bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial Clinical Results of Stereotactic Radiotherapy for the Treatment of Craniopharyngiomas
Authors: Selch Michael T. , DeSalles Antonio A.F. , Wade Maria , Lee Steve P. , Solberg Timothy D. , Wallace Robert E. , Ford Judith M. , Rubino Gregory , Cabatan-Awang Cynthia , Withers H. Rodney
Published: October 2014

The efficacy and toxicity of stereotactic radiotherapy (SRT) for the treatment of craniopharyngioma has been retrospectively evaluated in 16 patients. The median tumor diameter was 2.8 cm (range 1.5–6.1) and the median tumor volume was 7.7 cc (range 0.7–62.8). SRT was delivered to a single isocenter using a dedicated 6 MV linear accelerator to patients immobilized with a relocatable stereotactic head frame. The three-year actuarial overall survival was 93% and the rate of survival free of any imaging evidence of progressive disease was 75%. The three-year actuarial survival rates free of solid tumor growth or cyst enlargement were 94% and 81% respectively. Our results suggest that SRT is a safe and effective treatment approach for patients with craniopharyngioma. Long-term follow-up is required to determine whether the normal tissue-sparing inherent with SRT results in reduction of the neurocognitive effects of conventional radiotherapy for craniopharyngioma. SRT can be delivered to craniopharyngioma that may be difficult to treat with stereotactic radiosurgery due to proximity of the optic chiasm. Further clinical experience is necessary to determine the clinical utility of beam shaping in the setting of SRT.
Role of Proteomics in Diagnosis of Cancer
Authors: Jain K. K.
Published: October 2014

Proteomic technologies have emerged as an important addition to the genomic and antibody-based technologies for the diagnosis of cancer. Important technologies include 2-D gel electrophoresis, mass spectrometry, laser capture microdissection, detection of molecular markers of cancer and protein patterns. For clinical applications, the most likely technologies to be used widely are protein biochips. Application of these technologies to various cancers are described. Proteomic technologies have a potential in developing molecular diagnostics and markers for the early detection of cancer. However, information from various diagnostic technologies should be integrated to obtain the optimal information required for clinical management of a patient.
Electric Field Enhanced Plasmid Delivery to Liver Hepatocellular Carcinomas
Authors: Gilbert Richard , Jaroszeski Mark J. , Heller Loree , Heller Richard
Published: October 2014

Electric field enhanced molecular delivery for cancer research and treatment is a new technology that has demonstrated its effectiveness in clinical trials using bleomycin or cisplatin (Heller, R., Gilbert, R., Jaroszeski, M. J. Clinical applications of electrocemotherapy. Advanced Drug Delivery Reviews 35, 119–129 (1999)), as chemotherapeutic agents. The technology is being investigated in research applications for applicability as a method to enhance gene expression in a target tumor. Success is predicated on an appropriate effective electric field mediated delivery protocol that triggers significant appropriate gene expression duration and levels.

An electric field mediated delivery protocol includes a set of conditions associated with the electric field, the electroporation signature, as well as parameters associated with the plasmid and the electric field applicator. Manipulation of the electrical parameters within the electroporation signature generates different gene expression levels in liver hepatocellular carcinomas. Statistically significant gene expression levels were obtained that differed by an order of magnitude when two different electric field strength and duration conditions were employed.
Measurement of Volumetric and Vascular Changes with Dynamic Contrast Enhanced MRI for Cancer Therapy Monitoring
Authors: Su Min-Ying. , Yu Hon , Chiou Jr-Yuan , Wang Jun , Nalcioglu Orhan , Fruehauf John P. , Mehta Rita S. , Baick Choong Hyun
Published: October 2014

Longitudinal dynamic contrast enhanced MRI studies were undertaken to monitor therapy induced volumetric and vascular changes. Three study components are presented in this work: one animal tumor chemotherapy study (R3230 AC adenocarcinoma treated with Taxotere), one patient with invasive lobular breast cancer undergoing neoadjuvant chemotherapy (AC regimen), and one patient with brain metastasis of primary breast cancer undergoing radiation therapy (40 Gray whole brain irradiation). In the animal study two contrast media with different molecular weights, Gadodiamide and Gadomer-17, were used. Only Gadomer-17 revealed significant changes in vascular properties. The responders showed decreased Vb (vascular volume index) and K2 (out-flux transport rate), which preceded tumor regression. The control tumors showed increased Vb and K2, before tumor growth became much faster. In the patient undergoing neoadjuvant therapy, the tumor was shrinking by 45% after 2 cycles of treatment, then again by 45% after 2 additional cycles. K2 was decreasing over time with treatment. In the patient with brain metastasis, the 2 follow-up studies were much longer apart to monitor the regression and relapse of lesions. The pre-treatment volumes of lesions in the group without recurrence were significantly smaller compared to those with recurrence. In summary, the tumor volume was more sensitive than the vascular parameters measured by the small extracellular contrast medium for the assessment of therapy response and prediction of recurrence. The vascular properties measured by macromolecular contrast medium may have the potential to serve as early therapeutic efficacy indicators.
RFA: CA-03-002 Network for Translational Research: Optical Imaging
Authors: Clarke Laurence P. , Baker Houston , Kelloff Gary , Sullivan Daniel
Published: October 2014

The National Cancer Institute (NCI) invites applications for cooperative agreement (U54) awards to establish a Specialized Research Resource Center that will participate as a member of a network of inter-disciplinary, inter-institutional research teams for the purpose of supporting translational research in optical imaging and/or spectroscopy in vivo. The network is to be named the “Network for Translational Research: Optical Imaging” (NTROI) and will operate under the guidance of a Steering Committee (SC). The goal of this request for applications (RFA) is to organize a consortium with flexibility in scope, funding, and incentives to encourage inter- and intra-team collaborations on translational cancer research. The objective is to accelerate the pace of translational research by developing a consensus process to improve methods for system integration, optimization and validation of next-generation in vivo optical imaging and/or spectroscopy methods and technologies, including contrast agents. Investigators are encouraged to include in vivo molecular imaging methods that give information about molecular events in cells or the extra-cellular milieu. The research scope includes feasibility studies for the detection of pre-cancerous lesions, cancer detection and diagnosis, and measurement or prediction of response to therapy.
The Rationale for Adjuvant Whole Brain Radiation Therapy with Radiosurgery in the Treatment of Single Brain Metastases
Authors: Patchell Roy A. , Regine William F.
Published: October 2014

Randomized trials have established the efficacy of focal treatment (either stereotactic radiosurgery or conventional surgery) for single brain metastases. In the past, adjuvant whole brain radiation therapy (WBRT) was routinely given with focal therapy. Recently, the utility of adjuvant WBRT has been called into question. This paper examines the scientific evidence and the arguments, pro and con, concerning the use of adjuvant WBRT in association with stereotactic radiosurgery or conventional surgery.
The Timing of Immunotherapy and Nephrectomy in Multimodality Treatment of Metastatic Renal Cell Carcinoma
Authors: Bex Axel , Horenblas Simon , de Gast Gijsbert C.
Published: October 2014

Multimodality treatment of metastatic renal cell carcinoma with immunotherapy and cytoreductive surgery is controversial. Especially the benefit of removing asymptomatic primary tumors in synchronous metastatic renal cell cancer has been debated since several non-randomized, retrospective studies revealed an improved response to immunotherapy and prolonged survival following initial nephrectomy. Two recent randomized prospective trials both demonstrated a prolonged survival in those who were randomly assigned to undergo nephrectomy of the primary tumor prior to treatment with interferon alfa-2b than in those who were assigned to undergo treatment with interferon alfa-2b alone. In these trials the survival benefit was limited and strongly influenced by overall performance score. The timing of immunotherapy, either as neoadjuvant (prior to nephrectomy) or adjuvant treatment (following nephrectomy) in the multimodality approach of synchronous metastatic renal cell carcinoma remains controversial. Selection of patients, the possible mechanisms underlying the survival advantage of the combination of nephrectomy and immunotherapy, and the timing of the treatment modalities are discussed herein.
Radiation Enhances the Anti-tumor Effects of Vaccinia-p53 Gene Therapy in Glioma
Authors: Timiryasova Tatyana M. , Gridley Daila S. , Chen Bing , Andres Melba L. , Dutta-Roy Radha , Miller Glen , Bayeta Erben J. M. , Fodor Istvan
Published: October 2014

The overall goal of this study was to analyze the effect and mechanism of radiation in combination with vaccinia viruses (VV) carrying the p53 gene against glioma. Comparison of two alternative treatments of cultured C6 (p53+) and 9L (p53−) rat glioma cells showed significantly reduced survival for both cell lines, especially 9L, when radiation was applied prior to virus versus radiation alone. High p53 protein expression mediated by VV-TK-p53 was measured in infected cells. Single modality treatment of C6 cells with psoralen and UV (PUV)-inactivated VV-TK-p53 (PUV-VV-TK-53) or radiation significantly decreased survival compared with PUV-inactivated L-15 (PUV-L-15) control virus. However, no difference was observed between radiation and combination treatments of C6 cells. In contrast, radiation followed by PUV-VV-TK-53 resulted in dramatic reduction of 9L cell viability, compared to single modality treatment. Flow cytometry analysis of Annexin-V-stained 9L cells showed that radiation and PUV-VV-TK-53 caused a significant decrease in live cells (17.2%) as compared to other treatments and control (61.6–98.3%). Apoptosis was observed in 37.2% of cells, while the range was 0.7–7.8% in other treatment groups; maximal p53 level was measured on day 7 post-infection. In athymic mice bearing C6 tumors, VV-TK-53 plus radiation in both single and multiple therapies resulted in significantly smaller tumors by day 30 compared to the agents given only once. Immunohistochemical analysis of tumor sections demonstrated p53 protein expression over 20 days after VV-TK-53 treatment. Analysis of blood and spleen cells of mice given multiple combination treatments showed significant splenomegaly, leukocytosis, and increased DNA synthesis and response to mitogen. Multiple combination treatments were also associated with significantly elevated natural killer and B cells in the spleen. There were no overt toxicities, although depression in red blood cell and thrombocyte parameters was noted. Collectively, the data demonstrate that radiation significantly improves the efficacy of VV-mediated tumor suppressor p53 therapy and may be a promising strategy for glioma treatment. Furthermore, the results support the conclusion that the mechanisms underlying the enhanced anti-tumor effect of combination treatment include apoptosis/necrosis and upregulation of innate immune defenses.
Virtual Bronchoscopy: Comparison of Different Surface Rendering Models
Authors: Seemann Marcus D. , Heuschmid Martin , Vollmar Joachim , Küttner Axel , Schöber Wolfgang , Schäfer Jürgen F. , Bitzer Michael , Claussen Claus D.
Published: October 2014

The aim of this study was to compare different representation models of surface-rendered virtual bronchoscopy. 10 consecutive patients with inoperable primary lung tumors underwent thin-section spiral computed tomography. The structures of interest, the tracheobronchial system and anatomical and pathological thoracic structures were segmented using an interactive threshold interval volume-growing segmentation algorithm and visualized with the aid of a color-coded surface rendering method. For virtual bronchoscopy, the tracheobronchial system was visualized using a triangle-surface rendering model, a shaded-surface rendering model and a transparent shaded-surface rendering model. The triangle-surface rendering model allowed optimum detailed spatial representation of the dimensions of extraluminal anatomical and pathological mediastinal structures. As the lumen of the tracheobronchial system was less well defined, the rendering model was of limited use for depiction of the airway surface. The shaded-surface rendering model facilitated an optimum assessment of the airway surface, but the mediastinal structures could not be depicted. The transparent shaded-surface rendering model provides simultaneous adequate to optimum visualization and assessment of the intraluminal airway surface and the extraluminal mediastinal structures as well as a quantitative assessment of the spatial relationship between these structures. Fast data acquisition with a multi-slice detector spiral computed tomography scanner and the use of virtual bronchoscopy with the transparent shaded-surface rendering model obviate the need for time consuming detailed analysis and presentation of axial source images by providing improved the diagnostic imaging of endotracheal and endobronchial diseases and offering a useful alternative to fiberoptic bronchoscopy.
Optical Detection and Eradication of Dysplastic Barrett's Esophagus
Authors: Song Louis-Michel Wong Kee , Wang Kenneth K.
Published: October 2014

Dysplastic Barrett's esophagus is a condition that offers multiple diagnostic and therapeutic challenges. The diagnosis of dysplasia within Barrett's esophagus currently relies on periodic endoscopic surveillance with multiple biopsies, a methodology limited by random sampling error, inconsistent histopathologic interpretation and delay in diagnosis. Optical spectroscopic and imaging techniques have the potential to identify dysplastic or early neoplastic lesions in real-time. These diagnostic modalities are needed to enhance the endoscopic surveillance of Barrett's esophagus in the future as well as help to define lesions for endoscopic therapy. Esophagectomy has been the standard of care for Barrett's esophagus with high-grade dysplasia although it is a procedure associated with significant morbidity and mortality. Minimally invasive endoscopic ablative therapies are attractive and less morbid alternatives to esophagectomy, with promising results obtained from the use of light-activated drugs (i.e., photodynamic therapy). The combination of novel optical diagnostic techniques and therapies will provide the endoscopist with much needed tools that can considerably enhance the management of patients with Barrett's esophagus. This article reviews the current status and future prospects of optical-based modalities for diagnosis and therapy of dysplastic Barrett's esophagus.
Instrumentation for Multi-modal Spectroscopic Diagnosis of Epithelial Dysplasia
Authors: Tunnell James W. , Desjardins Adrien E. , Galindo Luis , Georgakoudi Irene , McGee Sasha A. , Mirkovic Jelena , Mueller Markus G. , Nazemi Jon , Nguyen Freddy T. , Wax Adam , Zhang Qingguo , Dasari Ramachandra R. , Feld Michael S.
Published: October 2014

Reflectance and fluorescence spectroscopies have shown great promise for early detection of epithelial dysplasia. We have developed a clinical reflectance spectrofluorimeter for multimodal spectroscopic diagnosis of epithelial dysplasia. This clinical instrument, the FastEEM, collects white light reflectance and fluorescence excitation-emission matrices (EEM's) within a fraction of a second. In this paper we describe the FastEEM instrumentation, designed for collection of multi-modal spectroscopic data. We illustrate its performance using tissue phantoms with well defined optical properties and biochemicals of known fluorescence properties. In addition, we discuss our plans to develop a system that combines a multi-spectral imaging device for wide area surveillance with this contact probe device.
Dynamic Infrared Imaging of Newly Diagnosed Malignant Lymphoma Compared with Gallium-67 and Fluorine-18 Fluorodeoxyglucose (FDG) Positron Emission Tomography
Authors: Janicek Milos J. , Demetri George , Janicek Milos R. , Shaffer Kitt , Fauci Mark A.
Published: October 2014

Staging and therapy monitoring of malignant lymphomas relies heavily on imaging using arbitrary size criteria from computed tomography (CT) and sometimes non-specific radionuclide studies to assess the activity of the disease. Treatment decisions are based on early assessment of the response to therapy and the residual volume of the disease. Our initial experience is reported using a new noninvasive, inexpensive, and reproducible passive imaging modality, Dynamic Infrared Imaging (DIRI), which may add a new dimension to functional imaging. This system relies on its ability to filter the raw infrared signal using biological oscillatory behavior. It detects and analyzes minute oscillations of temperature and heat distribution in tumors.
Polarized Reflectance Spectroscopy for Pre-Cancer Detection
Authors: Sokolov Konstantin , Nieman Linda T. , Myakov Alexey , Gillenwater Ann
Published: October 2014

Early detection of cancer and its curable precursors remains the best way to ensure patient survival and quality of life. Thus, highly selective, sensitive and cost-effective screening and diagnostic techniques to identify curable pre-cancerous lesions are desperately needed. Precancers are characterized by increased nuclear size, increased nuclear/cytoplasmic ratio, hyperchromasia and pleomorphism, which currently can only be assessed through an invasive, painful biopsy. Here, we describe the development of a non-invasive optical technique based on polarized reflectance spectroscopy that has the potential to provide in real time diagnostically useful information for pre-cancer detection. Our results demonstrate that polarized reflectance spectroscopy can be used to selectively detect the size-dependent scattering characteristics of nuclei in vivo. We gradually progress from cell suspensions to realistic three-dimensional tissue models of epithelium, then to cervical biopsies and, finally to in vivo studies on normal volunteers and clinical patients.
Computed Tomographic Colonography (CTC): Possibilities and Limitations of Clinical Application in Colorectal Polyps and Cancer
Authors: Heuschmid Martin , Luz Oliver , Schaefer Juergen F. , Kopp Andreas F. , Claussen Claus D. , Seemann Marcus D.
Published: October 2014

Colorectal cancer is the second leading cause of cancer-related deaths in Europe and the United States. Most colorectal cancers develop from adenomatous polyps over a number of years. Early detection of polyps eliminates the risk of subsequent carcinomas.

Computed tomographic (CT) colonography is a diagnostic technique detecting colorectal neoplasms. With the introduction of multidetector-row computed tomography (MD-CT), CT colonography (CTC) has gained influence as a new diagnostic tool in early detection of colonic pathologies by acquiring volumetric CT data sets of the abdomen. This volumetric data is analyzed using CTC workstations, which provide an interactive display of 2D and 3D images of the colon. In several studies, CTC revealed a high accuracy (sensitivity/patient: 83–100% and specificity/patient: 93–100%) in detecting pathological colonic changes. Furthermore, CTC is an excellent diagnostic technique for the evaluation of patients with incomplete conventional colonoscopy and allows the assessment of extracolonic abdominal and pelvic organs.

In this article, the status of CT colonography as a method of detecting colonic polyps and colorectal carcinomas using single- and multidetector-row CT will be reviewed.
Lung Cancer Radiation Therapy: Monte Carlo Investigation of “Under Dose” by High Energy Photons
Authors: DesRosiers Paul M. , Moskvin Vadim P. , DesRosiers Colleen M. , Timmerman Robert D. , Randall Marcus E. , Papiez Lech S.
Published: October 2014

Loss of electronic equilibrium in lung tissue causes a build-up region in the tumor. Increasing the photon energy increases the depth at which electronic equilibrium is reestablished within the lung tumor. This study uses the Monte Carlo code PENELOPE for simulations of radiation treatment of tumor surrounded by lung. Six MV photons were compared to 15 MV photons using four beam arrangements in both homogeneous and heterogeneous media. The experimental results demonstrate that for every beam arrangement in heterogeneous media 15 MV photons delivered 5% to 10% lower dose to the tumor periphery than 6 MV photons. The simulations also show that in axial coplanar treatment plans, the loss of electronic equilibrium was greatest in the coronal plane. In conclusion there is a tumor sparing effect at the tumor-lung interface that is a function of beam energy. As an alternative to increasing beam energy, the addition of multiple beam angles with lower energy photons improved target coverage. If higher energy beams are required for patients with large separation, then adding multiple beam angles does offer some improved target coverage. The non-coplanar technique with the lower energy photons covered the tumor with a greatest isodose at the tumor periphery without tangential sparing in the coronal plane.
Improved Targeting of Photosensitizers by Intratumoral Administration of Immunoconjugates
Authors: Gupta Seema , Mishra A.K. , Muralidhar K. , Jain Viney
Published: October 2014

Biodistribution of technetium (99m Tc) labeled hematoporphyrin derivative (HpD, Photosan-3) conjugated to a monoclonal antibody to carcinoembryonic antigen (anti-CEA) was compared following intravenous ( i.v.) and intratumoral ( i.t.) administration in solid Ehrlich ascites tumor bearing mice. Images of mice at different time intervals were acquired after injection of radiolabeled PS-3 in either conjugated or unconjugated forms. Quantitative estimation of the radiolabel in different tissues was performed by selecting the different region of interests (ROIs). Maximum accumulation of both free and antibody conjugated PS-3 following i.v. administration was observed in liver followed by tumor. Tumor/muscle (T/N) ratio was more with free PS-3 compared to conjugated PS-3. Pharmacokinetics of free and conjugated PS-3 was also different with faster accumulation of conjugated PS-3 in the tumor. With intratumoral administration of anti-CEA-PS-3-99m Tc, specific accumulation and retention of the sensitizer was observed in the tumor tissue. Since, direct injection of antibody conjugated photosensitizer into the tumor resulted in longer retention of the dye in the tumor with no accumulation in the normal tissues, the present results imply that the toxicity to normal tissues could be reduced significantly with selective destruction of the tumor following photodynamic treatment with the use of i.t. administration of specific antibodies conjugated to photosensitizers.
Evaluation of Intra- and Inter-fraction Motion in Breast Radiotherapy Using Electronic Portal Cine Imaging
Authors: Kron Tomas , Lee Chrison , Perera Francisco , Yu Edward
Published: October 2014

Breast irradiation is one of the most challenging problems in radiotherapy due to the complex shape of the target volume, proximity of radiation sensitive normal structures and breathing motion. It was the aim of the present study to use electronic portal imaging (EPI) during treatment to determine intra- and inter-fraction motion in patients undergoing radiotherapy and to correlate the magnitude of motion with patient specific parameters. EPI cine images were acquired from the medial tangential fields of twenty radiotherapy patients on a minimum of 5 days each over the course of their treatment. The treatments were administered using 10 MV X-rays and dynamic wedges on a Varian Clinac 2100CD linear accelerator. Depending on the incident dose and the angle of the wedge, between 4 and 16 images could be acquired in one session using an EPI device based on liquid ionization chambers (Varian). The border between lung and chest-wall could be easily detected in all images and quantitative measurements were taken for the amount of lung in the field and the distance of the breast tissue from the field edges. Inter-fraction variability was found to be about twice as large as intra-fraction variability. The largest variability was detected in cranio/caudal direction (intra-fraction: 1.3 +/- 0.4 mm; inter-fraction: 2.6 +/- 1.3 mm) while the lung involvement varied by 1.1 +/- 0.2 mm and 1.8 +/- 0.6 mm intra- and inter-fraction, respectively. This indicates that the effect of breathing motion on the amount of radiated lung was not of major concern in the patients studied. Of other patient specific parameters such as body weight, breast separation, field size and location of the target, only increasing age was significantly correlated with larger inter-fraction motion. Acquisition of EPI cine loops proved to be a quick and easy technique to establish the amount of patient movement during breast radiotherapy. The relatively small variability found in the present pilot study justifies considerations for more conformal dose delivery.
Quantitative Assessment of Percent Breast Density: Analog versus Digital Acquisition
Authors: Harvey Jennifer A.
Published: October 2014

Breast density is a moderate risk factor for breast cancer based on quantitative measurement of percent breast density from film-screen mammograms. In this study, percent breast density was determined using computer-assisted interactive thresholding software from sixty consecutive mammograms of women undergoing digital screening mammography with a prior film-screen mammogram obtained within the last two years. Observations were made regarding discrepancies in density readings. Percent breast density was significantly lower for digital mammograms (mean 32.2%) compared to analog mammograms (mean 40.3%) (p<0.0001). This was not significant for women with less than 20% breast density (range +0.3 to −2.7%), but larger differences were seen with increasing density (12.5–14.9% lower for >50% density). Differences in density readings between analog and digital mammography were largely observed to be due to better recognition of the skin line on digital mammograms resulting in inclusion of more subcutaneous fat. Difficulties with appropriate recognition of subcutaneous breast tissue and fatty tissue near the chest wall were present for both analog and digital mammography. In conclusion, percent breast density is significantly lower when the mammogram is acquired in digital format compared to film-screen, largely due to better recognition of the skin line with resultant inclusion of more subcutaneous fat. Breast cancer risk predictions based on computerized assessment of breast density may be underestimated when applied to digital mammography.
Quantitative Target Sizes for Breast Tumor Detection Prior to Metastasis: A Prerequisite to Rational Design of 4D Scanners for Breast Screening
Authors: Vinh-Hung Vincent , Gordon Richard
Published: October 2014

It is important to determine a breast cancer tumor target size for new screening equipment and molecular detection. Records of women aged 40–69 years diagnosed in 1988–1997 with a nonmetastasized, node-negative, or node-positive T1-stage breast cancer were abstracted from the Surveillance, Epidemiology, and End Results (SEER) public-use database. The linear, Gompertzian, lognormal, and power-exponential models of the effect of tumor size on breast cancer specific mortality were compared using corresponding transforms of size in multivariate Cox proportional hazard models. Criteria for comparison were the linearization of the size transforms and the Nagelkerke R2 N index for the Cox models. Our results show that the assumption of a linear effect of tumor size was rejected by the linearity test ( P=0.05). The Gompertzian, lognormal, and power-exponential transforms satisfied the test with P-values of 0.08, 0.29, and 0.14, respectively. The corresponding R2 N were 0.08410, 0.08420, and 0.08414, respectively, showing a marginally best fit with the lognormal model, which was selected as a model for small tumors. The lognormal function with unadjusted crude death rates gave a lognormal-location parameter of 25 and shape parameter of 1.7, while the corresponding values in multivariate models were 18 and 2, respectively. The derivation of the lognormal model indicates tumor growth acceleration starting at 3 mm (unadjusted crude data) or 2 mm (multivariate model). The breast cancer tumor target size for screening equipment, whether by imaging or molecular detection, is therefore 2 mm.
Computer Aided Detection (CAD) for Breast MRI
Authors: Wood Chris
Published: October 2014

Since 1999, there has been a 40 percent increase per year in the number of breast MR studies performed in the United States. In addition, over 1200 sites in the United States have purchased surface coils for use in breast MR. This number is expected to grow to over 2,000 coils by the end of 2007.

It is well accepted that MR sensitivity for invasive breast cancers is near 100%, but as the use of breast MRI increases, radiologists interpreting breast MR are challenged to achieve high specificity while retaining high sensitivity. Reading the large number of acquired MR images in a reasonable amount of time also becomes more important as the number of studies increases.

Breast MR acquisition and image interpretation techniques have been refined through clinical optimization. The number of images to interpret, however, has increased to several hundred per case. Computer Aided Detection (CAD) algorithms have allowed radiologists to regain efficiency while maintaining optimized acquisition techniques.

The first CAD system for breast MR (CADstream by Confirma, Inc.) was launched in January 2003. The CAD installed base has since grown to over 150 systems in the US. The primary reason for this quick adoption of CAD for breast MR is that the CAD software enables readers to increase their efficiency while potentially improving their overall accuracy. The full benefits CAD for Breast MR are realized when the interpreting radiologist has a thorough understanding of the algorithms used, and the limitations of CAD.
Two-dimensional MR Spectroscopic Characterization of Breast Cancer In Vivo
Authors: Thomas M. Albert , Wyckoff Nathaniel , Yue Kenneth , Binesh Nader , Banakar Shida , Chung Hyun-Kyung , Sayre James , DeBruhl Nanette
Published: October 2014

The major goal of this work was to characterize invasive ductal carcinoma and healthy fatty breast tissues noninvasively using the classification and regression tree analysis (CART) of 2D MR spectral data. 2D L-COSY spectra were acquired in 14 invasive breast carcinoma and 21 healthy fatty breasts using a GE 1.5 Tesla MRI/MRS scanner equipped with a 2-channel phased-array breast MR coil. The 2D spectra were recorded in approximately 10 minutes using a minimum voxel size of 1 ml without any water suppression technique. For healthy breasts, spectra were acquired from at least one fatty region. 2D L-COSY spectra were recorded in a total of 43 voxels. Five diagonal and six cross peak volumes were integrated and at least eighteen ratios were selected as potential features for the statistical method, namely CART. The 2D L-COSY data showed a significant increase for the majority of these ratios in invasive breast carcinomas compared to healthy fatty tissues. Better accuracy of identifying carcinomas and fatty tissues is reported using CART analysis of different combinations of ratios calculated from the relative levels of water, choline, and saturated and unsaturated lipids. This is a first report on the statistical classification of 2D L-COSY in human breast carcinomas in vivo.
Density Estimation for Positron Emission Tomography
Authors: Pawlak Barbara , Gordon Richard
Published: October 2014

PET (positron emission tomography) scans are still in the experimental phase, as one of the newest breast cancer diagnostic techniques. There are two traditional approaches to the computation of images from data collected in PET. In the first, standard CT (computed tomography) algorithms are used on rays designated by pairs of detectors receiving coincidence events. The problem generated by this approach is that generally only the mean can be used by such algorithms. With the relatively small numbers of events in PET, and with Poisson statistics for which variance equals the mean, the noise sensivity of standard CT algorithms becomes limiting. This is exasperated further by 3D imaging with cylindrical arrays of detectors. Statistical CT algorithms take the variance into account. As in the list-mode approach, we consider each coincidence event individually. However, we estimate the location of the annihilation event that caused each coincidence event, one by one, based on the previously assigned location of events processed earlier. The estimated annihilation locations form the image. To accomplish this, we construct a probability distribution along each coincidence line. This is generated from previous annihilation points by density estimation. In this paper we present our density estimation approach to positron emission tomography. Nonparametric methods of density estimation are overviewed followed by numerical examples. Our goal here is to determine which density estimation approach is most suitable for PET.
Current Status of Salvage Cryoablation for Prostate Cancer following Radiation Failure
Authors: Chin Joseph L. , Touma Naji
Published: October 2014

The role of salvage cryoablation of the prostate for patients with clinically localized prostate cancer that have failed radiotherapy to the prostate is reviewed with reference to alternatives including salvage radical prostatectomy and brachytherapy. The diagnosis and work-up of local recurrence/persistence of cancer in the prostate are reviewed and the patient selection criteria for salvage cryoablation is discussed. Technical aspects of the cryoablation procedure along with the outcome in terms of cancer control and treatment-related complications are detailed. The five-year biochemical disease-free rate is approximately 40%. The complication rate is acceptable. Salvage cryoablation definitely has a role in the management of localized prostate cancer treatment failure following radiotherapy, especially in older patients and those with some comorbidities.
Perineural Invasion of Squamous Cell Carcinoma of the Lip with Occult Involvement of the Infra-orbital Nerve Detected by PET-CT and Treated with MRI-based IMRT: A Case Report
Authors: Bhatnagar Ajay K. , Heron Dwight E. , Schaitkin Barry
Published: October 2014

A 51 year old male with a history of right facial numbness developed progressive upper lip swelling for one year, but an MRI of the head was unremarkable. A wide local excision of the upper lip was performed and pathology revealed a 1.7 cm mass, poorly differentiated squamous cell carcinoma with perineural invasion. Surgical margins were free of tumor. Two months postoperatively, a hybrid PET-CT of the whole body was performed due to the persistent right facial numbness. The CT portion identified an equivocal lesion at the base of the right orbit correlating to the right infraorbital nerve. However, the PET-CT image revealed avid uptake in this location suggesting perineural invasion which was confirmed with biopsy of the right infraorbital nerve demonstrating carcinoma. Subsequently, the patient was treated with Intensity Modulation Radiation Therapy (IMRT) using MRI fusion for proper delineation of the right infraorbital nerve to its origin in the base of skull. This case exemplifies the superiority of hybrid PET-CT over CT or MRI alone in head and neck imaging which can lead to significant impact on management for patients with head and neck cancer.
Analysis of Spatial Correlation between 99mTc-Sestamibi Uptake and Radiographic Breast Density
Authors: Moré Mitali J. , Narayanan Deepa , Goodale Patricia J. , Harvey Jennifer , Williams Mark B.
Published: October 2014

Breast scintigraphy is a technique by which the biological properties of breast lesions can be assessed using an injected radiopharmaceutical. It may be particularly useful for women with radiographically dense breasts, in whose mammograms, lesions are often obscured by breast tissue. We are evaluating a dual modality breast scanner developed at the University of Virginia for its ability to distinguish between benign and malignant lesions. The scanner obtains a digital mammogram and a gamma ray emission image in quick succession with the breast held under mild compression, resulting in a fused image in which structures in the digital mammogram can be directly correlated with those in the scintigram. Our experience has shown that radiopharmaceutical uptake by normal breast tissue can sometimes obscure uptake by small lesions. It would therefore be advantageous to correct for this background uptake if possible. One potential way of accomplishing this is to use the information from the digital mammogram to help predict the background radiopharmaceutical distribution. With this in mind, we retrospectively investigated the degree of spatial correlation between the distribution of background activity and the distribution of radiodense breast tissue in normal breasts. Using a histogram-based analysis, we have quantified the degree of correlation in 16 images obtained from a total of 8 patients. We also used the mammographic images to quantify the radiographic density of each breast. Our results suggest that spatial correlation between areas of high radiopharmaceutical uptake and parenchymal density exists in the most dense regions of the breast for either extremely dense or heterogeneously dense breasts. High correlation was also observed for some homogeneously fatty breasts. In the latter case however, variation in breast thickness appeared to be the cause of the increased correlation. Correlation properties are approximately equal in both right and left breasts for a particular patient, except in cases exhibiting focal radiotracer uptake in a lesion. Although our preliminary results suggest that correlation between radiopharmaceutical uptake and parenchymal density exists, the number of cases thus far is too small for definitive conclusions. In addition, the planar nature of the dual modality scans imposes an inherent limitation on our ability to take into account attenuation of the emitted gamma radiation, which thus constitutes an uncontrolled variable in the correlation analysis. In principle, this problem can be eliminated by 3-dimensional imaging.
Survey of Resident Education in Intensity-Modulated Radiation Therapy
Authors: Malik Renuka , Oh Julia L. , Roeske John C. , Mundt Arno J.
Published: October 2014

Intensity-modulated radiation therapy (IMRT) has been gaining increasing popularity among practicing physicians in the U.S., but the extent to which radiation oncology residents are taught the principles of this technology and are trained to use IMRT remains unknown. In this paper, we assessed the current level of resident education in IMRT in the United States.

Chief residents at all 77 accredited radiation oncology programs were sent a 13-question survey addressing formal didactics and hands-on experience in IMRT. The survey assessed the frequency, subject, and format of IMRT didactics. Questions also addressed the number of IMRT patients and anatomical sites treated, resident involvement in the IMRT process, and the intent of IMRT use. Finally, residents were asked for their opinions on their IMRT education.

Sixty-one surveys (79%) were completed. Overall, forty-three respondents (71%) reported receiving formal IMRT didactics, with nearly one-third reporting extensive didactics (≥ 3 lectures/seminars et cetera per year). The most common didactic formats were lectures (95%) and journal clubs (63%), most commonly supervised by physicists (98%). Involvement by physicians and radiobiologists were reported by 63% and 7% of respondents, respectively. Overall, 87% of respondents had hands-on IMRT training, with nearly one-half having treated >25 patients. The most common sites treated were head and neck (94%) and prostate (81%). Involvement in all aspects of the IMRT process was common, particularly target and tissue delineation (98%) and plan evaluation (93%). Most respondents (79%) with hands-on experience reported receiving formal didactics. However, nearly one-third received no or only minimal formal didactics. The percentage of respondents desiring increased IMRT didactics and hands-on experience were 70% and 47%, respectively.

Our results suggest that the great majority of radiation oncology residents in the United States are currently exposed to didactics and hands-on training in IMRT. Areas of potential improvement include increased involvement of physicians and radiobiologists in formal IMRT didactics.
Functional Display of an α2 Integrin-Specific Motif (RKK) on the Surface of Baculovirus Particles
Authors: Riikonen Reetta , Matilainen Heli , Rajala Nina , Pentikäinen Olli , Johnson Mark , Heino Jyrki , Oker-Blom Christian
Published: October 2014

The use of baculovirus vectors shows promise as a tool for gene delivery into mammalian cells. These insect viruses have been shown to transduce a variety of mammalian cell lines, and gene transfer has also been demonstrated in vivo. In this study, we generated two recombinant baculovirus vectors displaying an integrin-specific motif, RKK, as a part of two different loops of the green fluorescent protein (GFP) fused with the major envelope protein gp64 of Autographa californica M nucleopolyhedrovirus. By enzyme linked immunosorbent assays, these viruses were shown to bind a peptide representing the receptor binding site of an α2 integrin, the α2I-domain. However, the interaction was not strong enough to overcome binding of wild type gp64 to the unknown cellular receptor(s) on the surface of α2 integrin-expressing cells (CHO-α2β1) or enhance the viral uptake. After treatment of these cells with phospholipase C, internalization of all viruses was blocked or decreased significantly. However, one of the RKK displaying viruses, AcGFP(K)gp64, was still able to internalize into CHO-α2β1 cells, although at a lower level as compared to non-treated cells. This may indicate the possible utilization of a PLC independent alternative route via, in this case, the α2β1 integrin.
Nanotechnology in Cancer Detection and Treatment
Authors: Singh Keshav K.
Published: October 2014

Nanotechnology is an emerging interdisciplinary field dedicated to the manipulations of atoms and molecules that lead to the construction of structures in the nanometer scale size range that retain unique properties (1). In the past decade, the field of nanotechnology has grown into a diverse interdisciplinary mix of engineering, computer science, biology, and medicine. Through nanotechnology, we are now able to study unique biology, chemistry, and physics at nanoscale levels. The field of nanotechnology shows promise in cancer. This special issue on nanotechnology in cancer contains articles that focus on the application of nanotechnology in advancing cancer detection, diagnosis, and treatment. The aim of the issue is to present to the cancer community a review of the current status of cancer nanotechnology, which is rapidly advancing. Recently, many nanotechnology tools have become available which can make it possible for clinicians to detect tumors at an early stage. The nanostructures can potentially enter the single tumor cell, which can help improve the current detection limit by imaging techniques described in this issue. The goal, for example, in the case of breast cancer is to accurately detect less than 100 tumor cells in contrast to mammography, which requires more than 1,000,000 cells for clinical diagnosis. Targeting and local tumor delivery is the key challenges in both diagnosis and treatment of cancer. Nanotechnology can help diagnose cancer using dendrimers and kill tumor cells without harming normal healthy cells by tumor selective delivery of genes using nanovectors. These and other technologies currently are in various stages of discovery and development. The papers presented in this issue give an overall view of how the field is advancing.
In Vivo Biodistribution of Dendrimers and Dendrimer Nanocomposites — Implications for Cancer Imaging and Therapy
Authors: Khan Mohamed K. , Nigavekar Shraddha S. , Minc Leah D. , Kariapper Muhammed S. T. , Nair Bindu M. , Lesniak Wojciech G. , Balogh Lajos P.
Published: October 2014

Our results indicate that the surface chemistry, composition, and 3-D structure of nanoparticles are critical in determining their in vivo biodistribution, and therefore the efficacy of nanodevice imaging and therapies. We demonstrate that gold/dendrimer nanocomposites in vivo, present biodistribution characteristics different from PAMAM dendrimers in a B16 mouse tumor model system.

We review important chemical and biologic uses of these nanodevices and discuss the potential of nanocomposite devices to greatly improve cancer imaging and therapy, in particular radiation therapy. We also discuss major issues confronting the use of nanoparticles in the near future, with consideration of toxicity analysis and whether biodegradable devices are needed or even desirable.
Role of Nanobiotechnology in Developing Personalized Medicine for Cancer
Authors: Jain K. K.
Published: October 2014

Personalized medicine simply means the prescription of specific therapeutics best suited for an individual. Personalization of cancer therapies is based on a better understanding of the disease at the molecular level. Nanotechnology will play an important role in this area. Nanobiotechnology is being used to refine discovery of biomarkers, molecular diagnostics, drug discovery and drug delivery, which are important basic components of personalized medicine and are applicable to management of cancer as well. Examples are given of the application of quantum dots, gold nanoparticles, and molecular imaging in diagnostics and combination with therapeutics - another important feature of personalized medicine. Personalized medicine is beginning to be recognized and is expected to become a part of medical practice within the next decade. Personalized management of cancer, facilitated by nanobiotechnology, is expected to enable early detection of cancer, more effective and less toxic treatment increasing the chances of cure.