bluuebunny/crossref_metadata_2025_split huggingface dataset:
TH‐C‐218‐01: How to Implement an IGRT and SBRT with Siemens Linacs and the Brainlab ExacTrac System
Authors: Mihailidis D 
Published: June 2012

Image guided stereotactic radiotherapy is a treatment modality that combines a variety of new technologies from imaging, to treatment planning and treatment delivery. It has been the primary method of treatment for several cranial and extra cranial tumors, where accurate patient immobilization and setup, tumor delineation, complex treatment planning and pre‐treatment imaging, are necessary for accurate treatment delivery. Typically, the coverage of the topic has been for a single‐technology, single‐vendor system, for example, MVCBCT by Siemens was presented, against kVCBCT by Elekta and Varian or MVCT by Tomotherapy, all for IG and/or SBRT purposes. The clinical reality many times is far from single‐vendor technology. Many medium and small size clinics upgrade their delivery systems (linacs) for IG and SBRT by add‐ons coming from multiple vendors. As an example, a Siemens linac with Brainlab Exactrac IG system and third party treatment planning system, all put together to provide IG and SBRT programs within the clinical environment. Users find themselves up against issues that are not necessarily addressed by a course that describes a closed single‐vendor IG/SBRT systems, like a Novalis TX with i‐plan or Tomotherapy or Cyberknife or others. This presentation will outline the main issues and give a step‐by‐step method for clinical implementation of all the components in order to achieve the final goal. Points of caution for the user, limitations and financial considerations will be part of the presentation.Learning objectives:1. To gain insight into the issues that come up when technologies from various vendors are combined towards an integrated IG and/or SBRT program.2. To understand the step‐by‐step method of integration of the involved technologies towards their clinical implementation.3. To develop the understanding of the importance of benchmarking of IG and SBRT programs and usefulness of end‐to‐end testing.4. To develop the ability to deal with the technical limitations of the technologies chosen to be implemented in the clinic.
TH‐C‐218‐03: IGRT in Prostate Cancer: The Calypso 4D Localization System
Authors: Djemil T 
Published: June 2012

There is mounting evidence that for prostate cancer patients treated with EBRT, dose escalation to the prostate increases local control. This benefit comes at the cost of toxicities and complications. Therefore, restricting the dose to normal tissue becomes of utmost importance. Image guidance for accurate treatment delivery and intra‐fraction motion monitoring is critical in this environment of dose escalation and hypo fractionation.A variety of systems could be utilized for this purpose, such as transabdominal ultrasound, KV X‐rays, and KV/MV CBCT. However, these systems have several disadvantages: they only provide snapshots of the prostate position; they are not available during radiation delivery; they cause an additional ionizing radiation exposure; and they may be subjective and operator dependant in acquisition and interpretation. A newer technology using non ionizing electromagnetic field and implanted fiducial markers (transponders) to locate and track patient tumors is available by Calypso Medical. In this presentation, our experience with IMRT and SBRT prostate treatments at the Cleveland Clinic will be presented. The treatment plans are generated with the Pinnacle treatment planning system, the localization and tracking is performed by the 4D Calypso system, and the treatment delivery is done on an Elekta Synergy S linac.Learning Objectives:1. Understand the clinical rationale for localization and tracking2. Understand the necessity of hybrid technologies and systems3. Understand the physics behind the Calypso localization mechanism and its principles of operation4. Understand operational and quality assurance aspects of Calypso combined with Synergy‐S and Pinnacle TPS5. Understand the technical limitations of the hybrid system6. Describe clinical implementation of the system and typical cases treated
TH‐E‐211‐01: Economics of Light Ion Teletherapy
Authors: Moyers M 
Published: June 2012

Treatment of patients with beams of light ions (including protons) began in 1954. Despite the dosimetric advantages of these beams, 58 years later less than 1% of patients treated with radiation in the United States currently receive light ion teletherapy. This is primarily due to the large initial investment needed to construct light ion facilities. This course will provide the audience with example estimates of equipment, construction, maintenance, and salary costs along with projections of estimated reimbursement over the lifetime of the equipment. Comparisons of individual project costs will be given to demonstrate which items have the most impact on project success. Several example methods for reducing both the operating costs and initial costs will be presented including a brief discussion of new technology. Some cost reduction measures, however, can result in decreased performance which may affect the patient population that may be treated. Several cost/performance tradeoff examples will bepresented.Learning Objectives:1. Become familiar with estimated costs associated with starting and operating a light ion teletherapy facility.2. Become familiar with the relative costs of various items important for the success of a project.3. Become familiar with tradeoffs in performance for various cost saving methods.
TH‐E‐BRCD‐03: Automatic Treatment Planning for IMRT, VMAT and IMPT
Authors: Zhang X 
Published: June 2012

In intensity‐modulated radiotherapy (IMRT), including intensity modulated X‐ray therapy (IMXT), volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT), the quality of the treatment plan, which is highly dependent upon the treatment planner's level of experience, greatly affects the potential benefits of the radiotherapy (RT). Furthermore, the planning process is complicated and requires a great deal of iteration, and it is often the most time‐consuming aspect of the RT process. There is also a long learning curve to design the “optimal” plan for the newest technology such as IMPT. However, recent optimization algorithm technology development, especially automatically planning based on some kind of machine learning, have reached a point in treatment planning process where treatment plan can be designed without or with minimum human intervention. In this work, we describe the methodology and validation results of mdaccAutoPlan system: this system has the potential to automate IMXT/VMAT/IMPT treatment planning to the extent that human intervention is minimal. For every new patient, the mdaccAutoPlan system could automatically generate plans (the autoplans) that meet or exceed the institution's dose‐volume constraints by one button click in the TPS. The methodology 1) automatically sets beam angles based on a data mining of previously plans designed by experienced dosimetristsand a beam angle automation algorithm, 2) judiciously designs the planning structures, which were shown to be effective for all the patient cases we studied, and 3) automatically adjusts the objectives of the objective function based on a parameter automation algorithm. We compared treatment plans created in this system (mdaccAutoPlan) based on the overall methodology with plans from the plans created by the experienced dosimetrists. The “autoplans” were consistently better, or no worse, than the plans produced by experienced medical dosimetrists in terms of tumor coverage and normal tissue sparing. This lecture will provide an overview of overall methodology in the “autoplan” system and its validation on the treatment planning process in IMRT, VMAT, IMPT and adaptive radiotherapy planning (ART).Learning Objectives:1. Understand the bottleneck of current inverse planning and evaluation process2. Understand the importance of data mining of pre‐existing treatment plans3. Understand the impact of automation on reducing the learning curve of new technologies4. Understand the importance of automatic planning on improving quality and consistence of radiation therapy5. Understand the clinical workflow of automatic planning
Immediate Effects of Acupuncture and Cryotherapy on Quadriceps Motoneuron Pool Excitability: Randomised Trial Using Anterior Knee Infusion Model
Authors: Park Jihong , Ty Hopkins J 
Published: June 2012

Objective The authors asked the following research questions: will an anterior knee infusion model induce constant pain? will perceived pain alter motoneuron pool (MNP) excitability? and will treatments alter perceived pain and/or MNP excitability? Methods Thirty-six neurologically healthy volunteers participated in this randomised controlled laboratory study. To induce anterior knee pain (AKP), 5% hypertonic saline (0.12 ml/min with a total volume of 8.5 ml over 70 min) was injected into the infrapatellar fat pad of the dominant leg. One of four 30-min treatments was randomly assigned to each subject after pain was induced (acupuncture, cryotherapy, sham cryotherapy and no treatment). Five acupuncture needles (SP9, SP10, ST36, GB34 and an ah shi point) were inserted to a depth of 1 cm. Vastus medialis (VM) maximum Hoffmann reflexes normalised by maximum motor response were recorded from each subject at baseline, 20 min post-injection, 50 min post-injection and 70 min post-injection. To record pain perception, a visual analogue scale was used every 5 min after injection. Results An anterior knee infusion pain model increased perceived pain (p<0.0001). No change was found in VM MNP excitability among the four treatments (p<0.19) or at any of the time intervals (p<0.52). Cryotherapy reduced perceived pain compared with acupuncture (p=0.0003) and sham treatment (p=0.0002). Conclusions A pain model may be used in other neurophysiological intervention studies related to AKP. AKP alone may not directly alter quadriceps activation. None of the treatments altered VM MNP excitability. Cryotherapy reduced pain while a single session of acupuncture and sham treatments did not.
The impact of an invasive predator (Orconectes rusticus) on freshwater snail communities: insights on habitat-specific effects from a multilake long-term study
Authors: Kreps Timothy A. , Baldridge Ashley K. , Lodge David M. 
Published: June 2012

Most studies of the impacts of invasive species are done at small spatial and short temporal scales, greatly limiting generalizations to natural ecosystems. In contrast, we examined the long-term, whole-lake impacts of predation by the introduced rusty crayfish ( Orconectes rusticus ) on snail communities in 10 lakes in northern Wisconsin, USA. In 1987 and 2002, crayfish and snails were surveyed in lakes that initially differed in O. rusticus abundance; during the 15 years between surveys, crayfish abundance changed substantially in four lakes. In the two lakes where O. rusticus populations increased from low to high densities, large reductions occurred in snail abundance. As predicted, snails declined much more in habitats preferred by O. rusticus (sand and cobble) than in habitats that are avoided by the crayfish (muck). In the two lakes where O. rusticus abundance decreased dramatically after 1987, no significant increase occurred in snail densities, illustrating the difference in response time of snail populations to release from predation relative to increasing predation. Contrary to prediction, no consistent difference in snail species composition existed between high and low crayfish density lakes.
Local- versus landscape-scale effects on the demography of three forest-breeding songbirds in Ontario, Canada
Authors: Richmond S. , Nol E. , Burke D. 
Published: June 2012

Reproductive success of songbirds breeding in forest fragments can be influenced by local habitat characteristics and by anthropogenic land uses in the surrounding matrix such as exurban development and agriculture. Effectively managing these songbirds requires an understanding of which spatial scales most strongly influence their demography. We conducted a multiscale study to investigate the relative influence of local vegetation characteristics and landscape composition at two spatial scales (100 and 2000 m) in a predominantly agricultural landscape on songbird demography. Density, pairing success, nest success, and productivity were assessed for Ovenbirds ( Seiurus aurocapilla (L., 1766)), Wood Thrush ( Hylocichla mustelina (J.F. Gmelin, 1789)), and American Robins ( Turdus migratorius L., 1766) in 16 deciduous forest fragments in southeastern Ontario. Demography of Ovenbirds was most strongly associated with local vegetation characteristics, while demography of Wood Thrush and American Robins was most strongly related to landscape composition within a 2000 m buffer. For all three species, cross-scale correlations influenced nest success, although other demographic parameters were less affected. We conclude that relationships between local- and landscape-scale metrics and songbird demography are complex, species-specific, and differ among reproductive parameters, necessitating a multiscale approach to management.
Regulation of ERBB2 Receptor by t-DARPP Mediates Trastuzumab Resistance in Human Esophageal Adenocarcinoma
Authors: Hong Jun , Katsha Ahmed , Lu Pengcheng , Shyr Yu , Belkhiri Abbes , El-Rifai Wael 
Published: June 2012

Abstract
Esophageal adenocarcinoma (EAC) is an aggressive malignancy with a poor outcome. Although targeting ERBB2 with trastuzumab has been evaluated in clinical trials, the molecular mechanisms of trastuzumab resistance remain uncharacterized in EAC. The dopamine and cyclic AMP-regulated phosphoprotein of MR 32000 (DARPP-32), also known as PPP1R1B, is located together with ERBB2 at the 17q12-q21 amplicon. We evaluated the expression of a transcript variant of DARPP-32 (t-DARPP) and ERBB2 in 141 primary tumors and investigated the role of t-DARPP in trastuzumab resistance using OE19 and OE33 EAC cell models. Overexpression of t-DARPP mRNA was detected in two-thirds of tumors with a correlation between ERBB2 and t-DARPP overexpression levels (r = 0.58, P = 0.003). Cell viability and clonogenic survival assays showed that t-DARPP increased survival by 40% in response to trastuzumab (P &lt; 0.01). The Annexin-V staining and Western blot analysis indicated that t-DARPP effectively abrogated trastuzumab-induced apoptosis, inhibited cleavage of caspase-3, and blocked trastuzumab-induced dephosphorylation of ERBB2 and AKT proteins. The knockdown of endogenous t-DARPP reversed these effects and sensitized cells to trastuzumab (P &lt; 0.01). The cycloheximide-based protein degradation analysis indicated that t-DARPP extended the half-life of ERBB2, explaining the increase in the basal levels of ERBB2, p-ERBB2(Y1248), and p-AKT(S473). Coimmunoprecipitation and Western blot analysis showed that t-DARPP associated with ERBB2 in a protein complex, and interfered with trastuzumab binding to the ERBB2 receptor. Using EAC-xenografted mouse model, t-DARPP enhanced tumor growth and rendered tumors unresponsive to trastuzumab. This study establishes t-DARPP as a mediator of trastuzumab resistance and underscores its potential importance in clinical trials of EAC. Cancer Res; 72(17); 4504–14. ©2012 AACR.
Conditional Survival after Hepatic Resection for Hepatocellular Carcinoma in Cirrhotic Patients
Authors: Cucchetti Alessandro , Piscaglia Fabio , Cescon Matteo , Ercolani Giorgio , Terzi Eleonora , Bolondi Luigi , Zanello Matteo , Pinna Antonio D. 
Published: June 2012

Abstract
Purpose: Survival estimates are commonly reported as actuarial survival after the first observation, but future survival probabilities can change over time. Conditional survival is a measure of prognosis for patients who have sometimes already survived several years since diagnosis; however, data on conditional survival for cirrhotic patients, resected for hepatocellular carcinoma (HCC), are lacking.
Experimental Design: Clinical data from 300 consecutive cirrhotic patients who underwent HCC resection were reviewed and the actuarial survival estimated. The 5-year conditional survival was calculated as CS = S(x + 5)/S(x) and represents the probability of surviving an additional 5 years, given that the patient has already survived x years.
Results: The 3-, 5-, and 10-year survival rates were, respectively, 69.0%, 57.7%, and 25.3% and were lower in cases of portal hypertension, Model for End-stage Liver Disease (MELD) score ≥9, United Network for Organ-Sharing T3 tumor, GIII–GIV tumors, and microscopic vascular invasion. However, the 5-year conditional survival calculation showed that patients resected for more advanced (T3) tumors or with adverse histologic features will experience the same survival probabilities as patients with less advanced tumors or favorable histology from the third year after surgery onward, as they had probably escaped recurrence from intrahepatic metastases. Patients who underwent repeated hepatectomy for recurrence presented higher conditional survival.
Conclusions: Conditional survival showed that the impact of different variables influencing survival is not linear over time after hepatic resection. Information derived from conditional survival can be used to better manage patients with HCCs, including the potential future setting of adjuvant therapies and the choice of listing, or not, for transplantation resected patients not recurring within 2 years. Clin Cancer Res; 18(16); 4397–405. ©2012 AACR.
Crenolanib Inhibits the Drug-Resistant PDGFRA D842V Mutation Associated with Imatinib-Resistant Gastrointestinal Stromal Tumors
Authors: Heinrich Michael C. , Griffith Diana , McKinley Arin , Patterson Janice , Presnell Ajia , Ramachandran Abhijit , Debiec-Rychter Maria 
Published: June 2012

Abstract
Purpose: To determine the potential of crenolanib, a potent inhibitor of PDGFRA, to treat malignancies driven by mutant PDGFRA.
Experimental Design: The biochemical activity of crenolanib was compared with imatinib using a panel of PDGFRA-mutant kinases expressed in several different cell line models, including primary gastrointestinal stromal tumors (GIST) cells. The antiproliferative activity of crenolanib was also studied in several cell lines with PDGFRA-dependent growth.
Results: Crenolanib was significantly more potent than imatinib in inhibiting the kinase activity of imatinib-resistant PDGFRA kinases (D842I, D842V, D842Y, DI842-843IM, and deletion I843). For example, crenolanib was 135-fold more potent than imatinib against D842V in our isogenic model system, with an IC50 of approximately 10 nmol/L. The relative potency of crenolanib was further confirmed in BaF3 and primary GIST cells expressing PDGFRA D842V. In contrast, imatinib was at least 10-fold more potent than crenolanib in inhibiting the V561D mutation. For all other tested PDGFRA mutations, crenolanib and imatinib had comparable potency.
Conclusions: Crenolanib is a potent inhibitor of imatinib-resistant PDGFRA kinases associated with GIST, including the PDGFRA D842V mutation found in approximately 5% of GISTs. The spectrum of activity of crenolanib suggests that this drug is a type I inhibitor (inhibitor of activated conformation of kinase). Based in part on these results, a phase II clinical study of this agent to treat GIST with the PDGFRA D842V mutation has been initiated. Clin Cancer Res; 18(16); 4375–84. ©2012 AACR.
Heat Shock Cognate 70 Regulates the Translocation and Angiogenic Function of Nucleolin
Authors: Ding Yanping , Song Nan , Liu Chang , He Ting , Zhuo Wei , He Xiaoli , Chen Yang , Song Xiaomin , Fu Yan , Luo Yongzhang 
Published: June 2012

Objective—
Cell surface nucleolin (NCL) plays fundamental roles in tumor angiogenesis. However, the mechanism underlying its surface translocation remains obscure. The present study discovered that heat shock cognate 70 (Hsc70) is essential in both the surface translocation and the angiogenic function of NCL.

Methods and Results—
We identified that Hsc70 interacted with NCL in endothelial cells via the peptide-binding domain of Hsc70 and the RNA-binding domain of NCL. Functional knockdown of Hsc70 remarkably inhibited the expression of surface NCL, which was rescued by wild-type Hsc70 rather than its truncations. Phosphorylation of NCL by either protein kinase C-ξ or casein kinase 2 mediated its interaction with Hsc70 and the surface expression. Hsc70 regulated NCL translocation via stabilizing NCL and enhancing its interaction with nonmuscle myosin heavy chain 9. Moreover, Hsc70 was associated with NCL-induced endothelial cell migration and tubule formation in vitro and angiogenesis in both matrigel plugs and xenograft tumors. Tissue array analysis revealed that the expression levels of NCL and Hsc70 were intimately correlated in human lung adenocarcinomas.

Conclusion—
Our study demonstrates that Hsc70 is a prerequisite for the surface translocation and angiogenic function of NCL, which suggests strategies to target both Hsc70 and NCL for more effective antiangiogenic therapies.
Both Internalization and AIP1 Association Are Required for Tumor Necrosis Factor Receptor 2-Mediated JNK Signaling
Authors: Ji Weidong , Li Yonghao , Wan Ting , Wang Jing , Zhang Haifeng , Chen Hong , Min Wang 
Published: June 2012

Objective—
The proinflammtory cytokine tumor necrosis factor (TNF), primarily via TNF receptor 1 (TNFR1), induces nuclear factor-κB (NF-κB)–dependent cell survival, and c-Jun N-terminal kinase (JNK) and caspase-dependent cell death, regulating vascular endothelial cell (EC) activation and apoptosis. However, signaling by the second receptor, TNFR2, is poorly understood. The goal of this study was to dissect how TNFR2 mediates NF-κB and JNK signaling in vascular EC, and its relevance to in vivo EC function.

Methods and Results—
We show that TNFR2 contributes to TNF-induced NF-κB and JNK signaling in EC as TNFR2 deletion or knockdown reduces the TNF responses. To dissect the critical domains of TNFR2 that mediate the TNF responses, we examine the activity of TNFR2 mutant with a specific deletion of the TNFR2 intracellular region, which contains conserved domain I, domain II, domain III, and 2 TNFR-associated factor-2-binding sites. Deletion analyses indicate that different sequences on TNFR2 have distinct roles in NF-κB and JNK activation. Specifically, deletion of the TNFR-associated factor-2-binding sites (TNFR2–59) diminishes the TNFR2-mediated NF-κB, but not JNK activation; whereas, deletion of domain II or domain III blunts TNFR2-mediated JNK but not NF-κB activation. Interestingly, we find that the TNFR-associated factor-2-binding sites ensure TNFR2 on the plasma membrane, but the di-leucine LL motif within the domain II and aa338–355 within the domain III are required for TNFR2 internalization as well as TNFR2-dependent JNK signaling. Moreover, domain III of TNFR2 is responsible for association with ASK1-interacting protein-1, a signaling adaptor critical for TNF-induced JNK signaling. While TNFR2 containing the TNFR-associated factor-2-binding sites prevents EC cell death, a specific activation of JNK without NF-κB activation by TNFR2–59 strongly induces caspase activation and EC apoptosis.

Conclusion—
Our data reveal that both internalization and ASK1-interacting protein-1 association are required for TNFR2-dependent JNK and apoptotic signaling. Controlling TNFR2-mediated JNK and apoptotic signaling in EC may provide a novel strategy for the treatment of vascular diseases.