S. Ahn

Magnetic Resonance Imaging in Acute Ischemic Stroke Treatment

Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis.

Role of Perfusion-Weighted Imaging in a Diffusion-Weighted-Imaging-Negative Transient Ischemic Attack

Background and Purpose The absence of acute ischemic lesions in diffusion-weighted imaging (DWI) in transient ischemic attack (TIA) patients makes it difficult to diagnose the true vascular etiologies. Among patients with DWI-negative TIA, we investigated whether the presence of a perfusion-weighted imaging (PWI) abnormality implied a true vascular event by identifying new acute ischemic lesions in follow-up magnetic resonance imaging (MRI) in areas corresponding to the initial PWI abnormality. Methods The included patients underwent DWI and PWI within 72 hours of TIA and also follow-up DWI at 3 days after the initial MRI. These patients had visited the emergency room between July 2009 and May 2015. Patients who demonstrated initial DWI lesions were excluded. The initial PWI abnormalities in the corresponding vascular territory were visually classified into three patterns: no abnormality, focal abnormality, and territorial abnormality. Results No DWI lesions were evident in initial MRI in 345 of the 443 TIA patients. Follow-up DWI was applied to 87 of these 345 DWI-negative TIA patients. Initial PWI abnormalities were significantly associated with follow-up DWI abnormalities: 8 of 43 patients with no PWI abnormalities (18.6%) had new ischemic lesions, whereas 13 of 16 patients with focal perfusion abnormalities (81.2%) had new ischemic lesions in the areas of initial PWI abnormalities [odds ratio (OR)=15.1, 95% confidence interval (CI)=3.6–62.9], and 14 of 28 patients with territorial perfusion abnormalities (50%) had new lesions (OR=3.7, 95% CI=1.2–11.5). Conclusions PWI is useful in defining whether or not the transient neurological symptoms in DWI-negative TIA are true vascular events, and will help to improve the understanding of the pathomechanism of TIA.

The second elevation of neuron-specific enolase peak after ischemic stroke is associated with hemorrhagic transformation.

BACKGROUND Neuron-specific enolase (NSE) is a surrogate marker for the extent of brain damage after ischemic stroke and affords a good predictor of stroke prognosis. We hypothesized that the pattern of NSE level changes in the peripheral blood during the acute period of ischemic stroke is dependent on stroke mechanism and is associated with hemorrhagic transformation. METHODS Acute ischemic stroke patients visiting our center within 24 hours of symptom onset were recruited into the study. NSE levels were obtained serially at various time points after stroke, and the pattern of change was categorized into no significant change, continuously increasing, continuously decreasing, with 1 peak and with 2 peaks. Clinical, laboratory, and imaging variables were compared among the patient groups. Multivariate analysis was performed to verify the independent association between the second NSE peak and hemorrhagic transformation after adjusting for potential confounders. RESULTS Among 83 patients, NSE levels were stationary in 22 (26.5%) of the patients, increased in 9 (10.8%), decreased in 18 (21.7%), and showed 1 peak in 17 (20.5%) and 2 peaks in 17 (20.5%) patients. The incidence of atrial fibrillation and hemorrhagic transformation was significantly elevated (P = .02) in patients with 2 NSE peaks. Furthermore, the second NSE peak and the initial lesion volume were associated independently with hemorrhagic transformation after we adjusted for potential confounders (odds ratio = 6.844 and 1.024, P = .04 and .02, respectively). CONCLUSIONS Serial NSE analysis during the acute period of ischemic stroke is useful for monitoring hemorrhagic transformation and the blood-brain barrier disruption status.

Color-Coded Fluid-Attenuated Inversion Recovery Images Improve Inter-Rater Reliability of Fluid-Attenuated Inversion Recovery Signal Changes Within Acute Diffusion-Weighted Image Lesions

Background and Purpose— Diffusion-weighted image fluid-attenuated inversion recovery (FLAIR) mismatch has been considered to represent ischemic lesion age. However, the inter-rater agreement of diffusion-weighted image FLAIR mismatch is low. We hypothesized that color-coded images would increase its inter-rater agreement. Methods— Patients with ischemic stroke <24 hours of a clear onset were retrospectively studied. FLAIR signal change was rated as negative, subtle, or obvious on conventional and color-coded FLAIR images based on visual inspection. Inter-rater agreement was evaluated using &kgr; and percent agreement. The predictive value of diffusion-weighted image FLAIR mismatch for identification of patients <4.5 hours of symptom onset was evaluated. Results— One hundred and thirteen patients were enrolled. The inter-rater agreement of FLAIR signal change improved from 69.9% (k=0.538) with conventional images to 85.8% (k=0.754) with color-coded images (P=0.004). Discrepantly rated patients on conventional, but not on color-coded images, had a higher prevalence of cardioembolic stroke (P=0.02) and cortical infarction (P=0.04). The positive predictive value for patients <4.5 hours of onset was 85.3% and 71.9% with conventional and 95.7% and 82.1% with color-coded images, by each rater. Conclusions— Color-coded FLAIR images increased the inter-rater agreement of diffusion-weighted image FLAIR recovery mismatch and may ultimately help identify unknown-onset stroke patients appropriate for thrombolysis.

SU‐F‐P‐60: Optimization of Cyberknife Treatment Planning Using a Dose‐Limiting Auto‐Shells Method for Brain Metastases

PURPOSE In pursuit of high precision in target localization and steeper dose fall-off in stereotactic radiosurgery, we investigated the impact of optimizing dose-limiting auto-shell function on the quality of Cyberknife (CK) plans in treating brain metastases (BMs). METHODS Nineteen BMs previously treated using CK were selected for this study. The original CK plans (CK_original) had been produced using one to three dose-limiting auto-shells at prescription dose (PD) level and low dose levels of 10 to 30% of PD. In each case, a modified CK plan (CK_modified) was generated using five dose-limiting shells at PD level, intermediate dose level of 50% of PD, and low dose levels with an optimal shell-dilation size based on our experience. In addition, a Gamma Knife plan (GK) was also produced using the original contour set. Thus, a triplet data set of dosimetric parameters was generated and analyzed. RESULTS While no differences in conformity index (mean±SD 1.22 ± 0.1, 1.18 ± 0.1, and 1.24 ± 0.1 in CK_original, CK_modified, and GK, respectively; over all P > 0.05) and tumor coverage (mean±SD 99.5 ± 0.4%, 99.5 ± 0.3%, and 99.4 ± 0.2% in CK_original, CK_modified, and GK, respectively; over all P > 0.05) were observed among the plans, the normal tissue volume receiving 50% of PD was significantly decreased in CK_modified and GK compared with CKoriginal by 1.28 and 1.27-fold, respectively (P < 0.001, each). No significant differences in dose fall-off were observed between CK_modified and GK (P = 0.345). CONCLUSION By optimizing auto-shell function, a significantly steeper dose fall-off can be achieved in CK system, while maintaining high precision in target localization.

Psychosine inhibits osteoclastogenesis and bone resorption via G protein-coupled receptor 65

BackgroundIt was recently reported that G protein-coupled receptor 65 (GPR65) suppresses ovariectomy-induced bone loss.AimThe present study investigated the role of the lysosphingolipid psychosine, a GPR65 ligand, on osteoclastic differentiation and bone resorption.MethodsOsteoclasts were differentiated from mouse bone marrow macrophages. Tartrate-resistant acid phosphatase-positive multinucleated cells were considered to be osteoclasts, and the resorption area was measured by incubating the cells on dentine discs. The expression levels of osteoclast differentiation markers were assessed by qRT-PCR. GPR65 siRNA and its scrambled siRNA were transfected with lipofectamine. Intracellular cyclic adenosine monophosphate (cAMP) levels were assessed using a direct enzyme immunoassay.ResultsPsychosine inhibited osteoclastogenesis and in vitro bone resorption without any significant effect on the viability of pre-osteoclasts, decreased the expression of osteoclast differentiation markers significantly, and increased intracellular cAMP levels. The knockdown of GPR65 by its siRNA restored osteoclastogenesis and decreased cAMP levels in the presence of psychosine.ConclusionPsychosine inhibits osteoclastogenesis by increasing intracellular cAMP levels via GPR65.

Triple Negative Breast Cancer Has a Worse Prognosis within 3 Years after Treatment Compared to Non-Triple Negative Breast Cancer.

Background Triple negative breast cancers (TNBC) become known as poor prognosis generally. Our purpose was to compare the clinical features and outcomes for TNBC with other subtypes of breast cancers in Korea. Methods We included 2,907 patients who diagnosed breast cancer and treated at Asan Medical Center from 2003 to 2005. Clinical and pathologic parameters, disease-free survival (DFS) and overall survival (OS) were compared between patients with TNBC and non-TNBC. All features were reviewed throughout medical records retrospectively. Results 622 patients (21.4%) had TNBC. TNBC patients was associated with younger age, larger size, positive nodal involvement, overweight, family history, elevation of CaAg15-3, high tumor grade, positive p53 compared non-TNBC. The patients were followed for a median of 54 months (range 1-76 months). Relapse-free survival was 86.3% and 92.6% for TNBC and non-TNBC, respectively, with significant difference (P Conclusions TNBC has a worse prognosis than non-TNBC patients, but this effect is limited within 3 years after diagnosis. The most competent prognostic factor of recurrence and death for TNBC is a nodal status. We plan that perform analysis for prognosis according to hormone receptor and HER-2 receptor status sooner. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4044.

SU-F-T-460: Dosimetric Matching Between Trilogy Tx and TrueBeam STx

PURPOSE To compare the commissioned beam data for one flattening filter photon mode (6 MV) and two flattening filter-free (FFF) photon modes (6 and 10 MV-FFF) between Trilogy Tx and TrueBeam STx and evaluate the possibility of dosimetric matching METHODS: Dosimetric characteristics of the new Trilogy Tx including percent depth doses (PDDs), profiles, and output factors were measured for commissioning. Linear diode array detector and ion chambers were used to measure dosimetric data. The depth of dose maximum (dmax) and PDD at 10 cm (PDD10) were evaluated: 3×3 cm2 , 10×10 cm2 , and 40×40 cm2 . The beam profiles were compared and then penumbras were evaluated. As a further test of the dosimetric matching, the same VMAT plans were delivered, measured with film, and compared with TPS calculation. RESULTS All the measured PDDs matched well across the two units. PDD10 showed less than 0.5% variation and dmax were within 1.5 mm at the field sizes evaluated. Within the central 80% of transverse axis, profile data were almost identical. TrueBeam data resulted in a slightly greater penumbra width (up to 1.9 mm). The greatest differences of output factors were found at 40 × 40 cm2 : 2.40%, 2.03%, and 2.22% for 6 MV, 6 MV-FFF, and 10 MV-FFF, respectively. For smaller field sizes, less than 1% differences were observed. The film measurements demonstrated over 97.3% pixels passing-gamma analysis (2%/2mm). The results showed excellent agreement between measurements of two machines. CONCLUSION The differences between Trilogy Tx and TrueBeam STx found could possibly affect small field and also very large field sizes in dosimetric matching considerations. These differences encountered are mostly related with the changes in the head design of the TrueBeam. Although it cannot guarantee full interchangeability of two machines, dosimetric matching by field size of 25 × 25 cm2 might be clinically acceptable.

Abstract P5-13-06: Concurrent gonadotropin-releasing hormone (GnRH) agonist administration with chemotherapy improves neoadjuvant chemotherapy responses in young premenopausal breast cancer patients

Background Gonadotropin-releasing hormone (GnRH) agonist therapy for ovarian function preservation shows promising results. This study aimed to determine the oncologic efficacy of GnRH agonist treatment concurrent with chemotherapy in a neoadjuvant setting. Patients and Methods A retrospective analysis was performed on 332 cases of invasive breast cancer in patients who were Results The median age was 32 ± 3.9 and 36 ± 3.0 years old in the GnRH agonist group and neochemotherapy-alone group, respectively (P Conclusion Concurrent administration of GnRH agonists during neoadjuvant chemotherapy improved pCR rates and suppressed Ki-67 expression especially in HR-negative tumors. Citation Format: Yoon TI, Kim HJ, Yu JH, Sohn G, Ko BS, Lee JW, Son BH, Ahn SH. Concurrent gonadotropin-releasing hormone (GnRH) agonist administration with chemotherapy improves neoadjuvant chemotherapy responses in young premenopausal breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-13-06.

SU-E-T-185: Feasibility Study of Dose Rate Modulated Arc Therapy (DrMAT) for Lung SBRT

PURPOSE To show the feasibility of clinical application of DrMAT for SBRT in lung cancer patients. DrMAT is a form of dynamic conformal arc therapy where MLC segments and dose rates are controlled through simple field weight optimization. METHODS To show feasibility a new treatment plan was created based on the CT of SBRT lung cancer patients. Static plans with 33 fields are made, which have 11deg in between each field and are acquired rotating gantry angle from 180deg to 188deg in CCW direction, total 352deg is rotated. MLC maintained static aperture for each field. To optimize 33 individual fields, field weight was adjusted accordingly using weight optimization algorithm. Keeping weights and MU of static plan, static MLC aperture was converted to multiple arc segments. Arc plan could be created with the fields in the intervals of 11deg. Static MLC should be converted to arc segment MLC. Dynamic conformal arc therapy plan consists of 33 arc fields, is converted to one dose rate modulated arc therapy (DrMAT) plan. DrMAT plan consists of 166 control points which becomes a single arc plan that changes the shape of MLC for every 2.2deg. The resulting DrMAT plan is not an inverse plan it is a simple form of dynamic conformal arc plan using field weight obtained from static plan. This is compared and evaluated with the VMAT plan. RESULTS DrMAT and VMAT plans have been compared based on the RTOG1021. Both DrMAT and VMAT plans satisfy 100% irradiation to 95% of PTV and critical organs did not exceed dose limit suggested in RTOG1021. DrMAT plan is almost similar with VMAT plan in Result. CONCLUSION Field weight optimization method did not show better Resultcompared to VMAT optimization. However, considering simplicity, DrMAT satisfies the condition in RTOG1021. Therefore clinical application of DrMAT is feasible.