Dosimetric evaluation of dose shaping by adaptive aperture and its impact on plan quality.

Mevion's single-room HYPERSCAN proton therapy system employs a proton multileaf collimator called the adaptive aperture (AA), which collimates individual spots in the proton delivery as determined by the Treatment Planning System (TPS). The purpose of this study is to assess the dosimetric benefits of the AA, specifically in the dynamic aperture (DA) mode, and evaluate its impact on proton treatment plan quality as compared to a traditional pencil beam scanning (PBS) system (Varian ProBeam). The spot dose distributions with dynamic collimation (DA), a unique AA shape for each energy layer, and with static collimation (SA), a single AA collimation shape shared by all energy layers per field, were calculated and compared with the spot dose distribution of the Varian ProBeam proton therapy system. The lateral and distal dose falloff gradients and their dependence on air gap were evaluated quantitatively. Treatment plans for ten arbitrarily selected intracranial target image sets were created, and the HYPERSCAN and ProBeam beam models were compared. The spot sizes of the HYPERSCAN system are significantly larger than ProBeam system, especially at low energy. With the help of DA, the lateral dose penumbra of the HYPERSCAN is dramatically improved at lower energy and comparable at higher to ProBeam PBS beams. While the ProBeam spot size does not change with the air gap, beam penumbra of the HYPERSCAN with DA increases with the air gap. The distal dose falloff gradient for the HYPERSCAN with or without DA remains consistently around 4.8 mm through all energies due to the beamline design, not substantially varying with energy or air gap. Treatment plans of ten randomly selected intracranial cases demonstrated favorable OAR sparing but unfavorable dose uniformity for the HYPERSCAN with DA compared to ProBeam. Dose shaping by adaptive aperture substantially improves the lateral penumbra without a significant change in the distal dose gradient. The dose gradients of the multiple beam DA plans with layer-by-layer blocking are improved compared with SA plans and are close to the ProBeam plans for the ten randomly selected brain cases. With layer-by-layer DA blocking, the HYPERSCAN plans have similar plan conformality indices as the ProBeam plans, but the overall plan quality indices are lower than ProBeam plans, largely due to the lower dose homogeneity. In some cases, DA blocking was found to be superior in sparing OAR surrounding the target.

Targetability of cervical cancer by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated hyperthermia (HT) for patients receiving radiation therapy.

PURPOSE: To evaluate the targetability of late-stage cervical cancer by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-induced hyperthermia (HT) as an adjuvant to radiation therapy (RT). METHODS: Seventy-nine cervical cancer patients (stage IIIB-IVA) who received RT with lesions visible on positron emission tomography-computed tomography (PET-CT) were retrospectively analyzed for targetability using a commercially-available HT-capable MRgHIFU system. Targetability was assessed for both primary targets and/or any metastatic lymph nodes using both posterior (supine) and anterior (prone) patient setups relative to the transducer. Thirty-four different angles of rotation along subjects' longitudinal axis were analyzed. Targetability was categorized as: (1) Targetable with/without minimal intervention; (2) Not targetable. To determine if any factors could be used for prospective screening of patients, potential associations between demographic/anatomical factors and targetability were analyzed. RESULTS: 72.15% primary tumors and 33.96% metastatic lymph nodes were targetable from at least one angle. 49.37% and 39.24% of primary tumors could be targeted with patient laying in supine and prone positions, respectively. 25°-30° rotation and 0° rotation had the highest rate of the posterior and anterior targetability, respectively. The ventral depth of the tumor and its distance to the coccyx were statistically correlated with the anterior and posterior targetability, respectively. CONCLUSION: Most late-stage cervical cancer primaries were targetable by MRgHIFU HT requiring either no/minimal intervention. A rotation of 0° or 25°-30° relative to the transducer might benefit anterior and posterior targetability, respectively. Certain demographic/anatomic parameters might be useful in screening patients for treatability.

Characterization of Dosimetric Differences in Strut-Adjusted Volume Implant Treatment Plans Calculated With TG-43 Formalism and a Model-Based Dose Calculation Algorithm.

PURPOSE: To comprehensively characterize dosimetric differences between calculations with a commercial model-based dose calculation algorithm (MBDCA) and the TG-43 formalism in application to accelerated partial breast irradiation (APBI) with the strut-adjusted volume implant (SAVI) applicator. METHODS: Dose for 100 patients treated with the SAVI applicator was recalculated with an MBDCA for comparison to dose calculated via TG-43. For every pair of dose calculations, dose-volume histogram (DVH) metrics including V90%, V95%, V100%, V150%, and V200% for the PTV_EVAL were compared. Features were defined for each case including (1) applicator size, (2) ratio between PTV_EVAL contour and 1-cm rind surrounding SAVI applicator, (3) ratio between dwell time in central catheter and total dwell time, and (4) mean computed tomography (CT) number within the lumpectomy cavity. Wilcoxon rank sum tests were performed to test whether treatment plans could be stratified according to feature values into groups with statistically significant dosimetry differences between MBDCA and TG-43. RESULTS: For all DVH metrics, differences between TG-43 and MBDCA calculations were statistically significant (P < .05). Minimum (maximum) relative percent differences between the MBDCA and TG-43 for V90%, V95%, and V100% were -2.1% (0.1%), -3.1% (-0.1%), and -5.0% (-0.5%), respectively. The median relative percent difference in mean PTV_EVAL dose between the MBDCA and TG-43 was -3.9%, with minimum (maximum) difference of -6.5% (-1.8%). For V90%, V95%, and V100%, plan quality worsened beyond defined thresholds in 26, 23, and 31 cases with no instances of coverage improvement. Features 1, 2, and 4 were shown to be able to stratify treatment plans into groups with statistically significant differences in dosimetry metrics between MBDCA and TG-43. CONCLUSIONS: Investigated dose metrics for SAVI treatments were found to be systematically lower with MBDCA calculation in comparison to TG-43. Plans could be stratified according to several features by the magnitude of dosimetric differences between these calculations.

Initial experience and lessons learned with implementing Lutetium-177-dotatate radiopharmaceutical therapy in a radiation oncology-based program.

PURPOSE: To assist radiation oncology centers in implementing Lutetium-177-dotatate (177Lu) radiopharmaceutical therapy for midgut neuroendocrine tumors. Here we describe our workflow and how it was revised based on our initial experience on an expanded access protocol (EAP). METHODS: A treatment team/area was identified. An IV-pump-based infusion technique was implemented. Exposure-based techniques were implemented to determine completion of administration, administered activity, and patient releasability. Acute toxicities were assessed at each fraction. A workflow failure modes and effects analysis (FMEA) was performed. RESULTS: A total of 22 patients were treated: 11 patients during EAP (36 administrations) and 11 patients after EAP (44 administrations). Mean 177Lu infusion time was 37 min (range 26-65 min). Mean administered activity was 97% (range 90-99%). Mean patient exposures at 1 m were 1.9 mR/h (range 1.0-4.1 mR/h) post-177Lu and 0.9 mR/h (range 0.4-1.8 mR/h) at discharge, rendering patients releasable with instructions. Treatment area was decontaminated and released same day. All patients in the EAP experienced nausea, and nearly half experienced emesis despite premedication with antiemetics. Peripheral IV-line complications occurred in six treatments (16.7%), halting administration in 2 cases (5.6%). We transitioned to peripherally inserted central catheter (PICC)-lines and revised amino acid formulary after the EAP. The second cohort of 11 patients after EAP were analyzed for PICC-line complications and acute toxicity. Nausea and emesis rates decreased (nausea G1+ 61%-27%; emesis G1+ 23%-7%), and no PICC complications were observed. FMEA revealed that a failure in amino acid preparation was the highest risk. CONCLUSION: 177Lu-dotatate can be administered safely in an outpatient radiation oncology department.

Characterization of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-induced large-volume hyperthermia in deep and superficial targets in a porcine model.

PURPOSE: To characterize temperature fields and tissue damage profiles of large-volume hyperthermia (HT) induced by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) in deep and superficial targets in vivo in a porcine model. METHODS: Nineteen HT sessions were performed in vivo with a commercial MRgHIFU system (Sonalleve® V2, Profound Medical Inc., Mississauga, ON, Canada) in hind leg muscles of eight pigs with temperature fields of cross-sectional diameter of 58-mm. Temperature statistics evaluated in the target region-of-interest (tROI) included accuracy, temporal variation, and uniformity. The impact of the number and location of imaging planes for feedback-based temperature control were investigated. Temperature fields were characterized by time-in-range (TIR, the duration each voxel stays within 40-45 °C) maps. Tissue damage was characterized by contrast-enhanced MRI, and macroscopic and histopathological analysis. The performance of the Sonalleve® system was benchmarked against a commercial phantom. RESULTS: Across all HT sessions, the mean difference between the average temperature (Tavg) and the desired temperature was -0.4 ± 0.5 °C; the standard deviation of temperature 1.2 ± 0.2 °C; the temporal variation of Tavg for 30-min HT was 0.6 ± 0.2 °C, and the temperature uniformity was 1.5 ± 0.2 °C. A difference of 2.2-cm (in pig) and 1.5-cm (in phantom) in TIR dimensions was observed when applying feedback-based plane(s) at different locations. Histopathology showed 62.5% of examined HT sessions presenting myofiber degeneration/necrosis within the target volume. CONCLUSION: Large-volume MRgHIFU-mediated HT was successfully implemented and characterized in a porcine model in deep and superficial targets in vivo with heating distributions modifiable by user-definable parameters.

Predictors of Distant Metastases in Triple-Negative Breast Cancer Without Pathologic Complete Response After Neoadjuvant Chemotherapy.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) predicts decreased distant metastasis. However, most patients do not experience pCR, and other risk factors for distant metastasis after NAC are poorly characterized. This study investigated factors predictive of distant metastasis in TNBC without pCR after NAC. METHODS: Women with TNBC treated with NAC, surgery, and radiation therapy in 2000 through 2013 were reviewed. Freedom from distant metastasis (FFDM) was compared between patients with and without pCR using the Kaplan-Meier method. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of distant metastasis. RESULTS: We identified 153 patients with median follow-up of 4.0 years (range, 0.5-14.0 years). After NAC, 108 had residual disease (pCR, 29%). Five-year FFDM was 98% and 55% in patients with and without pCR, respectively (P<.001). Factors independently predicting FFDM in patients without pCR were pathologic nodal positivity (hazard ratio, 3.08; 95% CI, 1.54-6.14; P=.001) and lymphovascular space invasion (hazard ratio, 1.91; 95% CI, 1.07-3.43; P=.030). Patients with a greater number of factors had worse FFDM; 5-year FFDM was 76.5% for patients with no factors (n=38) versus 54.9% and 27.5% for patients with 1 (n=44) and 2 factors (n=26), respectively (P<.001). CONCLUSIONS: Lack of pCR after NAC resulted in worse overall survival and FFDM, despite trimodality therapy. In patients with residual disease after NAC, pathologic lymph node positivity and lymphovascular space invasion predicted worse FFDM.

Long-Term Outcomes with 3-Dimensional Conformal External Beam Accelerated Partial Breast Irradiation.

PURPOSE: Long-term tumor control and cosmetic outcomes for accelerated partial breast radiation (APBI) delivered with 3-dimensional conformal external beam radiation (3D-CRT) remain limited. We seek to address these concerns by reporting our experience of 3D-CRT APBI with extended follow-up. METHODS AND MATERIALS: All patients treated with APBI delivered with 3D-CRT from January 2006 through December 2012 at a single institution were identified. Those with more than a year of follow-up were analyzed for ipsilateral breast tumor recurrence (IBTR), progression-free survival (PFS), cosmesis, and pain. Disease outcomes were analyzed by margin status (<2 mm, ≥2 mm), total radiation dose prescribed, presence of invasive disease, and American Society for Radiation Oncology (ASTRO) 2016 updated consensus groupings (suitable, cautionary, and unsuitable). RESULTS: Two hundred ninety-three patients were identified, of whom 266 had >1 year of follow-up. Median follow-up was 87 months (range, 13-156). Of the 266, 162 (60.9%) were ASTRO "suitable," 87 (32.7%) were "cautionary," and 17 (6.4%) were "unsuitable." Seven-year rates of IBTR and PFS were 1.8% and 95.2%, respectively. Margin status, invasive versus in situ disease, prescribed dose, and ASTRO grouping were not prognostic for either IBTR or PFS on univariate analysis. Cosmesis was good to excellent in 75.2%. Two patients (0.8%) had subsequent plastic surgery owing to poor cosmesis. Narcotic medication for treatment site pain was needed by 6 (2.3%). CONCLUSIONS: External beam APBI results in excellent long-term disease control. Good to excellent cosmetic outcomes are achieved in most patients, although increasing dose per fraction and greater percentage of irradiated breast were predictive of adverse posttreatment cosmetic outcomes. Select patients in "cautionary" and "unsuitable" consensus groupings do not appear to have inferior outcomes.

Feasibility and safety assessment of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated mild hyperthermia in pelvic targets evaluated using an in vivo porcine model.

Purpose: To evaluate the feasibility and assess safety parameters of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated hyperthermia (HT; heating to 40-45 °C) in various pelvic targets in a porcine model in vivo.Methods: Thirteen HT treatments were performed in six pigs with a commercial MRgHIFU system (Sonalleve V2, Profound Medical Inc., Mississauga, Canada) to muscle adjacent to the ventral/dorsal bladder wall and uterus to administer 42 °C (±1°) for 30 min (±5%) using an 18-mm target diameter and 100 W power. Feasibility was assessed using accuracy, uniformity, and MR-thermometry performance-based metrics. Safety parameters were assessed for tissues in the targets and beam-path by contrast-enhanced MRI, gross-pathology and histopathology.Results: Across all HT sessions, the mean difference between average temperature (Tavg) and the target temperature within the target region-of-interest (tROI, the cross-section of the heated volume at focal depth) was 0.51 ± 0.33 °C. Within the tROI, the temperature standard deviation averaged 1.55 ± 0.31 °C, the average 30-min Tavg variation was 0.80 ± 0.17 °C, and the maximum difference between Tavg and the 10th- or 90th-percentile temperature averaged 2.01 ± 0.44 °C. The average time to reach ≥41 °C and cool to ≤40 °C within the tROI at the beginning and end of treatment was 47.25 ± 27.47 s and 66.37 ± 62.68 s, respectively. Compared to unheated controls, no abnormally-perfused tissue or permanent damage was evident in the MR images, gross pathology or histological analysis.Conclusions: MRgHIFU-mediated HT is feasible and safety assessment is satisfactory for treating an array of clinically-mimicking pelvic geometries in a porcine model in vivo, implying the technique may have utility in treating pelvic targets in human patients.

Ultrasound Hyperthermia Technology for Radiosensitization.

Hyperthermia therapy (HT) raises tissue temperature to 40-45°C for up to 60 min. Hyperthermia is one of the most potent sensitizers of radiation therapy (RT). Ultrasound-mediated HT for radiosensitization has been used clinically since the 1960s. Recently, magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU), which has been approved by the United States Food and Drug Administration for thermal ablation therapy, has been adapted for HT. With emerging clinical trials using MRgHIFU HT for radiosensitization, there is a pressing need to review the ultrasound HT technology. The objective of this review is to overview existing HT technology, summarize available ultrasound HT devices, evaluate clinical studies combining ultrasound HT with RT and discuss challenges and future directions.

Standardization and automation of quality assurance for high-dose-rate brachytherapy planning with application programming interface.

PURPOSE: To standardize and automate the high-dose-rate (HDR) brachytherapy planning quality assurance (QA) process utilizing scripting with application programming interface (API) in a commercially available treatment planning system (TPS). METHODS AND MATERIALS: Site- and applicator-dependent plan quality (PQ) evaluation criteria and plan integrity (PI) checklists were established based on published guidelines, clinical protocols, and institutional experience. User designed C# programs ("scripts") were created and executed through the API to access planning information in TPS. A set of standardized quality control reports, focusing on PQ evaluations and PI checks, were automatically generated. Information derived from the TPS was compared against predetermined QA metrics with color-coded pass/fail indicators to aid and enhance the efficiency of plan evaluation. Five independent, blinded observers reviewed mock plans with simulated errors to validate the scripts and to quantify the improvement of plan review efficiency. RESULTS: Scripts were developed for HDR prostate and breast. Forty-one parameters were reported/checked in the PI report; the PQ report returned dose-volume indices and an independent check of dwell time. All simulated errors were detected by the PI scripts with appropriate warning messages displayed, and any values failing to meet the planning constraints were red-flagged successfully in the PQ report. An average time reduction of 16 min for plan review was observed when using the scripts. CONCLUSIONS: API scripting-based automated planning QA for HDR brachytherapy including PI checks and PQ evaluations was designed and implemented. The simulated error study showed promising results in terms of error catching and efficiency improvement.

A convenient, reliable, and fast acoustic pressure field measurement method for magnetic resonance-guided high-intensity focused ultrasound systems with phased array transducers.

BACKGROUND: With the expanding applications of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU), there is an urgent need for a convenient, reliable, and fast acoustic pressure field measurement method to aid treatment protocol design, ensure consistent and safe operation of the transducer, and facilitate regulatory approval of new techniques. Herein, we report a method for acoustic pressure field characterization of MR-HIFU systems with multi-element phased array transducers. This method integrates fiber-optic hydrophone measurements and electronic steering of the ultrasound beam with MRI-assisted HIFU focus alignment to the fiber tip. METHODS: A clinical MR-HIFU system (Sonalleve V2, Profound Medical Inc., Mississauga, Canada) was used to assess the proposed method. A fiber-optic hydrophone was submerged in a degassed water bath, and the fiber tip location was traced using MRI. Subsequently, the nominal transducer focal point indicated on the MR-HIFU therapy planning software was positioned at the fiber tip, and the HIFU focus was electronically steered around the fiber tip within a 3D volume for 3D pressure field mapping, eliminating the need for an additional, expensive, and MRI-compatible 3D positioning stage. The peak positive and negative pressures were measured at the focus and validated using a standard hydrophone measurement setup outside the MRI magnet room. RESULTS: We found that the initial MRI-assisted HIFU focus alignment had an average offset of 2.23 ± 1.33 mm from the fiber tip as identified by the 3D pressure field mapping. MRI guidance and electronic beam steering allowed 3D focus localization within ~ 1 h, i.e., faster than the typical time required using the standard laboratory setup (~ 3-4 h). Acoustic pressures measured using the proposed method were not significantly different from those obtained with the standard laboratory hydrophone measurements. CONCLUSIONS: In conclusion, our method offers a convenient, reliable, and fast acoustic pressure field characterization tool for MR-HIFU systems with phased array transducers.

Evaluation and selection of anatomic sites for magnetic resonance imaging-guided mild hyperthermia therapy: a healthy volunteer study.

PURPOSE: Since mild hyperthermia therapy (MHT) requires maintaining the temperature within a narrow window (e.g. 40-43 °C) for an extended duration (up to 1 h), accurate and precise temperature measurements are essential for ensuring safe and effective treatment. This study evaluated the precision and accuracy of MR thermometry in healthy volunteers at different anatomical sites for long scan times. METHODS: A proton resonance frequency shift method was used for MR thermometry. Eight volunteers were subjected to a 5-min scanning protocol, targeting chest wall, bladder wall, and leg muscles. Six volunteers were subjected to a 30-min scanning protocol and three volunteers were subjected to a 60-min scanning protocol, both targeting the leg muscles. The precision and accuracy of the MR thermometry were quantified. Both the mean precision and accuracy <1 °C were used as criteria for acceptable thermometry. RESULTS: Drift-corrected MR thermometry measurements based on 5-min scans of the chest wall, bladder wall, and leg muscles had accuracies of 1.41 ± 0.65, 1.86 ± 1.20, and 0.34 ± 0.44 °C, and precisions of 2.30 ± 1.21, 1.64 ± 0.56, and 0.48 ± 0.05 °C, respectively. Measurements based on 30-min scans of the leg muscles had accuracy and precision of 0.56 ± 0.05 °C and 0.42 ± 0.50 °C, respectively, while the 60-min scans had accuracy and precision of 0.49 ± 0.03 °C and 0.56 ± 0.05 °C, respectively. CONCLUSIONS: Respiration, cardiac, and digestive-related motion pose challenges to MR thermometry of the chest wall and bladder wall. The leg muscles had satisfactory temperature accuracy and precision per the chosen criteria. These results indicate that extremity locations may be preferable targets for MR-guided MHT using the existing MR thermometry technique.

Efficiency of using the day-of-implant CT for planning of SAVI APBI.

PURPOSE: The purpose of the study was to develop an optimized, efficient workflow for using the day-of-implant (DOI) CT for treatment planning of accelerated partial breast irradiation brachytherapy using the strut-adjusted volume implant (SAVI) device. METHODS AND MATERIALS: For 62 consecutive SAVI patients, a DOI CT was acquired and used for treatment planning. A "verification" CT was acquired 24-72 h after implant and immediately before the first fraction, then registered to the DOI CT. If the DOI CT-based plan was no longer optimal, a replan was performed. An array of metrics describing the geometry of the device and its relative position in the patient from the DOI CTs for these patients was collected. These metrics from the DOI CT were evaluated to determine what features could predict for the need to replan before the first treatment fraction. Logistical regression analysis including χ2 tests was used to determine if different factors correlated with replanning. RESULTS: Twenty-two of 62 patients (35%) required replanning. Only the presence of splayed struts, where splay was toward the skin, and the use of a nine strut ("8-1") SAVI were significantly correlated (p < 0.05) with replanning. Within these individual populations, no additional factors showed a significant statistical correlation for requiring replanning. CONCLUSIONS: For strut-based accelerated partial breast irradiation brachytherapy, it was feasible to treat with a plan based on the DOI CT for a majority (65%) of patients. Some factors correlate to needing replanning; recognizing these could be used to optimize treatment workflow for certain patients, increasing clinical efficiency while enhancing the quality of patient care.

Acoustic field characterization of a clinical magnetic resonance-guided high-intensity focused ultrasound system inside the magnet bore.

PURPOSE: With the expanding clinical application of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU), acoustic field characterization of MR-HIFU systems is needed for facilitating regulatory approval and ensuring consistent and safe power output of HIFU transducers. However, the established acoustic field measurement techniques typically use equipment that cannot be used in a magnetic resonance imaging (MRI) suite, thus posing a challenge to the development and execution of HIFU acoustic field characterization techniques. In this study, we developed and characterized a technique for HIFU acoustic field calibration within the MRI magnet bore, and validated the technique with standard hydrophone measurements outside of the MRI suite. METHODS: A clinical Philips MR-HIFU system (Sonalleve V2, Philips, Vantaa, Finland) was used to assess the proposed technique. A fiber-optic hydrophone with a long fiber was inserted through a 24-gauge angiocatheter and fixed inside a water tank that was placed on the HIFU patient table above the acoustic window. The long fiber allowed the hydrophone control unit to be placed outside of the magnet room. The location of the fiber tip was traced on MR images, and the HIFU focal point was positioned at the fiber tip using the MR-HIFU therapy planning software. To perform acoustic field mapping inside the magnet, the HIFU focus was positioned relative to the fiber tip using an MRI-compatible 5-axis robotic transducer positioning system embedded in the HIFU patient table. To perform validation measurements of the acoustic fields, the HIFU table was moved out of the MRI suite, and a standard laboratory hydrophone measurement setup was used to perform acoustic field measurements outside the magnetic field. RESULTS: The pressure field scans along and across the acoustic beam path obtained inside the MRI bore were in good agreement with those obtained outside of the MRI suite. At the HIFU focus with varying nominal acoustic powers of 10-500 W, the peak positive pressure and peak negative pressure measured inside the magnet bore were 3.87-68.67 MPa and 3.56-12.06 MPa, respectively, while outside the MRI suite the corresponding pressures were 3.27-67.32 MPa and 3.06-12.39 MPa, respectively. There was no statistically significant difference (P > 0.05) between measurements inside the magnet bore and outside the MRI suite for the p+ and p- at any acoustic power level. The spatial-peak pulse-average intensities (ISPPA ) for these powers were 312-17816 W/cm2 and 220-15698 W/cm2 for measurements inside and outside the magnet room, respectively. In addition, when the scanning step size of the HIFU focus was increased from 100 µm to 500 µm, the execution time for scanning a 4 × 4 mm2 area decreased from 210 min to 10 min, the peak positive pressure decreased by 14%, the peak negative pressure decreased by 5%, and the lateral full width at half maximum dimension of pressure profiles increased from 1.15 mm to 1.55 mm. CONCLUSIONS: The proposed hydrophone measurement technique offers a convenient and reliable method for characterizing the acoustic fields of clinical MR-HIFU systems inside the magnet bore. The technique was validated for use by measurements outside the MRI suite using a standard hydrophone calibration technique. This technique can be a useful tool in MR-HIFU quality assurance and acoustic field assessment.

Process improvement for the safe delivery of multidisciplinary-executed treatments-A case in Y-90 microspheres therapy.

PURPOSE: To develop a safe and robust workflow for yttrium-90 (Y-90) radioembolization procedures in a multidisciplinary team environment. METHODS AND MATERIALS: A generalized Define-Measure-Analyze-Improve-Control (DMAIC)-based approach to process improvement was applied to a Y-90 radioembolization workflow. In the first DMAIC cycle, events with the Y-90 workflow were defined and analyzed. To improve the workflow, a web-based interactive electronic white board (EWB) system was adopted as the central communication platform and information processing hub. The EWB-based Y-90 workflow then underwent a second DMAIC cycle. Out of 245 treatments, three misses that went undetected until treatment initiation were recorded over a period of 21 months, and root-cause-analysis was performed to determine causes of each incident and opportunities for improvement. The EWB-based Y-90 process was further improved via new rules to define reliable sources of information as inputs into the planning process, as well as new check points to ensure this information was communicated correctly throughout the process flow. RESULTS: After implementation of the revised EWB-based Y-90 workflow, after two DMAIC-like cycles, there were zero misses out of 153 patient treatments in 1 year. CONCLUSIONS: The DMAIC-based approach adopted here allowed the iterative development of a robust workflow to achieve an adaptable, event-minimizing planning process despite a complex setting which requires the participation of multiple teams for Y-90 microspheres therapy. Implementation of such a workflow using the EWB or similar platform with a DMAIC-based process improvement approach could be expanded to other treatment procedures, especially those requiring multidisciplinary management.

Accelerated partial breast irradiation dosimetric criteria for the strut-adjusted volume implant.

PURPOSE: Current guidelines for high-dose-rate accelerated partial breast irradiation using single-entry implants are based on the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol, which assumed a balloon implant geometry. We have developed robust plan evaluation criteria specifically for the strut-adjusted volume implant (SAVI). METHODS AND MATERIALS: Plan evaluation criteria were established using a "training data set" of 62 SAVI treatment plans and included the percentage volume of target receiving 90%, 95%, and 100% of the prescription dose (V90, V95, and V100), the absolute volume of target receiving 150% and 200% of prescription (V150 and V200), and the maximum doses to skin (Dskin max) and ribs (Drib max). "Ideal" and "expected" (routinely achievable) thresholds were determined for each criterion and compared to B-39 guidelines. A "test data set" collected from the next 25 patients was analyzed using the developed plan evaluation criteria. RESULTS: Ideal (expected) dosimetric thresholds established from the training data set were V90 ≥ 98% (95%), V95 ≥ 95% (92%), V100 ≥ 91% (88%), Dskin max < 90% (100%), and Drib max < 100%. Thresholds for V150 and V200 were stratified by SAVI size: V150 ≤ 30 cc (50 cc) and V200 ≤ 15 cc (20 cc) for 6-1 and Mini; V150 ≤ 50 cc (50 cc) and V200 ≤ 20 cc (20 cc) for 8-1 and 10-1. There was no significant difference between the training and test data sets in the fractions of patients meeting the criteria. Overall, 58% and 95% of 87 plans met all ideal and all expected criteria, respectively. CONCLUSIONS: The plan evaluation criteria developed specifically for the SAVI device are robust, providing increased target coverage and increased skin sparing compared to B-39 guidelines.

Accelerated Partial Breast Irradiation: A Safe, Effective, and Convenient Early Breast Cancer Treatment Option.

Accelerated partial breast irradiation (APBI) is an excellent treatment option for many women with early stage breast cancer. Patient selection criteria include age over 40, status post lumpectomy, breast cancer (invasive or in situ disease) measuring <3 cm, negative margins (at least 2 mm), negative lymph nodes, and no lymphovascular space invasion. APBI is effective, well tolerated, and convenient. Women with early stage breast cancer and theii caregivers should be aware of this potential treatment option.

The potential of iodine for improving breast cancer diagnosis and treatment.

Early detection through modalities such as mammography remains pivotal in the fight against breast cancer. The detectability of breast cancer through mammography is rooted in the differential X-ray attenuation properties of cancerous and normal breast tissue. An unexplored component of the X-ray contrast between fibrous breast tissue and similarly composed tumor tissue is the presence of naturally localized iodine in the cancer but not healthy breast tissue. It is hypothesized that differing amounts of iodine are present in tumor versus normal breast tissue that leads to more easily detectable cancer due to an increased Z value of the tumor tissue relative to the healthy tissue, which results in enhanced differences in X-ray attenuation properties between the two tissues and thus greater radiographic contrast. The hypothesis is supported by experimental observations explaining how iodine could localize in the tumor tissue but not surrounding healthy tissue. Breast cancer cells express the sodium-iodide symporter (NIS), an ion pump which sequesters iodine in tumor cells. Healthy non-lactating breast tissue, in contrast, does not express NIS. Further evidence for the differential expression of NIS resulting in X-ray contrast enhancement in breast cancer is the established correlation between expression of insulin growth factor (IGF) and enhanced X-ray contrast, and the evidence that IGF is a promoter for NIS. Ultimately, if the expression of iodine can be shown to be a component of radiographic contrast between healthy and tumor breast tissue, this could be used to drive the development of new technology and techniques for use in the detection and treatment of breast cancer. The proof of this hypothesis could thus have a substantial impact in the fight against breast cancer.

Practical methods for improving dose distributions in Monte Carlo-based IMRT planning of lung wall-seated tumors treated with SBRT.

Current commercially available planning systems with Monte Carlo (MC)-based final dose calculation in IMRT planning employ pencil-beam (PB) algorithms in the optimization process. Consequently, dose coverage for SBRT lung plans can feature cold-spots at the interface between lung and tumor tissue. For lung wall (LW)-seated tumors, there can also be hot spots within nearby normal organs (example: ribs). This study evaluated two different practical approaches to limiting cold spots within the target and reducing high doses to surrounding normal organs in MC-based IMRT planning of LW-seated tumors. First, "iterative reoptimization", where the MC calculation (with PB-based optimization) is initially performed. The resultant cold spot is then contoured and used as a simultaneous boost volume. The MC-based dose is then recomputed. The second technique uses noncoplanar beam angles with limited path through lung tissue. Both techniques were evaluated against a conventional coplanar beam approach with a single MC calculation. In all techniques the prescription dose was normalized to cover 95% of the PTV. Fifteen SBRT lung cases with LW-seated tumors were planned. The results from iterative reoptimization showed that conformity index (CI) and/or PTV dose uniformity (UPTV) improved in 12/15 plans. Average improvement was 13%, and 24%, respectively. Nonimproved plans had PTVs near the skin, trachea, and/or very small lung involvement. The maximum dose to 1cc volume (D1cc) of surrounding OARs decreased in 14/15 plans (average 10%). Using noncoplanar beams showed an average improvement of 7% in 10/15 cases and 11% in 5/15 cases for CI and UPTV, respectively. The D1cc was reduced by an average of 6% in 10/15 cases to surrounding OARs. Choice of treatment planning technique did not statistically significantly change lung V5. The results showed that the proposed practical approaches enhance dose conformity in MC-based IMRT planning of lung tumors treated with SBRT, improving target dose coverage and potentially reducing toxicities to surrounding normal organs.

Part II. Initial molecular and cellular characterization of high nitric oxide-adapted human tongue squamous cell carcinoma cell lines.

It is not understood why some head and neck squamous cell carcinomas, despite having identical morphology, demonstrate different tumor aggressiveness, including radioresistance. High levels of the free radical nitric oxide (NO) and increased expression of the NO-producing enzyme nitric oxide synthase (NOS) have been implicated in tumor progression. We previously adapted three human tongue cancer cell lines to high NO (HNO) levels by gradually exposing them to increasing concentrations of an NO donor; the HNO cells grew faster than their corresponding untreated ("parent") cells, despite being morphologically identical. Herein we initially characterize the HNO cells and compare the biological properties of the HNO and parent cells. HNO/parent cell line pairs were analyzed for cell cycle distribution, DNA damage, X-ray and ultraviolet radiation response, and expression of key cellular enzymes, including NOS, p53, glutathione S-transferase-pi (GST-pi), apurinic/apyrimidinic endonuclease-1 (APE1), and checkpoint kinases (Chk1, Chk2). While some of these properties were cell line-specific, the HNO cells typically exhibited properties associated with a more aggressive behavior profile than the parent cells (greater S-phase percentage, radioresistance, and elevated expression of GST-pi/APE1/Chk1/Chk2). To correlate these findings with conditions in primary tumors, we examined the NOS, GST-pi, and APE1 expression in human tongue squamous cell carcinomas. A majority of the clinical samples exhibited elevated expression levels of these enzymes. Together, the results herein suggest cancer cells exposed to HNO levels can develop resistance to free radicals by upregulating protective mechanisms, such as GST-pi and APE1. These upregulated defense mechanisms may contribute to their aggressive expression profile.