bluuebunny/crossref_metadata_2025 huggingface dataset:
PET/CT in the Evaluation of Response to Treatment of Liver Metastases from Colorectal Cancer with Bevacizumab and Irinotecan
Authors: Goshen Elinor , Davidson Tima , Zwas S. Tzila , Aderka Dan
Published: October 2014

The present approach at our institution for the treatment of patients with colorectal (CRC) cancer and with liver metastases planned for metastasectomy is the neoadjuvant administration of Bevacizumab with Irinotecan based therapy. Metabolic imaging of tumor viability with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and simultaneous anatomic localization provided by low-dose non-enhanced computed tomography (CT), can be obtained in a combined modality FDG-PET/CT scan. The purpose of this study was to evaluate the possible contribution of FDG-PET/CT as a surrogate marker to evaluate treatment response of liver metastases in vivo. This is a retrospective evaluation of 18F-FDG PET and CT findings in the first seven consecutive patients. FDG-PET/CT scans were performed before the start of the neoadjuvant and after four cycles of therapy, just prior to surgery. Results were compared to concurrent contrast-enhanced CT, when required, and pathology. Response to treatment was determined according to RECIST size criteria obtained from data from thin (3–5mm) slice CT, and changes in uptake of 18F-FDG uptake on PET.

A total of 20 liver lesions were evaluated in seven patients. Overall, 6/7 patients had favorable response to treatment, and only one had progression of disease. One patient was found to be inoperable at surgery. Biopsy was obtained in 1/4 lesions in this patient, while pathology was unable for the remaining three lesions. As such, pathologic validation of findings was available for 17/20 lesions. Complete response (CR) was evident on FDG-PET in 10/17 (58%) lesions, whereas only 4/17(23%) were deemed CR by CT. Similarly, only 1/17 (6%) lesion appeared stable by FDG-PET criteria, whereas three (18%) were termed stable disease (SD) according to size on CT.

FDG-PET findings correlated better than CT with pathology, and were more indicative of pathology. Overall PET/CT correctly predicted necrosis at pathology in 70% vs. 35% by CT. Our results suggest that 18F-FDG PET may be instrumental for predicting the pathologic response to Bevacizumab based therapy.
Downregulation of PIK3CB by siRNA Suppresses Malignant Glioma Cell Growth In Vitro and In Vivo
Authors: Pu Peiyu , Kang Chunsheng , Zhang Zhiyong , Liu Xiaozhi , Jiang Hao
Published: October 2014

EGFR overexpression is the most frequent and important molecular event in the development of astrocytic gliomas, and the P13K signaling pathway is one of the most important downstream pathways of EGFR. EGFR and other members of the receptor tyrosine kinases (RTKs) family, such as VEGFR, PDGFR, and IGFR, et cetera, are often overexpressed in most of malignant gliomas and share common downstream signaling pathways. Therefore, it is considered that directly targeting the downstream PI3K pathway may be more effective in blocking multiple inputs. The PIK3CB gene encoding the class 1A PI3K catalytic subunit p110β was selected as the target of therapeutic approach for malignant gliomas in the present study. Human U251 glioblastoma cells with high endogenous p110β expression were transfected with plasmid-based siRNA targeting PIK3CB gene. It was found that downregulation of p110β expression resulted in the suppression of cell proliferation, arrest of cell cycle, reduction of cell invasion, and promotion of cell apoptosis in vitro. In addition, the growth of the subcutaneous U251 glioma in the nude mice treated with siRNA targeting PIK3CB was significantly inhibited. These results demonstrate that PIK3CB overexpression may play an oncogenic role in the PI3K pathway, and the plasmid-based siRNA targeting of PIK3CB is a potential and promising approach for the treatment of malignant gliomas.
Stereotactic Radiosurgery and Fractionated Stereotactic Radiotherapy in the Treatment of Uveal Melanoma
Authors: Henderson Mark A. , Shirazi Haider , Lo Simon S. , Mendonca Marc S. , Fakiris Achilles J. , Witt Thomas C. , Worth Robert M. , Timmerman Robert D.
Published: October 2014

Uveal melanoma is the most common primary intraocular malignant tumor. Radiation therapy has now replaced enucleation as the treatment of choice, with radioactive eye plaques and proton therapy being the two most studied radiotherapy modalities. More recently, stereotactic radiosurgery and fractionated stereotactic radiotherapy have emerged as promising, non-invasive treatments for uveal melanoma. This review summarizes the available literature on these newer treatment modalities.
Confidence Intervals for the True Classification Error Conditioned on the Estimated Error
Authors: Xu Qian , Hua Jianping , Braga-Neto Ulisses , Xiong Zixiang , Suh Edward , Dougherty Edward R.
Published: October 2014

Bias and variance for small-sample error estimation are typically posed in terms of statistics for the distributions of the true and estimated errors. On the other hand, a salient practical issue asks, given an error estimate, what can be said about the true error? This question relates to the joint distribution of the true and estimated errors, specifically, the conditional expectation of the true error given the error estimate. A critical issue is that of confidence bounds for the true error given the estimate. We consider the joint distribution of the true error and the estimated error, assuming a random feature-label distribution. From it, we derive the marginal distributions, the conditional expectation of the estimated error given the true error, the conditional expectation of the true error given the estimated error, the conditional variance of the true error given the estimated error, and the 95% upper confidence bound for the true error given the estimated error. Numerous classification and estimation rules are considered across a number of models. Massive simulation is used for continuous models and analytic results are derived for discrete classification. We also consider a breast-cancer study to illustrate how the theory might be applied in practice. Although specific results depend on the classification rule, error-estimation rule, and model, some general trends are seen: (I) if the true error is small (large), then the conditional estimated error is generally high (low)-biased; (II) the conditional expected true error tends to be larger (smaller) than the estimated error for small (large) estimated errors; and (III) the confidence bounds tend to be well above the estimated error for low error estimates, becoming much less so for large estimates.
Breast Skin Doses from Brachytherapy Using MammoSite® HDR, Intensity Modulated Radiation Therapy, and Tangential Fields Techniques
Authors: Selvaraj Raj N , Bhatnagar Ajay , Beriwal Sushil , Huq M. Saiful , Heron Dwight E. , Sonnik Debbie , Brandner Edward , Surgent Robert , Mogus Robert , Deutsch Melvin , Gerszten Kristina , Wu Andrew , Kalnicki Shalom , Yue Ning J. , Saw Cheng B.
Published: October 2014

Skin doses from brachytherapy using MammoSite® HDR, Intensity Modulated Radiation Therapy (IMRT), and conventional tangential fields techniques were compared. For each treatment technique, skin doses were measured using paired thermoluminescent dosimeters placed on the patient's skin: (i) directly above the balloon catheter during MammoSite® HDR brachytherapy treatments and (ii) 4 cm inside the treatment borders during the IMRT and conventional breast treatments. The mean dose measured was about 58% of the prescription dose for the patients treated using the MammoSite® technique. On the other hand, for patients treated with IMRT and tangential fields, the mean dose was found to be about 69% and 71% of the corresponding prescription dose. This study suggests that in breast cancer radiation treatments the MammoSite® HDR technique reduces skin doses compared to IMRT and tangential field techniques.

PACS numbers: 87.53.Jw, 87.53.Xd, 87.66.Sq
Impact of Integrated PET/CT on Variability of Target Volume Delineation in Rectal Cancer
Authors: Patel Deep A. , Chang Stephanie T. , Goodman Karyn A. , Quon Andrew , Thorndyke Brian , Gambhir Sanjiv S. , McMillan Alex , Loo Billy W. , Koong Albert C.
Published: October 2014

Several studies have demonstrated substantial variability among individual radiation oncologists in defining target volumes using computed tomography (CT). The objective of this study was to determine the impact of combined positron emission tomography and computed tomography (PET/CT) on inter-observer variability of target volume delineation in rectal cancer. We also compared the relative concordance of two PET imaging tracers, 18F-fluorodeoxyglucose (FDG) and 18F-fluorodeoxythymidine (FLT), against conventional computed tomography (CT). Six consecutive patients with locally advanced rectal cancer were enrolled onto an institutional protocol involving preoperative chemoradiotherapy and correlative studies including FDG- and FLT-PET scans acquired in the treatment position. Using these image data sets, four radiation oncologists independently delineated primary and nodal gross tumor volumes (GTVp and GTVn) for a hypothetical boost treatment. Contours were first defined based on CT alone with observers blinded to the PET images, then based on combined PET/CT. An inter-observer similarity index (SI), ranging from a value of 0 for complete disagreement to 1 for complete agreement of contoured voxels, was calculated for each set of volumes. For primary gross tumor volume (GTVp), the difference in estimated SI between CT and FDG was modest (CT SI = 0.77 vs. FDG SI = 0.81), but statistically significant (p = 0.013). The SI difference between CT and FLT for GTVp was also slight (FLT SI = 0.80) and marginally non-significant (p < 0.082). For nodal gross tumor volume, (GTVn), SI was significantly lower for CT based volumes with an estimated SI of 0.22 compared to an estimated SI of 0.70 for FDG-PET/CT (p < 0.0001) and an estimated SI of 0.70 for FLT-PET/CT (p < 0.0001). Boost target volumes in rectal cancer based on combined PET/CT results in lower inter-observer variability compared with CT alone, particularly for nodal disease. The use of FDG and FLT did not appear to be different from this perspective.
Monitoring of Chemotherapy-Induced Cell Death in Melanoma Tumors by N,N′-Didansyl-L-cystine
Authors: Cohen Avi , Ziv Ilan , Aloya Tali , Levin Galit , Kidron Dvora , Grimberg Hagit , Reshef Ayelet , Shirvan Anat
Published: October 2014

Early assessment of the efficacy of anticancer agents is a highly desirable and an unmet need in clinical oncology. Clinical imaging of cell-death may be useful in addressing this need, as induction of tumor cell-death is the primary mechanism of action of most anticancer drugs. In this study, we examined the performance of N,N′-Didansyl-L-cystine (DDC), a member of the ApoSense family of novel small molecule detectors of cell-death, as a potential tool for monitoring cell-death in cancer models. Detection of cell-death by DDC was examined in fluorescent studies on B16 melanoma cells both in vitro and ex vivo following its in vivo administration. In vitro, DDC manifested selective uptake and accumulation within apoptotic cells that was highly correlated with Annexin-V binding, changes in mitochondrial membrane potential, and caspase activation. Uptake was not ATP-dependent, and was inducible by calcium mobilization. In vivo, DDC selectively targeted cells undergoing cell-death in melanoma tumors, while not binding to viable tumor cells. Chemotherapy caused marked tumor cell-death, evidenced by increased DDC uptake, which occurred before a detectable change in tumor size and was associated with increased animal survival. These data confirm the usefulness of imaging of cell-death by DDC as a tool for early monitoring of tumor response to anti-cancer therapy.
Conductive Interstitial Thermal Therapy (CITT) Device Evaluation in VX2 Rabbit Model
Authors: Shafirstein Gal , Hennings Leah , Kaufmann Yihong , Novak Petr , Moros Eduardo G. , Ferguson Scott , Siegel Eric , Klimberg Suzanne V. , Waner Milton , Spring Paul
Published: October 2014

We have developed a conductive interstitial thermal therapy (CITT) device to precisely and reliably deliver controlled thermal doses to the surgical margins at the cavity site following tumor resection, intraoperatively. The temperature field created by CITT ablation of a perfused tissue was modeled with a finite element package Femlab™. The modeling suggested that a maximum probe temperature of 120°C and an ablation time of 20 minutes were required to ablate highly perfused tissue such as the VX2 carcinoma. Deployable pins enable faster and more reliable thermal ablation. The model predictions were tested by thermal ablation of VX2 carcinoma tumors implanted in adult New Zealand rabbits. The size of the ablated region was confirmed with a viability stain, triphenyltetrazolium chloride (TTC). Histopathological examination revealed 3 regions in the ablated area: a carbonized region (1–3 mm); a region that contained thermally fixed cells; and an area of coagulated necrosis cells. Cells in the thermally fixed region stained for PCNA (proliferating cell nuclear antigen) and were bounded by the carbonized layer at the cavity wall, and by necrotic cells that exhibit nuclear fragmentation and cell dissociation, 5 to 10 mm away from the CITT probe. Adjacent tissue outside the target region was spared with a clear demarcation between ablated and normal viable tissue. It is suggested that the CITT device can be used, clinically, to inhibit local recurrence by creating negative surgical margins following the resection of a primary tumor in non-metastatic early staged tumors.
Cryoablation Induces Necrosis and Apoptosis in Lung Adenocarcinoma in Mice
Authors: Wen JuYi , Duan YunYou , Zou YueKun , Nie Zhoushan , Feng HuaSong , Lugnani Franco , Baust John G.
Published: October 2014

This study evaluated cryoablation on subcutaneously transplanted tumors of lung adenocarcinoma LA795 in T739 mice in vivo, in an effort to assess the feasibility of cryoablation in treatment of NSCLC. Subcutaneously transplanted lung adenocarcinoma LA795 was implanted into T739 mice yielding tumors of approximately 2.5 cm in diameter. Following cryoablation, the various modes of cell death were studied: necrosis in the central frozen zone by light microscopy and apoptosis in periphery of the frozen zone by in situ end labeling (TUNEL). Bc1-2 and bax expression were detected by immunohistochemical SABC procedures, and the cleavage and activation of Caspase 3 and PARP in peripheral zone by Western blot.

We find that in central cryoablated zone, necrosis was the dominant mode of cell death occurring at three hours and four days post-thaw. The first three-hour necrosis peak involved approximately 47% of the tumor while the four-day peak increased in volume to 68% of the tumor. In peripheral cryoablation zone, definite cell apoptosis could be observed by morphological examination under light microscope and TUNEL staining, peaking at 8–16 h after cryoablation. Immunohistochemical results yielded little change in bcl-2 protein expression before and after cryoablation. However, bax protein expression was up-regulated significantly after cryoablation. In addition, cleavage and activation of Caspase-3 and PARP occurred in the peripheral freeze zone after the treatment.

It indicated that Cryoablation efficiently induces cell death both by necrosis and apoptosis. Cryoablation appears to induce apoptosis in the peripheral freeze zone through the intrinsic mitochondrial caspase pathway based on bax upregulation. This observation allows us to suggest that cryoablation may be combined with chemotherapy to increase cancer destruction.
Accelerators for Heavy-charged-particle Radiation Therapy
Authors: Coutrakon George B.
Published: October 2014

This paper focuses on current and future designs of medical hadron accelerators for treating cancers and other diseases. Presently, five vendors and several national laboratories have produced heavy-particle medical accelerators for accelerating nuclei from hydrogen (protons) up through carbon and oxygen. Particle energies are varied to control the beam penetration depth in the patient. As of the end of 2006, four hospitals and one clinic in the United States offer proton treatments; there are five more such facilities in Japan. In most cases, these facilities use accelerators designed explicitly for cancer treatments. The accelerator types are a combination of synchrotrons, cyclotrons, and linear accelerators; some carry advanced features such as respiration gating, intensity modulation, and rapid energy changes, which contribute to better dose conformity on the tumor when using heavy charged particles. Recent interest in carbon nuclei for cancer treatment has led some vendors to offer carbon-ion and proton capability in their accelerator systems, so that either ion can be used. These features are now being incorporated for medical accelerators in new facilities.
The University of Pennsylvania/Walter Reed Army Medical Center Proton Therapy Program
Authors: McDonough James , Tinnel Brent
Published: October 2014

The design of the proton therapy center being constructed at the University of Pennsylvania is based on several principles that distinguish it from other proton facilities. Among these principles is the recognition that advances in imaging, and particularly in functional imaging, will have a large impact on radiotherapy in the near future and that the conformation of proton dose distributions can utilize that information to a larger degree than other treatment techniques. The facility will contain four-dimensional CT-simulators, an MR-simulator capable of spectroscopy, and a PET-CT scanner.

A second principle applied to the facility design is to incorporate into proton radiotherapy the recent progress in conventional radiotherapy; including imaging and monitoring of patients during treatment, imaging of soft tissue, accounting for respiratory motion, and expanding the use of intensity-modulated treatments.

A third principle is to understand that the facility must be operated efficiently. To that end the specifications for the equipment have included requirements for high beam intensity, fast switching times between treatment rooms, a multileaf collimator to permit multiple fields to be treated quickly, and plans for an intelligent beam scheduler to determine where the beam can be best used at any given time. We expect to use “universal” nozzles, which can switch rapidly from scattering mode to scanning mode, and there will be a set-up room used for the first day of treatment to verify alignment rather than spend valuable time in a gantry room.

Many of these ideas require development, including the applications of existing radiotherapy techniques to proton gantries, so a series of research and development projects have started to address these issues. Walter Reed Army Medical Center, which will provide a portal through which military personnel and their dependants can receive proton radiotherapy, is involved in several of these development projects as well as the creation of process to remotely perform treatment planning for the military patients under treatment at the proton facility.
A Knowledge-Based Imaging Informatics Approach for Managing Proton Beam Therapy of Cancer Patients
Authors: Liu Brent J.
Published: October 2014

The need for a unified patient-oriented information system to handle complex proton therapy (PT) imaging and informatics data during the course of patient treatment is becoming steadily apparent due to the ever increasing demands for better diagnostic treatment planning and more accurate information. Currently, this information is scattered throughout each of the different treatment and information systems in the oncology department. Furthermore, the lack of organization with standardized methods makes it difficult and time-consuming to navigate through the maze of data, resulting in challenges during patient treatment planning. We present a methodology to develop this electronic patient record (ePR) system based on DICOM standards and perform knowledge-based medical imaging informatics research on specific clinical scenarios where patients are treated with PT. Treatment planning is similar in workflow to traditional radiation therapy (RT) methods such as intensity-modulated radiation therapy (IMRT), which utilizes a priori knowledge to drive the treatment plan in an inverse manner. In March 2006, two new RT objects were drafted in a DICOM-RT Supplement 102 specifically for ion therapy, which includes PT. The standardization of DICOM-RT-ION objects and the development of a knowledge base as well as decision-support tools that can be add-on features to the ePR DICOM-RT system were researched. This methodology can be used to extend to PT and the development of future clinical decision-making scenarios during the course of the patient's treatment that utilize “inverse treatment planning.” We present the initial steps of this imaging and informatics methodology for PT and lay the foundation for development of future decision-support tools tailored to cancer patients treated with PT. By integrating decision-support knowledge and tools designed to assist in the decision-making process, a new and improved “ knowledge-enhanced treatment planning” approach can be realized.
Long-lasting In vivo Gene Silencing by Electrotransfer of shRNA Expressing Plasmid
Authors: Escoffre Jean-Michel , Debin Arnaud , Reynes Jean-Paul , Drocourt Daniel , Tiraby Gérard , Hellaudais Laëtitia , Teissie Justin , Golzio Muriel
Published: October 2014

RNA interference appears as a promising tool for therapeutic gene silencing. A key limit is the delivery of the siRNA. A safe approach is to use a physical method such as in vivo electropulsation with contact electrodes. Getting a long lived silencing can be better approached by using the in situ expression of shRNA. This is presently obtained by using co-electrotransfer of specific plasmids coding for expression and silencing of a fluorescent protein. Using a non invasive fluorescence imaging assay, electrodelivery in mouse muscles is observed to induce complete silencing over more than two months in a specific way. The proper choices of the plasmids (sequence and relative amounts) and of the electric pulsing conditions appear as key parameters in the successful silencing.
Integration of Cone-Beam CT in Stereotactic Body Radiation Therapy
Authors: Yin Fang-Fang , Wang Zhiheng , Yoo Sua , Wu Q. Jackie , Kirkpatrick John , Larrier Nicole , Meyer Jeffrey , Willett Christopher G. , Marks Lawrence B.
Published: October 2014

This report describes the technique and initial experience using cone beam CT (CBCT) for localization of treatment targets in patients undergoing stereotactic body radiation therapy (SBRT). Patients selected for SBRT underwent 3-D or 4-D CT scans in a customized immobilization cradle. GTV, CTV, ITV, and PTV were defined. Intensity-modulated radiation beams, multiple 3-D conformal beams, or dynamic conformal arcs were delivered using a Varian 21EX with 120-leaf MLC. CBCT images were obtained prior to each fraction, and registered to the planning CT by using soft tissue and bony structures to assure accurate isocenter localization. Patients were repositioned for treatment based on the CBCT images. Radiographic images (kV, MV, or CBCT) were taken before and after beam delivery to further assess set-up accuracy. Ten patients with lung, liver, and spine lesions received 29 fractions of treatment using this technique. The prescription doses ranged 1250 ~ 6000 cGy in 1 ~ 5 fractions. Compared to traditional 2-D matching using bony structures, CBCT corrects target deviation from 1 mm to 15 mm, with an average of 5 mm. Comparison of pre-treatment to post-treatment radiographic images demonstrated an average 2 mm deviation (ranging from 0–4 mm). Improved immobilization may enhance positioning accuracy. Typical total “in-room” times for the patients are approximately 1 hour. CBCT-guided SBRT is feasible and enhances setup accuracy using 3-D anatomical information.
Taxotere Chemosensitivity Evaluation in Mice Prostate Tumor: Validation and Diagnostic Accuracy of Quantitative Measurement of Tumor Characteristics by MRI, PET, and Histology of Mice Tumor
Authors: Sharma Rakesh , Katz Jose K.
Published: October 2014

Increased PET and MRI image intensities of mouse prostate tumors were correlated with histostaining tumor characteristics. The hypothesis was that increased intracellular sodium μMRI signal intensities and flouro-2-deoxy-glucose utilization by μPET in apoptosis rich regions in tumors were positively correlated as chemosensitivity assay of Taxotere. The PC-3 cancer cell line induced prostate tumor MRI and PET images and histology slices were digitally captured and compared in pre- and post-Taxotere treated tumors. The optimization of inversion recovery MRI parameters was done to generate sodium images of phantom. The 18FDG biotransformation was optimized to measure PET image intensities. A criterion was developed to evaluate malignancy by histology. For correlation, regression analysis was done using imaging, histology, and immunostaining data from PC3 tumor after 24 and 48 hours post-Taxotere treatment. Apoptosis indices were calculated by histostaining and ss-DNA antibody assay. Sodium MRI and PET signal intensity distributions were comparable at specific locations relatively and measured in tumor tissue regions. In tumors, Taxotere induced an increase in intracellular sodium MRI signal 30% (p<0.001) with decreased tumor size (20%; p<0.001) and micro-PET showed FDG uptake increase 15% (p<0.001) with decreased tumor size (10%; p<0.001) than that of control tumors after 24 hours. Histological features indicated tumor risk (high ‘intracellular/extracellular ratio’, high mitotic index, and apoptotic index), decreased tumor viability (reduced mitotic figures, reduced diploidy or aneuploidy, and proliferation index) after Taxotere treatment. These features in co-registered intracellular sodium, μPET hypermetabolic, and monoclonal antibody (ss-DNA) sensitive regions showed (% difference > 6%). Apoptosis rich regions showed characteristic nuclei with S phase DNA histogram, appearing brighter on IC-Na images and mild active on PET images (sensitivity=65%; specificity=70%). In conclusion, MRI and PET multimodal imaging may be rapid non-invasive chemosensitivity assay to monitor the drug anticancer effect.
Latest Discoveries and Trends in Translational Cancer Research: Highlights of the 2008 Annual Meeting of the American Association for Cancer Research
Authors: Cho William C. S.
Published: October 2014

The Annual Meeting of the American Association for Cancer Research (AACR) is the world's largest and most comprehensive gathering of cancer researchers. At the 2008 AACR Annual Meeting, innovative research approaches, novel technologies, potentially life-saving therapies in the pipeline, late-breaking clinical trial findings, and new approaches to cancer prevention were presented by top scientists. Reflecting the global state of cancer research with an eye toward future trends, several areas of great science and discovery in the cancer field were shared in this report, which include cancer biomarkers, the role of microRNAs in cancer research, cancer stem cells, tumor microenvironment, targeted therapy, and cancer prevention. This article presents an overview of hot topics discussed at the 2008 AACR Annual Meeting and recapitulates some scientific sessions geared toward new technologies, recent progress, and current challenges reported by cancer researchers. For those who did not attend the meeting, this report may serve as a highlight of this important international cancer research meeting.
Importance of Contact Surface between Electrodes and Treated Tissue in Electrochemotherapy
Authors: Čorović Selma , Al Sakere Bassim , Haddad Vincent , Miklavčič Damijan , Mir Lluis M.
Published: October 2014

Electrochemotherapy is an effective antitumor treatment employing locally applied high voltage electric pulses delivered through conductive electrodes to the tumor in combination with chemotherapeutic drugs. The efficiency of electrochemotherapy strongly depends on the local electric field distribution inside the target tissue. For successful therapy the entire target tissue has to be exposed to the local electric field strength above the reversible threshold. The aim of this study is to demonstrate the influence of the contact surface between electrode and treated tissue on the coverage of the tumor tissue by sufficiently high local electric field. The electric field distribution is calculated by means of numerical modeling using finite element method. Numerical results are confirmed with in vivo experiments. We demonstrated that the placement of electrodes giving larger electrode-tissue contact surface leads to improved electrochemotherapy outcome. Our results provide guidance on electrochemotherapy for treatment of protruding cutaneous tumors using parallel plate electrodes.
Treatment of Primary Liver Tumors with Yttrium-90 Microspheres (TheraSphere®) in High Risk Patients: Analysis of Survival and Toxicities
Authors: Reardon Kelli A. , McIntosh Alyson F. , Shilling A. Tanner , Hagspiel Klaus D. , Al-Osaimi Abdullah , Berg Carl , Caldwell Stephen H. , Northup Patrick G. , Angle Fritz , Mulder Robert , Rich Tyvin A.
Published: October 2014

This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3–5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.
Autofluorescence Videobronchoscopy (AFI) for the Assessment of Tumor Extension in Lung Cancer
Authors: Zaric Bojan , Canak Vukasin , Stojanovic Goran , Jovelic Aleksandra , Sarcev Tatjana , Kuruc Vesna , Eri Zivka , Panjkovic Milana , Milovancev Aleksandar
Published: October 2014

The major objective of our study was to determine the specificity and sensitivity of AFI videobronchoscopy vs. white light videobronchoscopy, in the assessment of lung cancer extent. Secondary objective was to investigate whether or not AFI can reveal greater extension of the tumor, and can it influence therapy making decision. Autofluorescence videobronchoscopy systems are new technology for visualization of bronchial mucosa, and the proper indications for such systems will be determined in the near future. In this prospective trial we have enrolled 27 patients with suspected lung cancer in whom we performed 108 diagnostic biopsies and 54 control biopsies. All patients underwent WL videobronchoscopy followed by Auto Fluorescence Imaging (AFI) examination of tracheobronchial tree. We were using videobronchoscope BF-F260 and EVIS LUCERA SPECTRUM processor unit. Overall specificity for AFI in the diagnostics of lung cancer was found to be 85%, sensitivity was 90%, positive predictive value (PPV) 78%, and negative predictive value (NPV) 94%. Specificity, sensitivity, PPV, and NPV for WL videobronchoscopy in lung cancer diagnostics were 54%, 64%, 51%, and 69%, respectively. Relative sensitivity ratio of AFI over WL videobronchoscopy, which is calculated to be 1.41, confirmed superiority of AFI in lung cancer diagnostics. We confirmed significant correlation between the greater extension of the tumor (assessed with AFI) and the therapeutical decision in lung cancer treatment (p = 0.01). Influence of AFI on therapeutical decision was significant (p = 0.034). AFI videobronchoscopy system yields significantly higher sensitivity and specificity for the assessment of lung cancer extent than WLB videobronchoscopy alone. It had shown to be able to influence therapeutic option for lung cancer treatment. Further studies are needed to evaluate and validate these results.
Effect of Continuous High Intensity Focused Ultrasound in a Squamous Cell Carcinoma Tumor Model Compared to Muscle Tissue Evaluated by MRI, Histology, and Gene Expression
Authors: Hundt Walter , Yuh Esther L. , Steinbach Silke , Bednarski Mark D.
Published: October 2014

The purpose of this study was to investigate the effect of the continuous mode of high intensity focused ultrasound (HIFU) in a mouse head and neck cancer model (SCCVII) compared to muscle tissue. HIFU was applied to SCCVII tumors and to muscle tissue in C3H/Km mice using a dual ultrasound system (imaging 6 MHz/therapeutic 1 MHz). A continuous HIFU mode (total time 20 sec, intensity 6730.6 W/cm2) was applied. Three hours after HIFU treatment pre- and post-contrast T1-wt, T2-wt images, and a diffusion-wt STEAM sequence were obtained. After MR imaging, the animals were euthenized and the treated tumor and muscle tissue was taken out for histology and functional genomic analysis.

T2 images showed increased signal intensity, post-contrast T1 showed a decreased contrast uptake in the central parts in the tumor tissue as well as in the muscle tissue. In addition a significant higher diffusion coefficient was found in both tissue types. Histological evaluation (H&E, Immunohistochemistry) of the tumors and the muscle tissue revealed areas of significant necrosis. In the tumor tissue 23 genes were up-regulated (> 2 fold change) and 4 genes were down-regulated (< −2 fold change). In the muscle tissue 29 genes were up-regulated and 17 genes down-regulated. Thirteen genes were up-regulated in both tissue types, 8 genes only in the SCCVII tissue, and 11 genes only in the muscle tissue. The use of HIFU treatment on tumor and muscle tissue results in dramatic changes in gene expression. The expression of some genes are tissue specific, the expression of other genes are independent of the tissue type.
Monte Carlo Modeling and Commissioning of a Dual-layer Micro Multileaf Collimator
Authors: Giantsoudi D. , Stathakis S. , Liu Y. , Shi C. , Papanikolaou N.
Published: October 2014

The purpose of this study was to commission a first-of-its-kind dual-layer micro multileaf collimator (mMLC) system by using Monte Carlo dose calculations. The mMLC is attached on a Varian 600C linac. Having a lower and an upper layer of MLC leaves, this mMLC allows for field shaping in two orthogonal directions. The commissioning of the system was performed in two steps: without and with the mMLC attached on the linac. The treatment head without and with the mMLC was modeled in the BEAMnrc Monte Carlo (MC) code. The scoring planes for the phase space files were specified below the linac's secondary collimators (jaws) and above and below the mMLC. With the mMLC attached to the linac the field size was defined by the jaws as 10 × 10 cm2, which is also the maximum possible field size that can be shaped by the mMLC. For the commissioning of the linac, several fields of various sizes were simulated and compared against ionization chamber measurements in a water phantom. Output factors for several field sizes, as well as percent depth dose curves and dose profiles for rectangular and irregular shape fields, were calculated and compared against measurements in water. Agreement between measured and calculated data was better than 1% and less than 1.0 mm in the penumbra region for open fields. With the mMLC attached, the agreement between measurements and MC calculations is within 1.0% or 1.0 mm in the penumbra region.
Simulating Sharp Gradients for Short-term, Ca2+ Transients and Long-term Chemotaxis in Cancer Cells
Authors: Yen Chin-Ching , Soon Lilian Li Li
Published: October 2014

Rapid progress in the elucidation of candidate genes and proteins that play a role in disease processes such as cancer has been possible with widespread use of genomics and proteomics in the last ten years. It is becoming important to adapt the knowledge gained from mass analytical techniques to visual techniques that enable spatial-temporal discernment of molecular events. This is significant, particularly for the study of pathways that regulate dynamic processes such as cell migration or early events associated with differentiation such as Ca2+ signaling. This paper describes the use of techniques that create sharp growth factor gradients suitable for local activation of cell surface receptors. The methods involve retardation of the direct flow to create steep gradients at the surface plane where cells are grown. These methods are shown to be suitable for rapid biological assays such as Ca2+ transients that occur within 1 min of receptor activation, demonstrating that the speed and level of Ca2+ transients are related to gradient strength. A microfabricated chamber is also determined to be suitable for longer-term analyses such as cancer cell chemotaxis.
Advances in Technology for Intracranial Stereotactic Radiosurgery
Authors: Sahgal Arjun , Ma Lijun , Chang Eric , Shiu Almon , Larson David A. , Laperriere Normand , Yin Fang-Fang , Tsao May , Ménard Cynthia , Basran Parminder S. , Létourneau Daniel , Heydarian Mostafa , Beachey David , Shukla Vershalee , Cusimano Michael , Hodaie Mojgan , Zadeh Gelareh , Bernstein Mark , Schwartz Michael
Published: October 2014

Stereotactic radiosurgery (SRS) refers to a single radiation treatment delivering a high dose to an intra-cranial target localized in three-dimensions by CT and/or MRI imaging. Traditionally, immobilization of the patient's head has been achieved using a rigid stereotactic head frame as the key step in allowing for accurate dose delivery. SRS has been delivered by both Cobalt-60 (Gamma Knife®) and linear accelerator (linac) technologies for many decades. The focus of this review is to highlight recent advances and major innovations in SRS technologies relevant to clinical practice and developments allowing for non-invasive frame SRS.
Towards Solid Tumor Treatment by Nanosecond Pulsed Electric Fields
Authors: Esser Axel T. , Smith Kyle C. , Gowrishankar T. R. , Weaver James C.
Published: October 2014

Local and drug-free solid tumor ablation by large nanosecond pulsed electric fields leads to supra-electroporation of all cellular membranes and has been observed to trigger nonthermal cell death by apoptosis. To establish pore-based effects as the underlying mechanism inducing apoptosis, we use a multicellular system model (spatial scale 100 μm) that has irregularly shaped liver cells and a multiscale liver tissue model (spatial scale 200 mm). Pore histograms for the multicellular model demonstrate the presence of only nanometer-sized pores due to nanosecond electric field pulses. The number of pores in the plasma membrane is such that the average tissue conductance during nanosecond electric field pulses is even higher than for longer irreversible electroporation pulses. It is shown, however, that these nanometer-sized pores, although numerous, only significantly change the permeability of the cellular membranes to small ions, but not to larger molecules. Tumor ablation by nanosecond pulsed electric fields causes small to moderate temperature increases. Thus, the underlying mechanism(s) that trigger cell death by apoptosis must be non-thermal electrical interactions, presumably leading to different ionic and molecular transport than for much longer irreversible electroporation pulses.
Dosimetric Comparison of Intensity-Modulated Radiosurgery and Helical Tomotherapy for the Treatment of Multiple Intracranial Metastases
Authors: VanderSpek Lauren , Bauman Glenn , Wang Jia-Zhu , Yartsev Slav , Ménard Cynthia , Cho Young-Bin , Mundt Arno J. , Lawson Joshua D. , Murphy Kevin T.
Published: October 2014

The purpose of this study was to evaluate the dosimetry of single fraction, single-isocenter intensity-modulated radiosurgery (IMRS) plans for multiple intracranial metastases and to compare Helical Tomotherapy (HT). Ten treatment plans with 3–6 brain metastases treated with IMRS were re-planned with HT. The mean number of lesions was 5 and mean PTV 22 cm3. The prescribed dose was 16–20 Gy. The mean V100% was similar for IMRS and HT, and the mean conformity index was 1.4, mean Paddick confirmity index was 0.7, and mean MDPD was 1.1 for both. The mean gradient index was similar for both. The mean 50% isodose volume was 179.2 cm3 for IMRS and 277.0 cm3 for HT (p=0.01). The mean maximum doses to organs at risk were lower for IMRS except brainstem and right optic nerve. For brain, the integral dose was 5.1 and 6.8 Gy-kg (p<0.001) and mean dose 4.0 and 5.4 Gy (p<0.001) for IMRS and HT, respectively. The mean treatment times were 23 (IMRS) and 41 (HT) minutes. Conformity and homogeneity indices were equivalent and sparing of the organs at risk was clinically acceptable for both IMRS and HT. Though the gradient index was similar for IMRS and HT, the mean 50% isodose volume and integral dose to normal brain were lower for IMRS as was treatment time.
Dosimetric Comparisons of Three-dimensional Conformal Radiotherapy, Intensity-Modulated Radiotherapy, and Helical Tomotherapy in Whole Abdominopelvic Radiotherapy for Gynecologic Malignancy
Authors: Kim Yong Bae , Kim Joo Ho , Jeong Kyung Keun , Seong Jinsil , Suh Chang Ok , Kim Gwi Eon
Published: October 2014

Objectives

The goal of this study was to dosimetrically compare 3-dimensional radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and helical tomotherapy (TOMO) plans for whole abdominopelvic radiotherapy (WART) in patients with gynecologic cancer.

Methods

Ten patients were selected for WART planning. Doses were prescribed to planning target volumes (PTVs) as the followings: 30 Gy to PTV-whole abdominopelvis (PTV-WA), 40 Gy to PTV-para-aortic lymph node (PTV-PALN), 44 Gy to PTV-pelvis, and 50 Gy to gross target volume (GTV) in 20 fractions. Dose to whole liver, both kidneys, and spinal cord were constrained below each tissue tolerance, and bone marrow (BM)-sparing technique was adopted in IMRT and TOMO. Dosimetric parameters and treatment times were compared among plans.

Results

Calculated doses in TOMO came most closely to the prescribed dose for coverage of PTV-WA, PTV-PALN, PTV-pelvis, and GTV compared to 3DCRT, and IMRT. In normal organs, TOMO had significantly better dosimetric profiles compared to IMRT and 3DCRT. TOMO significantly reduced V20Gy, and mean dose of whole liver, both kidneys, and spinal cord. The use of BM-sparing technique (BMS) did not impair coverage of target volume in IMRT and TOMO. While IMRT showed no differences of irradiated BM dose using BMS, TOMO with BMS reduced half V20Gy of BM compared to TOMO without BMS.

Conclusions

TOMO showed dosimetric superiority in target coverage, sparing BM, and other normal organs compared to 3DCRT and IMRT. Clinical experiences will be needed for evaluation of feasibility of WART using TOMO in patients with gynecologic cancer.
Search for Cancer Risk Factors with Microarray-Based Genome-Wide Association Studies
Authors: Zhang Lina , Zhang Wei , Chen Kexin
Published: October 2014

Large-scale genome-wide association studies (GWASs) have emerged as a powerful approach to identify genetic polymorphisms that are associated with risk of developing cancer and other complex diseases. Currently, microarrays are the genotype screening technology of choice in GWASs because they permit interrogation of more than one-million single-nucleotide polymorphisms (SNPs) at the same time. Many novel loci and genetic variants have been identified as markers of cancer risk in a series of recent reports. With improvement of microarray technologies, population-based GWASs coupled with more quantitative validation methods are poised to reveal, in a systematic manner, numerous small changes in complex genetic networks that in combination can have a major impact on a patient's risk of developing cancer. Here, we review recent advancement in GWAS in the search and identification of cancer risk factors.
Profiling DNA Methylomes from Microarray to Genome-Scale Sequencing
Authors: Huang Yi-Wen , Huang Tim H.-M. , Wang Li-Shu
Published: October 2014

DNA cytosine methylation is a central epigenetic modification which plays critical roles in cellular processes including genome regulation, development and disease. Here, we review current and emerging microarray and next-generation sequencing based technologies that enhance our knowledge of DNA methylation profiling. Each methodology has limitations and their unique applications, and combinations of several modalities may help build the entire methylome. With advances on next-generation sequencing technologies, it is now possible to globally map the DNA cytosine methylation at single-base resolution, providing new insights into the regulation and dynamics of DNA methylation in genomes.
Comparison of Intensity-Modulated Radiotherapy Using Helical Tomotherapy and Segmental Multileaf Collimator-based Techniques for Nasopharyngeal Carcinoma: Dosimetric Analysis Incorporating Quality Assurance Guidelines from RTOG 0225
Authors: Chen Allen M. , Lee Nancy Y. , Yang Claus C. , Liu Tianxiao , Narayan Samir , Vijayakumar Srinivasan , Purdy James A.
Published: October 2014

Intensity-modulated radiotherapy (IMRT) treatment plans generated by segmental multileaf collimator (SMLC) and helical tomotherapy (HT) techniques for patients with nasopharyngeal carcinoma were compared using standardized criteria proposed by Radiation Therapy Oncology Group (RTOG) protocol 0225. The goal was to deliver a prescribed dose of 70 Gy to at least 95% of the planning target volume (PTV) encompassing gross tumor, and 59.4 Gy and 50.4 Gy, respectively, to areas at high and low risk for microscopic disease, over 33 treatments while respecting constraints to organs at risk (OAR). HT-IMRT significantly reduced dose to the contralateral parotid gland and improved dose homogeneity to the PTVs. Mean doses to the inner and middle ears were also reduced by 18% and 24%, respectively, on the ipsilateral side, and 24%, and 35%, respectively, on the contralateral side using HT-IMRT compared to SMLC-IMRT. Additionally, HT-IMRT reduced mean doses to brainstem (p = 0.02), larynx (p = 0.03), and oral cavity (p = 0.03). These findings suggest that HT-IMRT may be of improve the therapeutic ratio in the radiotherapeutic treatment of nasopharyngeal carcinoma.