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At least 127 records · Page 7

Outcomes of Post Mastectomy Radiation Therapy in Patients Receiving Axillary Lymph Node Dissection After Positive Sentinel Lymph Node Biopsy

Purpose: We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS). Methods and Materials: All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologic stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR. Results: A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy. On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001). The rate of 10-year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with ≥3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, ≥3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034). Conclusions: A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with ≥3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A Positive Charge in the Outer Coordination Sphere of an Artificial Enzyme Increases CO 2 Hydrogenation

The protein scaffold around the active site of enzymes is known to influence catalytic activity, but specific scaffold features responsible for favorable influences are often not known. This study focuses on using an artificial metalloenzyme to probe one specific feature of the scaffold, the position of a positive charge in the outer coordination sphere around the active site. Previous work showed that a small molecular complex, [Rh(P Et 2 N glycine P Et 2 )2 ] – , immobilized covalently within a protein scaffold was activated for CO 2 hydrogenation. In this work, using an iterative design where the effect of arginine, histidine, or lysine residues placed in the outer coordination sphere of the catalytic active site were evaluated, we tested the hypothesis that positively charged groups facilitate CO 2 hydrogenation with seven unique constructs. Single-, double-, and triple-point mutations were introduced to directly compare catalytic activity, as monitored by turnover frequencies (TOFs) measured in real time with 1 H NMR spectroscopy, and evaluate related structural and electronic properties. Two of the seven constructs showed a 2- and 3-fold increase relative to the wild type, with overall rates ranging from 0.2 to 0.7 h –1 , and a crystal structure of the fastest of these shows the positive charge positioned next to the active site. A crystal structure of the arginine-containing complex shows that the arginines are positioned near the metal. Molecular dynamics (MD) studies also suggest that the positive charge is oriented next to the active site in the two constructs with faster rates but not in the others and that the positive charge near the active site holds the CO 2 near the metal, all consistent with a positive charge appropriately positioned in the scaffold benefiting catalysis. The MD studies also suggest that changes in the water distribution around the active site may contribute to catalytic activity, while modest structural changes and movement of the complex within the scaffold do not.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

SU-E-T-33: An EPID-Based Method for Testing Absolute Leaf Position for MLC Without Backup Jaws

Purpose: Methods in common use for MLC leaf position QA are limited to measurements relative to an arbitrary reference position. The authors previously presented an EPID-based method for efficiently testing accuracy of leaf position relative to the mechanical isocenter for MLC with backup jaws. The purpose of this work is to extend that method to the general case of MLC without backup jaws. Methods: A pair of collimator walkout images is used to determine the location of the mechanical isocenter relative to the center of one field using a parameter called X-offset. The method allows for shift of the imager panel to cover subsets of MLC leaves within the limited field of view of the imager. For a shifted panel position, an image of three beam strips defined by a subset of MLC leaves allows determination of the position of each leaf relative to the isocenter. The location of the isocenter is determined by applying X-offset to an image of a single rectangular field obtained at that panel position. The method can also be used to test backup jaws instead of MLC leaves. A software tool was developed to efficiently analyze the images. Results: The software tool reports leaf position and deviation from nominal position, and provides visual displays to facilitate rapid qualitative interpretation. Test results using this method agree well with results using the previous method requiring backup jaws. Test results have been successfully used to recalibrate one model MLC (Elekta MLCi2™). Work in progress includes extension of the software tool to other MLC models, and quantification of reproducibility of the measurements. Conclusion: This work successfully demonstrates a method to efficiently and accurately measure MLC leaf position, or backup jaw position, relative to the mechanical isocenter of the collimator.

60 APPLIED LIFE SCIENCES↗

SU-E-P-54: Evaluation of the Accuracy and Precision of IGPS-O X-Ray Image-Guided Positioning System by Comparison with On-Board Imager Cone-Beam Computed Tomography

Purpose: The purpose of this study is to assess the positioning accuracy and precision of IGPS-O system which is a novel radiographic kilo-voltage x-ray image-guided positioning system developed for clinical IGRT applications. Methods: IGPS-O x-ray image-guided positioning system consists of two oblique sets of radiographic kilo-voltage x-ray projecting and imaging devices which were equiped on the ground and ceiling of treatment room. This system can determine the positioning error in the form of three translations and three rotations according to the registration of two X-ray images acquired online and the planning CT image. An anthropomorphic head phantom and an anthropomorphic thorax phantom were used for this study. The phantom was set up on the treatment table with correct position and various “planned” setup errors. Both IGPS-O x-ray image-guided positioning system and the commercial On-board Imager Cone-beam Computed Tomography (OBI CBCT) were used to obtain the setup errors of the phantom. Difference of the Result between the two image-guided positioning systems were computed and analyzed. Results: The setup errors measured by IGPS-O x-ray image-guided positioning system and the OBI CBCT system showed a general agreement, the means and standard errors of the discrepancies between the two systems in the left-right, anterior-posterior, superior-inferior directions were −0.13±0.09mm, 0.03±0.25mm, 0.04±0.31mm, respectively. The maximum difference was only 0.51mm in all the directions and the angular discrepancy was 0.3±0.5° between the two systems. Conclusion: The spatial and angular discrepancies between IGPS-O system and OBI CBCT for setup error correction was minimal. There is a general agreement between the two positioning system. IGPS-O x-ray image-guided positioning system can achieve as good accuracy as CBCT and can be used in the clinical IGRT applications.

60 APPLIED LIFE SCIENCES↗

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↗

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↗