bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.
Convection-Enhanced and Local Delivery of Targeted Cytotoxins in the Treatment of Malignant Gliomas
Authors: Muro Kenji , Das Sunit , Raizer Jeffrey J. 
Published: October 2014

Despite advances in our knowledge about the genesis, molecular biology, and natural history of malignant gliomas and the use of a multi-disciplinary approach to their treatment, patients harboring this diagnosis continue to face a grim prognosis. At the time of diagnosis, patients typically undergo surgery for the establishment of a histologic diagnosis, the reduction of tumor burden, and the relief of mass effect, with the maintenance of the patient's neurological function in mind. This is followed by the administration of adjuvant therapeutics, including radiation therapy and chemotherapy. Many investigational agents with laboratory evidence of efficacy against malignant gliomas have not met their promise in the clinical setting, largely due to the barriers that they must overcome to reach the tumor at a therapeutically meaningful concentration for a durable period of time. The relevant aspects of the blood-brain barrier, blood-tumor barrier, and blood-cerebrospinal fluid barrier, as they pertain to the delivery of agents to the tumor, will be discussed along with the strategies devised to circumvent them. This discussion will be followed by a description of agents currently in preclinical and clinical development, many of which are the result of intense ongoing research into the molecular biology of gliomas.
Locoregional Proton Radiotherapy of a Primary Cavernous Sinus Non-Hodgkin's Lymphoma: Case Report
Authors: Ronson Brian , Rossi Carl , Johnson Stéphane , Berdeja Antonio , Slater James M. , Slater Jerry D. 
Published: October 2014

Primary B cell lymphomas of the skull base are uncommon and lack well-defined treatment guidelines. We report a case of diffuse, large B-cell lymphoma of the cavernous sinus with sphenoid sinus and clival extension, treated with partial resection, chemotherapy, and proton beam irradiation. To our knowledge, this is the first report of a skull-base lymphoma treated with protons. A 53-year-old female presented with a two-month history of diplopia, persistent headaches, and paresthesia over the left side of her mouth. A skull MRI revealed an enhancing mass in the right cavernous sinus and right sphenoid sinus. Transsphenoidal subtotal resection of the mass confirmed the presence of a diffuse, large B-cell lymphoma. Treatment consisted of CHOP-R chemotherapy and locoregional radiation with protons. Locoregional radiation of the lesion required moderate doses, below the radiation tolerance of adjacent normal structures. Conformal protons were utilized to minimize the volume of normal brain receiving radiation. Conformal proton beam radiotherapy to a moderate dose proved valuable in this case because it minimized the volume of normal brain receiving low to moderate doses of radiation.
Multi-detector CT in the Evaluation of Patients with Recurrence of Rectal Cancer
Authors: Stueckle Christoph A. , Adams Stefan , Stueckle Kerstin F. , Szpakowski Michael , Schneider Oliver , Friedrich Christoph , Thiem Ulrich , Pientka Ludger , Liermann Dieter 
Published: October 2014

The advantages of multiplanar reconstruction in rectal cancer recurrence diagnostics using medium resolution multi-detector CT are evaluated. We included 40 patients after a rectal cancer operation in this study. During follow-up ten patients developed a recurrence. All patients received a minimum of two CT-examinations in their follow-up program. A total of 131 CT-scans were evaluated. Each examination was reviewed by two experienced radiologists in respect to recurrence. Each examination was presented in axial reconstruction with a slice thickness of 8mm with an increment of 7mm and a slice thickness of 3mm with an increment of 2mm. The thin slices were used for the multi-planar reconstruction. Multi-planar reconstructions showed better results for the detection of recurrence than axial reconstruction. A reduced slice thickness did not lead to better results in axial reconstruction. Multi-planar reconstruction showed a sensitivity of 0.88, a specificity of 1.0 and an accuracy of 0.97. Our axial reconstruction results were: 0.86, 0.96, and 0.93, respectively. Sensitivity and accuracy showed a significant increase after the first and second examinations. Multi-planar reconstructions allow for better detection of rectal cancer recurrence when compared to axial reconstructions. Thinner axial slice thickness shows no diagnostic advantage.
Killing Two Birds with One Stone: A Dosimetric Study of Dual Target Radiosurgery Using a Single Isocenter
Authors: Roberge David , Ruo Russell , Souhami Luis 
Published: October 2014

The treatment of hematogenous brain metastases is a frequent indication for stereotactic radiosurgery (SRS). It is common for more than one metastasis to be treated during the same SRS session. We retrospectively identified four cases where our m3 micro multileaf collimator (mMLC) was used to create two distinct apertures and treat adjacent lesions using a single isocenter. For these four cases, single isocenter plans with static conformal beams were dosimetrically compared to plans utilizing two isocenters with static conformal beams or conformal arcs. The effects on dose homogeneity, dose conformity, and the minimum isodose separating the two targets are minor and variable. On the other hand, the use of a single isocenter technique consistently halves delivery time and decreases the integral dose to normal tissue. For small adjacent metastases, which can simultaneously be encompassed within the high-resolution portion of the m3/Novalis mMLC collimator, the use of a single rather than a dual isocenter technique is feasible and generally advantageous.
Design of an Irreversible Electroporation System for Clinical Use
Authors: Bertacchini Claudio , Margotti Pier Mauro , Bergamini Enrico , Lodi Andrea , Ronchetti Mattia , Cadossi Ruggero 
Published: October 2014

Irreversible electroporation is an ablation modality in which microseconds, high-voltage electrical pulses are applied to induce cell necrosis in a target tissue. To perform irreversible electroporation it is necessary to use a medical device specifically designed for this use. The design of an irreversible electroporation system is a complex task in which the effective delivery of high energy pulses and the safety of the patient and operator are equally important. Pulses of up to 3000 V of amplitude and 50 A of current need to be generated to irreversibly electroporate a target volume of approximately 50 to 70 cm3 with as many as six separate electrodes; therefore, a traditional approach based on high voltage amplifiers becomes hard to implement. In this paper, we present the process that led to the first irreversible electroporator capable of such performances approved for clinical use. The main design choices and its architecture are outlined. Safety issues are also explained along with the solutions adopted.
CyberKnife Radiosurgery for Lesions of the Foramen Magnum
Authors: Cheshier Samuel H. , Hanft Simon J. , Adler John R. , Chang Steven D. 
Published: October 2014

The region of the foramen magnum (FM) presents an especially difficult area for therapeutic intervention. Indeed, this location is challenging to access surgically, particularly in the case of intramedullary and anterior lesions. Therefore, the potential for morbidity associated with therapy to the foramen magnum, most frequently in the form of lower cranial nerve deficits, has encouraged the search for methods that can effectively treat lesions of this region while sparing the important neighboring structures. We report our experience in the use of Cyberknife radiosurgery as a treatment option for these lesions. Thirty-five patients (17 men, 18 women; mean age, 51 yr; range, 18–83) with 35 lesions either spanning or approximating the foramen magnum were treated with the CyberKnife radiosurgical system. Histologies were determined either by prior surgery or radiographic criteria and included 25 benign tumors (nine meningiomas, five schwannomas, four neurofibromas, three hemangioblastomas, two ependymomas, one chordomas, and one pilocytic astrocytoma) along with 10 malignant growths (nine metastases and one chondrosarcoma). Twenty-seven (77%) patients presented with at least one sign and/or symptom, while eight (23%) patients were completely asymptomatic. The most common symptoms were headache, limb numbness, and limb/truncal ataxia, all of which were reported by ten (29%) patients. Among cranial neuropathies, CN XII dysfunction was evident in four (11%) patients. The specific fractionation schedule (mean of 1.8 sessions; range, 1–5) was based on the size of the treated lesion. The mean dose utilized was 19 Gy. Radiographic follow-up was obtained for twenty-three (66%) patients. Nine of the twenty-three (39%) were stable in size, ten lesions decreased in size (43%), and four lesions increased in size (17%). In terms of symptom relief, follow-up was collected for twenty-four (69%) patients. Eleven (46%) of these patients experienced no change in their signs or symptoms, while seven (29%) patients experienced improvement. Six (25%) patients witnessed deterioration in their signs and symptoms. Overall, eighteen (75%) patients had their signs and symptoms either stabilize or improve. There were eleven (31%) deaths in our series, eight of which were related to the disease (though not directly related to CyberKnife treatment) and three of which were from unrelated causes. Complications directly related to CyberKnife radiosurgery were noted in four (11%) of the thirty-five patients. These included one case of temporary emesis immediately following treatment, one case of cystic enlargement two months out, and two cases of radiation necrosis (occurring 1.5 yrs and 2.5 yrs out from treatment). Cyberknife radiosurgery can be an effective treatment for many foramen magnum lesions.
Absorption Characteristics of Protons and Photons in Tissue
Authors: Dicello John F. 
Published: October 2014

This presentation reviews the radiation quality of protons and other energetic ion beams, where radiation quality refers to those relevant physical properties other than the dose of the different types of radiations that can contribute to differences in the absorption characteristics in various tissues and the corresponding clinical outcomes. Prior to initiation of clinical trials with protons, neutrons, pions, and heavy ions, it was generally believed that such particles might have a therapeutic advantage resulting from their greater relative biological effectiveness (RBE). Potential clinical advantages resulting from a greater biological effectiveness, however, have generally been overshadowed during the last three decades by improved controls or reduced complications resulting primarily from the better dose delivery and localization that was possible with these heavier particles in conjunction with improved imaging. The successes both in delivery and in the clinical responses with protons and other light ions resulting from improved dose localization have arguably led the way in stereotactic radiosurgery, intensity modulated radiation therapy, and tomotherapy, stimulating improved methods with conventional radiations as well. Protons or light ions differ significantly in comparison with photon or electron beams in how they interact with the tissue atoms and molecules, and in how they transfer energy to those tissues. Microscopically, the heavier particles tend to travel in straight lines and produce long tracks with the energy concentrated closer to the track of the primary particle, while photons or electrons tend to scatter more easily and produce a more uniform distribution of energy transfers. Because they are hadrons, i.e., nuclear particles, protons and ions are more likely to produce long-range nuclear secondaries with higher masses. This higher concentration of energy associated with the heavier particle beams and the more massive secondaries results in differences in dose localization, clinically and microscopically, and therefore potential differences in short-term and long-term chemical and biological processes. Protons tend to have the least differences in clinical response in comparison with photons and electrons, the radiations used conventionally in therapy, but biological differences have been observed for these particles; it behooves us, therefore, to understand these different mechanisms if we are to take full advantage of their benefits. This article reviews the physical properties of these different particles in terms of microdosimetric distributions of energy deposition in order to compare protons with photons and heavy ions.
High Energy Shock Waves (HESW) Increase Paclitaxel Efficacy in a Syngeneic Model of Breast Cancer
Authors: Canaparo Roberto , Serpe Loredana , Zara Gian Paolo , Chiarle Roberto , Berta Laura , Frairia Roberto 
Published: October 2014

The combined effect of high energy shock waves (HESW), generated by a piezoelectric device, and paclitaxel on Mat B-III rat breast cancer cells in vitro and in an in vivo animal model is presented. A significant reduction of in vitro Mat B-III cell proliferation versus cells treated with paclitaxel alone was observed with the combined exposure to paclitaxel (0.1, 1, or 10 nM) and HESW (0.22 mJ/mm2, 1000 shots). Moreover earlier induction and enhanced apoptosis occurred in cells subjected to the combined treatment with paclitaxel and HESW at 1 and 10 nM versus paclitaxel alone (p<0.01 and p<0.001, respectively). The percentage of apoptotic cells along with BAD mRNA expression, confirm a significant enhancement of apoptosis in tumor tissues subjected to the combined treatment with paclitaxel (2.5 mg/kg on days 7 and 11) and HESW (0.50 mJ/mm2, 500 shots on day 11) in comparison with paclitaxel alone. In conclusion, these data suggest that HESW enhance paclitaxel cytotoxicity in the Mat B-III syngeneic model of breast cancer.
Hypofractionated Breast and Chest Wall Irradiation Using Simultaneous in-field Boost IMRT Delivered via Helical Tomotherapy
Authors: Rong Yi , Fahner Tasha , Welsh James S. 
Published: October 2014

Although helical tomotherapy has been described as a means of administering accelerated partial breast irradiation, its practicality in routine whole breast irradiation as part of breast conserving therapy or chest wall irradiation has been questioned. In this technical note we describe our method of whole breast or chest wall irradiation using helical tomotherapy based image-guided, hypofractionated, simultaneous in-field boost intensity modulated radiation therapy. We have observed that excellent dose-distributions can be achieved with helical tomotherapy through a careful selection of treatment planning parameters. Dose homogeneity to the whole breast and simultaneously targeted lumpectomy region appears superior to conventional “tangents” with minimal hot or cold spots. Dose-volume histogram analysis documents effective reduction of high dose to critical sensitive structures (heart and lung) although a greater volume of these non-target organs receives low dose compared to what is typical with tangential beams. Treatment planning is efficient and is usually completed within one to two hours, although physician contouring requires more time and attention than non-IMRT approaches. Pretreatment megavoltage CT (MVCT) imaging has proved invaluable in aiding set-up and engenders greater confidence that the planned IMRT dose distributions are truly being delivered. In some situations, MVCT can provide visual feedback when a seroma or overall breast volume has changed significantly since simulation, thereby identifying cases where replanning might be prudent. Treatment is brief, typically completed in 6 to 9 minutes. Initial clinical application has confirmed the feasibility and practicality of helical tomotherapy as an efficient means of administering radiation therapy for routine breast-conserving therapy and post-mastectomy chest wall irradiation. A simultaneous in-field boost technique reduces the length of the overall course by about a week thereby adding convenience and reducing costs. Further refinements of our technique are being explored and formal prospective clinical evaluation is underway.
Planning and Delivery of Whole Brain Radiation Therapy with Simultaneous Integrated Boost to Brain Metastases and Synchronous Limited-field Thoracic Radiotherapy Using Helical TomoTherapy: A Preliminary Experience
Authors: Gupta T. , Basu A. , Master Z. , Jalali R. , Munshi A. , Sarin R. 
Published: October 2014

Lung cancer is the commonest source of brain metastases, which has been traditionally treated with Whole Brain Radiation Therapy (WBRT) with or without focal boost. We herein report our preliminary experience of the planning and delivery of WBRT with Simultaneous Integrated Boost (SIB) to brain metastases along with synchronous limited-field thoracic radiotherapy using Helical TomoTherapy in four patients with lung cancer. All plans were iteratively optimized for maximal target volume coverage and organ-at-risk (OAR) sparing. Standardized dose metrics were used for plan evaluation. All treated regions were imaged with a megavoltage computed tomography (CT) prior to treatment and co-registered with planning CT for image-guidance. Helical TomoTherapy was able to achieve highly conformal and homogeneous dose distributions with excellent OAR sparing both in the brain and the chest. The mean (standard deviation) Dose Homogeneity Index (DHI) and Conformity Index (CI) was 0.06 (0.01) & 0.79 (0.07); 0.04 (0.02) & 0.57 (0.22); and 0.03 (0.02) & 0.77 (0.06) for whole brain, brain metastases, and chest, respectively. The mean monitor units (MU) per fraction and time taken for delivery were 8595 and 9898 MU and 9.8 and 11.3 minutes for the brain and chest plans, respectively. Although the dosimetric equivalence of SIB to a single fraction radiosurgery might still be questionable, our preliminary experience of WBRT with SIB to individual brain metastases using Helical TomoTherapy has been encouraging. In addition, it allows synchronous irradiation of other involved primary or metastatic sites for palliative effect.