bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Theorectical Radiation Dose Enhancement from Nanoparticles
Authors: Roeske John C. , Nuñez Luis , Hoggarth Mark , Labay Edwardine , Weichselbaum Ralph R.
Published: October 2014

Recently, nanoparticles have been considered as a method of providing radiation dose enhancement in tumors. In order to quantify this affect, a dose enhancement factor (DEF) is defined that represents the ratio of the dose deposited in tumor with nanoparticles, divided by the dose deposited in the tumor without nanoparticles. Materials with atomic numbers (Z) ranging from 25 to 90 are considered in this analysis. In addition, the energy spectrum for a number of external beam x-ray sources and common radionuclides are evaluated. For a nanoparticle concentration of 5 mg/ml, the DEF is < 1.05 for Co-60, Ir-192, Au-198, Cs-137, 6, 18, and 25 MV x-rays for all materials considered. However, relatively large increases in the DEF are observed for 50, 80, 100, and 140 KVp x-rays as well as Pd-103 and I-125. The DEF increases for all sources as Z varies from 25–35. From Z = 40–60, the DEF plateaus or slightly decreases. For higher Z materials (Z>70), the DEF increases and is a maximum for the highest Z materials. High atomic number nanoparticles coupled with low energy external beam x-rays or brachytherapy sources offer the potential of significantly enhancing the delivered dose.
Radiosurgery for Glomus Jugulare Tumors
Authors: Lim Michael , Bower Regina , Nangiana Jasvinder Singh , Adler John R. , Chang Steven D.
Published: October 2014

Results for treating glomus jugulare tumors with radiosurgery have been limited by short follow-up and small number of patients. We report our experience using LINAC or CyberKnife in 21 tumors with a median follow-up of 66 months (Mean follow-up of 60 months). In addition, we have a subset of eight patients that were followed out for more than 10 years. Patients were treated with doses ranging from 1400 cGy to 2700 cGy. We retrospectively assessed patients for efficacy and post treatment side effects. All patients had stable neurological symptoms, and two patients experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. One patient experienced transient ipsilateral vocal cord paresis; however, this patient received previous external beam radiotherapy. All tumors remained stable or decreased in size by MRI exam. Our results support radiosurgery as an effective and safe method of treatment for glomus jugulare tumors with low morbidity as evidenced by a larger number of patients and long term follow-up.
An Overview of Subatomic Particles for Non-Physicists
Authors: Lederman Leon M.
Published: October 2014

The particles used in radiation therapy are part of a larger universe of particles discovered by experimental physicists. May of these particles are themselves composed of particles. Understanding the way particles interact, and the forces underlying their interactions, is basic to the quest to understand the universe. High-energy physics studies in the past have identified the particles used in medicine; future studies may identify still others, but if not, may contribute to a better knowledge of the milieu in which medicine and other human endeavors exist.
Dosimetry Aspects of Proton Therapy
Authors: Patyal Baldev
Published: October 2014

High-energy photons and high-energy protons are very different in the ways they interact with matter. These differences lead to distinct advantages of protons over photons for treatment of cancer. Some aspects of proton interactions with tissue that make this modality superior for treating cancer are: (i) Initially, the protons lose energy very slowly as they enter the body; this results in a low entrance dose and low doses to the normal tissues proximal to the tumor. (ii) Near the end of range, protons lose energy very rapidly and deposit all their energy over a very small volume before they come to rest. This is the Bragg peak, a property that results in delivery of the maximum dose to the tumor. (iii) Beyond the Bragg peak, the energy deposited by the protons is zero; no dose is received by normal tissues distal to the tumor. Therefore, protons deliver their maximum dose to the tumor, a low dose to normal structures proximal to the tumor, and no dose to the normal structures beyond the tumor, ideal properties of a radiation modality to treat cancer. One distinct advantage of protons over photons is the ease with which the tumor target can be irradiated conformably to a high dose, and at the same time the normal structures in the vicinity of the tumor can be protected conformably from that high dose. Given the same dose to the tumor via photons and protons, protons inherently deliver less integral dose and, thus, lead to fewer normal-tissue complications. In addition, proton interactions also offer distinct radiobiological advantages over photons. Superior physical and radiobiological proton interactions lead naturally to the concepts of dose escalation and hypofractionation. The superiority of treatment delivery with protons as contrasted with photons is demonstrated by treatment plans.
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.
The Impact of Protons on the Incidence of Second Malignancies in Radiotherapy
Authors: Hall Eric J.
Published: October 2014

Protons represent a logical step forward as a modality for radiotherapy because it is possible to concentrate dose in the tumor region and minimize dose to normal tissue. The pencil beam emerging from a cyclotron or synchrotron needs to be expanded to a larger size to cover tumors of realistic size. Ideally, this should be accomplished by scanning the pencil beam using magnetic fields, but this is technically challenging. The simpler method is to use passive modulation, the downside of which is that neutrons are produced in the scattering foil, which results in a total body dose to the patient. Neutrons are highly effective at inducing second cancers and so, for the full potential of protons to be realized, spot scanning is essential.
Proton Treatment Room Concepts for Precision and Efficiency
Authors: Schulte Reinhard W.
Published: October 2014

Proton radiation therapy involves accurate delivery of proton beams to targets inside the body without direct visual control of the internal anatomy. Targeting of the tumor and avoidance of critical structures within the patient have to be both accurate and precise to achieve the desired therapeutic results. Good understanding of proton radiation delivery and patient alignment concepts in the treatment room is essential to achieve this goal. This overview article presents treatment room concepts that will ensure precise proton beam delivery and, at the same time, guarantee an efficient patient throughput. Concepts discussed include effective patient immobilization, image-guided alignment verification, appropriate training of radiotherapists, and the physician's integrative role in understanding the complex spatial relationships between tumor, organs at risk, treatment beam configuration, and application of proton radiation dose. It will be demonstrated that in addition to the technical armamentarium, now commonplace in modern radiation oncology departments, the interaction between radiation oncologist, medical physicist and radiotherapist is important for efficient operation of a proton treatment facility.
Optically Guided Stereotactic Radiotherapy for Lacrimal Sac Tumors: A Report on Two Cases
Authors: Lu Heming , Yao Min , Anderson Kathleen , Buatti John
Published: October 2014

Adjuvant radiation treatment is often offered for lacrimal sac tumors. However, due to the adjacent critical structures, conventional radiation technique may result in severe side effects. We have treated two patients with lacrimal sac tumors using optically guided stereotactic radiotherapy. One patient with lacrimal sac melanoma was treated with optical-guidance intensity-modulated radiotherapy (IMRT). The other with mixed transitional and squamous cell carcinoma was treated with optical-guidance 3-D conformal radiation. Dose volume analysis revealed excellent target coverage and sparing of critical structures. Both patients tolerated the treatment well with no significant acute or late side effects. One patient died of metastatic melanoma 30 months after radiation; another died of coexisting disease 41 months after radiation. Both had no clinical evidence of local recurrence at the time of death. Our report show that optically guided stereotactic radiotherapy is well tolerated. It offers excellent tumor coverage and sparing of critical structures. It can be used for tumors adjacent to radiation sensitive critical structures such as skull base tumors.
Gene Electrotransfer into Murine Skeletal Muscle: A Systematic Analysis of Parameters for Long-term Gene Expression
Authors: Tevz Gregor , Pavlin Darja , Kamensek Urska , Kranjc Simona , Mesojednik Suzana , Coer Andrej , Sersa Gregor , Cemazar Maja
Published: October 2014

Skeletal muscle is an attractive target tissue for delivery of therapeutic genes, since it is well vascularized, easily accessible, and has a high capacity for protein synthesis. For efficient transfection in skeletal muscle, several protocols have been described, including delivery of low voltage electric pulses and a combination of high and low voltage electric pulses. The aim of this study was to determine the influence of different parameters of electrotransfection on short-term and long-term transfection efficiency in murine skeletal muscle, and to evaluate histological changes in the treated tissue. Different parameters of electric pulses, different time lags between plasmid DNA injection and application of electric pulses, and different doses of plasmid DNA were tested for electrotransfection of tibialis cranialis muscle of C57Bl/6 mice using DNA plasmid encoding green fluorescent protein (GFP). Transfection efficiency was assessed on frozen tissue sections one week after electrotransfection using a fluorescence microscope and also noninvasively, followed by an in vivo imaging system using a fluorescence stereo microscope over a period of several months. Histological changes in muscle were evaluated immediately or several months after electrotransfection by determining infiltration of inflammatory mononuclear cells and presence of necrotic muscle fibers. The most efficient electrotransfection into skeletal muscle of C57Bl/6 mice in our experiments was achieved when one high voltage (HV) and four low voltage (LV) electric pulses were applied 5 seconds after the injection of 30 μg of plasmid DNA. This protocol resulted in the highest short-term as well as long-term transfection. The fluorescence intensity of the transfected area declined after 2–3 weeks, but GFP fluorescence was still detectable 18 months after electrotransfection. Extensive inflammatory mononuclear cell infiltration was observed immediately after the electrotransfection procedure using the described parameters, but no necrosis or late tissue damage was observed. This study showed that electric pulse parameters, time lag between the injection of DNA and application of electric pulses, and dose of plasmid DNA affected the duration of transgene expression in murine skeletal muscle. Therefore, transgene expression in muscle can be controlled by appropriate selection of electrotransfection protocol.
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.
Development of a Novel Post-processing Treatment Planning Platform for 4D Radiotherapy
Authors: Lin Lan , Shi Chengyu , Liu Yaxi , Swanson Gregory , Papanikolaou Nikos
Published: October 2014

The aim of this study is to develop an Automatic Post-processing Tool for four-dimensional (4D) treatment planning (APT4D) that enables the user to perform some necessary procedures related to 4D treatment planning, such as automated image registration, automatic propagation of regions of interest, and dose distribution transformation. Demons-based deformable registrations were performed to map the moving phase images (such as the end-inhalation phase or 0% phase) to the reference phase (typically the end-exhalation fixed phase or 50% phase). Contours were automatically propagated into the moving phase using the image registration results. The dose distribution of each moving phase was transformed to the fixed phase and subsequently was summed as an average with equal weighting factor. To validate the application of APT4D utility, the 4D computed tomography (CT) images of a lung cancer patient and an abdominal cancer patient were acquired and resorted into ten respiratory phases. 4D plans based on the 4D CT images were developed. The correlation coefficient ranged from 0.992 to 0.999 for the re-sampled deformed moving phase image against the fixed phase image for the lung patient plan and from 0.977 to 0.999 for the abdominal patient plan. For all the organs, the match indices between the manual contours and automatic contour propagation results were around 0.92 to 0.95. The 4D composite dose-volume histogram showed dosimetric reductions for liver and kidneys in the high dose region. The APT4D adds automation, efficiency, and functionality, while integrating the whole process of 4D treatment planning.
Stereotactic Body Radiation Therapy: Evaluation of Setup Accuracy and Targeting Methods for a New Couch Integrated Immobilization System
Authors: Heinzerling John H. , Papiez Lech , Chien Stanley , Anderson John , Forster Kenneth , Zhang Geoffrey , Timmerman Robert
Published: October 2014

A new stereotactic frame system was designed at Indiana University to utilize the precision motion control of newer accelerator couches and treat obese patients previously untreatable in other frame systems during stereotactic body radiation therapy (SBRT). The repositioning accuracy and target reproducibility of this frame was evaluated in the treatment of both lung and liver tumors. The external coordinate system on the new frame was validated using a phantom system. Translational motions were carried out using couch motors. Five patients were treated with SBRT and twenty-three verification CT scans were acquired. The displacement of the gross tumor volume (GTV) and adjacent vertebral body between the original CT scan and the verification CT scans was determined. The mean setup accuracy for the patient study was less than 5 mm. Mean displacement of the GTV was 3.0 mm (0.0–6.0 mm) in the lateral (x) direction, 4.1 mm (0.0–8.9 mm) in the superior-inferior (y) direction, and 2.6 mm (0.0–10.0 mm) in the cranio-caudal (z) direction. Comparison of vertebral body position showed mean displacement of 2.4 mm (0.0 to 8.0 mm), 1.9 mm (0.0 mm to 2.0 mm), and 0.9 mm (0.0 to 5.0 mm) for the same shift directions. Repositioning could be accurately carried out from an initial reference position using the treatment couch controllers. Adequate set-up accuracy using a frame system capable of accommodating wide girth patients was achieved and was comparable to other published studies for narrower frames. With these results, a 5 mm expansion for PTV margins remains the standard for our institution.
Dosimetric Impacts of Gantry Angle Misalignment on Prostate Cancer Treatment using Helical Tomotherapy
Authors: Su Fan-Chi , Shi Chengyu , Crownover Richard , Swanson Gregory , Papanikolaou Niko
Published: October 2014

During helical tomotherapy, gantry angle accuracy is one of the vital geometric factors that assure accurate dose delivery to the target and organs at risk adjacent to it. The purpose of this study is to investigate the dosimetric impact of gantry angle misalignment on the target volume and critical organs during helical tomotherapy treatment. Five prostate cases were chosen to calculate the effects of gantry angle deviations on both patient-specific delivery quality assurance (DQA) and helical tomotherapy treatment plans. For DQA plans, the cheese phantom was rotated for up to +/- 5° from the preset position to simulate the gantry angle deviations during tomotherapy. Point doses at 5 mm below the isocenter and the dose distribution for each gantry angle were measured and reconstructed, respectively. For helical tomotherapy treatment plans, the same gantry misalignment effect was simulated by adjusting the automatic roll correction for up to +/- 5° using Planned Adaptive software. Variations of dose volume histograms (DVHs) and isodose lines were evaluated for both target and critical organs. There was no significant difference found, however, among the point dose measurements for gantry rotation up to +/- 5° in DQA plans. Shifts of isodose lines could be observed for gantry rotations larger than +/- 2°. Dosimetric discrepancies (less than 2%) were also found among DVHs of the PTV in the cases when gantry angle misalignment was larger than +/- 2°. However, for DVHs of either bladder or rectum under different gantry rotations, no significant differences were detected when gantry angle errors were up to +/- 5°. In summary, point dose measurements alone cannot reveal the dosimetric deviation due to gantry angle misalignment in DQA plans. For a 5° gantry deviation, the dose to PTV increased by 0.5% comparing to the planned dose. The influence on organs at risk, i.e., rectum and bladder, is also negligible. Further studies are needed on the dosimetric impacts of gantry angle deviations for other treatment sites.
Surface Dose for Five Telecobalt Machines, 6MV Photon Beam from Four Linear Accelerators and a Hi-Art TomoTherapy
Authors: Kinhikar Rajesh A.
Published: October 2014

The purpose of this study was to estimate the surface dose for five telecobalt machines (four from Best Theratronics Limited, Canada, one from Panacea Medical Technologies, India), 6 MV photon beam (static) from four linear accelerators (three Varian linear accelerators and one Siemens) and Hi-Art Tomotherapy unit. The surface dose was measured with Thermoluminescent dosimeters in phantom slabs. For Tomotherapy 6 MV beam the surface dose was estimated as 32% while it was 35%, 33%, and 36% for Clinac 6EX, Clinac 2100CD, and Clinac 2100C linear accelerators, respectively. Similarly, the surface dose for 6 MV photon beam from Primus linear accelerator was estimated as 35%. Surface doses from telecobalt machines Equinox-80, Elite-80, Th-780C, Th-780, and Bhabhatron-II was found to be 30%, 29.1%, 27.8%, 29.3%, and 29.9% for 10 cm × 10 field size, respectively. Measured surface dose from all four linear accelerators were in good agreement with that of the Tomotherapy. The surface dose measurements were useful for Tomotherapy to predict the superficial dose during helical IMRT treatments.
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.
Design and Testing of a Simulation Framework for Dosimetric Motion Studies Integrating an Anthropomorphic Computational Phantom into Four-dimensional Monte Carlo
Authors: Riboldi M. , Chen G. T. Y. , Baroni G. , Paganetti H. , Seco J.
Published: October 2014

We have designed a simulation framework for motion studies in radiation therapy by integrating the anthropomorphic NCAT phantom into a 4D Monte Carlo dose calculation engine based on DPM. Representing an artifact-free environment, the system can be used to identify class solutions as a function of geometric and dosimetric parameters. A pilot dynamic conformal study for three lesions (~ 2.0 cm) in the right lung was performed (70 Gy prescription dose). Tumor motion changed as a function of tumor location, according to the anthropomorphic deformable motion model. Conformal plans were simulated with 0 to 2 cm margin for the aperture, with additional 0.5 cm for beam penumbra. The dosimetric effects of intensity modulated radiotherapy (IMRT) vs. conformal treatments were compared in a static case. Results show that the Monte Carlo simulation framework can model tumor tracking in deformable anatomy with high accuracy, providing absolute doses for IMRT and conformal radiation therapy. A target underdosage of up to 3.67 Gy (lower lung) was highlighted in the composite dose distribution mapped at exhale. Such effects depend on tumor location and treatment margin and are affected by lung deformation and ribcage motion. In summary, the complexity in the irradiation of moving targets has been reduced to a controlled simulation environment, where several treatment options can be accurately modeled and quantified The implemented tools will be utilized for extensive motion study in lung/liver irradiation.
Options for Combining Altered Fractionation with IMRT
Authors: Allen Aaron M. , Wolfsberger Luciant , Tishler Roy B. , Court Laurence E.
Published: October 2014

We set out to investigate IMRT-based concomitant boost. Eight patients with stage III/IV squamous cell carcinoma of the head and neck treated with once daily with chemoradiotherapy at the Dana-Farber/Brigham and Women's Hospital had their treatment plans reviewed with IRB approval. Each case was replanned for treatment with a a concomitant boost regimen. Plans delivered 1.9 Gy in 30 fractions to 57 Gy with a boost of 1.5 Gy in 10 fractions for a total dose of 72 Gy. The boost was planned with both IMRT and 3-D conformal, to compare the two techniques. For each patient, both plans (IMRT-IMRT and IMRT-3DCRT) were evaluated for target and avoidance coverage, monitor units and integral dose. Finally, we evaluated the plans for time to completion. The IMRT-IMRT and IMRT-3-DCRT techniques were equivalent for target coverage. 100% coverage of the GTV and PTV was achieved with 97% of the prescription dose. Hot spots were seen 104% to 108% with IMRT-IMRT plan and from 102–111% with the IMRT-3DCRT plans. The IMRT-IMRT boost had double the monitor units as the 3-DCRT boosts. When the total monitor units from both the initial and boost portions of the plans were e combined there was not a significant differnce. There was a slight increase in integral dose with the IMRT-IMRT plans of mean 3.8%. Planning time was increased for the 3-DCRT boost as opposed to the IMRT boost (mean 3.5 hours vs. 1.5 hours). More time was needed for quality assurance of the IMRT-IMRT plans (3.0 hours vs. 1.5 hours for IMRT-3-DCRT). We found that both IMRT-based concomitant-boost strategies are achievable and produce good dosimetric results.
Design and Benchtop Validation of a Handheld Integrated Dynamic Breast Imaging System for Noninvasive Characterization of Suspicious Breast Lesions
Authors: Xu Ronald X. , Ewing Joseph , El-Dahdah Hamid , Wang Bei , Povoski Stephen P.
Published: October 2014

We have developed a portable, handheld, integrated, dynamic breast imaging system that integrates a near infrared tissue oximeter, clinical ultrasound, and two pressure sensors for noninvasive detection of pressure-induced structural and functional dynamics of suspicious breast lesions. A series of benchtop tests were conducted to validate multiple performance characteristics of the integrated dynamic near infrared/ultrasound breast imaging system (idNIRUS), including the reconstruction of the absorptive heterogeneities and the generation of the dynamic compression stimuli. In absorptive heterogeneity testing, we reconstructed the absorption coefficients of transparent polypropylene tubing circulated with a skim milk-India ink mixture and embedded in a gel wax tissue simulating phantom. High linear correlations (R2 greater than 0.989) were observed between the reconstructed and the measured absorption coefficients of the embedded tubing. In dynamic compression testing, five volunteer operators generated ten successive compression sessions by compressing the idNIRUS imager on a breast self examination wearable model following the computer simulated pressure profile. The manually generated pressure profiles demonstrated an accuracy of 95.7% and operator-dependent variation of less than 5%. The results of the current benchtop tests will help to optimize the most appropriate testing conditions for our future planned clinical trial.
Recent Advances in Protection against Doxorubicin-induced Toxicity
Authors: Injac Rade , Strukelj Borut
Published: October 2014

Anthracycline antibiotics are among the most effective and commonly used anticancer drugs. Unfortunately, their clinical use is restricted by dose-dependent toxicity. Doxorubicin is an anthracycline antibiotic and cytotoxic (antineoplastic) agent. It is commonly used against ovarian, breast, lung, uterine and cervical cancers, Hodgkin's disease, soft tissue and primary bone sarcomas, as well against in several other cancer types. It has been shown that free radicals are involved in doxorubicin-induced toxicity. Doxorubicin causes the generation of free radicals and the induction of oxidative stress, associated with cellular injury. This review illustrates recent applications of different natural products, drugs, drug delivery systems, and approaches for protection against doxorubicin-induced toxicity (2006-present).
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.
Multimodality Image Guided Total Marrow Irradiation and Verification of the Dose Delivered to the Lung, PTV, and Thoracic Bone in a Patient: A Case Study
Authors: Hui Susanta K. , Verneris M. R. , Froelich Jerry , Dusenbery K. , Welsh James S.
Published: October 2014

This work reports our initial experience using multimodality image guidance to improve total marrow irradiation (TMI) using helical tomotherapy. We also monitored the details of the treatment delivery to glean information necessary for the implementation of future adaptive processes. A patient with metastatic Ewing's sarcoma underwent MRI, and bone scan imaging prior to TMI. A whole body kilovoltage CT (kVCT) scan was obtained for intensity modulated TMI treatment planning, including a boost treatment to areas of bony involvement. The delivered dose was estimated by using MVCT images from the helical tomotherapy treatment unit, compared to the expected dose distributions mapped onto the kVCT images. Clinical concerns regarding patient treatment and dosimetric uncertainties were also evaluated. A small fraction of thoracic bone volume received lower radiation dose than the prescribed dose. Reconstructed planned treatment volume (PTV) and the dose delivered to the lung were identical to planned dose. Bone scan imaging had a higher sensitivity for detecting skeletal metastasis compared to MR imaging. However the bone scan lacked sufficient specificity in three dimensions to be useful for planning conformal radiation boost treatments. Inclusion of appropriate imaging modalities improves detection of metastases, which allows the possibility of a radiation dose boost to metastases during TMI. Conformal intensity modulated radiation therapy via helical tomotherapy permitted radiation delivery to metastases in the skull with reduced dose to brain in conjunction with TMI. While TMI reduces irradiation to the lungs, onboard megavoltage computed tomography (MVCT) to verify accurate volumetric dose coverage to marrow-containing thoracic bones may be essential for successful conformal TMI treatment.
Total Marrow Irradiation with Helical Tomotherapy for Bone Marrow Transplantation of Multiple Myeloma: First Experience in Asia
Authors: Shueng Pei-Wei , Lin Shih-Chiang , Chong Ngot-Swan , Lee Hsing-Yi , Tien Hui-Ju , Wu Le-Jung , Chen Chien-An , Lee Jason J. S. , Hsieh Chen-Hsi
Published: October 2014

Three Asian patients with plasma cell myeloma stage IIIa with IgG predominant were selected for autologous hematopoietic cell transplantation (HSCT). Total marrow irradiation (TMI) tomotherapy planned with melphalan 140 mg/m2 as a preconditioning regimen of HSCT. Two image sets of computed tomography (CT) were scanned with 2.5 mm and 5 mm for the upper and lower part of the plan, respectively. The junction was determined and marked at 15 cm above knee on both thighs for upper and lower part of the plan. The clinical target volume (CTV) included the entire skeletal system. The planning target volume (PTV) was generated with with 0.8 cm for CTVextremities and with 0.5 cm margin for all other bones of CTV.

A total dose of 800 cGy (200 cGy/fraction) was delivered to the PTV. Update to presentation, all of three patients post transplant without evidence of active disease were noted. During TMI treatment, one with grade 1 vomiting, two with grade 1 nausea, one with grade 1 mucositis, and three with grade 1 anorexia were noted. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). The average for upper part versus lower part of PTVBone marrow of CI and H-index were 1.5 and 1.4 versus 1.2 and 1.2, respectively. The dose reduction of TMI tomotherapy to various OARs of head, chest, and abdomen relative to TBI varied from 31% to 74%, 21% to 51%, and 46% to 63%, respectively.

The maximum average value of registration for upper torso versus lower extremities in different translation directions were 5.1 mm versus 4.1 mm for pretreatment and 1.5 mm versus 0.7 mm for post-treatment, respectively. The average treatment time for the upper versus lower part in beam-on time, setup time, and MVCT registration time took roughly 49.9, 23.3, and 11.7 min versus 11.5, 10.0, and 7.3 min, respectively. The margin of PTV could be less than 1 cm under good fixation and close position confirmation with MVCT. Antiemetics should be prescribed in the whole course of TMI for emesis prevention. TMI technique replaced TBI technique with 8 Gy as conditioning regiment for multiple myeloma could be acceptable for the Asian and the outcomes were feasible for the Asian.
Growth Inhibition against Intracranial C6 Glioma Cells by Stereotactic Delivery of BCNU by Controlled Release from poly(D,L-lactic acid) Nanoparticles
Authors: Kang ChunSheng , Yuan XuBo , Zhong Yue , Pu PeiYu , Guo YanShuang , Albadany Ammar , Yu ShiZhu , Zhang ZhiYong , Li YanHe , Chang Jin , Sheng Jing
Published: October 2014

Transferrin (Tf), an iron-transporting serum glycoprotein, which binds to receptors expressed at the surface of most proliferating cells with particularly high expression on erythroblasts and cancer cells, was chosen as the ligand to develop BCNU-loaded biodegradable poly(D,L-lactic acid) nanoparticles (NPs) containing a ligand, which specifically binds to glioma cells, and their anti-tumor ability was evaluated using a C6 glioma model. In vitro drug release behavior demonstrated that BCNU-loaded PLA NPs show certain sustained release characteristics. NPs with low molecular weight PLA showed a higher burst effect and a significantly faster drug release from PLA samples. The biodistribution of Tf-coated nanoparticles investigated by 99Tc-labeled SPECT showed that the surface-containing transferrin PLA nanoparticles were concentrated in the brain and no radioactive foci could be found outside the brain. Inhibition of tumor growth in the C6 tumor-bearing animal model showed that BCNU-loaded PLA NPs had stronger cytotoxicity and prolonged the average survival time of rats. Especially when treated at an early stage with a higher dosage of NPs, the average survival time of rats was prolonged 88.37%. Furthermore, one rat maintained normal behavior continuously for an observation period of up to 60 days.
The Use of Intraoperative MRI for the Treatment of Glioblastoma Multiforme
Authors: Lenaburg Harry J. , Inkabi Kofi E. , Vitaz Todd W.
Published: October 2014

Outcome for patients with glioblastoma multiforme (GBM) is improved with aggressive surgical resection followed by standard chemotherapy and radiation therapy. Intraoperative MRI (iMRI) is a recent surgical advancement that gives neurosurgeons direct radiographic feedback throughout a surgical procedure and thus enables maximal surgical resection of such lesions.

We reviewed our series of 35 cases in 29 patients who underwent surgical resections of their GBM's using iMRI. The average extent of resection was 94% with only three patients having resections of less than 90%. However, even with such technology complete resection may not always be possible because of tumor location near critical brain structure or involvement of surrounding vascular structures.

The addition of iMRI to the surgical armamentarium for treatment of patients with GBM improves the degree of tumor resection while minimizing complications and thus may positively impact survival in this patient population.
Complications of High Intensity Focused Ultrasound for Patients with Hepatocellular Carcinoma
Authors: Li Jian-Jun , Gu Mo-Fa , Luo Guang-Yu , Liu Li-Zhi , Zhang Rong , Xu Guo-Liang
Published: October 2014

High intensity focused ultrasound (HIFU) is a noninvasive treatment modality that induces complete coagulative necrosis of a deep tumor through the intact skin. This study was conducted to analyze and evaluate the complications of HIFU for the treatments of hepatocellular carcinoma. A total of 59 patients with hepatocellular carcinoma, with a total of 72 lessions were enrolled in this study. Tumor size ranged from 2.5 to 14.0 cm in diameter, with a mean diameter of 7.6 cm. All patients had accepted HIFU treatment, and the median number of HIFU sessions was 1.32 per patient. Results: The common complications from HIFU therapy were skin burns of various grades (eight cases of grade 1 skin burns, 48 of grade 2, three cases of 3), and pain in the treatment regions (15 cases of mild pain, 37 cases of moderate pain, 7 cased of severe pain). Other systemic complications were relatively rare and included fever (5 cases), hypertension (8 cases), supraventricular tachycardia (3 cases), mild impairment of hepatic function (48 cases), and mild mpairment of renal function (2 cases). Local damage consisted of acute cholecystitis (2 cases), hematuria (6 cases), cholangiectasis (5 cases), light pericardial effusion (2 cases), impairment of peripheral nerves (10 cases), pleural effusion in the right thorax (3 cases), and impairment of vertebral column (1 case). No gastric or intestinal tract perforation, big vessel rupture, or hepatic rupture occurred. Conclusions: HIFU is a minimally invasive treatment for patients with hepatocellular carcinoma; however, there are some systemic and local complications that should be taken into consideration in evaluating HIFU for therapeutic use.
SELDI-TOF-MS-based Serum Proteomic Screening in Combination with CT Scan Distinguishes Renal Cell Carcinoma from Benign Renal Tumors and Healthy Persons
Authors: Xu Gang , Xiang Cui Qin , Lu Ye , Wang Wen Jing , Kang Xiao Nan , Liao Ping , Ding Qiang , Zhang Yuan Fang
Published: October 2014

In order to identify the proteomic differences between renal cell carcinoma (RCC) and benign renal tumors, we analyzed 168 serum samples from 65 RCC patients, 34 patients with benign renal tumors, and 69 healthy persons using the IMAC-Cu2+ ProteinChip system by surface enhanced laser desorption/ionization mass spectrometry technology. Two decision trees were generated by Biomarker Pattern software to distinguish between RCC versus healthy and RCC versus patients with benign tumors, respectively. Although the sensitivity and specificity of the RCC vs. healthy decision tree were 97.6% and 95.7%, respectively, it could not be used to distinguish RCC from benign renal tumors. The sensitivity of a blind test process using RCC, benign tumors and healthy persons were 92%. The specificity of the test process was 35.3% for benign tumors and 95.5% for healthy persons. The sensitivity and specificity of the RCC-Benign tumors decision tree were 85.7% and 95.5%, respectively. The blind test process using RCC, benign tumors and healthy persons also showed significant results. The sensitivity was 90.0%. The specificity was 95.7% for healthy persons and 90.0% for benign tumors. Combining these data with the results of CT scanning, the sensitivity can be improved over the use of either CT and decision tree analysis and the specificity may reach 100%. Two peaks with molecular masses of 3887.11 Da and 11079.8 Da were detected that are potentially useful for the diagnosis or screening of RCC. It was found that these two peaks can be used, not only to distinguish the RCC vs. healthy cases, but also to distinguish RCC from benign renal tumors. In combination with CT scanning, the sensitivity and specificity of the diagnosis of renal tumors can be improved. However, the decision tree constructed for RCC and healthy persons may not present good specificity for use in distinguishing malignant from benign renal tumors.
Clinical Feasibility of Microscopically-Guided Breast Needle Biopsy Using a Fiber-Optic Probe with Computer-Aided Detection
Authors: Zysk Adam M. , Nguyen Freddy T. , Chaney Eric J. , Kotynek Jan G. , Oliphant Uretz J. , Bellafiore Frank J. , Johnson Patricia A. , Rowland Kendrith M. , Boppart Stephen A.
Published: October 2014

Needle biopsy of small or nonpalpable breast lesions has a high nondiagnostic sampling rate even when needle position is guided by stereotaxis or ultrasound. We assess the feasibility of using a near-infrared fiber optic probe and computer-aided detection for the microscopic guidance of needle breast biopsy procedures. Specimens from nine consented patients undergoing breast-conserving surgery were assessed intraoperatively using a needle device with an integrated fiber-optic probe capable of assessing two physical tissue properties highly correlated to pathology. Immediately following surgical resection, specimens were probed by inserting the optical biopsy needle device into the tissue, simulating the procedure used to position standard biopsy needles. Needle positions were marked and correlated with histology, which verified measurements obtained from 58 needle positions, including 40 in adipose and 18 in tumor tissue. This study yielded tissue classifications based on measurement of optical refractive index and scattering. Confidence-rating schemes yielded combined sensitivity of 89% (16/18) and specificity of 78% (31/40). Refractive index tests alone identified tumor tissue with a sensitivity of 83% (15/18) and specificity of 75% (30/40). Scattering profiles independently identified tumor tissue with a sensitivity of 61% (11/18) and specificity of 60% (24/40). These results show that a biopsy needle with an integrated fiber optic probe can be used to identify breast tumor tissue for sampling. Integration of this probe into current practices offers the potential to reduce nondiagnostic sampling rates by directly evaluating in situ microscopic tissue properties in real-time, before removal.
Protein Profiling of Pleural Effusions to Identify Malignant Pleural Mesothelioma Using SELDI-TOF MS
Authors: Hegmans Joost P.J.J. , Veltman Joris D. , Fung Eric T. , Verch Thorsten , Glover Curtis , Zhang Fujun , Allard W. Jeffrey , T'Jampens Davy , Hoogsteden Henk C. , Lambrecht Bart N. , Aerts Joachim
Published: October 2014

Diagnosis of malignant pleural mesothelioma (MM) is limited. Novel proteomic technologies can be utilized to discover changes in expression of pleural proteins that might have diagnostic value. The objective of this study was to detect protein profiles that could be used to identify malignant pleural mesothelioma with surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS). Pleural effusions were collected from patients with confirmed mesothelioma (n = 41) and from patients with effusions due to other causes ([n = 48] cancerous and non-cancerous). Samples were fractionated using anion exchange chromatography and bound to different types of ProteinChip array surfaces. All samples were also subjected to other commercially available immunoassays (human epididymes protein 4 [HE4], osteopontin [OPN], soluble mesothelin-related proteins [SMRP], and the cytokeratin 19 fragment [CYFRA 21–1]). Peak intensity data obtained by SELDI-TOF were subjected to classification algorithms in order to identify potential classifier peaks. A protein peak at m/z 6614 was characterized as apolipoprotein (Apo) CI. In this setting, the sensitivity and specificity of this potential biomarker was 76 % and 69 %, respectively. The area under the receiver operating characteristic curve (AUC) for Apo CI was 0.755, thereby outperforming OPN, HE4, and CYFRA 21–1. SMRP performed best with an AUC of 0.860 with a sensitivity of 83% and specificity of 74%. Our study validates the use of SMRP as a diagnostic marker for pleural mesothelioma and furthermore suggests that Apo CI levels could be used in the future to discriminate pleural mesothelioma from other causes of exudates.