bluuebunny/crossref_metadata_2025 huggingface dataset:
Photodynamic Therapy for Esophageal Cancer: A Useful and Realistic Option
Authors: Barr Hugh , Kendall Catherine , Stone Nicholas
Published: October 2014

The use of light therapy for tissue destruction is highly attractive for the endoscopic and minimally invasive therapy of esophageal cancer. Photodynamic therapy (PDT) offers the possibility of palliation of advanced obstructing tumors. However, there are other competing techniques, which can be used to open the esophageal lumen. It has also proved very effective in providing prolonged palliation of patients with advanced irresectable cancer. Completely obstructing tumors, tortuous and long lesions, and tumors near the upper end of the esophagus are particularly suitable for photodynamic therapy. Patients with obstruction to an esophageal prosthesis are also well palliated with PDT. A more interesting and exciting development is its use for the eradication of early asymptomatic mucosal disease. Photodynamic therapy is particularly useful for the eradication of field cancerous change in patients with pre-malignant Barrett's esophagus, or early tumors in patients unfit for radical therapy.
Treatment Planning for Stereotactic Radiosurgery with Photon Beams
Authors: Yu Cedric , Shepard David
Published: October 2014

Stereotactic Radiosurgery (SRS) has evolved as a unique discipline that combines aspects of both surgery and radiation oncology. Technological developments in the past few decades have provided a wide array of treatment techniques, including (i) the Gamma KnifeTM; (ii) Linac-based stereotactic techniques using circular collimators or using micro multileaf collimators (mMLCs); (iii) the Cyber KnifeTM, using an x-band linac mounted on a robotic arm; and (iv) serial and spiral tomotherapy. This paper provides a review of the treatment planning methods for stereotactic radiosurgery. Because of the differences in planning strategies used for each SRS technique, this paper will provide both a general review of the pre-requisites and common features of SRS treatment planning and the planning techniques specific to each of the SRS techniques.
Cytokines and Antitumor Immunity
Authors: Müller Ludmila , Pawelec Graham
Published: October 2014

Currently, the notion of immunosurveillance against tumors is enjoying something of a renaissance. Even if we still refuse to accept that tumors arising in the normal host are unable to trigger an immune response because of the lack of initiation (“danger”) signals, there is no doubt that the immune system can be manipulated experimentally and by implication therapeutically to exert anti-tumor effects. For this activity to be successful, the appropriate cytokine milieu has to be provided, making cytokine manipulation central to immunotherapy. On the other hand, the major hurdle currently preventing successful immunotherapy is the ability of tumors to evolve resistant variants under the pressure of immune selection. Here, too, the cytokine milieu plays an essential role. The purpose of this brief review is to consider the current status of the application of cytokines in facilitating antitumor immunity, as well their role in inhibiting responses to tumors. Clearly, encouraging the former but preventing the latter will be the key to the effective clinical application of cancer immunotherapy.
The Efficacy of Linear Accelerator Stereotactic Radiosurgery in Treating Glomus Jugulare Tumors
Authors: Lim Michael , Gibbs Iris C. , Adler John R. , Martin David P. , Chang Steven D.
Published: October 2014

Treatment of glomus jugulare tumors with radiosurgery has grown in acceptance since the first reported treatment in 1995, but only a few centers have reported their experiences with limited follow up time. We report our experience with stereotactic radiosurgery in nine patients with ten glomus tumors. All patients were treated either with frame based LINAC or Cyberknife with doses ranging from 1600 cGy to 2500 cGy. Three patients received no previous therapy and one patient received additional external beam radiation for concomitant treatment of carotid body tumors. Patients were then followed for post treatment side effects in addition to change in tumor size by MRI evaluation. The median clinical follow-up time was 26 months (mean 54 months), median radiographic follow-up was 21.5 months (mean 46 months), with a range from 3 to 126 months. The results from our center demonstrated nine of ten tumors to be stable in size by MRI exam, and one tumor which regressed in size. Nine patients had stable neurological symptoms, and one patient experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. Our results continue to support radiosurgery as a suitable form of treatment for glomus jugulare tumors as evidenced by results from this four and a half year follow-up.
Factors Associated with Improved Survival in Patients with Brain Metastases from Esophageal Cancer: A Retrospective Review
Authors: Khuntia Deepak , Sajja Ratna , Chidel Mark A. , Lee Shih-Yuan , Rice Thomas W. , Adelstein David J. , Carlson Thomas P. , Saxton Jerrold P. , Barnett Gene H. , Suh John H.
Published: October 2014

There are over 200,000 cases of brain metastases (BrM) every year, but very few are from esophageal cancer primaries. In order to determine predictors for outcome of these patients, the authors conducted a retrospective review of twenty-seven patients with BrM from esophageal carcinoma diagnosed at the Cleveland Clinic Foundation between 1991 and 2001. For the entire cohort, median follow-up and median survival was 3.6 months and 3.6 months, respectively. On univariate analysis, patients with Karnofsky Performance Status (KPS) ≥ 70, low recursive partitioning analysis score, single BrM, no systemic disease, and aggressive treatment [surgery, stereotactic radiosurgery (SRS) + whole brain radiation (WBRT), SRS + surgery + WBRT, surgery + WBRT)] had a significantly improved survival. In a multivariate model, patients with higher KPS and aggressive treatment had improved survival. The 1-year survival for the WBRT alone group and the aggressive treatment group was 6%, and 36% respectively. We conclude that based on the data presented here, patients with BrM from esophageal cancer have poor outcome. Aggressive treatment and favorable KPS are associated with longer survival for selected patients. We recommend esophageal cancer patients with BrM be enrolled in clinical trials to better delineate the role of treatment and potentially improve results.
Photodynamic Therapy (PDT) in Esophageal Cancer: A Surgical View of its Indications Based on 14 Years Experience
Authors: Moghissi K. , Dixon Kate
Published: October 2014

The aim of this paper is to present the updated experience of the Yorkshire Laser Centre in PDT for esophageal cancer and to identify its role in specific subsets of patients. Also, in the light of this experience, to compare and contrast the results of PDT with appropriate subsets of patients treated in my esophageal surgery practice. 102 consecutive patients; 84 with advanced (Group A) and 18 with early (Group E) stage esophageal cancer undergoing endoscopic PDT were entered into a prospective study. Every patient had standard work up including clinical staging. PDT protocol was intravenous administration of Photofrin 2mg/kg body weight followed 24–72 hours later by endoscopic illumination using 630 nm laser light. Assessment of results was made on the basis of mortality, morbidity, patient satisfaction to treatment, symptom relief and survival. For comparison of PDT role with non PDT treated patients, reference is made to 3 previous publications comprising over 1100 patients [Moghissi, K., Br. J. Surg. 79, 935–937 (1992) (ref. 1); Sawant, D., Moghissi, K. Eur. J. Cardio-Thorac. Surg. 8, 113–117 (1994) (ref. 2); Sharpe, D. A. C., Moghissi, K. Eur. J. Cardiothorac. Surg. 10, 359–364 (1996) (ref. 3)]. There was no mortality associated with PDT. All patients expressed satisfaction to treatment. Post PDT complications consisted of photosensitivity skin reaction (sunburn) in 5 patients (5%) and esophageal stricture in 8 (8%) patients.

Group A: There was significant symptom and dysphegia grade improvement. Mean survival was 9.5 months. Group E: There were no significant symptoms pre or post PDT and mean survival was 60.5 months.

Comparison of PDT results in Group A with results of other palliative treatment methods, indicates that palliation can be achieved in all intraluminal cancer using PDT which is at least as good as other treatments. There is, in addition, advantage over other methods in patients with cervical esophageal cancer and in cases with re-growth of tumor obstructing previously placed stents. In early cases PDT appears capable of replicating surgical results in selected cases. PDT is an effective and safe treatment method in esophageal cancer. In advance disease it improves swallowing. In early stage disease it offers long survival and the prospect of cure in some patients. At present the role of PDT in early stage cancer should be limited to patients who are unsuitable for surgical resection. Therefore, PDT should be considered as a valid oncological option to be applied in selected cases.
Raman Spectral Mapping in the Assessment of Axillary Lymph Nodes in Breast Cancer
Authors: Smith J. , Kendall C. , Sammon A. , Christie-Brown J. , Stone N.
Published: October 2014

This paper is the first reported description of Raman Spectroscopy in the assessment of axillary lymph nodes in breast cancer patients. Raman Spectroscopy is an inelastic scattering spectroscopic technique appropriate for the assessment of unprocessed complex biological tissues. Spectra represent biochemical signatures of the tissue under scrutiny. The described method of Raman spectral mapping produces false-color spectral images of lymph node sections. These can be compared with standard histopathology slides and white light images of nodal tissue. This method has the potential to allow the detailed biochemical assessment of heterogeneous lymph node features, and to contribute towards the development of an optical diagnostic tool for use in a clinical setting.
Standardizing Dosimetry in Esophageal PDT: An Argument for Use of Centering Devices and Removal of Misleading Units
Authors: Stone Nicholas
Published: October 2014

A simple standardization of esophageal photodynamic therapy light dosimetry is proposed. Calculations of the effect on local treatment dose of using non-centered diffusing fibers have been made and the methods of calculating light energy dose to the treatment area within a centering balloon are discussed. A requirement for centering devices and standard units of Joules per cm2 of treatment area are indicated.
Viral and Non-viral Vectors in Gene Therapy: Technology Development and Clinical Trials
Authors: Lundstrom Kenneth , Boulikas Teni
Published: October 2014

Gene therapy as part of modern molecular medicine holds great promise for the treatment of both acute and chronic diseases and has the potential to bring a revolutionary era to cancer treatment. Gene therapy has been named the medicine of the future. For the past 10 years various viral and non-viral vectors have been engineered for improved gene and drug delivery. Although various diseases have been targeted, cancer therapy has been addressed to a large extent because of the straight forward approach. Delivery of toxic or immunostimulatory genes by viral and non-viral vectors has been investigated and encouraging results have been obtained in animal models. A large number of clinical trials have been conducted with some highly promising outcome. We propose that combinations of viruses with lipo-somes or polymers will solve the problem of systemic viral delivery and tumor targeting, bringing a revolution in molecular medicine and in applications of gene therapy in humans.
Nanoshell-Enabled Photonics-Based Imaging and Therapy of Cancer
Authors: Loo Christopher , Lin Alex , Hirsch Leon , Lee Min-Ho , Barton Jennifer , Halas Naomi , West Jennifer , Drezek Rebekah
Published: October 2014

Metal nanoshells are a novel type of composite spherical nanoparticle consisting of a dielectric core covered by a thin metallic shell which is typically gold. Nanoshells possess highly favorable optical and chemical properties for biomedical imaging and therapeutic applications. By varying the relative the dimensions of the core and the shell, the optical resonance of these nanoparticles can be precisely and systematically varied over a broad region ranging from the near-UV to the mid-infrared. This range includes the near-infrared (NIR) wavelength region where tissue transmissivity peaks. In addition to spectral tunability, nanoshells offer other advantages over conventional organic dyes including improved optical properties and reduced susceptibility to chemical/thermal denaturation. Furthermore, the same conjugation protocols used to bind biomolecules to gold colloid are easily modified for nanoshells. In this article, we first review the synthesis of gold nanoshells and illustrate how the core/shell ratio and overall size of a nanoshell influences its scattering and absorption properties. We then describe several examples of nanoshell-based diagnostic and therapeutic approaches including the development of nanoshell bioconjugates for molecular imaging, the use of scattering nanoshells as contrast agents for optical coherence tomography (OCT), and the use of absorbing nanoshells in NIR thermal therapy of tumors.
Progress toward Optimization of Cryosurgery
Authors: Baust J. G. , Gage A. A.
Published: October 2014

Cryosurgery for diverse neoplastic and non-neoplastic diseases has expanded in applicability in recent years, especially since intraoperative ultrasound became available as a method of monitoring the process of tissue freezing. However, persistence of disease after presumably adequate cryosurgical treatment has disclosed deficiencies in the technique, perhaps due to faulty application of the freeze-thaw cycles or due to shortcomings in the imaging method. Clearly cryosurgical technique is less than optimal. The optimal dosimetry for tissue freezing, the recent improvements in imaging techniques, and the need for adjunctive therapy are defined in this review, which assesses the progress toward improving the efficacy of cryosurgery.
Distributed Network Imaging and Electrical Impedance Tomography of Minimally Invasive Surgery
Authors: Otten David M. , Onik Gary , Rubinsky Boris
Published: October 2014

Minimally invasive surgery has become highly dependent on imaging. For instance, the effectiveness of cryosurgery in treating cancer is dependent on knowledge of freezing extent, and relies on real-time imaging techniques for monitoring. However, medical imaging is often very expensive and therefore not available to most of the world population. Here we propose the concept of distributed network imaging (DNI) which could make medical imaging and minimally invasive surgery available to all who need these advanced medical modalities. We demonstrate the concept through electrical impedance tomography (EIT) of cryosurgery. The central idea is to develop an inexpensive measurend (data collection hardware) at a remote site and then to connect the measurend apparatus to an advanced image reconstruction server, which can serve a large number of distributed measurends at remote sites, using existing communication conduits (Ethernet, telephone, satellite, etc.). These conduits transfer the raw data from the measurend to the server and the reconstructed image from the server to the measurend. Electrical impedance tomography (EIT) is an imaging modality which utilizes tissue impedance variation to construct an image. The EIT measurend which consists of electrodes, a power supply, and means to measure voltage is inexpensive, and therefore suitable for DNI. EIT is also very well-suited to imaging cryosurgery since frozen tissue impedance is much higher than that of unfrozen tissue. In this study, we first develop numerical models to illustrate the theoretical ability of EIT to image cryosurgery. We begin with a simplified two dimensional model, and then extend the study to the more appropriate three dimensional model. Our simulated finite element phantoms and pixel-based Newton-Raphson reconstruction algorithms were able to produce easily identifiable images of frozen regions within tissue. Then, we demonstrate the feasibility of the DNI concept though a case study using EIT to image an in vitro liver cryosurgery procedure through a modem. We find that the acquired raw data packets are less than 5KB per image and the images, using compression, do not exceed 50KB per image.
Assessing pH and Oxygenation in Cryotherapy-induced Cytotoxicity and Tissue Response to Freezing
Authors: Griffin Robert J. , Williams Brent W. , Roberts Kenneth P. , Swanlund David J. , Bischof John C.
Published: October 2014

The microenvironmental pH and oxygenation is known to influence tumor cell response to heat, radiation, photodynamic and even chemotherapy. We have studied the previously untested influence of acidity and hypoxia on tumor and endothelial cell sensitivity to freezing. In addition, we have measured changes in oxygenation in vivo in murine FSaII fibrosarcomas after freeze injury. A low pH or low oxygenation environment was found to increase the sensitivity of tumor and endothelial cells to freezing at −20° C or −40° C in vitro. However, low pH and low oxygenation combined did not further increase cryosensitivity of the cells. In vivo, tumor oxygenation after freeze injury was studied immediately or 1–3 days after a standard freezing protocol was applied to FSaII tumors ranging from 250–500 mm3 grown in the rear-limb of C3H mice. Tumor oxygenation at the edge of the iceball was found to transiently increase 1–2 hours after freezing. At 1–3 days after freezing, a treatment that delayed FSaII tumor growth by approximately 1.5-fold, the mean tumor oxygenation was significantly increased by up to 2.5-fold from a control level of 5 mmHg partial pressure of oxygen (pO2), especially at the periphery of the tumor. We conclude that manipulation of pH or oxygenation has potential to increase the anti-tumor effects of minimally invasive cryosurgical techniques. Furthermore, the dynamic changes in oxygenation after freeze injury in vivo suggests value in combining cryotherapy with treatments dependent on oxygenation levels. Ultimately, these may be routes to more reliable treatment response with fewer recurrences.
High Dose Rate Brachytherapy: Its Clinical Applications and Treatment Guidelines
Authors: Nag Subir
Published: October 2014

Brachytherapy has the advantage of delivering a high dose to the tumor while sparing the surrounding normal tissues. With proper case selection and delivery technique, high-dose-rate (HDR) brachytherapy has great promise, because it eliminates radiation exposure, allows short treatment times, and can be performed on an outpatient basis. Additionally, use of a single-stepping source, allows optimization of dose distribution by varying the dwell time at each dwell position. However, when HDR brachytherapy is used, the treatments must be executed carefully, because the short treatment times do not allow any time for correction of errors, and mistakes can result in harm to patients. Hence, it is very important that all personnel involved in HDR brachytherapy be well trained and be constantly alert.

It is expected that the use of HDR brachytherapy will greatly expand over the next decade and that refinements will occur primarily in the integration of imaging (computed tomography, magnetic resonance imaging, intraoperative ultrasonography) and optimization of dose distribution. It is anticipated that better tumor localization and normal tissue definition will help to optimize dose distribution to the tumor and reduce normal tissue exposure. The development of well-controlled randomized trials addressing issues of efficacy, toxicity, quality of life, and costs-versus-benefits will ultimately define the role of HDR brachytherapy in the therapeutic armamentarium.
Magnetic Resonance Imaging Detects Early Changes in Microvascular Permeability in Xenograft Tumors after Treatment with the Matrix Metalloprotease Inhibitor Prinomastat
Authors: Wiart Marlene , Fournier Laure S , Novikov Viktor Y , Shames David M , Roberts Timothy P , Fu Yanjun , Shalinsky David R , Brasch Robert C
Published: October 2014

Macromolecular contrast medium-enhanced magnetic resonance imaging was applied to monitor the effect of matrix metalloprotease (MMP) inhibition on microvascular characteristics of human breast cancers implanted in athymic rats. Twice-daily intraperitoneal administration of Prinomastat over 1.5 days induced significant declines in MRI-assayed microvascular permeabilities (p<0.05); but this leak suppression effect had extinguished by the 10th day of MMP treatment using the same dose and time schedule. Results demonstrate that Prinomastat produces a rapid but transient decrease in tumor vascular permeability. Contrast-enhanced MRI using macromolecular contrast medium may prove useful as a biomarker for the dynamic MMP biological effect in cancers.
Quantitative Assessment of Tumor Vasculature and Response to Therapy in Kaposi's Sarcoma Using Functional Noninvasive Imaging
Authors: Hassan Moinuddin , Little Richard F. , Vogel Abby , Aleman Karen , Wyvill Kathleen , Yarchoan Robert , Gandjbakhche Amir H.
Published: October 2014

Two noninvasive methods, thermography and laser Doppler imaging (LDI), were assessed for their ability to quantitatively assess parameters of vascularity in lesions of HIV-associated Kaposi's sarcoma (KS). Thermography and LDI images of a representative KS lesion were recorded in 16 patients and compared to normal skin either adjacent to the lesion or on the contralateral side. Eleven of the 16 patients had greater than 0.5 °C increased temperature and 12 of the 16 patients had increased flux (measured by LDI) as compared to normal skin. There was a strong correlation between these two parameters (R = 0.81, p < 0.001). In ten patients, measurements were obtained prior to therapy and after receiving a regimen of liposomal doxorubicin and interleukin-12. After 18 weeks of therapy, temperature and blood flow of the lesions were significantly reduced from the baseline (p = 0.004 and 0.002 respectively). These techniques hold promise to assess physiologic parameters in KS lesions and their changes with therapy.
Enhanced Cell Growth Inhibition following PTEN Nonviral Gene Transfer Using Polyethylenimine and Photochemical Internalization in Endometrial Cancer Cells
Authors: Maurice-Duelli Aurore , Ndoye Alioune , Bouali Sanae , Leroux Agnès , Merlin Jean-Louis
Published: October 2014

PTEN is a tumor suppressor gene mapped on chromosome 10q23.3 and encodes a dual specificity phosphatase. PTEN has major implication in PI3 kinase (PI3K) signal transduction pathway and negatively controls PI3 phosphorylation. It has been reported to be implicated in cell cycle progression and cell death control through inhibition of PI3K-Akt signal transduction pathway and in the control of cell migration and spreading through its interaction with focal adhesion kinase. Somatic mutations of PTEN are frequently detected in several cancer types including brain, prostate and endometrium with more than 30% of tumor tissue specimens bearing PTEN mutations and/or deletions. Because of its high frequency of mutations and its important function as tumor suppressor gene, PTEN is a good candidate for gene therapy. Inducible expression of PTEN has been also reported. In cancer cells bearing PTEN abnormalities, the reversion of PTEN function by external gene transfer becomes more and more investigated in cancer treatment research. Several technologies including the photochemical internalization (PCI) and aiming at improving the transfection efficiency have been reported. PCI is an innovative procedure based on light-induced delivery of macromolecules such as DNA, proteins and other therapeutic molecules from endocytic vesicles to the cytosol of target cells. PCI has been reported to enhance the gene delivery potential of viral and nonviral vectors. The present study was designed to evaluate the influence of photochemical internalization on polyethylenimine (PEI)-mediated PTEN gene transfer and its effects on the cellular viability in Ishikawa endometrial cancer cells bearing PTEN abnormalities. PCI was found to significantly (P < 0.01) enhance PTEN mRNA expression (4.2 fold increase). Subsequently, following PEI-mediated PTEN gene transfer, the restoration of the PTEN protein expression was observed. As a consequence, significant cell growth inhibition (44%) was observed in Ishikawa endometrial cells. Using PCI for PEI-mediated PTEN gene transfer was found to further enhance PTEN mRNA and protein expression as well as PTEN-related cell growth inhibition reaching 89%.
Biomarkers for Risk Assessment in Molecular Epidemiology of Cancer
Authors: Verma Mukesh
Published: October 2014

One out of four deaths in the USA is due to cancer. Identification of populations at risk of developing cancer is important as it provides opportunities for prevention and treatment of cancer. Biomarkers are measurable indicators of exposure effects and susceptibility or disease state, and are used to understand the mechanisms of cancer progression. In recent molecular epidemiology studies genomic, proteomic, and epigenomic markers have been utilized which exhibit high sensitivity and specificity for different tumor types and can be assayed in biofluids and other specimens collected by non-invasive technologies. The current challenges and future directions in the field are discussed in this article.
Transvenous Cryoablation of Cardiac Arrhythmias
Authors: Rodriguez Luz-Maria , Timmermans Carl
Published: October 2014

This study reports on the acute and long-term results of cryoablation in patients with supraventricular and ventricular tachycardia. One hundred fifty nine patients with cardiac arrhythmias (147 with supraventricular and 12 with ventricular tachycardia) were consecutively enrolled in our institution to undergo trnasvenous cryoablation with a new cryotechnology system (CryoCor™). This cryoablation system consists of a console, an articulating arm housing a pre-cooler, and a disposable sterile steerable bipolar 10-fr catheter. The N2O is used as a main refrigerant. The acute and chronic outcomes (after 15 months for patients with supraventricular tachycardia and 9 months for patients with ventricular tachycardia) were comparable to those using radiofrequency energy. From this study we concluded that transvenous cryoablation is a safe and effective therapy for the treatment of cardiac arrhythmias.
Imaging of the Ovary
Authors: Brewer Molly A. , Utzinger Urs , Barton Jennifer K. , Hoying James B. , Kirkpatrick Nathaniel D. , Brands William R. , Davis John R. , Hunt Katherine , Stevens Sally J. , Gmitro Arthur F.
Published: October 2014

Epithelial ovarian cancer has the highest mortality rate among the gynecologic cancers and spreads beyond the ovary in 90% of the women diagnosed with ovarian cancer. Detection before the disease has spread beyond the ovary would significantly improve the survival from ovarian cancer, which is currently only 30% over 5 years, despite extensive efforts to improve the survival. This study describes initial investigation of the use of optical technologies to improve the outcome for this disease by detecting cancers at an earlier and more treatable stage. Women undergoing oophorectomy were recruited for this study. Ovaries were harvested for fluorescence spectroscopy, confocal microscopy, and optical coherence tomography. Fluorescence spectroscopy showed large diagnostic differences between normal and abnormal tissue at 270 and 340 nm excitation. Optical coherence tomography was able to image up to 2mm deep into the ovary with particular patterns of backscattered intensity observed in normal versus abnormal tissue. Fluorescence confocal microscopy was able to visualize sub-cellular structures of the surface epithelium and underlying cell layers. Optical imaging and/or spectroscopy has the potential to improve the diagnostic capability in the ovary, but extended systematic investigations are needed to identify the unique signatures of disease. The combination of optical technologies supported by modern molecular biology may lead to an instrument that can accurately detect early carcinogenesis.
Image Quality Assessment via Segmentation of Breast Lesion in X-ray and Ultrasound Phantom Images from Fischer's Full Field Digital Mammography and Ultrasound (FFDMUS) System
Authors: Suri Jasjit , Guo Yujun , Coad Cara , Danielson Tim , Elbakri Idris , Janer Roman
Published: October 2014

Fischer has been developing a fused full-field digital mammography and ultrasound (FFDMUS) system funded by the National Institute of Health (NIH). In FFDMUS, two sets of acquisitions are performed: 2-D X-ray and 3-D ultrasound. The segmentation of acquired lesions in phantom images is important: (i) to assess the image quality of X-ray and ultrasound images; (ii) to register multi-modality images; and (iii) to establish an automatic lesion detection methodology to assist the radiologist.

In this paper we developed lesion segmentation strategies for ultrasound and X-ray images acquired using FFDMUS. For ultrasound lesion segmentation, a signal-to-noise (SNR)-based method was adapted. For X-ray segmentation, we used gradient vector flow (GVF)-based deformable model. The performance of these segmentation algorithms was evaluated. We also performed partial volume correction (PVC) analysis on the segmentation of ultrasound images. For X-ray lesion segmentation, we also studied the effect of PDE smoothing on GVF's ability to segment the lesion.

We conclude that ultrasound image qualities from FFDMUS and Hand-Held ultrasound (HHUS) are comparable. The mean percentage error with PVC was 4.56% (4.31%) and 6.63% (5.89%) for 5 mm lesion and 3 mm lesion respectively. The mean average error from the segmented X-ray images with PDE yielded an average error of 9.61%. We also tested our program on synthetic datasets. The system was developed for Linux workstation using C/C++.
Impact on Late Toxicity of using Transabdominal Ultrasound for Prostate Cancer Patients Treated with Intensity Modulated Radiotherapy
Authors: Jani Ashesh B. , Gratzle John , Muresan Emil , Martel Mary K.
Published: October 2014

An analysis of the effects of using the B-mode ultrasound Acquisition and Targeting (BAT) system for positioning of prostate cancer patients receiving external beam radiotherapy (EBRT) on late gastrointestinal (GI) and genitourinary (GU) toxicity is provided. The records of 49 consecutive patients treated using the BAT were reviewed; additionally, a comparison (No-BAT) group treated in a similar manner was identified, consisting of 49 patients treated immediately prior to this BAT group. There were no other fundamental differences between the two groups. The daily BAT movements were charted and late toxicity was scored for all patients using established toxicity scales. The results demonstrated similar GU toxicity rates between the two groups, but slightly lower rates of GI toxicity in the BAT group vs. the No-BAT group. However, regression analyses revealed that no factors, including BAT use, were significantly correlated with late GI or GU toxicity. Further efforts, perhaps better undertaken in a multi-institutional setting, are needed to determine whether BAT use can significantly reduce late GI toxicity.
Industry Perspective: Maximizing the Benefit of Improved Detection with Guided and Monitored Thermal Ablation of Small Tumors
Authors: Nields Morgan W.
Published: October 2014

The continuous growth of mammography is driven by global acceptance of the demonstrated ability of screening mammography to reduce mortality from breast cancer. An increasing number of benign and malignant tumors are being diagnosed as a result of the growth in mammography, improvements in technology, especially digital mammography, as well as by an increase in patient surveillance. Breast imaging technology for cancer screening continues to improve, with the integration of ultrasound with digital mammography showing promise that an even larger number of small abnormalities will be detected in screening programs. The results of minimally invasive ablative techniques as tested in pilot clinical studies for breast tumor ablation are reviewed. A new x-ray based thermal monitoring method is described. An improved ability to intraoperatively monitor thermal ablative methods may enable more accurate minimally invasive treatment of an ever increasing number of both benign and malignant breast tumors.
Precautions in the Use of Intensity-Modulated Radiation Therapy
Authors: Welsh James S. , Limmer Jeffery P. , Howard Steven P. , Diamond David , Harari Paul M. , Tomé Wolfgang
Published: October 2014

Intensity-modulated radiation therapy (IMRT) represents a significant technological advancement in the ability to deliver highly conformal radiation therapy. Thanks to increased availability, general clinical implementation has become progressively more common. However, there are several precautions worthy of comment regarding the clinical applications of IMRT.

In theory, the increased irradiated volume and leakage radiation that occasionally accompanies IMRT could contribute to unanticipated complications and safety concerns. The protracted delivery time of IMRT with the associated increased linac monitor units can result in photoactivation of elements within the linac collimator, thereby inadvertently increasing radiation exposure to patients and staff when high-energy photons are used. The increased volumes of normal tissue exposed to lower doses of radiation through IMRT theoretically could promote carcinogenesis and complications due to the bystander effect, low-dose hyper-radiosensitivity, and diminished repair of double strand DNA breaks at very low doses. Tumor control may be adversely affected by the lower radiation dose-rates of delivery sometimes associated with IMRT as well the occasionally seen low dose “cold shoulder” on the dose-volume histograms. Unusual clinical reactions can appear as a result of the complex, unfamiliar dose-distributions occasionally generated by IMRT treatment planning. Here we discuss some of the precautions worthy of consideration when using IMRT and how these might be addressed in routine practice.
Pharmacokinetic Parameters Analyzed from MR Contrast Enhancement Kinetics of Multiple Malignant and Benign Breast Lesions Detected in the Same Patients
Authors: Su Min-Ying , Yu J. , Carpenter Phillip M. , McLaren Christine E. , Nalcioglu Orhan
Published: October 2014

Ninety-nine patients with confirmed breast cancer were reviewed to identify patients who had two confirmed malignant lesions of identical pathology (Group-1, N=17), and patients who had one malignant lesion and the second benign lesion (Group-2, N=8). Contrast enhancement kinetics from every lesion was measured and analyzed using three different models to obtain fitting parameters related to up-slope, enhancement amplitude, and wash-out, including Model-1: modified Tofts model ( vp, Ktrans, kep), Model-2: standard Tofts model ( Ktrans, kep), and Model-3: a 3-parameter heuristic model ( Tc, A, C). By analyzing lesions from same patients, the differences in whole body hemodynamics thus the blood kinetics could be controlled. Two questions were addressed in this study: i) What is the association between pharmacokinetic parameters analyzed from multiple cancers of identical pathology in same patients?; and ii) What is the difference between secondary malignant lesions and secondary benign lesions with reference to the primary cancer? All three models could fit the enhancement kinetics satisfactorily. Regardless of the analysis model the parameter obtained from the primary cancer and the secondary cancer showed significant correlations. In comparison between Group-1 and Group-2 subjects, the wash-out parameter kep in Models-1 and 2 could significantly differentiate benign from malignant lesions, but not the magnitude parameters, Ktrans in Model-2 or the parameter A in Model-3. If analyzed using appropriate models the early up-slope parameters, vp in Model-1 and Tc in Model-3, might be able to distinguish between benign and malignant lesions. When more data are available a reference database can be established with the method described in this study, and from which to determine the likelihood of malignancy for each incidental lesion found in preoperative MRI, with reference to the primary cancer.
Radiogenic Therapy: Novel Approaches for Enhancing Tumor Radiosensitivity
Authors: Robson T. , Worthington J. , McKeown S. R. , Hirst D. G.
Published: October 2014

Radiotherapy (RT) is a well established modality for treating many forms of cancer. However, despite many improvements in treatment planning and delivery, the total radiation dose is often too low for tumor cure, because of the risk of normal tissue damage. Gene therapy provides a new adjunctive strategy to enhance the effectiveness of RT, offering the potential for preferential killing of cancer cells and sparing of normal tissues. This specificity can be achieved at several levels including restricted vector delivery, transcriptional targeting and specificity of the transgene product. This review will focus on those gene therapy strategies that are currently being evaluated in combination with RT, including the use of radiation sensitive promoters to control the timing and location of gene expression specifically within tumors. Therapeutic transgenes chosen for their radiosensitizing properties will also be reviewed, these include:

gene correction therapy, in which normal copies of genes responsible for radiation-induced apoptosis are transfected to compensate for the deletions or mutated variants in tumor cells (p53 is the most widely studied example). enzymes that synergize the radiation effect, by generation of a toxic species from endogenous precursors ( e.g., inducible nitric oxide synthase) or by activation of non toxic prodrugs to toxic species ( e.g., herpes simplex virus thymidine kinase/ganciclovir) within the target tissue. conditionally replicating oncolytic adenoviruses that synergize the radiation effect. membrane transport proteins ( e.g., sodium iodide symporter) to facilitate uptake of cytotoxic radionuclides.

The evidence indicates that many of these approaches are successful for augmenting radiation induced tumor cell killing with clinical trials currently underway.
Scanning Time-domain Optical Mammography: Detection and Characterization of Breast Tumors In Vivo
Authors: Rinneberg Herbert , Grosenick Dirk , Moesta K. Thomas , Mucke Jörg , Gebauer Bernd , Stroszczynski Christian , Wabnitz Heidrun , Moeller Michael , Wassermann Bernhard , Schlag Peter M.
Published: October 2014

Optical mammography is one of several new techniques for breast cancer detection and characterization presently under development for clinical use that provide information other than morphologic, in particular on the biochemical and metabolic state of normal and diseased tissue. In breast tissue, scattering of red to near infrared (NIR) light dominates absorption and NIR light may penetrate several centimeters through the breast. Optical mammography avoids the use of ionizing radiation and offers the power of diffuse optical spectroscopy. However, because of strong light scattering, spatial resolution of optical mammography is generally low. The paper reviews the results of a clinical study on scanning time-domain optical mammography comprising 154 patients carrying a total of 102 carcinomas validated by histology. Ninety two of these tumors were detected in optical mammograms retrospectively and for 87 of the detected tumors optical properties and tissue parameters were derived. In addition developments on instrumentation and data analysis are covered and possible improvements of optical mammography are briefly discussed.
Thermoacoustic and Photoacoustic Tomography of Thick Biological Tissues toward Breast Imaging
Authors: Ku Geng , Fornage Bruno D. , Jin Xing , Xu Minghua , Hunt Kelly K. , Wang Lihong V.
Published: October 2014

Microwave-based thermoacoustic tomography (TAT) and laser-based photoacoustic tomography (PAT) in a circular scanning configuration were both developed to image deeply seated lesions and objects in biological tissues. Because malignant breast tissue absorbs microwaves more strongly than benign breast tissue, cancers were imaged with good spatial resolution and contrast by TAT in human breast mastectomy specimens. Based on the intrinsic optical contrast between blood and chicken breast muscle, an embedded blood object that was 5 cm deep in the tissue was also detected using PAT at a wavelength of 1064 nm.
Treating the Contents and Not the Container: Dosimetric Study of Hair-sparing Whole Brain Intensity Modulated Radiation Therapy
Authors: Roberge David , Parker William , Niazi Tamim M. , Olivares Marina
Published: October 2014

Hematogenous metastatases are the most common adult central nervous system malignancies. The standard treatment of these patients continues to include whole brain radiation. An unavoidable toxicity of this treatment is acute iatrogenic alopecia. This alopecia is a significant cause of patient distress. Our purpose was to quantify the sparing of the hair bearing skin that could be achieved by using a complex hair-sparing approach. To achieve this goal, we treat an anthropomorphic phantom with both conventional and inverse-planned intensity-modulated portals. The skin dose was evaluated through dose-volume histograms and thermo-luminescent dosimetry. The median calculated dose was reduced by 38%. The average measured dose at five surface points was reduced by 53% — from 95% of the prescription dose with the conventional plan, to 44%, with the IMRT plan. This sparing was achieved while maintaining adequate target coverage. Because of the low radiation tolerance of the hair follicle, this dose reduction is not expected, on its own, to eliminate radiation alopecia but bears promise in combination with other toxicity-sparing strategies.
Hypofractionated Stereotactic Radiotherapy for Low Grade Glioma at McGill University: Long-term Follow-up
Authors: Roberge David , Souhami Luis , Olivier André , Leblanc Richard , Podgoršak Ervin
Published: October 2014

Small, well-defined, unresectable low-grade gliomas are attractive targets for stereotactic irradiation. Fractionated stereotactic irradiation of these targets has the theoretical benefit of increased normal tissue sparing beyond that provided by the physical characteristics of stereotactic radiosurgery.

From July 1987 to November 1992, 21 patients were treated for low-grade glioma at our institution using a hypofractionated regimen of stereotactic radiotherapy. All patients had well-circumscribed, < 40 mm tumors. No patient had had prior radiotherapy. All lesions were histologically proven WHO grade I or II glial tumors. Lesions involved sensitive brain structures and were deemed unresectable. A typical dose of 42 Gy was delivered in 6 fractions over a two-week period using rigid immobilization and a linac-based dynamic stereotactic radiosurgical technique.

Patients had a median age of 23 years (9–74) and were predominantly female (60%). Median tumor diameter was 20 mm. With a median follow-up for living patients of 13.3 years, the actuarial 5, 10, and 15-year overall survival rates are 76%, 71%, and 63%, respectively. Treatment was acutely well tolerated although three patients experienced late post-therapy complications.

Our results and those of 241 patients treated in nine other institutional series are reviewed. Despite some examples of favorable short-term outcomes, all reported series are highly selected and thus likely biased. The data regarding the use of SRS is limited and, in our opinion, insufficient to claim a clear therapeutic advantage to SRS in the initial management of low-grade glioma. Our own results with hypofractionated stereotactic radiotherapy are similar to those expected with standard therapy.
Expanding the Therapeutic Index of Radiation Therapy by Combining In Situ Gene Therapy in the Treatment of Prostate Cancer
Authors: Tetzlaff Michael T. , Teh Bin S. , Timme Terry L. , Fujita Tetsuo , Satoh Takefumi , Tabata Ken-Ichi , Mai Wei-Yuan , Vlachaki Maria T. , Amato Robert J. , Kadmon Dov , Miles Brian J. , Ayala Gustavo , Wheeler Thomas M. , Aguilar-Cordova Estuardo , Thompson Timothy C. , Butler E. Brian
Published: October 2014

The advances in radiotherapy (3D-CRT, IMRT) have enabled high doses of radiation to be delivered with the least possible associated toxicity. However, the persistence of cancer (local recurrence after radiotherapy) despite these increased doses as well as distant failure suggesting the existence of micro-metastases, especially in the case of higher risk disease, have underscored the need for continued improvement in treatment strategies to manage local and micro-metastatic disease as definitively as possible. This has prompted the idea that an increase in the therapeutic index of radiotherapy might be achieved by combining it with in situ gene therapy. The goal of these combinatorial therapies is to maximize the selective pressure against cancer cell growth while minimizing treatment-associated toxicity. Major efforts utilizing different gene therapy strategies have been employed in conjunction with radiotherapy. We reviewed our and other published clinical trials utilizing this combined radio-genetherapy approach including their associated pre-clinical in vitro and in vivo models. The use of in situ gene therapy as an adjuvant to radiation therapy dramatically reduced cell viability in vitro and tumor growth in vivo. No significant worsening of the toxicities normally observed in single-modality approaches were identified in Phase I/II clinical studies. Enhancement of both local and systemic T-cell activation was noted with this combined approach suggesting anti-tumor immunity. Early clinical outcome including biochemical and biopsy data was very promising. These results demonstrate the increased therapeutic efficacy achieved by combining in situ gene therapy with radiotherapy in the management of local prostate cancer. The combined approach maximizes tumor control, both local-regional and systemic through radio-genetherapy induced cytotoxicity and anti-tumor immunity.
Evaluations of the Renal Cell Carcinoma Model Caki-1 Using a Silicon Based Microvascular Casting Technique
Authors: Salmon Howard W. , Mladinich Christopher , Siemann Dietmar W.
Published: October 2014

The vascular development of orthotopically grown human renal cell carcinoma (Caki-1) was examined using a silicon based casting technique in nude mice. Images taken of these vascular casts showed Caki-1 tumors to be highly vascularized and invasive. The spread of the tumor within the cortex of the kidney revealed that Caki-1 recruits the kidney's own vasculature, destroying the functional glomeruli in the process. The loss of these glomeruli was further highlighted by the presence of enlarged glomeruli resulting from the development of super nephrons. Vessel size and density measurements were then made in this model. This was done using both computer-based and manual measurement methods. In the vessel size studies the computer-based method tended to overestimate the number of larger diameter vessels whereas the vessels density assessment showed good agreement between the two techniques. Nevertheless, both methods showed that Caki-1 tumors possessed a higher proportion of larger diameter vessels and a lower vessel density than normal kidney cortex.

In summary, silicon based vascular casting proved to be a simple and effective tool for the study of tumor vasculature. In particular this technique could readily be used to examine the invasion of tumor into normal tissue. The computer-based technique for evaluating vessel number and vascular density was found to have merit in both normal and tumor tissues, particularly in the vascular density studies. However, in both settings this technique did tend to overestimate the number of larger diameter vessels.