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A clinically observed discrepancy between image-based and log-based MLC positions

Purpose: To present a clinical case in which real-time intratreatment imaging identified an multileaf collimator (MLC) leaf to be consistently deviating from its programmed and logged position by >1 mm. Methods: An EPID-based exit-fluence dosimetry system designed to prevent gross delivery errors was used to capture cine during treatment images. The author serendipitously visually identified a suspected MLC leaf displacement that was not otherwise detected. The leaf position as recorded on the EPID images was measured and log-files were analyzed for the treatment in question, the prior day’s treatment, and for daily MLC test patterns acquired on those treatment days. Additional standard test patterns were used to quantify the leaf position. Results: Whereas the log-file reported no difference between planned and recorded positions, image-based measurements showed the leaf to be 1.3 ± 0.1 mm medial from the planned position. This offset was confirmed with the test pattern irradiations. Conclusions: It has been clinically observed that log-file derived leaf positions can differ from their actual position by >1 mm, and therefore cannot be considered to be the actual leaf positions. This cautions the use of log-based methods for MLC or patient quality assurance without independent confirmation of log integrity. Frequent verification of MLC positions through independent means is a necessary precondition to trust log-file records. Intratreatment EPID imaging provides a method to capture departures from MLC planned positions.

60 APPLIED LIFE SCIENCES↗

Resolving the Issues with Flywheel Position Sensors

For the past few years, the Advanced Electrical Systems Branch here at NASA Glenn has been pursuing research in the area of flywheels. The purpose of these pursuits has been t o explore the potential for flywheels to replace current battery-powered systems in space. So far it has been learned that flywheels offer large momentum storage capacity, comparatively small volume, high durability, and near- complete discharge capabilities, all of which are advancements over the existing nickel hydrogen and nickel cadmium batteries. Another significant advantage of flywheels is the potential they offer for combining the function of attitude control with energy storage. During the summer of 2004, I worked with Dr. Barbara Kenny in the Advanced Electrical Systems Branch, supporting the work she is doing by analyzing and testing some new components for the new Generation-2 flywheel. To monitor the speed and angular position of the flywheel rotor, a once-around (OAR) signal along with a sensorless algorithm is used. The OAR signal is used for the magnetic bearings that keep the flywheel suspended for frictionless operation. The sensorless algorithm is used for the flywheel motor/generator control. The OAR is generated from position sensors that monitor a circular plate. The plate has a cut down the middle such that one half of the circle is on a slightly lower level than the other. Every half-turn, or 180, the sensors detect the "cut" on the plate, and trigger the OAR, telling the computer that the rotor has made half a revolution. This, however, doesn't provide needed detailed information about the angular position of the rotor, since it only provides a signal alert every half- revolution. This is enough information for the magnetic bearing control but is insufficient for the motor/generator control. A new resolver was designed such that it would give continuous angle information rather than the 180 degree information of the OAR. The new resolver has two separate observable pieces: a flat middle section to monitor vertical motion, and an angled section around the circumference, which, when observed from above, produces a sine-wave displacement through the entire 360" revolution. My first job when I arrived this summer was to calibrate the sensors that would be mounted on the inside of the flywheel casing to monitor the position (angular and vertical) of the shaft. After calibration, I used the sensors to evaluate voltage outputs created by position differences between two pairs of sensors on the angled portion of the resolver for eight different angular positions, moving the resolver vertically and laterally through its entire potential range of motion. The results of these tests will be used to determine the rotor angular (and axial) position from the sensor readings once the new flywheel unit is assembled. The sensorless algorighm mentioned above consists of two operations: the signal injection method and the back electro-motive force (EMF). The signal injection is meant to work at low speeds, while the back EMF algorithm is meant to work at higher speeds. Both work together to determine the correct estimate of rotor position and speed based on the measured motor/generator current. It was determined that we wanted to know exactly how accurate our estimation methods were, and so a resolver (a commercially available mechanical sensor mounted to the motor/generator shaft to measure rotor position and speed) and a "Resolver to Digital" (R2D) circuit board was purchased to make the comparison to the existing estimation. My work related to the R2D board has included the following: creating two connector cables (one to power the circuit and one to get readable output off the board), writing Simulink code to process the board's output, and building a dSpace panel to control and monitor the circuit. The next step in the process will be to perform tests to compare the estimated rotor position and speed from the sensorless algorithm to the actual rotor and speed from the resolver signal.

Fehrmann, Elizabeth A.↗

Development of Position-Sensitive Magnetic Calorimeters for X-Ray Astronomy

Metallic magnetic calorimeters (MMC) are one of the most promising devices to provide very high energy resolution needed for future astronomical x-ray spectroscopy. MMC detectors can be built to large detector arrays having thousands of pixels. Position-sensitive magnetic (PoSM) microcalorimeters consist of multiple absorbers thermally coupled to one magnetic micro calorimeter. Each absorber element has a different thermal coupling to the MMC, resulting in a distribution of different pulse shapes and enabling position discrimination between the absorber elements. PoSMs therefore achieve the large focal plane area with fewer number of readout channels without compromising spatial sampling. Excellent performance of PoSMs was achieved by optimizing the designs of key parameters such as the thermal conductance among the absorbers, magnetic sensor, and heat sink, as well as the absorber heat capacities. Micro fab ri - cation techniques were developed to construct four-absorber PoSMs, in which each absorber consists of a two-layer composite of bismuth and gold. The energy resolution (FWHM full width at half maximum) was measured to be better than 5 eV at 6 keV x-rays for all four absorbers. Position determination was demonstrated with pulse-shape discrimination, as well as with pulse rise time. X-ray microcalorimeters are usually designed to thermalize as quickly as possible to avoid degradation in energy resolution from position dependence to the pulse shapes. Each pixel consists of an absorber and a temperature sensor, both decoupled from the cold bath through a weak thermal link. Each pixel requires a separate readout channel; for instance, with a SQUID (superconducting quantum interference device). For future astronomy missions where thousands to millions of resolution elements are required, having an individual SQUID readout channel for each pixel becomes difficult. One route to attaining these goals is a position-sensitive detector in which a large continuous or pixilated array of x-ray absorbers shares fewer numbers of temperature sensors. A means of discriminating the signals from different absorber positions, however, needs to be built into the device for each sensor. The design concept for the device is such that the shape of the temperature pulse with time depends on the location of the absorber. This inherent position sensitivity of the signal is then analyzed to determine the location of the event precisely, effectively yielding one device with many sub-pixels. With such devices, the total number of electronic channels required to read out a given number of pixels is significantly reduced. PoSMs were developed that consist of four discrete absorbers connected to a single magnetic sensor. The design concept can be extended to more than four absorbers per sensor. The thermal conductance between the sensor and each absorber is different by design and consequently, the pulse shapes are different depending upon which absorber the xrays are received, allowing position discrimination. A magnetic sensor was used in which a paramagnetic Au:Er temperature-sensitive material is located in a weak magnetic field. Deposition of energy from an x-ray photon causes an increase in temperature, which leads to a change of magnetization of the paramagnetic sensor, which is subsequently read out using a low noise dc-SQUID. The PoSM microcalorimeters are fully microfabricated: the Au:Er sensor is located above the meander, with a thin insulation gap in between. For this position-sensitive device, four electroplated absorbers are thermally linked to the sensor via heat links of different thermal conductance. One pixel is identical to that of a single-pixel design, consisting of an overhanging absorber fabricated directly on top of the sensor. It is therefore very strongly thermally coupled to it. The three other absorbers are supported directly on a silicon-nitride membrane. These absorbers are thermally coupled to the sensor via Ti (5 nm)/Au250 nm) metal links. The strength of the links is parameterized by the number of gold squares making up the link. For detector performance, experimentally different pulse-shapes were demonstrated with 6 keV x-rays, which clearly show different rise times for different absorber positions. For energy resolution measurement, the PoSM was operated at 32 mK with an applied field that was generated using a persistent current of 50 mA. Over the four pixels, energy resolution ranges from 4.4 to 4.7 eV were demonstrated.

Bandler, SImon↗

Multi-loop positivity of the planar $ \mathcal{N} $ = 4 SYM six-point amplitude

We study the six-point NMHV ratio function in planar $ \mathcal{N} $ = 4 SYM theory in the context of positive geometry. The Amplituhedron construction of the integrand for the amplitudes provides a kinematical region in which the integrand was observed to be positive. It is natural to conjecture that this property survives integration, i.e. that the final result for the ratio function is also positive in this region. Establishing such a result would imply that preserving positivity is a surprising property of the Minkowski contour of integration and it might indicate some deeper underlying structure. We find that the ratio function is positive everywhere we have tested it, including analytic results for special kinematical regions at one and two loops, as well as robust numerical evidence through five loops. There is also evidence for not just positivity, but monotonicity in a “radial” direction. We also investigate positivity of the MHV six-gluon amplitude. While the remainder function ceases to be positive at four loops, the BDS-like normalized MHV amplitude appears to be positive through five loops.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Positive geometries and canonical forms

Recent years have seen a surprising connection between the physics of scattering amplitudes and a class of mathematical objects — the positive Grassmannian, positive loop Grassmannians, tree and loop Amplituhedra — which have been loosely referred to as “positive geometries”. The connection between the geometry and physics is provided by a unique differential form canonically determined by the property of having logarithmic singularities (only) on all the boundaries of the space, with residues on each boundary given by the canonical form on that boundary. The structures seen in the physical setting of the Amplituhedron are both rigid and rich enough to motivate an investigation of the notions of “positive geometries” and their associated “canonical forms” as objects of study in their own right, in a more general mathematical setting. In this paper we take the first steps in this direction. We begin by giving a precise definition of positive geometries and canonical forms, and introduce two general methods for finding forms for more complicated positive geometries from simpler ones — via “triangulation” on the one hand, and “push-forward” maps between geometries on the other. We present numerous examples of positive geometries in projective spaces, Grassmannians, and toric, cluster and flag varieties, both for the simplest “simplex-like” geometries and the richer “polytope-like” ones. We also illustrate a number of strategies for computing canonical forms for large classes of positive geometries, ranging from a direct determination exploiting knowledge of zeros and poles, to the use of the general triangulation and push-forward methods, to the representation of the form as volume integrals over dual geometries and contour integrals over auxiliary spaces. These methods yield interesting representations for the canonical forms of wide classes of positive geometries, ranging from the simplest Amplituhedra to new expressions for the volume of arbitrary convex polytopes.

97 MATHEMATICS AND COMPUTING↗

Long non-coding RNA MIAT is estrogen-responsive and promotes estrogen-induced proliferation in ER-positive breast cancer cells

Highlights: • lncRNA MIAT was over-expressed in ER-positive breast cancer tissues and cells. • Breast cancer cell MIAT expression was estrogen-dependent. • lncRNA MIAT promoted breast cancer cell growth. • lncRNA MIAT was required for breast cancer cell cycle progression. Estrogen drives the development and progression of estrogen receptor (ER)-positive breast cancer. However, the detailed mechanism underlying ER-driven carcinogenesis remains unclear despite extensive studies. Previously reports indicated higher expression of long non-coding RNA (lncRNA) myocardial infarction associated transcript (MIAT) in ER-positive breast cancer tissues than in ER-negative tissues. However, the functional relevance of MIAT in ER-positive breast cancer tumorigenesis was poorly understood. Here, we investigated the role of lncRNA MIAT in ER-positive breast cancer cells. MIAT was over-expressed in ER-positive breast cancer tissues and ER-positive breast cancer cell line MCF-7. Activating estrogen signaling by diethylstilbestrol (DES) led to a dose- and time-dependent up-regulation of MIAT in MCF-7 cells that was dependent on ERα, as evidenced by ERα silencing and pharmacological inhibition using ER antagonist ICI 182780. Silencing MIAT decreased DES-induced MCF-7 cell proliferation while overexpressing MIAT increased MCF-7 cell proliferation. Further mechanistic study identified that MIAT was critical for G1 to S phase cell cycle transition. Taken together, these results suggest that lncRNA MIAT is an estrogen-inducible lncRNA and a key regulator in ER-positive breast cancer cell growth. MIAT could serve as a potential biomarker and promising therapeutic target for ER-positive breast cancer.

60 APPLIED LIFE SCIENCES↗

Subsets of Women With Close or Positive Margins After Breast-Conserving Surgery With High Local Recurrence Risk Despite Breast Plus Boost Radiotherapy

Purpose: (1) To examine the effect of surgical margin status on local recurrence (LR) and survival following breast-conserving therapy; (2) To identify subsets with close or positive margins with high LR risk despite whole breast radiotherapy (RT) plus boost. Methods and Materials: Subjects were 2,264 women with pT1-3, any N, M0 invasive breast cancer, treated with breast-conserving surgery and whole breast {+-} boost RT. Five-year Kaplan-Meier (KM) LR, breast cancer-specific and overall survival (BCSS and OS) were compared between cohorts with negative (n = 1,980), close (n = 222), and positive (n = 62) margins. LR rates were analyzed according to clinicopathologic characteristics. Multivariable Cox regression modeling and matched analysis of close/positive margin cases and negative margin controls were performed. Results: Median follow-up was 5.2 years. Boost RT was used in 92% of patients with close or positive margins. Five-year KM LR rates in the negative, close and positive margin cohorts were 1.3%, 4.0%, and 5.2%, respectively (p = 0.001). BCSS and OS were similar in the three margin subgroups. In the close/positive margin cohort, LR rates were 10.2% with age <45 years, 11.8% with Grade III, 11.3% with lymphovascular invasion (LVI), and 26.3% with {>=}4 positive nodes. Corresponding rates in the negative margin cohort were 2.3%, 2.4%, 1.0%, and 2.4%, respectively. On Cox regression analysis of the entire cohort, close or positive margin, Grade III histology, {>=}4 positive nodes, and lack of systemic therapy were significantly associated with higher LR risk. When close/positive margin cases were matched to negative margin controls, the difference in 5-year LR remained significant (4.25% vs. 0.7%, p < 0.001). Conclusions: On univariable analysis, subsets with close or positive margins, in combination with age <45 years, Grade III, LVI, and {>=}4 positive nodes, have 5-year LR >10% despite whole breast plus boost RT. These patients should be considered for more definitive surgery.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

Purpose: To investigate the effect of tumor site, measurement precision, tumor-surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor-surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor-surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3-3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Whole-breast irradiation: a subgroup analysis of criteria to stratify for prone position treatment

To select among breast cancer patients and according to breast volume size those who may benefit from 3D conformal radiotherapy after conservative surgery applied with prone-position technique. Thirty-eight patients with early-stage breast cancer were grouped according to the target volume (TV) measured in the supine position: small ({<=}400 mL), medium (400-700 mL), and large ({>=}700 ml). An ad-hoc designed and built device was used for prone set-up to displace the contralateral breast away from the tangential field borders. All patients underwent treatment planning computed tomography in both the supine and prone positions. Dosimetric data to explore dose distribution and volume of normal tissue irradiated were calculated for each patient in both positions. Homogeneity index, hot spot areas, the maximum dose, and the lung constraints were significantly reduced in the prone position (p < 0.05). The maximum heart distance and the V{sub 5Gy} did not vary consistently in the 2 positions (p = 0.06 and p = 0.7, respectively). The number of necessary monitor units was significantly higher in the supine position (312 vs. 232, p < 0.0001). The subgroups analysis pointed out the advantage in lung sparing in all TV groups (small, medium and large) for all the evaluated dosimetric constraints (central lung distance, maximum lung distance, and V{sub 5Gy}, p < 0.0001). In the small TV group, a dose reduction in nontarget areas of 22% in the prone position was detected (p = 0.056); in the medium and high TV groups, the difference was of about -10% (p = NS). The decrease in hot spot areas in nontarget tissues was 73%, 47%, and 80% for small, medium, and large TVs in the prone position, respectively. Although prone breast radiotherapy is normally proposed in patients with breasts of large dimensions, this study gives evidence of dosimetric benefit in all patient subgroups irrespective of breast volume size.

61 RADIATION PROTECTION AND DOSIMETRY↗

Tbx18-positive cells-derived myofibroblasts contribute to renal interstitial fibrosis via transforming growth factor-β signaling

It has been demonstrated that the T-box family transcription factor 18 (Tbx18) -positive cells give rise to renal mesenchymal cells and contribute to the development of the urinary system. However, it is unclear whether Tbx18-positive cells are the origin of the myofibroblasts during renal fibrosis. The present study aimed to determine the contribution of Tbx18-positive cells in kidney fibrosis and their underlying mechanism. We show that Tbx18-positive cells contribute to the development of the urinary system, especially renal fibroblasts. Following unilateral ureteral obstruction (UUO), genetic fate tracing results demonstrated that Tbx18-positive cells not only proliferate but also expand and differentiate into fibroblasts and myofibroblasts, indicating that they may act as profibrotic progenitors. Cell culture results suggest that transforming growth factor (TGF)-β promotes Tbx18-positive cells differentiation into myofibroblasts and assist their contribution to kidney fibrosis. Overall, the present study demonstrated that Tbx18-positive cells may act as profibrotic progenitor cells in a pathological condition of UUO-induced injury. Moreover, TGF-β may play a role in differentiation of Tbx18-positive cells into myofibroblasts in kidney fibrosis. These findings may provide a potential target on Tbx18-positive myofibroblast progenitors in the treatment of renal fibrosis.

60 APPLIED LIFE SCIENCES↗

SU-E-T-195: Gantry Angle Dependency of MLC Leaf Position Error

Purpose: The aim of this study was to investigate the gantry angle dependency of the multileaf collimator (MLC) leaf position error. Methods: An automatic MLC quality assurance system (AutoMLCQA) was developed to evaluate the gantry angle dependency of the MLC leaf position error using an electronic portal imaging device (EPID). To eliminate the EPID position error due to gantry rotation, we designed a reference maker (RM) that could be inserted into the wedge mount. After setting up the EPID, a reference image was taken of the RM using an open field. Next, an EPID-based picket-fence test (PFT) was performed without the RM. These procedures were repeated at every 45° intervals of the gantry angle. A total of eight reference images and PFT image sets were analyzed using in-house software. The average MLC leaf position error was calculated at five pickets (-10, -5, 0, 5, and 10 cm) in accordance with general PFT guidelines using in-house software. This test was carried out for four linear accelerators. Results: The average MLC leaf position errors were within the set criterion of <1 mm (actual errors ranged from -0.7 to 0.8 mm) for all gantry angles, but significant gantry angle dependency was observed in all machines. The error was smaller at a gantry angle of 0° but increased toward the positive direction with gantry angle increments in the clockwise direction. The error reached a maximum value at a gantry angle of 90° and then gradually decreased until 180°. In the counter-clockwise rotation of the gantry, the same pattern of error was observed but the error increased in the negative direction. Conclusion: The AutoMLCQA system was useful to evaluate the MLC leaf position error for various gantry angles without the EPID position error. The Gantry angle dependency should be considered during MLC leaf position error analysis.

07 ISOTOPE AND RADIATION SOURCES↗

SU-E-T-417: A Method for Predicting and Correcting the Dosimetric Effect of a Radiotherapy Treatment Couch in Actual Treatment Position

Purpose: Although radiation attenuation by the treatment couch can be included in the calculation of radiotherapy dose, difference between planned and actual treatment couch positions can generate significant dose discrepancies. We propose a method to predict and correct the dosimetric effect of the couch in actual treatment position. Methods: The couch transmission factor, T, varies with beam angle, G, couch lateral position, x, and vertical position, y, i.e., T=T(x,y,G). If T(x,y,G) is known for a fixed couch vertical position y=h, the transmission of central-axis beam (CAX) T(x,y,G) can be obtained by T(x,y,G)=T(x{sup +},h,G), where x{sup +}=x-(y-h)tan(G) and G is the angle between the beam and the vertical axis. Similarly, the transmission of any off-CAX point can be obtained using a similar formula. We measured CAX couch transmission at a fixed couch vertical position over the couch lateral motion range for all gantry angles by continuously scanning rotating arc beams. A 2D couch transmission correction matrix can thus be generated from T(x,h,G) for each treatment field for the actual couch position. By applying the transmission correction matrix to the planned field dose, the couch effect can be predicted and corrected. To verify this method, we measured couch transmission T(x, y=10cm, G=225°)(225°=IEC 135°) and compared to that obtained from equivalent T(x{sup +}, y=3cm, G=225°) over the range of lateral motion with a step size of 2 cm . Results: The measured couch transmission factors T(x, y=10cm, G=225°) are in excellent agreement with those obtained from the equivalent T(x{sup +}, y=3cm, G=225°). The mean difference is 0.00406±0.00135. Conclusion: The couch transmission correction matrix for any couch position and beam angle can be obtained from one set of scanning measurements at a fixed couch vertical position. The dosimetric effect of the treatment couch can be predicted and corrected by applying the couch transmission correction to the planned dose.

60 APPLIED LIFE SCIENCES↗

SU-C-16A-01: In Vivo Source Position Verification in High Dose Rate (HDR) Prostate Brachytherapy Using a Flat Panel Imager: Initial Clinical Experience

Purpose: We report our initial clinical experience with a novel position-sensitive source-tracking system based on a flat panel imager. The system has been trialled with 4 prostate HDR brachytherapy patients (8 treatment fractions) in this initial study. Methods: The flat panel imaging system was mounted under a customised carbon fibre couch top assembly (Figure 1). Three gold fiducial markers were implanted into the prostate of each patient at the time of catheter placement. X-ray dwell position markers were inserted into three catheters and a radiograph acquired to locate the implant relative to the imaging device. During treatment, as the HDR source dwells were delivered, images were acquired and processed to determine the position of the source in the patient. Source positions measured by the imaging device were compared to the treatment plan for verification of treatment delivery. Results: Measured dwell positions provided verification of relative dwell spacing within and between catheters, in the coronal plane. Measurements were typically within 2.0mm (0.2mm – 3.3mm, s.d. 0.8mm) of the planned positions over 60 dwells (Figure 2). Discrimination between larger dwell intervals and catheter differentiation were clear. This confirms important delivery attributes such as correct transfer tube connection, source step size, relative catheter positions and therefore overall correct plan selection and delivery. The fiducial markers, visible on the radiograph, provided verification of treatment delivery to the correct anatomical location. The absolute position of the dwells was determined by comparing the measured dwell positions with the x-ray markers from the radiograph, validating the programmed treatment indexer length. The total impact on procedure time was less than 5 minutes. Conclusion: The novel, noninvasive HDR brachytherapy treatment verification system was used clinically with minor impact on workflow. The system allows verification of correct treatment delivery, free of most potential human related errors identified in ICRP 97. This research is supported by funding from the Australian Government Department of Health through Cancer Australia grant no. 616614.

60 APPLIED LIFE SCIENCES↗

SU-E-J-62: Breath Hold for Left-Sided Breast Cancer: Visually Monitored Deep Inspiration Breath Hold Amplitude Evaluated Using Real-Time Position Management

Purpose: We used Real-Time Position Management (RPM) to evaluate breath hold amplitude and variability when gating with a visually monitored deep inspiration breath hold technique (VM-DIBH) with retrospective cine image chest wall position verification. Methods: Ten patients with left-sided breast cancer were treated using VM-DIBH. Respiratory motion was passively collected once weekly using RPM with the marker block positioned at the xiphoid process. Cine images on the tangent medial field were acquired on fractions with RPM monitoring for retrospective verification of chest wall position during breath hold. The amplitude and duration of all breath holds on which treatment beams were delivered were extracted from the RPM traces. Breath hold position coverage was evaluated for symmetric RPM gating windows from ± 1 to 5 mm centered on the average breath hold amplitude of the first measured fraction as a baseline. Results: The average (range) breath hold amplitude and duration was 18 mm (3–36 mm) and 19 s (7–34 s). The average (range) of amplitude standard deviation per patient over all breath holds was 2.7 mm (1.2–5.7 mm). With the largest allowable RPM gating window (± 5 mm), 4 of 10 VM-DIBH patients would have had ≥ 10% of their breath hold positions excluded by RPM. Cine verification of the chest wall position during the medial tangent field showed that the chest wall was greater than 5 mm from the baseline in only 1 out of 4 excluded patients. Cine images verify the chest wall/breast position only, whether this variation is acceptable in terms of heart sparing is a subject of future investigation. Conclusion: VM-DIBH allows for greater breath hold amplitude variability than using a 5 mm gating window with RPM, while maintaining chest wall positioning accuracy within 5 mm for the majority of patients.

60 APPLIED LIFE SCIENCES↗

SU-E-J-236: Audiovisual Biofeedback Improves Breath-Hold Lung Tumor Position Reproducibility Measured with 4D MRI

Purpose: Audiovisual biofeedback breath-hold (AVBH) was employed to reproduce tumor position on inhale and exhale breath-holds for 4D tumor information. We hypothesize that lung tumor position will be more consistent using AVBH compared with conventional breath-hold (CBH). Methods: Lung tumor positions were determined for seven lung cancer patients (age: 25 – 74) during to two separate 3T MRI sessions. A breathhold training session was performed prior to the MRI sessions to allow patients to become comfortable with AVBH and their exhale and inhale target positions. CBH and AVBH 4D image datasets were obtained in the first MRI session (pre-treatment) and the second MRI session (midtreatment) within six weeks of the first session. Audio-instruction (MRI: Siemens Skyra) in CBH and verbal-instruction (radiographer) in AVBH were used. A radiation oncologist contoured the lung tumor using Eclipse (Varian Medical Systems); tumor position was quantified as the centroid of the contoured tumor after rigid registration based on vertebral anatomy across two MRI sessions. CBH and AVBH were compared in terms of the reproducibility assessed via (1) the difference between the two exhale positions for the two sessions and the two inhale positions for the sessions. (2) The difference in amplitude (exhale to inhale) between the two sessions. Results: Compared to CBH, AVBH improved the reproducibility of two exhale (or inhale) lung tumor positions relative to each other by 33%, from 6.4±5.3 mm to 4.3±3.0 mm (p=0.005). Compared to CBH, AVBH improved the reproducibility of exhale and inhale amplitude by 66%, from 5.6±5.9 mm to 1.9±1.4 mm (p=0.005). Conclusions: This study demonstrated that audiovisual biofeedback can be utilized for improving the reproducibility of breath-hold lung tumor position. These results are advantageous towards achieving more accurate emerging radiation treatment planning methods, in addition to imaging and treatment modalities utilizing breath-hold procedures.

60 APPLIED LIFE SCIENCES↗

A Positive Low Cloud–Sea Surface Temperature Feedback in the East Asian Marginal Seas during El Niño Mature Winters and Their Following Spring

During the winter and subsequent spring of an El Niño year, the East Asian marginal sea (EAMS) exhibits positive sea surface temperature anomalies (SSTAs) and fewer low clouds, while the western North Pacific experiences negative SSTAs. In this study, we suggest that the positive SSTAs in EAMS are maintained by a positive low cloud–SST feedback. In neutral winters and springs, the EAMS is covered by low clouds, which have a cooling effect on surface temperatures. During an El Niño year, a western North Pacific anomalous anticyclone is established, and along its northwestern flank, there are favorable conditions for convergence of moisture and weaker surface latent heat flux over the EAMS. Once a positive SSTA has been established, a further reduction of turbulent mixing results in less low cloud and enhanced solar heating of the ocean mixed layer; this reinforces and maintains both the positive SSTA and the lack of low cloud via a positive feedback mechanism. Further, the concurrent increase of low cloud–SST feedback and anticyclone circulation strengths is evident in the coupled-model simulations from phase 6 of the Coupled Model Intercomparison Project. Furthermore, sensitivity experiments, performed with the atmospheric components of Community Earth System Model (CESM2), reveal that a positive SSTA helps to maintain the western North Pacific anomalous anticyclone. Four pacemaker-coupled experiments by CESM2, with sea surface temperature in the equatorial Pacific restored to the observational anomalies plus the model climatology and altered low cloud feedback over EAMS, suggest that the low cloud–SST feedback results in more than the maintenance of a positive SSTA over the EAMS: the positive feedback is also a previously overlooked mechanism for the maintenance of the western North Pacific anomalous anticyclone.

54 ENVIRONMENTAL SCIENCES↗

Indocyanine Green Fluorescence Imaging with Lymphoscintigraphy for Sentinel Node Biopsy in Melanoma: Increasing the Sentinel Lymph Node-Positive Rate

Introduction: The goal of this study was to analyze patients who underwent a sentinel lymph node biopsy (SLNB) in melanoma with the combination of radioisotope lymphoscintigraphy and indocyanine green (ICG) fluorescence imaging to compare our true positive (TP) rate, a means to perform immediate analysis of the SLNB, with that of the literature. Methods: Consecutive cutaneous melanoma patients who underwent SLNB with lymphoscintigraphy and ICG-based fluorescence imaging by the senior author (BG) from 2012 to 2018 were prospectively enrolled. The average expected SLN-positive rate per T stage was calculated based on three studies and compared with our SLN-positive rate. Results: Overall, 574 consecutive patients were analyzed. Average Breslow thickness was 1.9 mm. A total of 1754 sentinel nodes were sampled; 1497 were identified by gamma probe signaling and ICG, 241 were identified by gamma probe signaling only, and 16 were identified by ICG only. There were 123 (21.4%) patients with at least one positive SLN; 113 (91.9%) had at least one positive node identified with both gamma probe signaling and ICG, 8 (6.5%) had positive node(s) identified with gamma probe signaling only, and 2 (1.6%) had positive node(s) identified with ICG only. There was an overall 21.4% SLN-positive rate, with 8% T1, 18.5% T2, 41.1% T3, and 52.4% T4, which is higher than the predicted rates for each stage. Conclusions: With the largest cohort of patients reported who underwent a melanoma SLNB with lymphoscintigraphy and ICG, we demonstrated that this technique results in higher SLN-positive rates than predicted. Patients are being followed but, given the TP data, knowledge of our results may foster the use of this modality to improve staging and treatment options.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Risk of Positive Sentinel Lymph Node After Neoadjuvant Systemic Therapy in Clinically Node-Negative Breast Cancer: Implications for Postmastectomy Radiation Therapy and Immediate Breast Reconstruction

Background: Residual axillary lymph node involvement after neoadjuvant systemic therapy (NST) is the determining factor for postmastectomy radiation therapy (PMRT). Preoperative identification of patients needing PMRT is essential to enable shared decision-making when choosing the optimal timing of breast reconstruction. We determined the risk of positive sentinel lymph node (SLN) after NST in clinically node-negative (cN0) breast cancer. Methods: All cT1-3N0 patients treated with NST followed by mastectomy and SLNB between 2010 and 2016 were identified from the Netherlands Cancer Registry. Rate of positive SLN for different breast cancer subtypes was determined. Logistic regression analysis was performed to determine correlated clinicopathological variables with positive SLN. Results: In total 788 patients were included, of whom 25.0% (197/788) had positive SLN. cT1-3N0 ER+HER2+, cT1-3N0 ER−HER2+ , and cT1-2N0 triple-negative patients had the lowest rate of positive SLN: 7.2–11.5%, 0–6.3%, and 2.9–6.2%, respectively. cT1-3N0 ER+HER2− and cT3N0 triple-negative patients had the highest rate of positive SLN: 23.8–41.7% and 30.4%, respectively. Multivariable regression analysis showed that cT2 (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.01–3.96), cT3 (OR 2.56; 95% CI 1.30–5.38), grade 3 (OR 0.44; 95% CI 0.21–0.91), and ER+HER2− subtype (OR 3.94; 95% CI 1.77–8.74) were correlated with positive SLN. Conclusions: In cT1-3N0 ER+HER2+, cT1-3N0 ER−HER2+, and cT1-2N0 triple-negative patients treated with NST, immediate reconstruction can be considered an acceptable option due to low risk of positive SLN. In cT1-3N0 ER+HER2− and cT3N0 triple-negative patients treated with NST, risks and benefits of immediate reconstruction should be discussed with patients due to the relatively high risk of positive SLN.

62 RADIOLOGY AND NUCLEAR MEDICINE↗