of 100 Source to Axis Distance (SAD), 10 cm × 10 cm field size, and 1.5 cm depth, commercial and desiccated films were irradiated to 50, 100, 200, 500, 1000, 2000, 3000 cGy and the latter to 4000, 5000, and 7000 cGy. A custom phantom equipped with optical fibers for real-time read-out was used for all measurements. Absorbance spectra were collected at ∼1 Hz before, during, and after irradiation. Data were collected for ∼1 h after the end of irradiation for 200 cGy experiments. The radiation-induced change in optical density (∆OD) was calculated with a 10 nm band around the primary absorbance peak. The post-exposure percent optical density change was calculated and compared to ∆OD at the end of irradiation. Both commercial and desiccated films were also irradiated and measured simultaneously as proof-of-concept for using two materials within one optical path. For electron microscopy imaging, active materials from commercial and desiccated films were imaged on a scanning electron microscope at an accelerating voltage of 10 kV. RESULTS: Scanning electron microscope images showed that desiccated film was similar in topographical structure to the commercial EBT-3 form. It maintained a non-linear ∆OD with dose but resulted in ∼1/3 signal compared to the commercial film. Evaluation of post-exposure response showed significantly lower percent increase in ∆OD for desiccated film initially, with no statistically significant difference at 1 h after the end of irradiation. Combining both films and simultaneously measuring their absorbance illustrated that the two absorbance peaks were identifiable and resolvable to allow for an independent determination of dose from each. CONCLUSIONS: Water is implicated in the crystal structure of the EBT-3 radiochromic film, with its removal through desiccation affecting both dosimetric and spectroscopic characteristics of the material. The two forms of radiochromic material (with and without water) are spectrally resolvable allowing for independent dose determination from each, opening up possibilities for dose measurements at different locations along a single fiber.

Tumor-targeted dose escalation for localized prostate cancer using MR-guided HDR brachytherapy (HDR) or integrated VMAT (IB-VMAT) boost: Dosimetry, toxicity and health related quality of life.

PURPOSE: To report dosimetry, preliminary toxicity and health-related quality of life (HRQoL) outcomes of tumor-targeted dose-escalation delivered by integrated boost volumetric arc therapy (IB-VMAT) or MR-guided HDR brachytherapy (HDR) boost for prostate cancer. MATERIALS AND METHODS: Patients diagnosed with localized prostate cancer, with at least 1 identifiable intraprostatic lesion on multiparametric MRI (mpMRI) were enrolled in a prospective non-randomized phase II study. All patients received VMAT to the prostate alone (76 Gy in 38 fractions) plus a GTV boost: IB-VMAT (95 Gy in 38 fractions) or MR-guided HDR (10 Gy single fraction). GTV was delineated on mpMRI and deformably registered to planning CT scans. Comparative dosimetry using EQD2 assuming α/ß 3 Gy was performed. Toxicity and health-related quality of life data (HRQoL) data were collected using CTCAE v.4.0, International Prostate Symptom Score (IPSS) and the Expanded Prostate Index Composite (EPIC). RESULTS: Forty patients received IB-VMAT and 40 HDR boost. Organs at risk and target minimal doses were comparable between the two arms. HDR achieved higher mean and maximal tumor doses (p < 0.05). Median follow-up was 31 months (range 25-48); Acute grade G2 genitourinary (GU) toxicity was 30% and 37.5% in IB-VMAT and HDR boost, while gastrointestinal (GI) toxicity was 7.5% and 10%, respectively. Three patients developed acute G3 events, two GU toxicity (one IB-VMAT and one HDR boost) and one GI (IB-VMAT). Late G2 GU toxicity was 25% and 17.5% in the IB-VMAT and HDR boost arm and G2 GI was 5% and 7.5%, respectively. Two patients, both on the IB-VMAT arm, developed late G3 toxicity: one GI and one GU. No statistically significant difference was found in HRQoL between radiotherapy techniques (p > 0.2). Urinary and bowel HRQoL domains in both groups declined significantly by week 6 of treatment in both arms (p < 0.05) and recovered baseline scores at 6 months. CONCLUSION: Intraprostatic tumor dose escalation using IB-VMAT or MR-guided HDR boost achieved comparable OAR dosimetry, toxicity and HRQOL outcomes, but higher mean and maximal tumor dose were achieved with the HDR technique. Further follow-up will determine long-term outcomes including disease control.

Feasibility study of navigated endoscopy for the placement of high dose rate brachytherapy applicators in the esophagus and lung.

PURPOSE: To evaluate the electromagnetic (EM) tracking of endoscopes and applicators as a method of positioning a high dose rate (HDR) luminal applicator. METHOD: An anatomical phantom consisting of a rigid trachea and flexible esophagus was used to compare applicator placement measurements using EM tracking vs the traditional method using two-dimensional (2D) fluoroscopy and surface skin markers. The phantom included a tumor in the esophagus and several pairs of optically visible points inside the lumen that were used to simulate proximal and distal ends of tumors of varying lengths. The esophagus tumor and lung points were visible on a computed tomography (CT) image of the phantom, which was used as ground truth for the measurements. The EM tracking system was registered to the CT image using fiducial markers. A flexible endoscope was tracked using the EM system and the locations of the proximal and distal ends of the tumor identified and this position recorded. An EM-tracked applicator was then inserted and positioned relative to the tumor markings. The applicator path was mapped using the EM tracking. The gross tumor length (GTL) and the distance between the first dwell position and distal edge of tumor (offset) were measured using the EM tracking and 2D fluoroscopy methods and compared to the same measurements on the CT image. RESULTS: The errors in GTL using EM tracking were on average -0.5 ± 1.7 mm and 0.7 ± 3.6 mm for esophagus and lung measurements, similar to errors measured using the 2D fluoroscopy method of -0.9 ± 1.2 mm and 3.4 ± 4.4 mm. Offset measurements were slightly larger while using EM tracking relative to the fluoroscopy method but these were not statistically significant. CONCLUSIONS: Electromagnetic tracking for placement of lumen applicators is feasible and accurate. Tracking of the endoscope that is used to identify the proximal and distal ends of the tumor and of the applicator during insertion generates accurate three-dimensional measurements of the applicator path, GTL and offset. Guiding the placement of intraluminal applicators using EM navigation is potentially attractive for cases with complex insertions, such as those with nonlinear paths or multiple applicator insertions.

Clinical Outcomes of Surgically Unresectable Endometrial Cancers.

OBJECTIVE: The objective of this study was to determine the outcomes of patients with unresectable endometrial cancer managed with definitive or neoadjuvant radiation (RT) and/or chemotherapy. MATERIALS AND METHODS: Patients with unresectable stages II to IVA endometrial cancer who were treated with curative intent between January 2000 and March 2018 were identified. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate logistic regression analysis was performed to identify factors associated with receipt of surgery. Multivariate Cox regression analysis was performed to identify factors associated with OS and DFS. RESULTS: Of the 59 patients identified, the median age was 63 years (range: 37 to 88 y) and histology was endometrioid in 59%. Median follow-up was 2.2 years (range: 0.3 to 9.8 y). Seventeen patients (29%) received neoadjuvant chemotherapy, 28 (47%) neoadjuvant radiation, and 14 (24%) definitive RT; 39 (66%) underwent surgery. Patients who received surgery had higher 3-year OS and DFS than those who did not (84% vs. 41%; P<0.001 and 56% vs. 11%; P<0.001, respectively). Factors associated with higher odds of surgical resection included younger age, endometrioid histology, and earlier stage. Younger age, endometrioid histology, and surgical resection were significantly associated with higher OS. Surgical resection was also associated with higher DFS. CONCLUSIONS: Surgical resection following RT and/or chemotherapy for locally advanced, unresectable endometrial cancer is associated with higher DFS and OS and more likely to be achieved in endometrioid subtypes.

Prediction of skin dose in low-kV intraoperative radiotherapy using machine learning models trained on results of in vivo dosimetry.

PURPOSE: The purpose of this study was to implement a machine learning model to predict skin dose from targeted intraoperative (TARGIT) treatment resulting in timely adoption of strategies to limit excessive skin dose. METHODS: A total of 283 patients affected by invasive breast carcinoma underwent TARGIT with a prescribed dose of 6 Gy at 1 cm, after lumpectomy. Radiochromic films were used to measure the dose to the skin for each patient. Univariate statistical analysis was performed to identify correlation of physical and patient variables with measured dose. After feature selection of predictors of in vivo skin dose, machine learning models stepwise linear regression (SLR), support vector regression (SVR), ensemble with bagging or boosting, and feed forward neural networks were trained on results of in vivo dosimetry to derive models to predict skin dose. Models were evaluated by tenfold cross validation and ranked according to root mean square error (RMSE) and adjusted correlation coefficient of true vs predicted values (adj-R2 ). RESULTS: The predictors correlated with in vivo dosimetry were the distance of skin from source, depth-dose in water at depth of the applicator in the breast, use of a replacement source, and irradiation time. The best performing model was SVR, which scored RMSE and adj-R2 , equal to 0.746 [95% confidence intervals (CI), 95% CI 0.737,0.756] and 0.481 (95% CI 0.468,0.494), respectively, on the tenfold cross validation. CONCLUSION: The model trained on results of in vivo dosimetry can be used to predict skin dose during setup of patient for TARGIT and this allows for timely adoption of strategies to prevent of excessive skin dose.

Comparison of dosimetric parameters derived from whole organ and wall contours for bladder and rectum in cervical cancer patients treated with intracavitary and interstitial brachytherapy.

For volumes up to 2 cm3 of the bladder and possibly up to 5 cm3 of the rectum, doses computed from the whole organ were good estimates of the doses in the wall in cervix brachytherapy, and there were no significant differences between patients treated with or without interstitial needles.

Technique adaptation, strategic replanning, and team learning during implementation of MR-guided brachytherapy for cervical cancer.

PURPOSE: MR-guided brachytherapy (MRgBT) with interstitial needles is associated with improved outcomes in cervical cancer patients. However, there are implementation barriers, including magnetic resonance (MR) access, practitioner familiarity/comfort, and efficiency. This study explores a graded MRgBT implementation strategy that included the adaptive use of needles, strategic use of MR imaging/planning, and team learning. METHODS AND MATERIALS: Twenty patients with cervical cancer were treated with high-dose-rate MRgBT (28 Gy in four fractions, two insertions, daily MR imaging/planning). A tandem/ring applicator alone was used for the first insertion in most patients. Needles were added for the second insertion based on evaluation of the initial dosimetry. An interdisciplinary expert team reviewed and discussed the MR images and treatment plans. RESULTS: Dosimetry-trigger technique adaptation with the addition of needles for the second insertion improved target coverage in all patients with suboptimal dosimetry initially without compromising organ-at-risk (OAR) sparing. Target and OAR planning objectives were achieved in most patients. There were small or no systematic differences in tumor or OAR dosimetry between imaging/planning once per insertion vs. daily and only small random variations. Peer review and discussion of images, contours, and plans promoted learning and process development. CONCLUSIONS: Technique adaptation based on the initial dosimetry is an efficient approach to implementing MRgBT while gaining comfort with the use of needles. MR imaging and planning once per insertion is safe in most patients as long as applicator shifts, and large anatomical changes are excluded. Team learning is essential to building individual and programmatic competencies.

Dosimetric impact of intrafraction changes in MR-guided high-dose-rate (HDR) brachytherapy for prostate cancer.

PURPOSE: To assess changes in implant and treatment volumes through the course of a prostate high-dose-rate brachytherapy procedure and their impact on plan quality metrics. METHODS AND MATERIALS: Sixteen MRI-guided high-dose-rate procedures included a post-treatment MR (ptMR) immediately after treatment delivery (135 min between MR scans). Target and organs at risk (OARs) were contoured, and catheters were reconstructed. The delivered treatment plan was applied to the ptMR image set. Volumes and dosimetric parameters in the ptMR were evaluated and compared with the delivered plan using a paired two-tailed t-test with p < 0.05 considered statistically significant. RESULTS: An average increase of 8.9% in prostate volume was observed for whole-gland treatments, resulting in reduction in coverage for both prostate and planning target volume, reflected in decreased V100 (mean 3.3% and 4.6%, respectively, p < 0.05), and D90 (mean 7.1% and 7.6%, respectively, of prescription dose, p < 0.05). There was no significant change in doses to OARs. For partial-gland treatments, there was an increase in planning target volume (9.1%), resulting in reduced coverage and D90 (mean 3.6% and 12.4%, respectively, p < 0.05). A decrease in D0.5cc for bladder (3%, p < 0.05) was observed, with no significant changes in dose to other OARs. CONCLUSIONS: Volumetric changes were observed during the time between planning MR and ptMR. Nonetheless, treatment plans for both whole- and partial-gland therapies remained clinically acceptable. These results apply to clinical settings in which patients remain in the same position and under anesthesia during the entire treatment process.

Brachytherapy patient safety events in an academic radiation medicine program.

PURPOSE: To describe the incidence and type of brachytherapy patient safety events over 10 years in an academic brachytherapy program. METHODS AND MATERIALS: Brachytherapy patient safety events reported between January 2007 and August 2016 were retrieved from the incident reporting system and reclassified using the recently developed National System for Incident Reporting in Radiation Treatment taxonomy. A multi-incident analysis was conducted to identify common themes and key learning points. RESULTS: During the study period, 3095 patients received 4967 brachytherapy fractions. An additional 179 patients had MR-guided prostate biopsies without treatment as part of an interventional research program. A total of 94 brachytherapy- or biopsy-related safety events (incidents, near misses, or programmatic hazards) were identified, corresponding to a rate of 2.8% of brachytherapy patients, 1.7% of brachytherapy fractions, and 3.4% of patients undergoing MR-guided prostate biopsy. Fifty-one (54%) events were classified as actual incidents, 29 (31%) as near misses, and 14 (15%) as programmatic hazards. Two events were associated with moderate acute medical harm or dosimetric severity, and two were associated with high dosimetric severity. Multi-incident analysis identified five high-risk activities or clinical scenarios as follows: (1) uncommon, low-volume or newly implemented brachytherapy procedures, (2) real-time MR-guided brachytherapy or biopsy procedures, (3) use of in-house devices or software, (4) manual data entry, and (5) patient scheduling and handoffs. CONCLUSIONS: Brachytherapy is a safe treatment and associated with a low rate of patient safety events. Effective incident management is a key element of continuous quality improvement and patient safety in brachytherapy.

Dosimetric feasibility of ablative dose escalated focal monotherapy with MRI-guided high-dose-rate (HDR) brachytherapy for prostate cancer.

PURPOSE: To determine the dosimetric feasibility of dose-escalated MRI-guided high-dose-rate brachytherapy (HDR-BT) focal monotherapy for prostate cancer (PCa). METHODS: In all patients, GTV was defined with mpMRI, and deformably registered onto post-catheter insertion planning MRI. PTV included the GTV plus 9mm craniocaudal and 5mm in every other direction. In discovery-cohort, plans were obtained for each PTV independently aiming to deliver ⩾16.5Gy/fraction (two fraction schedule) while respecting predefined organs-at-risk (OAR) constraints or halted when achieved equivalent single-dose plan (24Gy). Dosimetric results of original and focal HDR-BT plans were evaluated to develop a planning protocol for the validation-cohort. RESULTS: In discovery-cohort (20-patients, 32-GTVs): PTV D95% ⩾16.5Gy could not be reached in a single plan (3%) and was accomplished (range 16.5-23.8Gy) in 15 GTVs (47%). Single-dose schedule was feasible in 16 (50%) plans. In the validation-cohort (10-patients, 10-GTVs, two separate implants each): plans met acceptable and ideal criteria in 100% and 43-100% respectively. Migration to single-dose treatment schedule was feasible in 7 implants (35%), without relaxing OAR's constraints or increasing the dose (D100% and D35%) to mpMRI-normal prostate (p>0.05). CONCLUSION: Focal ablative dose-escalated radiation is feasible with the proposed protocol. Prospective studies are warranted to determine the clinical outcomes.

Single-fraction flattening filter-free volumetric modulated arc therapy for lung cancer: Dosimetric results and comparison with flattened beams technique.

PURPOSE: To report on single-fraction stereotactic body radiotherapy (RT) (SBRT) with flattening filter (FF)-free (FFF) volumetric modulated arc therapy (VMAT) for lung cancer and to compare dosimetric results with VMAT with FF. METHODS AND MATERIALS: Overall, 25 patients were treated with 6-MV FFF VMAT (Varian TrueBeam STx LINAC) to a prescribed dose of 24Gy in a single fraction. Treatment plans were recreated using FF VMAT. Dose-volume indices, monitor units (MU), and treatment times were compared between FFF and FF VMAT techniques. RESULTS: Dose constraints to PTV, spinal cord, and lungs were reached in FFF and FF plans. In FFF plans, average conformity index was 1.13 (95% CI: 1.07 to1.38). Maximum doses to spinal cord, heart, esophagus, and trachea were 2.9Gy (95% CI: 0.4 to 6.7Gy), 0.8Gy (95% CI: 0 to 3.6Gy), 3.3Gy (95% CI: 0.02 to 13.9Gy), and 1.5Gy (95% CI: 0 to 4.9Gy), respectively. Average V7Gy, V7.4Gy, and mean dose to the healthy lung were 126.5cc (95% CI: 41.3 to 248.9cc), 107.3cc (95% CI: 18.7 to 232.8cc), and 1.1Gy (95% CI: 0.3 to 2.2Gy), respectively. No statistically significant differences were found in dosimetric results and MU between FF and FFF treatments. Treatment time was reduced by an average factor of 2.31 (95% CI: 2.15 to 2.43) from FF treatments to FFF, and the difference was statistically significant. CONCLUSIONS: FFF VMAT for lung SBRT provides equivalent dosimetric results to the target and organs at risk as FF VMAT while significantly reducing treatment time.

High Dose Rate Brachytherapy as a Treatment Option in Endobronchial Tumors.

Purpose. To report our experience with high dose rate endobronchial brachytherapy (HDR-EBBT) and to assess its efficacy and tolerability with possibility of its use in selected cases with curative intent. Method. Retrospective review of patients with endobronchial tumors treated at our institution in 2007-2013 with HDR-EBBT. Subjective response and treatment related toxicity were extracted from patients' records. Clinical response was evaluated by chest CT +/- bronchoscopy 2-3 months after treatment. Local control (LC) and overall survival (OS) were analyzed. Results. Overall 23 patients were identified. Ten patients were treated with curative intent, in 8 of them HDR-EBBT was combined with external beam radiotherapy. Short term palliation was as follows: dyspnea (13/15), cough (12/14), and hemoptysis (3/3). Seventeen patients were evaluated, of whom 9 (53%) showed complete response. Four patients developed local failure (only 1 of them treated with curative intent) and were salvaged with HDR-EBBT (n = 1), chemotherapy (n = 2), and laser (n = 1). Among patients treated with curative intent, the 2-year LC and OS were 89% and 67%, respectively, and 2 out of 4 deaths were cancer-related. Late toxicity included bronchial stenosis (n = 1). Only 1 patient had fatal hemoptysis and postmortem examination indicated local recurrence. Conclusion. HDR-EBBT is promising treatment with tolerable complication if used in properly selected patients.

Lessons learned using an MRI-only workflow during high-dose-rate brachytherapy for prostate cancer.

PURPOSE: We report clinical observations of a technique using an MRI-only workflow for catheter insertion and treatment planning in patients receiving standard-care high-dose-rate brachytherapy before external beam radiotherapy for prostate cancer. METHODS AND MATERIALS: Forty patients with intermediate or high-risk prostate cancer were enrolled on a prospective clinical trial approved by our institution's research ethics board. Multiparametric MRI with stereotactic navigation was used to guide insertion of brachytherapy catheters, followed by MRI-based treatment planning. RESULTS: Sixty-two implants were performed. Median catheter insertion + imaging time was 100 minutes, and overall anesthesia time was 4.0 hours (range, 2.1-6.9 hours). MRI at the time of brachytherapy restaged 14 patients (35%) who were found to have a higher stage of disease. In 6 patients, this translated in directed insertion of brachytherapy catheters outside the prostate boundary (extracapsular disease [n = 2] or seminal vesicle invasion [n = 4]). Most patients (80%) had gross tumor visible on MRI, which influenced catheter insertion and treatment planning. MRI depicted postimplant anatomic boundaries clearly, with the exception of the apical prostate which was blurred by trauma after catheter insertion. Conventional dose-planning objectives for the rectum (V75 < 1.0 cc) were difficult to achieve, but toxicities were low (acute grade ≥ 2 genitourinary = 20%, late grade ≥ 2 genitourinary = 15%, and late grade ≥ 2 gastrointestinal = 7%). Urethral trauma visualized on MRI led to two transient Grade 3 events. CONCLUSIONS: Despite a standard-care approach, MRI acquired throughout the procedure altered catheter insertion and dose-planning strategies. An MRI-only workflow is feasible but must be streamlined for broader acceptance.

A facility for magnetic resonance-guided radiation therapy.

Magnetic resonance (MR) imaging is routinely employed in the design of radiotherapy (RT) treatment plans for many disease sites. It is evident that tighter integration of MR imaging into the RT process would increase confidence in dose placement and facilitate the integration of new MR imaging information (including anatomical and functional imaging) into the therapy process. To this end, a dedicated MR-guided RT (MRgRT) facility has been created that integrates a state-of-the-art linear accelerator delivery system, high-dose rate brachytherapy afterloader, and superconducting MR scanner to allow MR-based online treatment guidance, adaptive replanning, and response monitoring while maintaining the clinical functionality of the existing delivery systems. This system is housed within a dedicated MRgRT suite and operates in a coordinated fashion to assure safe and efficient MRgRT treatments.