bluuebunny/crossref_metadata_2025_split huggingface dataset:
SU‐BB‐BRB‐01: Close Encounters of the Media Kind
Authors: Fox M 
Published: July 2007

Out of nowhere, I was contacted by The New York Times to talk about medical physics, and suddenly seemed to have lost my knack of being able to communicate with the public. Questions of statistical nature were being asked and where were my resources? The AAPM website had not yet been set up for public friendly information, especially for reporters that want information NOW.The AAPM has made a commitment to raise media awareness of our profession and we need to be ready. The next two speakers will relate their experiences in this endeavor, and offer information on media communication and rapid response.
SU‐FF‐I‐127: Patient Specific Angiography Phantoms for Investigating New Endovascular Image‐Guided Interventional (EIGI) Devices
Authors: Sherman JR , Rangwalla HS , Dohatcu AC , Minsuok K , Ionita CN , Rudin S 
Published: July 2007

Purpose: To provide patient‐specific phantoms for investigating new endovascular image‐guided interventional (EIGI) devices such as stents. Methods and Materials: A human cerebral/saccular aneurysm phantom was constructed from a patient's segmented CT‐scan data. The CT‐derived vascular lumen was converted to a standard stereolithography (STL) computer file which was used, through a rapid‐prototyping process, to make a plastic resin (Accura 25) mold of the vessel with the aneurysm. In this process, an ultraviolet laser is used to selectively cure a liquid plastic layer by layer resulting in a highly accurate and very detailed positive model. RTV silicone is placed around this plastic aneurysm, allowed to cure, and then cut in half to create a mold with a cavity in the shape of the aneurysm. This mold is used to make a wax replica of the human aneurysm. The wax replica is then immersed in a silicone elastomer solution, the bubbles removed via vacuum, and the elastomer allowed to cure. The wax is then dissolved using boiling water. Results: The finished product is a clear elastomer model with a patient‐specific aneurysm cavity that may be used in both x‐ray and optical flow experiments. Multiple identical elastomer phantoms can be generated from one mold so that new EIGI devices such as an asymmetric stent with a low porosity patch region to occlude aneurysmal flow can be variously deployed under fluoroscopic guidance and evaluated angiographically. Additionally, the effects of contrast media can be studied by comparisons with optical flow studies. Comparisons of angiographic and optical time‐density curves for an anterior cerebral artery with multi‐lobular aneurysm will be presented. Conclusions: We have developed a unique system for the creation of realistic patient‐specific phantoms which enable the evaluation of detailed vascular flow and experimental EIGI treatment techniques for clinically representative pathology.(Support: NIH R01‐NS43924, R01‐EB002873, Toshiba Corp.).
WE‐C‐L100F‐01: The Promise of 256 Slice CT
Authors: Rifu T , Mather R 
Published: July 2007

Advancements in CT technology invariably lead to new clinical applications. Helical scanning opened up anatomy outside of the brain. Multislice technology allowed fast volumetric scanning. Sixteen slice introduced vascular applications. Sixty‐four slice scanners made cardiac scanning a matter of routine practice. In recent years, each of the evolutionary steps in CT technology has sought to improve the way helical scanning is accomplished.Toshiba Medical Systems has developed a Beta version of a 256 slice CT system to cover nearly 13 cm of anatomy in a single rotation with 0.5 mm slices to allow the complete organ coverage in a single rotation. This system can acquire images of an entire volume at a single, instantaneous time point which significantly reduces motion artifact and eliminates contrast phase differences within the volume. Since this system does not require helical acquisition for volumetric imaging, it will deliver significantly less dose for CT coronary angiography exams as well as reduced dose in most other applications.With its wide volume coverage, the 256 slice system promises to revolutionize the way we approach acute stroke patients, the way we look at myocardial perfusion imaging, and the way we image other moving body parts such as the lung during respiration and peripheral joint motion.
WE‐C‐M100J‐01: Cancer Treatment with MRI‐Guided High Intensity Focused Ultrasound
Authors: Chen L 
Published: July 2007

HIFU has long been known to offer the potential of very precise “Trackless lesioning” but has only recently with the current high quality methods of medical imaging, become a practical possibility for clinical treatment.Focused ultrasound uses ultrasound energy for tissue ablation. When the sound waves are focused to a small volume in the body, the intensity is high and the temperature at the focal point rises to 70–95°C, high enough to ablate the tissue. Proper treatment design will ensure that the energy density will be high at the focal point but low at other locations, and thus avoiding damages to nearby normal tissues.The volume of ablation (lesion) following a single HIFU exposure is small and will vary according to transducer characteristics, but it is typically cigar shaped with dimensions in the order of 1–3 mm (transverse) × 8–15 mm (along the beam axis). To ablate clinically relevant volumes these lesions must be placed side by side systematically to “paint out” the target tumor.Simply calculating an optimal treatment plan is not enough to ensure optimal outcome. Patient anatomic variability and tissue inhomogeneities have been shown to produce vastly different responses to thermal energy deposition, especially deep in the body. High quality imaging techniques can provide precise visualization and localization of the tissue damage. MR images enable the physician to localize the tumor and plan the treatment in the full 3 dimensions. Real‐time MR thermometry can provide an indication of tissue damage if critical temperatures are known.In several centers worldwide, HIFU is now being used clinically to treatment solid tumors (both malignant and benign), including those of the brain, breast, liver, kidney, prostate, bone matastases, pancreas and soft‐tissue sarcoma. The MRgFUS unit is currently available for clinical applications.This lecture will provide an overview of MrgFU and introduce the equipment that is commercially available for clinical applications in cancer treatment.Educational Objectives:1. The principles of MRgFUS.2. Advantages and limitations of MRgFUS for tissue ablation.3. Potential clinical applications of MRgFUS for cancer treatment.
WE‐C‐BRA‐05: Using Conformal Radiobiology to Find the Best Treatment Plan
Authors: Nahum A 
Published: July 2007

How can we use TCP and NTCP models in optimising radiotherapy outcome? The most basic or Level‐I optimisation is to take an existing ‘standard’ treatment plan with its standard total dose and fraction size, compute the NTCP and then adjust the total dose until an acceptable NTCP value is obtained: isotoxic customised dose prescription. This will yield immediate benefits in, for example, lung‐tumour radiotherapy. Level‐II optimisation uses the TCP and NTCP functions ‘upfront’ in the optimisation process to determine the beam weights and even angles, or, in the case of IMRT, to perform ‘inverse planning’. A typical criteria might be ‘Maximise the TCP for NTCP = 2.5%’ or ‘Minimise the NTCP for TCP = 90%’. In this Level‐II mode no constraints need be set regarding uniform dose in the target volume — the TCP model will take of this. However, maximum doses may well need to be set outside the target volume.Another exciting area is the connection between fractionation sensitivity and dose distributions in normal tissues. The ‘classical’ LQ‐based Withers isoeffect formula can be easily modified to reflect increasingly conformal dose distributions in organs at risk. The validity of this modification has been effectively demonstrated by the safe use of very large fractions in treating lung tumours with (highly conformal) body stereotaxy; the oversimplified BED concept would have forbidden such effective regimens.We need to start using radiobiologically based optimisation, without waiting until the TCP and NTCP models are ‘perfect’. The clinician may still use conventional tools such as single‐CT slice isodoses and DVHs to approve a radiobiologically optimised plan but she/he is going to find a marked improvement in the quality of such a plan.Educational Objectives:1. Appreciate the potential of using TCP and NTCP models in treatment plan optimisation.2. Understand what is meant by ‘isotoxic’ dose prescription.3. Understand the limitations of the Withers' isoeffect formula and how it can be modified to approximately account for dose distributions in organs at risk.
TH‐D‐M100F‐07: Topology Preserving Diffusion Registration Incorporating with Gradient Orientation Information
Authors: Gao S , Wang H , Zhang L , Mohan R , Dong L 
Published: July 2007

Purpose: The goal of this study was to develop an image intensity‐based diffusion registration algorithm that can be used for reliable automatic delineation of anatomical structures on daily CT images. The constraint of the topology preservation method used in this algorithm ensures that the transformations are reliable and accurate. Method and Materials: To achieve accurate deformable image registration using a diffusion‐based method, we proposed to incorporate the gradient orientation information into the driving force in diffusion registration. This is similar to the symmetric force in the demons algorithm. We also introduced to use the positive Jacobian constraint, which is the fundamental requirement for topology preservation, as a guideline to determine the smoothing parameter in the diffusion algorithm to ensure that a realistic registration can be achieved. The planning contours were mapped onto the daily CT image using the displacement field after the deformable image registration. The contour mapping serves as a validation of the algorithm proposed in this study. The performance of the proposed algorithm for register 3D CT images of prostate and head and neck cancer patients were evaluated by visually assessing the agreement of the anatomical structures with deformed contours in target image. Results: The contours deformed with the topology preservation method are more accurate segmentation of the anatomical structures, compared to a similar method without this constraint. The positivity of Jacobian provided a way to evaluate the performance of the registration and to serve as guidance for selecting smoothing parameters. Conclusion: We proposed a diffusion registration algorithm incorporated with the intensity gradient information and the positive Jacobian constraint that ensures the transformations to topologically preservation of anatomical structures. Compared to demons algorithm, the proposed algorithm is more computational efficient and accurate, especially for prostate CT images registration.The research is in part sponsored by Varian.
Transcriptional Functionality of Germ Line p53 Mutants Influences Cancer Phenotype
Authors: Monti Paola , Ciribilli Yari , Jordan Jennifer , Menichini Paola , Umbach David M. , Resnick Michael A. , Luzzatto Lucio , Inga Alberto , Fronza Gilberto 
Published: July 2007

Abstract
Purpose: The TP53 tumor suppressor gene encodes a sequence-specific transcription factor that is able to transactivate several sets of genes, the promoters of which include appropriate response elements. Although human cancers frequently contain mutated p53, the alleles as well as the clinical expression are often heterogeneous. Germ line mutations of TP53 result in cancer proneness syndromes known as Li-Fraumeni, Li-Fraumeni–like, and nonsyndromic predisposition with or without family history. p53 mutants can be classified as partial deficiency alleles or severe deficiency alleles depending on their ability to transactivate a set of human target sequences, as measured using a standardized yeast-based assay (see http://www.umd.be:2072/index.html). We have investigated the extent to which the functional features of p53 mutant alleles determine clinical features in patients who have inherited these alleles and have developed cancer.
Experimental Design: We retrieved clinical data from the IARC database (see http://www.p53.iarc.fr/Germline.html) for all cancer patients with germ line p53 mutations and applied stringent statistical evaluations to compare the functional classification of p53 alleles with clinical phenotypes.
Results: Our analyses reveal that partial deficiency alleles are associated with a milder family history (P = 0.007), a lower numbers of tumors (P = 0.007), and a delayed disease onset (median, 31 versus 15 years; P = 0.007) which could be related to distinct tumor spectra.
Conclusions: These findings establish for the first time significant correlations between the residual transactivation function of individual TP53 alleles and clinical variables in patients with inherited p53 mutations who develop cancer.
Correlation between Development of Rash and Efficacy in Patients Treated with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib in Two Large Phase III Studies
Authors: Wacker Bret , Nagrani Tina , Weinberg Jacqueline , Witt Karsten , Clark Gary , Cagnoni Pablo J. 
Published: July 2007

Abstract
Purpose: Data from two large phase III studies were analyzed to characterize the correlation between the occurrence of rash during treatment with the epidermal growth factor receptor inhibitor erlotinib and improved clinical outcomes.
Experimental Design: Overall survival, progression-free survival (PFS), and tumor response were compared between patients in a rash-evaluable subset who did or did not develop rash in National Cancer Institute of Canada Clinical Trials Group Studies BR.21 (single agent in non–small-cell lung cancer, n = 444 in erlotinib group and n = 229 in placebo group) and PA.3 (combination with gemcitabine in pancreatic cancer, n = 254 in erlotinib plus gemcitabine group and n = 245 in placebo plus gemcitabine group).
Results: Presence of rash strongly correlated with overall survival in both studies. In Study BR.21, these correlations increased with rash severity grade: grade 1 versus no rash [hazard ratio (HR), 0.41, P &lt; 0.001] and grade ≥2 versus no rash (HR, 0.29, P &lt; 0.001). Similar results were observed for PFS. Disease control (complete response + partial response + stable disease) seemed to increase with the presence and severity of rash. In Study PA.3, grade ≥2 rash (but not grade 1) strongly correlated with overall survival improvement: grade ≥2 versus no rash (HR, 0.47, P &lt; 0.001). Similarly, grade ≥2 rash was strongly correlated with improvements in PFS and disease control.
Conclusions: Physicians and patients should view rash development as a positive event indicative of greater likelihood of clinical benefit. Further studies are required to identify patients most likely to develop rash and to determine if dose escalation to induce rash can improve efficacy.
Prognostic Significance of the Immunohistochemical Staining of Cleaved Caspase-3, an Activated Form of Caspase-3, in Gliomas
Authors: Kobayashi Tatsuya , Masumoto Junya , Tada Tsuyoshi , Nomiyama Tetsuo , Hongo Kazuhiro , Nakayama Jun 
Published: July 2007

Abstract
Purpose: Gliomas are common tumors of the central nervous system, and the majority of patients with gliomas have a poor prognosis. The prediction of prognosis is very important in selecting treatment. In the present study, we retrospectively examined the immunohistochemical staining of cleaved caspase-3 (CC3), an activated form of caspase-3 that acts as a lethal protease at the most distal stage of the apoptosis pathway, in gliomas, and the correlation between the prognosis of patients and caspase-3 activation to find useful prognostic indicators.
Experimental Design: Immunohistochemical staining of CC3 was done in 65 patients with gliomas. The percentage of CC3 staining-positive cells was defined as the CC3 immunoreactivity score (IRS). Survival analysis between CC3 IRS of glioma patients and survival time was carried out using the Kaplan-Meier method with the log-rank test and the Cox proportional hazards regression model.
Results: CC3 IRS was statistically analyzed to designate the best provisional cutoff point, and when detected in &gt;10% of glioma cells, it was considered positive. The Kaplan-Meier method with the log-rank test revealed that patients with CC3 IRS-positive tumors had significantly greater survival than those with CC3 IRS-negative tumors among three grades, 2, 3, and 4 (P = 0.0061), and within grade 3 of anaplastic astrocytoma (P = 0.0458). After adjustment for known clinical prognostic factors, such as age, WHO grade, and performance status, the hazard ratio for CC3 IRS-positive was 0.39 with 95% confidence interval between 0.19 and 0.85 (P = 0.0187). Within high grades, including grades 3 and 4, the hazard ratio was 0.40 with 95% confidence interval between 0.20 and 0.86 (P = 0.0192).
Conclusions: CC3 IRS could be useful as a good prognostic indicator for glioma patients.
Granulocyte Macrophage Colony-Stimulating Factor–Secreting Allogeneic Cellular Immunotherapy for Hormone-Refractory Prostate Cancer
Authors: Small Eric J. , Sacks Natalie , Nemunaitis John , Urba Walter J. , Dula Eugene , Centeno Arthur S. , Nelson William G. , Ando Dale , Howard Catherine , Borellini Flavia , Nguyen Minh , Hege Kristen , Simons Jonathan W. 
Published: July 2007

Abstract
Purpose: This trial evaluated the safety, clinical activity, and immunogenicity of an allogeneic cellular immunotherapy in 55 chemotherapy-naïve patients with hormone-refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, is a combination of two prostate carcinoma cell lines modified with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene.
Experimental Design: HRPC patients with radiologic metastases (n = 34) or rising prostate-specific antigen (PSA) only (n = 21) received a prime dose of 500 million cells and 12 boost doses of either 100 million cells (low dose) or 300 million cells (high dose) biweekly for 6 months. End points were changes in PSA, time to progression, and survival.
Results: Median survival was 26.2 months (95% confidence interval, 17, 36) in the radiologic group: 34.9 months (8, 57) after treatment with the high dose (n = 10) of immunotherapy and 24.0 months (11, 35) with the low dose (n = 24). The median time to bone scan progression in the radiologic group was 5.0 months (2.6, 11.6) with the high dose and 2.8 months (2.8, 5.7) with the low dose. In the rising-PSA group (n = 21) receiving the low dose, the median time to bone scan progression was 5.9 months (5.6, not reached), and median survival was 37.5 months (29, 56). No dose-limiting or autoimmune toxicities were seen; the most common adverse events were injection site reaction and fatigue.
Conclusions: These results suggest that this GM-CSF–secreting, allogeneic cellular immunotherapy is well tolerated and may have clinical activity in patients with metastatic HRPC. Phase 3 trials to confirm these results are under way.
Age-Related DNA Methylation Changes in Normal Human Prostate Tissues
Authors: Kwabi-Addo Bernard , Chung Woonbok , Shen Lanlan , Ittmann Michael , Wheeler Thomas , Jelinek Jaroslav , Issa Jean-Pierre J. 
Published: July 2007

Abstract
Purpose: Prostate cancer is a leading cause of cancer death among the aging male population but the mechanism underlying this association is unclear. Aberrant methylation of promoter CpG islands is associated with silencing of genes and age-dependent methylation of several genes has been proposed as a risk factor for sporadic cancer. We examined the extent of gene methylation in pathologically normal human prostate as a function of age.
Experimental Design: We used pyrosequencing to quantitatively analyze the methylation status of nine CpG islands in normal prostate tissue DNA from 45 organ donors and 45 patients who had undergone cystoprostatectomy for bladder cancer. We also analyzed 12 pairs of matched benign and prostate cancer tissue DNA from patients with prostate cancer.
Results: Linear regression analysis revealed a significant increase in promoter methylation levels correlating with age for CpG islands at RARβ2 (r = 0.4; P &lt; 0.0001), RASSF1A (r = 0.27; P = 0.01), GSTP1 (r = 0.59; P &lt; 0.0001), NKX2-5 (r = 0.27; P = 0.008), and ESR1 (r = 0.244; P = 0.023) in the normal prostate tissue samples studied. A calculated average methylation (z score) at all nine CpG loci analyzed in the normal prostate tissues showed a strong correlation with age (r = 0.6; P &lt; 0.001). Comparison of the methylation level for the matched benign and prostate cancer tissues from individual patients with prostate cancer showed significantly higher methylation in the prostate cancer tissue samples for RARβ2 (P &lt; 0.001), RASSF1A (P = 0.005), GSTP1 (P &lt; 0.001), NKX2-5 (P = 0.003), ESR1 (P = 0.016), and CLSTN1 (P = 0.01).
Conclusions: Our findings show aberrant hypermethylation as a function of age in the normal prostate tissues. Such age-related methylation may precede and predispose to full-blown malignancy.
Long-Term Protective Effect of Mature DC-LAMP+ Dendritic Cell Accumulation in Sentinel Lymph Nodes Containing Micrometastatic Melanoma
Authors: Elliott Bruce , Scolyer Richard A. , Suciu Stefan , Lebecque Serge , Rimoldi Donata , Gugerli Oliver , Musat Elena , Sharma Raghwa N. , Lienard Danielle , Keilholz Ulrich , Testori Alessandro , Eggermont Alexander , MacKie Rona , Robert Caroline , Cook Martin , Thompson John F. , Angevin Eric , Spatz Alain ,   on behalf of the European Organization for Research and Treatment of Cancer Melanoma Group
Published: July 2007

AbstractPurpose: In a previous immunohistochemical study of dendritic cells (DC) in sentinel lymph nodes (SLN) draining regressing melanomas, we found that the accumulation of mature DC-LAMP+ DCs in SLNs was associated with local expansion of antigen-specific memory effector CTLs and the absence of metastasis in downstream lymph nodes. The aim of this study was to investigate the prognostic importance of the maximal density of mature DCs in SLNs.Experimental Design: A total of 458 consecutive patients with micrometastatic melanoma within SLNs were eligible for analysis. The maximal density of mature DC-LAMP+ DCs was evaluated by three independent observers and categorized into three classes (&lt;100, 100 to &lt;200, and ≥200/mm2).Results: There was excellent interobserver reproducibility for maximum density of mature DC-LAMP+ DC scores (κ score = 0.82). There were differences in the maximal density scores and staining intensity according to the treating melanoma center (P &lt; 0.001). The higher the mature DC density in the SLN is, the longer is the duration of survival [P = 0.047; hazard ratio, 0.70; 95% confidence interval, 0.50-1.00]. Adjusted by thickness and ulceration, the prognostic importance of DC density was lower (P = 0.36).Conclusion: This study is the first to report the prognostic value of DC-LAMP+ DC counts in SLNs containing metastatic melanoma. Patients with a high density of mature DCs (≥200/mm2) have the lowest risk of death. It also provides evidence that a lack of maturation in the SLNs is important in biological facilitation of melanoma progression.