bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Fluorescence and X-Ray Tomography for Quantitative In Vivo Detection of Fluorophore
Authors: Barber W. C. , Lin Y. , Nalcioglu O. , Iwanczyk J. S. , Hartsough N. E. , Gulsen G.
Published: October 2014

Initial results from a novel dual modality preclinical imager which combines non-contact fluorescence tomography (FT) and x-ray computed tomography (CT) for preclinical functional and anatomical in vivo imaging are presented. The anatomical data from CT provides a priori information to the FT reconstruction to create overlaid functional and anatomical images with accurate localization and quantification of fluorophore distribution. Phantoms with inclusions containing Indocyanine-Green (ICG), and with heterogeneous backgrounds including iodine in compartments at different concentrations for CT contrast, have been imaged with the dual modality FT/CT system. Anatomical information from attenuation maps and optical morphological information from absorption and scattering maps are used as a priori information in the FT reconstruction. Although ICG inclusions can be located without the a priori information, the recovered ICG concentration shows 75% error. When the a priori information is utilized, the ICG concentration can be recovered with only 15% error. Developing the ability to accurately quantify fluorophore concentration in anatomical regions of interest may provide a powerful tool for in vivo small animal imaging.
Preliminary Evaluation of a Combined MicroPET®-MR System
Authors: Hawkes R. C. , Fryer T. D. , Siegel S. , Ansorge R. E. , Carpenter T. A.
Published: October 2014

There are many motivations for adding simultaneously acquired MR images to PET scanning. The most straight forward are, superior registration of MR and PET images, the addition of morphological detail when there is non-rigid motion and for pre-clinical studies simultaneous imaging could lead to a significant reduction in the time that animals are required to be anesthetised. In addition simultaneous MR has the potential to provide accurate motion correction for PET image reconstruction. For functional imaging simultaneous acquisition is required to assess the subject in the same physiological state, such as acute stroke studies. The elimination of the additional radiation associated with combining CT with PET, by providing anatomic detail with MR, would be a crucial advantage for cancer screening. Combining the two instruments necessitates some engineering tradeoffs, especially associated with the use of the highly developed photomultiplier tube (PMT) used for light amplification, because of its incompatibility with strong magnetic fields. Our approach is to provide a split in the magnet and gradients to locate the magnetic sensitive components, the PMTs, in regions of low magnetic field, leaving only the essential PET components, the scintillator blocks, in the strong magnetic field region. The crystals are coupled to the PMTs by extending the optical fibres. A further advantage accrues by moving the PET electronics out of the region seen by the MR radio-frequency (RF) and gradient coils as electromagnetic interference effects between the PET and MR systems, which could cause artefacts in either modality, are eliminated. Here we describe a preliminary evaluation of the system, which is essentially a microPET Focus-120 located in a 1T split magnet, and compare its performance to previous microPET instruments.
Downregulation of miR-21 Enhances Chemotherapeutic Effect of Taxol in Breast Carcinoma Cells
Authors: Mei Mei , Ren Yu , Zhou Xuan , Yuan Xu-bo , Han Lei , Wang Guang-xiu , Jia Zhifan , Pu Pei-yu , Kang Chun-sheng , Yao Zhi
Published: October 2014

The successful of anti-cancer treatment are often limited by the development of drug resistance. Recent work has highlighted the involvement of non-coding RNAs, microRNAs(miRNAs) in cancer development, and their possible involvement in the evolution of drug resistance has been proposed. In this study, we combine taxol chemotherapy and miR-21 inhibitor treatment via polyamidoamine (PAMAM) dendrimers vector to evaluate the effects of combination therapy on suppression of breast cancer cells. The 50% inhibitory concentration (IC50) values for taxol were significantly decreased to a greater extent in the cells transfected with miR-21 inhibitor compared with cells treated with taxol alone. Taxol treatment also increased the percentage of apoptotic breast cancer cells in miR-21 inhibitor transfected cells compared with control cells. Furthermore, treatment of the miR-21 inhibitor-transfected cells with the anti-cancer drugs taxol resulted in significantly reduced cell viability and invasiveness compared with control cells. These results indicated that the miR-21 plays an important role in the resistance of breast carcinoma cells to chemotherapeutic drugs. Therefore, miR-21 inhibitor gene therapy combined with taxol chemotherapy might represent a promising novel therapeutic approach for the treatment of breast malignancies.
Data Mining Approach to Evaluating the use of Skin Surface Electropotentials for Breast Cancer Detection
Authors: Sree S. Vinitha , Ng E.Y.K. , Acharya U. Rajendra
Published: October 2014

The Biofield Diagnostic System (BDS) uses a score formed with measured skin surface electropotentials and a prior Level Of Suspicion (LOS) value (predicted by the physician based on the patient's ultrasound or mammography results) to calculate a revised Post-BDS LOS to indicate the presence of breast cancer. The demographic details, BDS test results, and the recorded electropotential values form a potentially useful dataset, which can be further explored with data mining tools to extract important information that can be used to improve the current predictive accuracy of the device. According to the proposed data mining framework, the BDS dataset with 291 cases was first pre-processed to remove outliers and then used to select relevant and informative features for classifier development and finally to evaluate the capability of the built classifiers in detecting the presence of the disease. Two popular feature selection techniques, namely, the filter and wrapper methods, were used in parallel for feature selection. A few statistical inference based classifiers and neural networks were used for classification. The proposed technique significantly improved the BDS prediction accuracy. Also, the use of prior LOS and, hence, the Post-BDS LOS, associates a mild subjective interpretation to the current prediction methodology used by BDS. However, the feature subset selected in our analysis that gave the best accuracy did not use either of these features. This result indicates the possibility of using BDS as a better objective assessment tool for breast cancer detection.
Relative Expression Analysis for Molecular Cancer Diagnosis and Prognosis
Authors: Eddy James A. , Sung Jaeyun , Geman Donald , Price Nathan D.
Published: October 2014

The enormous amount of biomolecule measurement data generated from high-throughput technologies has brought an increased need for computational tools in biological analyses. Such tools can enhance our understanding of human health and genetic diseases, such as cancer, by accurately classifying phenotypes, detecting the presence of disease, discriminating among cancer sub-types, predicting clinical outcomes, and characterizing disease progression. In the case of gene expression microarray data, standard statistical learning methods have been used to identify classifiers that can accurately distinguish disease phenotypes. However, these mathematical prediction rules are often highly complex, and they lack the convenience and simplicity desired for extracting underlying biological meaning or transitioning into the clinic. In this review, we survey a powerful collection of computational methods for analyzing transcriptomic microarray data that address these limitations. Relative Expression Analysis (RXA) is based only on the relative orderings among the expressions of a small number of genes. Specifically, we provide a description of the first and simplest example of RXA, the k-TSP classifier, which is based on k pairs of genes; the case k = 1 is the TSP classifier. Given their simplicity and ease of biological interpretation, as well as their invariance to data normalization and parameter-fitting, these classifiers have been widely applied in aiding molecular diagnostics in a broad range of human cancers. We review several studies which demonstrate accurate classification of disease phenotypes (e.g., cancer vs. normal), cancer subclasses (e.g., AML vs. ALL, GIST vs. LMS), disease outcomes (e.g., metastasis, survival), and diverse human pathologies assayed through blood-borne leukocytes. The studies presented demonstrate that RXA—specifically the TSP and k-TSP classifiers—is a promising new class of computational methods for analyzing high-throughput data, and has the potential to significantly contribute to molecular cancer diagnosis and prognosis.
APEX1 Gene Amplification and Its Protein Overexpression in Osteosarcoma: Correlation with Recurrence, Metastasis, and Survival
Authors: Yang Jilong , Yang Da , Cogdell David , Du Xiaoling , Li Haixin , Pang Yi , Sun Yan , Hu Limei , Sun Baocun , Trent Jonathan , Chen Kexin , Zhang Wei
Published: October 2014

The expression of apurinic/apyrimidinic exonuclease 1 (APEX1) in tumors has been linked with chemoresistance, radioresistance, and shorter patient survival times. We sought to gain insight into the role of APEX1 in human osteosarcoma by evaluation of gene copy number alterations and its protein expression in osteosarcoma patients treated at the Sarcoma Center of Tianjin Cancer Hospital (Tianjin, China). To evaluate the gene copy number alterations of APEX1, we acquired 10 fresh tissue samples from 9 patients and performed whole-genome array-based comparative genomic hybridization (aCGH). We next acquired formalin-fixed and paraffin embedded tissues from 57 well-annotated osteosarcoma cases and performed immunohistochemical analyses for APEX1. APEX1 gene amplification was observed in 50% (5/10) of the osteosarcoma samples. The overexpression of APEX1 protein was detected in 64.9% (37/57) of the osteosarcomas ranging from negative (35.1%, 20/57), weakly positive (35.1%, 20/57), moderate (14%, 8/57) and strongly positive (15.8%, 9/57). The APEX1 expression had significant correlation with osteosarcoma local recurrence and/or metastasis. Moreover, multivariate analysis showed that APEX1 expression was an independent molecular predictor for disease-free survival of patients with osteosarcomas. Our study for the first time showed that APEX1 gene was amplified in osteosarcomas and that APEX1 expression was an independent predictor of the osteosarcoma local recurrence and/or metastasis. Thus, APEX1 may serve as a prognostic marker and potential therapeutic target for osteosarcoma.
A Patient Set-up Protocol Based on Partially Blocked Cone-beam CT
Authors: Zhu Lei , Wang Jing , Xie Yaoqin , Starman Jared , Fahrig Rebecca , Xing Lei
Published: October 2014

Three-dimensional x-ray cone-beam CT (CBCT) is being increasingly used in radiation therapy. Since the whole treatment course typically lasts several weeks, the repetitive x-ray imaging results in large radiation dose delivered on the patient. In the current radiation therapy treatment, CBCT is mainly used for patient set-up, and a rigid transformation of the CBCT data from the planning CT data is also assumed. For an accurate rigid registration, it is not necessary to acquire a full 3D image. In this paper, we propose a patient set-up protocol based on partially blocked CBCT. A sheet of lead strips is inserted between the x-ray source and the scanned patient. From the incomplete projection data, only several axial slices are reconstructed and used in the image registration for patient set-up. Since the radiation is partially blocked, the dose delivered onto the patient is significantly reduced, with an additional benefit of reduced scatter signals. The proposed approach is validated using experiments on two anthropomorphic phantoms. As x-ray beam blocking ratio increases, more dose reduction is achieved, while the patient set-up error also increases. To investigate this tradeoff, two lead sheets with different strip widths are implemented, which correspond to radiation dose reduction of ~6 and ~11, respectively. We compare the registration results using the partially blocked CBCT with those using the regular CBCT. Both lead sheets achieve high patient set-up accuracies. It is seen that, using the lead sheet with radiation dose reduction by a factor of ~11, the patient set-up error is still less than 1 mm in translation and less than 0.2 degrees in rotation. The comparison of the reconstructed images also shows that the image quality of the illuminated slices in the partially blocked CBCT is much improved over that in the regular CBCT.
Tradeoffs for Assuming Rigid Target Motion in Mlc-Based Real Time Target Tracking Radiotherapy: A Dosimetric and Radiobiological Analysis
Authors: Roland Teboh , Shi Chengyu , Liu Yaxi , Crownover R. , Mavroidis Panayiotis , Papanikolaou Nikos
Published: October 2014

We report on our assessment of two types of real time target tracking modalities for lung cancer radiotherapy namely (1) single phase propagation (SPP) where motion compensation assumes a rigid target and (2) multi-phase propagation (MPP) where motion compensation considers a deformable target. In a retrospective study involving 4DCT volumes from six (n=6) previously treated lung cancer patients, four-dimensional treatment plans representative of the delivery scenarios were generated per modality and the corresponding dose distributions were derived. The modalities were then evaluated (a) Dosimetrically for target coverage adequacy and normal tissue sparing by computing the mean GTV dose, relative conformity gradient index (CGI), mean lung dose (MLD) and lung V20; (b) Radiobiologically by calculating the biological effective uniform dose ([Formula: see text]) for the target and organs at risk (OAR) and the complication free tumor control probability ( P+). As a reference for the comparative study, we included a 4D Static modality, which was a conventional approach to account for organ motion and involved the use of individualized motion margins. With reference to the 4D Static modality, the average percent decrease in lung V20 and MLD were respectively (13.1±6.9) % and (11.4±5.6) % for the MPP modality, whereas for the SPP modality they were (9.4±6.2) % and (7.2±4.7) %. On the other hand, the CGI was observed to improve by 15.3±13.2 and 9.6±10.0 points for the MPP and SPP modalities, respectively while the mean GTV dose agreed to better than 3% difference across all the modalities. A similar trend was observed in the radiobiological analysis where the P+ improved on average by (6.7±4.9) % and (4.1±3.6) % for the MPP and SPP modalities, respectively while the [Formula: see text] computed for the OAR decreased on average by (6.2±3.6) % and (3.8±3.5) % for the MPP and SPP tracking modalities, respectively. The [Formula: see text] calculated for the GTV for all the modalities was in agreement to better than 2% difference. In general, respiratory motion induces target displacement and deformation and therefore the complex MPP real time target tracking modality is the preferred. On the other hand, the SPP approach affords simplicity in implementation at the expense of failing to account for target deformation. Radiobiological and dosimetric analyses enabled us to investigate the consequences of failing to compensate for deformation and assess the impact if any on the clinical outcome. While it is not possible to draw any general conclusions on a small patient cohort, our study suggests that the two tracking modalities can lead to comparable clinical outcomes and as expected are advantageous when compared with the static conventional modality.
Quantitative Comparison of Yttrium-90 (90 Y)-Microspheres and Technetium-99m (99m Tc)-Macroaggregated Albumin SPECT Images for Planning 90 Y Therapy of Liver Cancer
Authors: Knešaurek Karin , Machac Josef , Muzinic Michael , DaCosta Maria , Zhang Zhuangyu , Heiba Sherif
Published: October 2014

Yttrium-90 (90 Y)-microspheres administered via the hepatic artery has been used for the treatment of unresectable primary or metastatic cancer in the liver. Prior to 90 Y therapy, however, the 90 Y administered activity and the percent shunting to lungs must be determined, most commonly by gamma camera imaging of technetium-99m (99m Tc)-macroaggregated albumin (MAA). The purpose of the current study was to identify and evaluate an objective measure of the correlation of 90 Y and MAA activity distributions and thus assess the reliability of MAA imaging for evaluation of 90 Y administered activity and tumor and liver radiation doses. The MAA study consisted of two acquisitions. After administration of 185 MBq of MAA, a partial-body or so-called breakthrough scan was performed in order to determine the percent shunting to lungs. Immediately after a breakthrough scan, a combined single-photon emission computed tomography (SPECT)/transmission computed tomography (CT) scanner was used to image MAA distribution in order to derived the prescribed 90 Y administered activity based on tumor and liver dosimetry. 90 Y SPECT/CT was performed 2–4 weeks later and activities used were in the range of 777–2,442 MBq. In order to compare 90 Y and MAA SPECT images, first the respective CT image sets were registered using a transform based on normalized mutual information. The transform thus derived was used to align the 90 Y and MAA SPECT image sets, and the Spearman's (rho) rank correlation as well as image distance (L2-norm) between the registered SPECT images were then calculated. The Spearman's rank correlation values ranged from 0.451 to 0.818 and the L2 distances from 0.626 to 2.889. Based on visual inspection, the registration of the 90 Y and MAA SPECT images appeared reasonably accurate. The regression coefficient (r) between visual scoring and the Spearman's rank correlation was 0.65 and between visual scoring and L2 distance 0.61. The Spearman's rank correlation thus appears to be more reliable than the image distance for assessing the correlation of the 90 Y and MAA images.
Dose Escalation Study with Two Different Hypofractionated Intensity Modulated Radiotherapy Techniques for Localized Prostate Cancer: Acute Toxicity
Authors: Zilli Thomas , Rouzaud Michel , Jorcano Sandra , Dipasquale Giovanna , Nouet Philippe , Toscas José Ignacio , Casanova Nathalie , Wang Hui , Escudé Lluìs , Mollà Meritxell , Linero Dolors , Weber Damien C. , Miralbell Raymond
Published: October 2014

To assess acute gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with a sequential dose escalation hypofractionated intensity-modulated radiotherapy (IMRT) study using two different delivery methods. Since 2003, 88 and 48 patients were sequentially treated to 56 Gy and to 60 Gy (4 Gy/fraction twice weekly), respectively. IMRT with 6 MV beams was delivered with five fields in Geneva and with nine in Barcelona. Acute GI and GU side effects were scored weekly during treatment and 6 weeks after treatment completion using the Radiation Therapy Oncology Group (RTOG) toxicity scale. Clinical, technical, and dosimetric parameters were analyzed in order to assess for a potential correlation with toxicity.

Grade 1–2, GU and GI toxicities during and 6 weeks after treatment completion were 64%, and 24%, and 35% and 12%, respectively. Only one Grade 4 GU toxicity, consisting of transitory urinary obstruction, was observed. Patients treated to 60 Gy in Geneva presented a higher rate of Grade 1–2 GU toxicity ( p = 0.01), while patients treated to both 56 and 60 Gy in Barcelona presented a higher Grade 1–2 GI toxicity ( p = 0.02). A lower rate of rectal toxicity was observed in the subgroup of 22 patients treated with a rectal balloon ( p = 0.02). The use of androgen deprivation therapy was associated with a higher rate of Grade 1–2 GU toxicity after the end of the treatment ( p = 0.02). Dose escalation with either 14 × 4 Gy or 15 × 4 Gy delivered with two different IMRT techniques is feasible and is associated with a tolerable acute toxicity.
Uncertainties in Lung Motion Prediction Relying on External Surrogate: A 4DCT Study in Regular vs. Irregular Breathers
Authors: Spadea Maria Francesca , Peroni Marta , Preve Eleonora , Riboldi Marco , Baroni Guido , Chen George TY , Sharp Gregory Charles
Published: October 2014

This paper examines the uncertainty in estimating lung motion from external surrogates for lung cancer patients with regular and irregular breathing. 4DCT data sets were analyzed using a template matching algorithm to track the spatial movement of vessel bifurcations in 12 patients. The detected internal movement of features in 3D was retrospectively synchronized with the RPM surrogate signal, and the correlation index R2 and the prediction error were computed. Patients were classified into two groups depending on the presence or not of irregularities in their breathing pattern. Peak-to-peak values of feature motion in the SI direction ranged from 0.8 mm (upper lung) to 25.3 mm (lower lung). Some patients exhibited large motion also in the latero-lateral (10.6 mm) and anterior-posterior (12.2 mm) directions. The median ± quartile of R2 in SI direction was 0.89 ± 0.09. Prediction error values were up to 4.2 mm (95th percentile) with a maximum value of 4.9 mm. Statistical differences between regular and irregular breathers were found for R2, while prediction error depended only on the range of motion. This study is relevant for image guided radiotherapy methods that rely on external surrogates to monitor motion.
Clinical Impact of Integrated Physiologic Brain Tumor Imaging
Authors: Pillai Jay J. , Zaca Domenico , Choudhri Asim
Published: October 2014

The development of new MRI techniques in the last two decades has provided neuroradiologists and neurosurgeons with additional noninvasive imaging tools for management and treatment of brain tumors. When coupled with standard structural MR sequences in imaging brain tumors, Blood Oxygenation Level Dependent (BOLD) functional MRI (fMRI), Perfusion Weighted Imaging (PWI) and Diffusion Tensor Imaging (DTI) provide additional physiologic information that is very useful for differential diagnosis, presurgical planning and prognosis. In this review after a brief technical description of BOLD fMRI, PWI and DTI, studies are described from the literature that have extensively validated these imaging techniques in comparison with invasive “gold standard” techniques such as intraoperative electrical cortical and subcortical stimulation mapping or biopsy. Additional studies are mentioned that demonstrate the positive impact of BOLD fMRI, PWI and DTI on brain tumor treatment and clinical outcome. In the final section an interesting clinical case treated at our institution is presented that highlights the clinical utility of this integrated physiologic brain tumor imaging approach.
Characterizing Human Cancer Metabolomics with ex vivo 1H HRMAS MRS
Authors: DeFeo Elita M. , Cheng Leo L.
Published: October 2014

Publications of proton high resolution magic angle spinning (1 H HRMAS) magnetic resonance spectroscopy (MRS) and its role in identification of metabolic markers for human cancer reported between 2005 and 2009 are reviewed according the anatomic sites of cancer: lung, breast, prostate, brain, colorectal, and cervical. Limited and insufficient screening options for the general public have indicated a need for more advanced tests that can identify and locate cancer at an early stage. 1 H HRMAS MRS is a valuable tool that can elucidate relevant biological metabolite information that is being used to distinguish cancer from benign tissue, and even classify types of tumors. Researchers are working to translate this ex vivo spectroscopy information into an in vivo system that could be implemented in cancer clinics. For instance, in the case of lung cancer, the goal is to identify the at risk population through a simple blood test, which would be the first level of screening. From these tests, patients identified as at risk will be able to undergo further non-invasive radiological testing for diagnostic purposes. Not only will this ex vivo technology become a valuable diagnostic tool, it will also provide a way to monitor treatments on an individual basis so they can be adjusted accordingly for the best possible outcome.
Reirradiation of Glioblastoma through the Use of a Reduced Dose Rate on a Tomotherapy Unit
Authors: Rasmussen Karl H. , Hardcastle Nicholas , Howard Steven P. , Tomé Wolfgang A.
Published: October 2014

Pulsed Reduced Dose Rate (PRDR) is a method of irradiation designed to minimize radiation-related toxicities in patients undergoing reirradiation for loco-regional reoccurrence of glioblastoma. PRDR delivers a standard 2 Gy fraction delivered on a conventional medical linear accelerator using conventional 3D conformal beam arrangements. To reduce the likelihood of normal tissue complications, radiation is delivered over ten 0.2 Gy sub-fractions with a 3 minute time interval between subfractions to give a maximal time averaged dose rate of 4 Gy/hr. However, a TomoTherapy unit has a fixed output rate of 8 Gy/min. If the dose per fraction is conventionally planned at less than 0.6 Gy/fraction, the result is a clinically unacceptable treatment plan. The method described in this paper involves a virtual grid style blocking scheme, where half of the beam angles are directionally blocked using 15 equally spaced segments surrounding the center of the image set. Ten patients treated using conventional PRDR with an average PTV volume of 353.3 ml were retrospectively re-planned using five techniques (standard 2 Gy fraction, 2 Gy in ten 0.2 Gy fractions without grid blocking, two grid patterns, and a combination plan incorporating both grids) and analyzed with conformation numbers (CN), homogeneity indexes (HI), and dose volumes to normal tissues. Plans were optimized using equal constraints and machine parameters. The grid method allowed for clinically acceptable treatment plans at 0.2 Gy with a treatment time ≤ 3min per subfraction. The average HI was slightly poorer for the combination plan versus the standard 2 Gy fraction plan (0.064 versus 0.027) and the CN was similar over all techniques (0.72 − 0.73) employed. Normal tissue dose volumes for each patient were also similar for each technique. Initial ion chamber measurements agree with predicted values for a 0.2 Gy subfraction. PRDR is deliverable on a TomoTherapy system using our virtual directional blocking method. Results can be slightly improved through the use of two grids alternated on a daily basis. The dose to normal structures for individual patients was similar for all methods.
Helical Tomotherapy for Solitary Lung Tumor: Feasibility Study and Dosimetric Evaluation of Treatment Plans
Authors: Tomita Natsuo , Kodaira Takeshi , Matsuo Masayuki , Furutani Kazuhisa , Tachibana Hiroyuki , Daimon Takashi , Shimizu Hidetoshi
Published: October 2014

The purpose of this study is to evaluate the feasibility of and treatment plans for helical tomotherapy (HT) for solitary lung tumors. Nine patients with stage IA non-small-cell lung cancer (NSCLC) and three patients with solitary lung metastasis were treated with HT. All patients were immobilized with the BodyFIX system, and the target volume shown on computed tomography in the 3 respiration phases were superimposed onto the 3-dimensional radiation treatment planning system to represent the internal target motion. All patients were treated with 54–60 Gy in 12 fractions over 8 to 13days. The median follow-up time was 14 months (range: 3–16 months). The overall response rate was 92%. The local control rate at 1 year was 100% with no difference between NSCLC and metastasis. Of 12 patients, one patient experienced Grade 2 radiation pneumonitis (RP), and the other patient with severe interstitial pneumonia and emphysema experienced Grade 5 RP. The mean lung dose (MLD) and the dose-volume histogram (DVH) for the normal lung volumes were converted into normalized total dose with an α/β ratio of 3 Gy. The DVH of the normal lung volumes demonstrated that the mean volumes of V10, V30, V50, and V70 were 40.4 ± 9.4%, 21.3 ± 6.4%, and 12.8 ± 4.6%, and 9.3 ± 4.2% in all patients, 28.8%, 18.7%, 12.3%, and 10.5% in the patient with Grade 2 RP, and 29.3%, 17.9%, 7.7%, and 5.4% in the patient with Grade 5 RP. The mean MLD of all patients was 13.5 ± 3.9 Gy, and those values of patients with Grade 2 and 5 RP were 12.9 and 21.8 Gy, respectively. Our study found that only the MLD was significantly correlated with RP ≥Grade 2 ( p = 0.030) using the Student's t-test. Our study found the conformity index value of 1.48 ± 0.15 and the homogeneity index value of 1.066 ± 0.023, which suggested the feasibility of using HT to treat lung tumors with hypofractionation. In conclusion, HT is a feasible non-invasive technique for treating solitary lung tumors and achieves high accuracy in terms of dose conformity and homogeneity. The decision of the indications for HT might be required caution in cases in which a severe pulmonary toxicity is predicted from the high MLD, especially in cases involving a severe pulmonary comorbidity.
Percutaneous Vertebroplasty for Treatment of Osteolytic Metastases of the C2 Vertebral Body Using Anterolateral and Posterolateral Approach
Authors: Sun Gang , Jin Peng , Li Min , Liu Xunwei , Li Fandong , Yu Alice K. F. , Lu Yang
Published: October 2014

Percutaneous vertebroplasty (PVP) of C2 vertebral body is a challenging procedure. The aim of this retrospective study was to evaluate the feasibility, safety, and efficacy of PVP for the C2 osteolytic metastases using anterolateral and posterolateral approaches. Ten patients (8 male, 2 female) with C2 metastases were treated with PVP under local anesthesia. Anterolateral route was used under the guidance of fluoroscopy in 9 cases, and posterolateral route was used under the guidance of CT in 1 case. Pain intensity was scored on a scale ranging from 0/10 (no pain) to 10/10 (maximum pain intensity). The mean volume of cement injected was 3 ± 0.8 mL (range, 2.0–4.0 mL), with average vertebral filling of more than 70%. Cement leakage was detected in 4 treated vertebrae. Pain improvement and spine stability were achieved in all patients. In conclusion, PVP of C2 using anterolateral approach is a feasible and minimal invasive procedure for treatment of patients with C2 osteolytic metastases. Posterolateral approach is a safe and effective option for PVP of C2 when hyperextension of the cervical spine is contraindicated or difficult to achieve.
The Effect of Electroporation Type Pulsed Electric Fields on DNA in Aqueous Solution
Authors: Golberg Alex , Rubinsky Boris
Published: October 2014

Electroporation is a physical phenomenon in which pulsed electric fields applied across a cell produce transient (reversible) or permanent (irreversible) permeabilization of the cell membrane. Irreversible electroporation is an important method of sterilization in the food industry and it is becoming an important minimally invasive tissue ablation technique in medicine. Motivated by recent observations of apoptosis like marker stains in irreversibly electroporated cells we performed a study on the effects of electroporation type electric pulses on the integrity of naked DNA in solution. Using gel electrophoresis analyses we show that pulses of the irreversible electroporation type have the ability to affect the naked DNA in solution. It is found that some electric parameters that lead to cell death by irreversible electroporation also cause changes in the naked DNA exposed to the same procedure. Our analysis tentatively suggests that some electroporation type electric pulses cause nicks in the DNA molecule. Therefore, it is possible that the mechanisms of cell death in irreversible electroporation also include damages to the DNA. However, this work did not investigate the possible effects of electroporation induced electrode corrosion byproducts, such as Al3+ ions on DNA integrity; which should be also studied in the future. In general, since electroporation phenomena based applications are widely used in medicine and biotechnology, the current study suggests that further research into the effects of electroporation type electric pulses on the DNA are warranted.
A Pilot Study of Intensity Modulated Radiation Therapy with Hypofractionated Stereotactic Body Radiation Therapy (SBRT) Boost in the Treatment of Intermediate- to High-Risk Prostate Cancer
Authors: Oermann Eric K. , Slack Rebecca S. , Hanscom Heather N. , Lei Sue , Suy Simeng , Park Hyeon U. , Kim Joy S. , Sherer Benjamin A. , Collins Brian T. , Satinsky Andrew N. , Harter K. William , Batipps Gerald P. , Constantinople Nicholas L. , Dejter Stephen W. , Maxted William C. , Regan James B. , Pahira John J. , McGeagh Kevin G. , Jha Reena C. , Dawson Nancy A. , Dritschilo Anatoly , Lynch John H. , Collins Sean P.
Published: October 2014

Clinical data suggest that large radiation fractions are biologically superior to smaller fraction sizes in prostate cancer radiotherapy. The CyberKnife is an appealing delivery system for hypofractionated radiosurgery due to its ability to deliver highly conformal radiation and to track and adjust for prostate motion in real-time. We report our early experience using the CyberKnife to deliver a hypofractionated stereotactic body radiation therapy (SBRT) boost to patients with intermediate- to high-risk prostate cancer. Twenty-four patients were treated with hypofractionated SBRT and supplemental external radiation therapy plus or minus androgen deprivation therapy (ADT). Patients were treated with SBRT to a dose of 19.5 Gy in 3 fractions followed by intensity modulated radiation therapy (IMRT) to a dose of 50.4 Gy in 28 fractions. Quality of life data were collected with American Urological Association (AUA) symptom score and Expanded Prostate Cancer Index Composite (EPIC) questionnaires before and after treatment. PSA responses were monitored; acute urinary and rectal toxicities were assessed using Common Toxicity Criteria (CTC) v3. All 24 patients completed the planned treatment with an average follow-up of 9.3 months. For patients who did not receive ADT, the median pre-treatment PSA was 10.6 ng/ml and decreased in all patients to a median of 1.5 ng/ml by 6 months post-treatment. Acute effects associated with treatment included Grade 2 urinary and gastrointestinal toxicity but no patient experienced acute Grade 3 or greater toxicity. AUA and EPIC scores returned to baseline by six months post-treatment. Hypofractionated SBRT combined with IMRT offers radiobiological benefits of a large fraction boost for dose escalation and is a well tolerated treatment option for men with intermediate- to high-risk prostate cancer. Early results are encouraging with biochemical response and acceptable toxicity. These data provide a basis for the design of a phase II clinical trial.
Stereotactic Radiotherapy of Hepatocellular Carcinoma: Preliminary Results
Authors: Louis C. , Dewas S. , Mirabel X. , Lacornerie T. , Adenis A. , Bonodeau F. , Lartigau E.
Published: October 2014

Stereotactic radiotherapy (SRT) offers a treatment option for hepatocellular carcinoma (HCC) patients that are not eligible for surgery, embolization, chemotherapy, or radiofrequency ablation. We have evaluated the feasibility, tolerance and toxicity of SRT for 25 HCC patients who were not eligible for these other modalities. The patients (6 women and 19 men) were treated with CyberKnife stereotactic radiotherapy using respiratory motion tracking. All patients had liver cirrhosis with an Eastern Cooperative Oncology Group (ECOG) performance score of less than 2 and pre-treatment Child scores ranging from A5 to B9. A total dose of 45 Gy in three fractions of 15 Gy each was prescribed to the 80% isodose line (95% of the PTV received 45 Gy) and delivered to the target volume over 10 to 12 days. Overall the treatment was well tolerated with two Grade 3 acute toxicities and no acute Grade 4 toxicities. Late toxicity was minimal with all observed late toxicities occurring within the first six months of follow-up. Three hepatic recurrences at a distance from the target and one metastasis were observed. The actuarial 1- and 2-year local control rate was 95% (95% CI: 69–95%). At a median overall follow-up of 12,7 months (range, 1–24 months), six of the twenty-five (24%) patients have died. Overall actuarial survival at 1- and 2-years was 79% (95% CI: 52–92%) and 52% (95% CI: 19–78%), respectively. Our results suggest promising therapeutic efficacy and good clinical tolerance to CyberKnife SRT treatment for HCC patients not eligible for other treatment modalities.
Combined Endoscopic Endonasal Surgery and Fractionated Stereotactic Radiosurgery (fSRS) for Complex Cranial Base Tumors—Early Clinical Outcomes
Authors: Paravati Anthony J. , Heron Dwight E. , Gardner Paul A. , Snyderman Carl , Ozhasoglu Cihat , Quinn Annette , Burton Steve A. , Seelman Kathleen , Mintz Arlan H.
Published: October 2014

Endoscopic endonasal surgery (EES) has been shown to be a feasible approach to cranial base tumors while reducing post-operative morbidity. Using the endoscopic endonasal approach alone or in combination with open approaches may provide advantages over conventional approaches. However, the balance between maximal resection and minimal injury to neurovascular structures frequently precludes gross total resection (GTR). Consequently, adjuvant radiation therapy may be an important option to improve local control (LC) of residual disease. In this retrospective series, we report clinical outcomes, morbidity, and LC of 40 patients with cranial base tumors treated with EES +/- combined open approach followed by fSRS (CyberKnife, Accuray Inc.). 26 patients had benign disease, 7 had newly diagnosed malignant disease, and 7 had previously resected malignant disease. Surgical outcomes were evaluable in all patients. LC after fSRS was evaluable in 39 patients and defined as no evidence of regrowth by MRI, CT, & physical examination. GTR was achieved in 12/40. Median post-operative length of stay (LOS) was 3 days. In multivariable analysis controlling for anatomic location and malignant histology, post-operative complications (n = 10) were significantly associated with patients having combined open and EES (p < 0.01, OR = 16.9). SRS was delivered in 1–5 sessions to a median marginal dose of 24.9 Gy. Median follow-up was 24.7 months (range, 1.5 to 61 months). LC was achieved in 89.7% (35/39) of evaluable patients. LC was achieved in 11/12 patients who had GTR. Median progression-free survival was 19.7 months (21.0 months for benign tumors (n = 26), 5.8 months for previously resected malignant disease (n = 7), and 21.2 months for newly diagnosed malignant disease (n = 7). Of the 31 patients who had symptomatic disease at presentation, 18 (58%) reported complete symptom resolution, 9 partial, and 4 no improvement. One patient who received two prior courses of radiation therapy developed osteosclerosis (grade III). Other adverse events were erythema (grade I, n = 5), nausea (grade II, n = 2), conjunctivitis (grade II, n = 1). EES followed by fSRS is a safe and effective management strategy for selected cranial base tumors. EES combined with an open surgical approach may result in increased complications. However, initial follow-up offers encouraging results indicating shorter time to recovery, acceptable LC rates compared to conventional approaches, and similar median time to progression for benign and newly diagnosed malignant disease.
CyberKnife Stereotactic Radiosurgery for Intracranial Neoplasms, with a Focus on Malignant Tumors
Authors: Bucholz Richard D. , Laycock Keith A. , Cuff Leah E.
Published: October 2014

Stereotactic radiosurgery is well established as a means of managing intracranial tumors, both as an adjuvant to surgical resection, and also as a primary treatment modality for those tumors that are considered unresectable by conventional surgical means. Of particular concern during radiosurgery of brain tumors is the risk of radiation damage to otherwise healthy tissue, potentially resulting in cognitive impairment. The conformality and precise targeting of the CyberKnife radiation beam enables this risk to be minimized to a greater extent than hitherto possible, which may allow treatment to be completed in a small number of fractions, thereby improving the quality of life for patients. The CyberKnife has proven particularly valuable in the treatment of metastases, which represent the great majority of brain tumors, though its role in the management of malignant glial tumors remains a subject of controversy. This article reviews the published studies on the efficacy of CyberKnife radiosurgery for brain tumors of both glial and metastatic origin, and considers its future role in the management of such lesions.
Apparatus-Dependent Dosimetric Differences in Spine Stereotactic Body Radiotherapy
Authors: Ma Lijun , Sahgal Arjun , Cozzi Luca , Chang Eric , Shiu Almon , Létourneau Daniel , Yin Fang-Fang , Fogliata Antonella , Kaissl Wolfgang , Hyde Derek , Laperriere Normand J. , Shrieve Dennis C. , Larson David A.
Published: October 2014

The purpose of this investigation was to study apparatus-dependent dose distribution differences specific to spine stereotactic body radiotherapy (SBRT) treatment planning. This multi-institutional study was performed evaluating an image-guided robotic radiosurgery system (CK), intensity modulated protons (IMP), multileaf collimator (MLC) fixed-field IMRT with 5 mm (11 field), 4 mm (9 field), and 2.5 mm (8- and 9-field) leaf widths and intensity modulated volumetric arc therapy (IMVAT) with a 2.5 mm MLC. Treatment plans were systematically developed for targets consisting of one, two and three consecutive thoracic vertebral bodies (VBs) with the esophagus and spinal cord contoured as the organs at risk. It was found that all modalities achieved acceptable treatment planning constraints. However, following normalization fixed field IMRT with a 2.5 mm MLC, IMVAT and IMP systems yielded the smallest ratio of maximum dose divided by the prescription dose (MD/PD) for one-, two- and three-VB PTVs (ranging from 1.1–1.16). The 2.5 mm MLC 9-field IMRT, IMVAT and CK plans resulted in the least dose to 0.1 cc volumes of spinal cord and esophagus. CK plans had the greatest degree of target dose inhomogeneity. As the level of complexity increased with an increasing number of vertebral bodies, distinct apparatus features such as the use of a high number of beams and a finer leaf size MLC were favored. Our study quantified apparatus-dependent dose-distribution differences specific to spine SBRT given strict, but realistic, constraints and highlights the need to benchmark physical dose distributions for multi-institutional clinical trials.
Low-dose Photon and Simulated Solar Particle Event Proton Effects on Foxp3+ T Regulatory Cells and other Leukocytes
Authors: Gridley Daila S. , Luo-Owen Xian , Rizvi Asma , Makinde Adeola Y. , Pecaut Michael J. , Mao Xiao Wen , Slater James M.
Published: October 2014

Radiation is a major factor in the spaceflight environment that has carcinogenic potential. Astronauts on missions are continuously exposed to low-dose/low-dose-rate (LDR) radiation and may receive relatively high doses during a solar particle event (SPE) that consists primarily of protons. However, there are very few reports in which LDR photons were combined with protons. In this study, C57BL/6 mice were exposed to 1.7 Gy simulated SPE (sSPE) protons over 36 h, both with and without pre-exposure to 0.01 Gray (Gy) LDR γ-rays at 0.018 cGy/h. Apoptosis in skin samples was determined by immunohistochemistry immediately post-irradiation (day 0). Spleen mass relative to body mass, white blood cells (WBC), major leukocyte populations, lymphocyte subsets (T, Th, Tc, B, NK), and CD4+ CD25+ Foxp3+ T regulatory (Treg) cells were analyzed on days 4 and 21. Apoptosis in skin samples was evident in all irradiated groups; the LDR+sSPE mice had the greatest expression of activated caspase-3. On day 4 post-irradiation, the sSPE and LDR+sSPE groups had significantly lower WBC counts in blood and spleen compared to non-irradiated controls ( p < 0.05 vs. 0 Gy). CD4+ CD25+ Foxp3+ Treg cell numbers in spleen were decreased at day 4, but proportions were increased in the sSPE and LDR+sSPE groups ( p < 0.05 vs. 0 Gy). By day 21, lymphocyte counts were still low in blood from the LDR+sSPE mice, especially due to reductions in B, NK, and CD8+ T cytotoxic cells. The data demonstrate, for the first time, that pre-exposure to LDR photons did not protect against the adverse effects of radiation mimicking a large solar storm. The increased proportion of immunosuppressive CD4+ CD25+ Foxp3+ Treg and persistent reduction in circulating lymphocytes may adversely impact immune defenses that include removal of sub-lethally damaged cells with carcinogenic potential, at least for a period of time post-irradiation.
Monitoring the Response to Primary Medical Therapy for Breast Cancer Using Three-Dimensional Time-Resolved Optical Mammography
Authors: Enfield L. C. , Cantanhede G. , Westbroek D. , Douek M. , Purushotham A. D. , Hebden J. C. , Gibson A. P.
Published: October 2014

Primary medical therapy is used to reduce tumour size prior to surgery in women with locally advanced breast cancer. Optical tomography is a functional imaging technique using near-infrared light to produce three-dimensional breast images of tissue oxygen saturation and haemoglobin concentration. Its advantages include the ability to display quantitative physiological information, and to allow repeated scans without the hazards associated with exposure to ionising radiation. There is a need for a non-invasive functional imaging tool to evaluate response to treatment, so that non-responders can be given the opportunity to change their treatment regimen. Here, we evaluate the use of optical tomography for this purpose. Four women with newly diagnosed breast cancer who were about to undergo primary medical therapy gave informed and voluntary consent to take part in the study. Changes in physiological and optical properties within the tumour were evaluated during the course of neoadjuvant chemotherapy. Optical imaging was performed prior to treatment, after the first cycle of chemotherapy, halfway through, and on completion of chemotherapy. Images of light absorption and scatter at two wavelengths were produced, from which images of total haemoglobin concentration and oxygen saturation were derived. All patients that showed a good or complete response to treatment on MRI showed a corresponding recovery in the haemoglobin concentration images. Changes in mean tumour total haemoglobin concentration could be seen four weeks into treatment. The tumour oxygen saturation was low compared to background in three out of four patients, and also showed a return to baseline over treatment. Optical imaging of the breast is feasible during primary medical therapy and can be used to assess response to treatment over six months.