bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Nanotechnology in Cancer
Authors: Banerjee Hirendra N. , Verma Mukesh
Published: October 2014

Nanotechnology refers broadly to a field of applied science and technology whose unifying theme is the control of matter on the molecular level in scales smaller than 1 micrometer, normally 1 to 100 nanometers, and the fabrication of devices within that size range. In the last five years this technology has been improved tremendously in disease diagnosis and prognosis and maximum research and clinical work has been completed in cancer. The use of various pharmaceutical nanocarriers has become one of the most important areas of nanomedicine. Novel nanotechnologies can complement and augment existing genomic and proteomic techniques to analyze variations across different tumor types, thus offering the potential to distinguish between normal and malignant cells. Sensitive biosensors constructed of nanoscale components ( e.g., nanocantilevers, nanowires, and nanochannels) can recognize genetic and molecular events and have reporting capabilities, thereby offering the potential to detect rare molecular signals associated with malignancy. Such signals may then be collected for analysis by nanoscale harvesters that selectively isolate cancer-related molecules from tissues. The implication of nanotechnology in cancer is discussed in this article with an emphasis on biomarker detection, imaging studies for diagnosis, and its role in therapeutic intervention.
Proteomic Evaluation of Urine from Renal Cell Carcinoma Using SELDI-TOF-MS and Tree Analysis Pattern
Authors: Wu Deng-Long , Zhang Wen-Hong , Wang Wen-Jing , Jing San-Bao , Xu Yue-Ming
Published: October 2014

There is no useful marker in screening and early diagnosis for renal cell carcinomas (RCCs), especially in the urine. To screen for specific markers in the urine of RCCs patients, surface enhanced laser desorption and ionization time of flight mass spectrometry (SELDI-TOF-MS) was used and coupled with a tree analysis pattern to develop SELDI protein profiling of urine. Urine samples from 58 RCC patients, 45 healthy volunteers, and 56 patients with other urogenital diseases were analyzed using IMAC-Cu ProteinChip capable of specifically binding metal interesting proteins. Proteomic spectra were generated by mass spectrometry. Bioinformatic calculations were performed with Biomarker Wizard software 3.0 (Ciphergen). Four differentially expressed potential biomarkers from urine were identified with the relative molecular weights of 4020, 4637, 5070, and 5500. The discriminatory classifier with a panel of the four biomarkers determined in the training set could precisely detect 24 of 30 (sensitivity, 80.0%) RCC and 52 of 58 (specificity, 89.6%) non-RCC samples. Furthermore, a sensitivity of 67.8% (19/28) and a specificity of 81.4% (35/43) for the blinded test were obtained when comparing the RCC vs. non-RCC. So SELDI-TOF combined with a tree analysis pattern could potentially serve as a useful tool for diagnosis of RCC by urine samples.
Differentiation of Melanoma from Non-Cancerous Tissue in an Animal Model Using Elastic Light Single-Scattering Spectroscopy
Authors: Canpolat Murat , Gökhan A. Güzide , Çiftçioğlu M. Akif , Erin Nuray
Published: October 2014

Cutaneous melanoma is the most serious form of skin cancer and is curable only if it is detected early. The most effective treatment for the melanoma is surgical excision of the lesion. Traditionally, wide margins of excision have been used for effective treatment, but are not always desirable due to increased risk of infection and esthetic reasons. Besides, safe surgical margins of the lesion are not always correlated well with the size of the lesions. We have previously developed a system using elastic light single-scattering spectroscopy to differentiate cancerous tissue from non-cancerous tissue and tested it in vitro. The goal of this study was, therefore, to determine the effectiveness of this system ex vivo by using a mouse model of melanoma. First, a melanoma cell line; B16F10 were injected subcutaneously at right mid flank region of C57BL6 mice (n=5) and allowed to develop for two weeks. Tumors were dissected and spectra were taken on tumor tissue and on normal looking skin tissue that was 10 mm distant from the incision. Since these tumors become markedly necrotic in the middle, spectra of necrotic area was also taken. Slopes of the spectra were positive taken on non-cancerous skin tissues that were later verified by histological examination. On the other hand, it gave negative slopes on melanomas. Increased sizes of the nuclei correlated with the negative slope while smaller nuclei found in non-cancerous tissue gave positive slope. Spectrum taken from necrotic area differed from both cancerous and non-cancerous tissue such that it gave a U-shaped spectrum. These results demonstrate that elastic light single-scattering spectroscopy system can differentiate cancerous tissue from non-cancerous and has potential to be used intraoperatively to determine the surgical margins.
Comparison of Daily Couch Shifts Using MVCT (TomoTherapy) and B-mode Ultrasound (BAT System) during Prostate Radiotherapy
Authors: Lin Steven H. , Sugar Elizabeth , Teslow Terrance , McNutt Todd , Saleh Habeeb , Song Danny Y.
Published: October 2014

The purpose of this study was to compare daily couch shifts after prostate localization between megavoltage CT (MVCT, Hi-ART® TomoTherapy) and b-mode ultrasound (BAT system). Nine hundred and thirteen couch shifts from 22 consecutive patients treated using MVCT localization were compared to 853 shifts from 23 randomly selected patients treated using b-mode ultrasound prostate localization. Shifts were made in three principal axes based on prostate position after comparing daily images to the initial planning CT. Mean shift for each axis and the shift variability both between and within individual subjects were calculated. Variability was higher for BAT compared to MVCT for vertical and cranial-caudal (CC) shifts (p = 0.0084 and 0.01037, respectively), while lateral shifts were significantly greater for MVCT. For each individual, the pairwise correlations between shifts in different axes were calculated. Among all the groups and pairings, only the pairing of vertical and cranial/caudal adjustments in BAT-localized patients showed significant evidence of correlation after adjustment for multiple pairwise comparisons (p = 0.0006). When compared to MVCT, the use of BAT for prostate localization results in greater variability of positional adjustments in vertical and CC directions. This likely reflects differences in the ability to precisely align b-mode ultrasound contours to KVCT images, as well as prostate excursion in vertical and CC direction caused by the ultrasound probe. These considerations need to be made when defining treatment volumes, and argue for the use of less disruptive techniques for daily prostate localization.
The Use of Tissue Electrical Characteristics for Breast Cancer Detection: A Perspective Review
Authors: Ng E. Y. K. , Sree S. Vinitha , Ng K. H. , Kaw G.
Published: October 2014

Breast cancer is the most frequently occurring malignancy in women. It is characterized by a high mortality rate. For the purpose of detecting this life threatening disease, research efforts are being made worldwide to exploit new technologies, to improve the detection accuracy of current devices and to develop new detection devices, comprehensive diagnostic procedures, and protocols. One such technology that is gaining popular attention over the recent years is the usage of electrical characteristics of the breast tissue to differentiate normal and cancerous tissues. Most of the devices using this technology are currently being used as adjunct diagnostic tools to improve the detection accuracy of established techniques like mammography and ultrasound. Also, early detection of breast cancer can help save many thousands of lives every year and can also reduce unnecessary healthcare expenditure caused by advanced stage treatment options. Hence, more research is also being done to adapt these devices into screening tools for early detection of breast cancer.

The main objective of this review is to highlight the features of the currently available commercial devices that use this technology for breast cancer detection. The electrical behavior of normal and cancerous breast tissues is first presented. The various commercial devices that utilize electrical impedance or electropotentials for breast cancer detection are then described. Finally, conclusions and potential areas of research are highlighted.
AKT1 (E17K) Mutation in Pancreatic Cancer
Authors: Mohamedali Azim , Lea Nicholas C. , Feakins Roger M. , Raj Kavita , Mufti Ghulam J. , Kocher Hemant M.
Published: October 2014

The prevalence of a novel somatic mutation (E17K) in the pleckstrin homology domain of AKT1 was investigated in pancreatic cancer using a quantitative pyrosequencing assay. This mutation was un-detectable in pancreatic cancer tissue samples (n=65) and pancreatic cell line (n=10) DNA suggesting that pancreatic cancer progression is mainly dependent on the K-Ras mutation.
Comparison between Real-time Intra-operative Ultrasound-based Dosimetry and CT-based Dosimetry for Prostate Brachytherapy Using Cesium-131
Authors: Jacobs Bruce L. , Gibbons Erin P. , Smith Ryan P. , Beriwal Sushil , Komanduri Krishna , Benoit Ronald M.
Published: October 2014

The purpose of this study was to evaluate the correlation between real-time intra-operative ultrasound-based dosimetry (USD) and day 0 post-implant CT dosimetry (CTD) 131 Cs permanent prostate brachytherapy. Fifty-two consecutive patients who underwent prostate brachytherapy with 131 Cs were evaluated. Real time operating room planning was performed using VariSeed 7.1 software. Post-needle placement prostate volume was used for real-time planning. Targets for dosimetry were D90 >110%, V100 >90%, V150 <50%, and V200 <20%. The CT scan for post-operative dosimetry was obtained on day 0. The mean values for USD, CTD, and the linear correlation, respectively, were, for D90: 114.0%, 105.61%, and 0.15; for V100: 95.1%, 91.6%, and 0.22; for V150: 51.5%, 46.4%, and 0.40; and for V200: 15.8%, 17.9%, and 0.42. The differences between the mean values for USD and CTD for D90 (p<0.01), V100 (p<0.01), and V150 (p<0.05) were statistically significant. For D90, 30.8% of patients had a >15% difference between USD and CTD and 51.9% of patients had a >10% difference between these values. In contrast, the USD and CTD for V100 were within 5% in 55.8% of patients and within 10% in 86.5% of patients. This study demonstrates a correlation between the mean intra-operative USD and post-implant day 0 CTD values only for V200. Significant variation in D90, V150, and V200 values existed for individual patients between USD and CTD. These results suggest that real-time intra-operative USD does not serve as a surrogate for post-operative CTD, and that post-operative CTD is still necessary.
Quality Assurance of an Image Guided Intracranial Stereotactic Positioning System
Authors: Soisson Emilie T. , Sobering Geoff , Lucas Daniel , Chao Edward , Olivera Gustavo , Tomé Wolfgang A.
Published: October 2014

This work reports on the development and testing of an intracranial stereotactic patient positioning system (ISPPS) for Tomotherapy. The ISPPS consists of the combination of a head frame, head frame couch interface (HCI), megavoltage CT (MVCT), and optical tracking camera system. Three quality assurance tests were designed to quantify the positioning system's ability to localize an intracranial target. The first two of these tests were designed to determine (a) the ability of the MVCT to detect a known shift applied to an anthropomorphic phantom and (b) the precision of fixing the phantom to the treatment couch via a head frame and specially designed head frame couch interface. A system verification test, using a phantom and EDR2 film, was used to determine the overall delivery precision through comparison of a measured dose distribution on film to calculated dose. The average net translational difference between a known shift applied to a phantom and that detected by MVCT image fusion was 0.62 mm. Setup reproducibility of the head frame was measured with both MVCT and optical tracking. The frame setup precision was found to be well within 1 mm for translations as well as rotations. A system delivery verification test in phantom using film showed spatial agreement between planned and delivered dose distributions to within 1 mm.
Modeling Combined Radiopharmaceutical Therapy: A Linear Optimization Framework
Authors: Besse Ian M. , Madsen Mark T. , Bushnell David L. , Juweid Malik E.
Published: October 2014

In this paper, we investigate a previously proposed mathematical model describing the effects that an innovative combined radiopharmaceutical therapy might have on the delivery of radiation to the tumor and limiting critical organs. While focused on a specific dual agent therapy, this investigation will prove mathematically that for any two therapeutic radiopharmaceuticals with different limiting critical organs the model provides patient specific conditions under which combination therapy is superior to single agent therapy. In addition, this paper outlines general methods for calculating the amounts of administered radioactivity for each drug required to optimize tumor radiation dose. We also consider extensions of this model to include an arbitrary number of independent radiopharmaceuticals and/or other treatment factors.
Utility of a 3-Dimensional Transrectal Ultrasound-guided Prostate Biopsy System for Prostate Cancer Detection
Authors: Chen Valerie H. , Mouraviev Vladimir , Mayes Janice M. , Sun Leon , Madden John F. , Moul Judd W. , Polascik Thomas J.
Published: October 2014

The 3-D transrectal ultrasound (TRUS)-guided prostate biopsy system is a novel device that allows precise needle placement in a template fashion. We evaluate its utility for prostate cancer (PCa) detection. A retrospective analysis was performed evaluating 68 prospective patients at the Duke Prostate Center who underwent a prostate biopsy using a 3-D TRUS-guided system. After creation of a three-dimensional map of the prostate, a computer algorithm identified an ideal biopsy scheme based on the measured dimensions of the prostate. The system then used a fixed template that allowed prostate biopsy at specific locations with the ability to target the same region of the prostate in the future if needed. For all patients, a 12-core biopsy pattern was used to cover medial and lateral areas of the base, mid-gland, and apex. In total, 68 patients underwent 3-D TRUS-guided prostate biopsies between April 2006 and November 2007 for prostate cancer detection. The indication for prostate biopsy was PSA ≥ 4.0 ng/ml in 47 (69%) patients, abnormal digital rectal examination (DRE) in 17 (25%), and atypia on previous biopsy in 4 (6%) patients. Prostate cancer was detected in 18 patients (26.5%) and 7 (10.3%) had atypical small acinar proliferation (ASAP). The highest frequency (55.5%) from all cases of cancer detected was identified when 3-D TRUS biopsy was used as the initial biopsy. This study demonstrates that a 3-D TRUS-guided biopsy system translates to a more frequent detection of prostate cancer among patients undergoing an initial prostate biopsy than a subsequent one. More comprehensive studies are warranted to corroborate and extend the results of this study.
Temporal Changes in IMRT Contouring of Organs at Risk for Nasopharyngeal Carcinoma — The Learning Curve Blues and a Tool that Could Help
Authors: Baxi Siddhartha , Park Eileen , Chong Vincent , Chung Hans T.
Published: October 2014

With improved target conformality, the transition to IMRT for nasopharyngeal cancer (NPC) has moved contouring accuracy and consistency to the forefront. At NUH, IMRT for NPC was implemented in 2005, with more than 70 patients treated since then. The objective was to measure the accuracy and variability of contouring organs at risk (OAR) over time. The first 10 patients, 5 from each of the two head and neck (H&N) Radiation Oncologists, treated by IMRT in 2005 formed cohort A. Ten patients, matched by stage, treated by IMRT in 2007 formed cohort B. The RTOG 0225 protocol was followed. These 20 plans were retrieved from archive. A H&N Radiologist, who is a member of the UICC Expert Panel for the TNM Staging of NPC, reviewed the original OAR contours and developed a standardized OAR contouring template. Using the template, the OAR volumes were then re-contoured in all 20 cases, representing the gold standard against which the original volume was compared. For each patient, comparisons were made between the original and standardized contours using volumetric and spatial parameters. Cohort A was then compared with cohort B to determine whether accuracy and variability changed over time. Evaluated OAR volumes included the temporal lobes, brainstem, optic nerves, optic chiasm, pituitary, temporo-mandibular joint (TMJ), parotid glands, inner ears, eyes, and thyroid. While the original temporal lobe contours were significantly larger in cohort B (60.2 vs. 106.8 mL, p=0.02), the absolute difference between the original and standardized volumes was reduced by 53% (p=0.02) and there was no difference in the centroid coordinates and the overlapping fraction. While the inner ear was consistently contoured between cohort A and B, there was systematic exclusion of the cochlea in the contours. The original optic nerve contours decreased from cohort A to B (p=0.008), with an improvement in overlap fraction (p=0.06). The TMJ original volumes were smaller for cohort B than A, with a correspondingly significant improvement in overlapping fraction (p=0.02) with the standardized volumes. No difference was seen in the remaining OAR.
The Impact of Hybrid PET-CT Scan on Overall Oncologic Management, with a Focus on Radiotherapy Planning: A Prospective, Blinded Study
Authors: Kruser Tim J. , Bradley Kristin A. , Bentzen Soren M. , Anderson Bethany M. , Gondi Vinai , Khuntia Deepak , Perlman Scott B. , Tome Wolfgang A. , Chappell Richard J. , Walker Wendy L. , Mehta Minesh P.
Published: October 2014

Functional imaging using fluorodeoxyglucose positron-emission tomography (FDG-PET) has been increasing incorporated into radiotherapy planning in conjunction with computed tomography (CT). Hybrid FDG-PET/CT scanners allow these images to be obtained in very close temporal proximity without the need for repositioning patients, thereby minimizing imprecision when overlying these images. To prospectively examine the impact of hybrid PET/CT imaging on overall oncologic impact, with a focus on radiotherapy planning, we performed a prospective, blinded trial in 111 patients. Patients with lung cancer (n=38), head-and-neck squamous cell carcinoma (n=23), breast (n=8), cervix (n=15), esophageal (n=9), and lymphoma (n=18) underwent hybrid PET/CT imaging at the time of radiation therapy planning. A physician blinded to the PET dataset designed a treatment plan using all clinical information and the CT dataset. The treating physician subsequently designed a second treatment plan using the hybrid PET/CT dataset. The two treatment plans were compared to determine if a major alteration in overall oncologic management occured. In patients receiving potentially curative radiotherapy the concordance between CT-based and PET/CT-based GTVs was quantified using an index of conformality (CI). In 76/111 (68%) of patients, the PET/CT data resulted in a change in one or more of the following: GTV volume, regional/local extension, prescribed dose, or treatment modality selection. In 35 of these 76 cases (46%; 31.5% of the entire cohort) the change resulted in a major alteration in the oncologic management (dose, field design, or modality change). Thus, nearly a third of all cases had a major alteration in oncologic management as a result of the PET/CT data, and 29 of 105 patients (27.6%) who underwent potentially curative radiotherapy had major alterations in either dose or field design. Hybrid PET/CT imaging at the time of treatment planning may be highly informative and an economical manner in which to obtain PET imaging, with the dual goals of staging and treatment planning.
Melding a New 3-Dimensional Agarose Colony Assay with the Emax Model to Determine the Effects of Drug Combinations on Cancer Cells
Authors: Kajiwara Yoshinori , Panchabhai Sonali , Liu Diane D. , Kong Maiying , Lee J. Jack , Levin Victor A.
Published: October 2014

The goal of our study was two-fold: (i) develop a robust 3D colony assay methodology to interrogate drug combinations using GelCount™ and (ii) to develop 2-drug combinations that might be useful in the clinic for the treatment of high-grade gliomas. We used three glioma cell lines (U251MG, SNB19, and LNZ308) and two adenocarcinoma cell lines (MiaPaCa and SW480) grown as colonies in a two-tiered agarose cultures. We evaluated two-drug combinations of difluoromethylornithine (DFMO), carboplatin, vorinostat (SAHA), and docetaxel. To analyze for antitumor efficacy we used GelCount™ to measure the area under the curve for tumor colony volumes (μm2 x OD) in each plate. The non-linear dose-response Emax model and the interaction index based on the Loewe additivity are applied to calculate two-drug synergy, additive, and antagonistic interactions.

For glioblastoma cell lines, (i) carboplatin followed by DFMO was synergistic or additive in 2/3 cell lines, (ii) carboplatin before SAHA was synergistic in 1 cell line, (iii) carboplatin before docetaxel was synergistic in 2/3 cell lines and partially additive in the third, (iv) SAHA before docetaxel was synergistic in 1/3 cell lines, (v) docetaxel before DFMO was additive or partially active in 3/3 cell lines, and (vi) DFMO plus SAHA was inactive regardless of order. In the MiaPaCA cell line, synergy occurred when DFMO followed carboplatin and, at short exposure times, when SAHA was combined with carboplatin (regardless of order). In the SW480 cell line synergy occurred only in short exposures for carboplatin followed by docetaxel; additive and mixed partial effects were also seen with DFMO plus carboplatin or docetaxel (regardless of order), carboplatin before DFMO, carboplatin before SAHA, and docetaxel before carboplatin.

In conclusion, by applying the Gelcount™ automated counting and sizing of colonies and the use of Emax and Loewe models to define drug interactions, we can reliably define drug combination efficacy as a function of log dose and duration of drug exposure.
Placement of MammoSite® Brachytherapy Catheter under Computed-Tomography Scan Guidance
Authors: Mutyala Subhakar , Yaparpalvi Ravindra , Choi Walter , Mehta Keyur , Spierer Marnee , Kalnicki Shalom
Published: October 2014

Placement of the MammoSite® breast brachytherapy catheter is most commonly performed either intraoperatively or under ultrasound-guided technique. Below, we present a case report of an alternate approach utilizing CT-scan guidance. This is the first reported case of a balloon brachytherapy catheter placement with this technique.
Effect of siRNA Targeting HIF-1α Combined L-ascorbate on Biological Behavior of Hypoxic MiaPaCa2 Cells
Authors: Chen Chuangui , Tang Peng , Yue Jie , Ren Peng , Liu Xiangming , Zhao Xijiang , Yu Zhentao
Published: October 2014

The aim of the study was to observe the effect of small interference RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α) combined L-ascorbate on proliferation, migration, and apoptosis of hypoxic MiaPaCa2 human pancreatic cancer cells. A cassette encoding siRNA targeting HIF-1α mediated by recombinant adeno-associated virus (rAAV) was constructed, giving rAAV-siHIF. rAAV-siHIF and L-ascorbate, which were used alone or in combination, were delivered to exponentially growing MiaPaCa2 cells under hypoxic conditions. Then, we observed the expression of HIF-1α mRNA and protein, the proliferation, apoptosis, and migration of MiaPaCa2 cells by real-time PCR, Western blot, MTT, TUNEL, and Transwell assay, respectively. Under hypoxic conditions, rAAV-siHIF inhibited the expression of HIF-1α mRNA in MiaPaCa2 cells but L-ascorbate did not. However, rAAV-siHIF and L-ascorbate both inhibited the expression of HIF-1α protein and the proliferation and migration of MiaPaCa2 cells and induced MiaPaCa2 cell apoptosis. The effect in the combined group was more efficient than that seen when rAAV-siHIF or L-ascorbate was used separately. rAAV-siHIF and L-ascorbate both affect biological behavior of hypoxic MiaPaCa2 cells through modulating HIF-1α protein expression and rAAV-siHIF and L-ascorbate have synergy under hypoxic conditions.
PET Lesion Segmentation Using Automated Iso-intensity Contouring in Head and Neck Cancer
Authors: Simon Edmund , Fox Timothy H. , Lee Daniel , Waller Anthony F. , Pantalone Paul , Jani Ashesh B.
Published: October 2014

To improve the objectivity of the integration of positron emission tomography (PET), we used the conformality index (CI) to measure the goodness of fit of a given PET iso-SUV (standardized uptake value) level with the GTV defined on PET (GTVPET) and CT (GTVCT). Twenty-two datasets involving 20 head and neck cancer patients were identified. GTVPET and GTVCT were delineated manually. An iso-intensity method was developed to automatically segment GTVPET-ISO using (a) SUV and (b) maximum intensity thresholding (%Max), over a range of intensities. For each intensity, GTVPET-ISO was compared to GTVPET using the conformality index CIPET (and, similarly, to GTVCT using CICT). Comparing GTVPET to GTVPET-ISO vs comparing GTVCT to GTVPET-ISO, the average peak CI was 0.68 ± 0.09 vs 0.49 ± 0.12 (p<0.001), the optimum iso-SUV was 2.7 ± 0.7 vs 2.9 ± 1.0 (p=0. 253), and the %Max SUV was 21.8% ± 7.6% vs 23.8% ± 8.6% (p=0. 310), respectively. The radiation oncologist's volumes corresponded to a lower iso-SUV (3.02 ± 0.58 vs 4.36 ± 0.77, p < 0.001) and lower %Max SUV (24.1 ± 9.1% vs 34.3 ± 11.2%, p<0.001) than those drawn by the nuclear medicine physician. Though manual editing may still be necessary, PET iso-contouring is one method to improve the objectivity of GTV definition in head and neck cancer patients. Iso-SUV's can also be used to study the differences between PET's role as a nuclear medicine diagnostic test versus a radiation oncology treatment planning tool.
Simulated Gamma Knife™ Head Frame Placement for Radiosurgical Pre-Planning
Authors: Wiant D. , Bourland J. D.
Published: October 2014

The Leksell Gamma Knife®(GK) is capable of targeting intracranial lesions with a high degree of accuracy. A headframe is rigidly attached to the patient's skull to establish a stereotactic coordinate system and provide a means for precisely positioning the patient in stereotactic space. After stereotactic target localization and radiosurgical treatment planning the skull and headframe are then moved with sub-millimeter precision to bring a target volume to the radiological focus of the GK unit. However, for GK models 4C and earlier, the treatable intracranial volume may be limited by collisions between the skull/headframe and the GK collimator helmet, or by mechanical travel limits of the skull/headframe within the collimator helmet. Both of these treatment-limiting conditions can be found only after the headframe has been placed on the patient. If the volume of interest cannot be treated with the initial headframe placement, additional headframe placements or a different course of treatment are needed. We have developed a software package that allows for simulated headframe placement and collision checks using pre-treatment day image sets, in order to minimize the need for multiple headframe placements. We performed a small validation experiment with an anthropomorphic head phantom to evaluate the software's capabilities for predicting a clinically useable headframe position. We also used the software in an IRB-approved retrospective review for twenty-five GK image sets for a group of patients that could not be treated with the initial headframe placement, to determine if the software tool could locate an optimized headframe position to enable GK radiosurgery of all identified targets with a single headframe placement. We found that four of the cases could have been completed with a single optimized headframe placement and twenty-four of the cases could not be treated with any single headframe placement.
Performance of a Commercial Macro Monte Carlo Dose Calculation Algorithm for Determining Output Factors of Clinical Electron Fields
Authors: Popple Richard A. , Brezovich Ivan A. , Pareek Prem N. , Duan Jun , Shen Sui , Wu Xingen
Published: October 2014

We compare measured output factors of clinical electron fields to those calculated by a commercial treatment planning system based on an electron Monte Carlo algorithm. The measured data is comprised of 195 fields with energies 6 to 18 MeV, applicator sizes 6 × 6 cm2 to 25 × 25 cm2, and source to surface distances (SSDs) of 97 to 107 cm. Due to a scarcity of clinical fields for the highest energies and the largest applicator sizes, additional measurements were made at arbitrarily chosen large field sizes at previously not used energies, for a total of 223 output factors. The difference between calculation and measurement ranged from −2.9% to 3.9%, with a mean difference of −0.2%. Half of the field shapes had a difference with magnitude less than 0.8%. Only 7 (3%) of the field shapes were outliers, having differences greater than 2%. All outliers had field widths at the normalization point < 3.5 cm, were applied at SSDs > 100 cm, were inserts for the 25 × 25 cm2 applicator, or had more than one of these characteristics. For narrow and elongated fields the TPS slightly overestimated output factors, whereas for field shapes with aspect ratio close to 1 the TPS slightly underestimated the output factors. No strong dependence of the difference on energy was observed.
Helical Tomotherapy Significantly Reduces Dose to Normal Tissues When Compared to 3D-CRT for Locally Advanced Rectal Cancer
Authors: Jhaveri Pavan M. , Teh Bin S. , Paulino Arnold C. , Smiedala Mindy J. , Fahy Bridget , Grant Walter , McGary John , Butler E. Brian
Published: October 2014

Combined modality treatment (neoadjuvant chemoradiotherapy followed by surgery) for locally advanced rectal cancer requires special attention to various organs at risk (OAR). As a result, the use of conformal dose delivery methods has become more common in this disease setting. Helical tomotherapy is an image-guided intensity modulated delivery system that delivers dose in a fan-beam manner at 7 degree intervals around the patient and can potentially limit normal tissue from high dose radiation while adequately treating targets. In this study we dosimetrically compare helical tomotherapy to 3D-CRT for stage T3 rectal cancer. The helical tomotherapy plans were optimized in the TomoPlan system to achieve an equivalent uniform dose of 45 Gy for 10 patients with T3N0M0 disease that was at least 5cm from the anal verge. The GTV included the rectal thickening and mass evident on colonoscopy and CT scan as well as with the help of a colorectal surgeon. The CTV included the internal iliac, obturator, and pre-sacral lymphatic chains. The OAR that were outlined included the small bowel, pelvic bone marrow, femoral heads, and bladder. Anatom-e system was used to assist in delineating GTV, CTV and OAR. These 10 plans were then duplicated and optimized into 3-field 3D-CRT plans within the Pinnacle planning system. The V[45], V[40], V[30], V[20], V[10], and mean dose to the OAR were compared between the helical tomotherapy and 3D-CRT plans. Statistically significant differences were achieved in the doses to all OAR, including all volumes and means except for V[10] for the small bowel and the femoral heads. Adequate dosimetric coverage of targets were achieved with both helical tomotherapy and 3D-CRT. Helical tomotherapy reduces the volume of normal tissue receiving high-dose RT when compared to 3D-CRT treatment. Both modalities adequately dose the tumor. Clinical studies addressing the dosimetric benefits are on-going.
Stereotactic Radiotherapy of the Liver: A Bridge to Transplantation
Authors: AlHamad AbdulAziz , Hassanain Mazen , Michel René P. , Metrakos Peter , Roberge David
Published: October 2014

Patients with hepatocellular carcinoma (HCC) have limited curative therapeutic options. In North America, liver transplantation is one of the most commonly used curative therapies. Many potential transplant patients will be treated with another therapeutic modality to prevent local disease progression while awaiting organ donation.

We present the case of 60-years old male diagnosed with HCC and awaiting liver transplantation. Prior to registration on the transplant list, the patient had a significant increase of his serum alpha-fetoprotein level. Due to his vascular anatomy and tumor location, he was not a candidate for more standard local ablative therapies. He was thus offered stereotactic radiotherapy as a bridge to liver transplantation. He received 50Gy in 5 fractions using respiratory gating. Following this, he had a complete radiological and serological response without worsening of his baseline Child-Pugh class C cirrhosis. Following transplant, 13 months later, pathological examination of the liver explant revealed only scarring at the site of radiation. This case illustrated the fact that hepatic stereotactic radiotherapy is a promising and safe treatment for patients with HCC. In selected patients, it can be a bridge to transplantation and, on its own, has the potential to induce complete pathological response in non-surgical candidates.
Pretreatment Verification of IMSRT Using Electronic Portal Imaging and Monte Carlo Calculations
Authors: Parker Brent C. , Shiu Almon , White R. Allen , Maor Moshe , Dong Lei , Liu H. Helen
Published: October 2014

The use of an amorphous silicon electronic portal imaging device (EPID) and Monte Carlo calculations were investigated for pretreatment fluence verification in intensity modulated stereotactic radiotherapy (IMSRT). Monte Carlo calculations were performed using BEAM, a general purpose Monte Carlo code to simulate radiation beams from radiotherapy units. The dose distribution to the EPID phosphor was calculated by BEAM and then converted to pixel value using a pixel calibration curve. The calibration correlated calculated pixel dose to the measured pixel value for a range of open fields. Points within the region bounded by the photon jaws were extracted for comparison. Criteria for successful verification were 5% local percent difference in high dose regions, 1 mm distance to agreement in high gradient regions, or 2% of the Monte Carlo calculated central axis pixel value in low dose regions. Software was written to quantitatively compare the measured and calculated EPID images. Successful verification of the modulated field required that ≥ 95% of compared points fall within the comparison criteria. Dose response of the EPID was found to be linear with Monte Carlo calculated doses over the dose ranges examined in this work Comparison of the measured and calculated EPID dose distributions showed good agreement with 97% of the points passing criteria. The sensitivity of the methodology to detect field shaping errors was tested by introducing positioning errors in segments of the modulated field. These sensitivity tests indicate that the comparison software designed for this work can detect a 1 mm positioning error in a single segment of the composite IMSRT field. It should be noted, however, that the work presented here is a proof of concept and currently not a clinically viable QA tool. It represents a limited evaluation using a single IMSRT field, and verification of additional fields will be required for a comprehensive evaluation of the described methods before broad conclusions can be drawn. Additionally, the results of this work are subject to the comparison criteria that were used. Clinical implementation of the proposed technique should be evaluated for the specific institutional criteria where it will be employed.
Optimization of a New Non-viral Vector for Transfection: Eudragit Nanoparticles for the Delivery of a DNA Plasmid
Authors: Gargouri M. , Sapin A. , Bouali S. , Becuwe P. , Merlin JL , Maincent P.
Published: October 2014

The development of new vectors to deliver DNA into cells for therapy of cancers or genetic diseases has been a major area of research for many years. However, the clinical application of this technology requires the development of efficient, reliable and sterile vectors enabling the transfer of genes in vivo. Non viral, polymer or lipid-based vectors offer a new impetus to gene therapy because they are less toxic than viral vectors (no endogenous recombination, fewer immunological reactions, easy production and delivery of large-sized plasmid). The aim of this study is to develop a new tool for DNA delivery composed of methacrylic polymeric (Eudragit® RS and RL) nanoparticles. These nanoparticles were prepared by two methods: nanoprecipitation and double emulsion. The nanoparticles were characterized by their size, zeta potential and amount of DNA adsorption. Cytotoxicity tests based on mitochondrial activity (MTT test) revealed that the nanoparticles had limited cytotoxicity and that this depended on both the cell type and the nanoparticle concentration. Transgene expression was observed using the Green Fluorescence Protein gene as reporter gene, and was evaluated by flow cytometry in FaDu, MDA-MB 231 and MCF-7 cell lines. The results showed that transfection rates ranging between 4 and 7% were achieved in FaDu and MDA-MB 231 cells with nanoparticles prepared by the nanoprecipitation method. In MCF-7 cells transfected with nanoparticles prepared by either the double emulsion or the nanoprecipitation method, the transfection efficiency was between 2 and 4%. Nanoparticles prepared by nanoprecipitation were slightly more efficient than nanoparticles prepared from a double emulsion. Particle size was not an important factor for transfection, since no significant difference was observed with size between 50 and 350 nm. We showed that Eudragit® RS and RL nanoparticles could introduce the transgene into different types of cells, but were generally less effective than the lipofectamine control.
Three Assays Show Differences in Binding of Wild-Type and Mutant p53 to Unique Gene Sequences
Authors: Chandrachud Uma , Gal Susannah
Published: October 2014

Cancer-associated mutations in the p53 gene often change amino acids in the protein's DNA binding domain. We used three different binding assays specifically gel shift, DNA binding scintillation proximity assay and a streptavidin magnetic bead assay to analyze the DNA binding of the tumor suppressor p53 from 4 human cell lines with different DNA sequences from the mdm2, p21 and cyclin G genes and a mutant form of the cyclin G sequence. Treatment of MCF-7 cells having wild-type p53 with hydrogen peroxide increased the binding of p53 to DNA as detected using all three assays, but to different extents. The p53 proteins from the thyroid cancer cell lines with different p53 mutations (ARO, WRO and NPA) have comparable binding reactions in the three assays, but show different specificities for the sequences. Here we show that multiple different binding assays allow us to generate a more complete picture of the function of DNA transcription factors in diseases such as cancer.
An X-ray Computed Tomography/Positron Emission Tomography System Designed Specifically for Breast Imaging
Authors: Boone John M. , Yang Kai , Burkett George W. , Packard Nathan J. , Huang Shih-ying , Bowen Spencer , Badawi Ramsey D. , Lindfors Karen K.
Published: October 2014

Mammography has served the population of women who are at-risk for breast cancer well over the past 30 years. While mammography has undergone a number of changes as digital detector technology has advanced, other modalities such as computed tomography have experienced technological sophistication over this same time frame as well. The advent of large field of view flat panel detector systems enable the development of breast CT and several other niche CT applications, which rely on cone beam geometry. The breast, it turns out, is well suited to cone beam CT imaging because the lack of bones reduces artifacts, and the natural tapering of the breast anteriorly reduces the x-ray path lengths through the breast at large cone angle, reducing cone beam artifacts as well.

We are in the process of designing a third prototype system which will enable the use of breast CT for image guided interventional procedures. This system will have several copies fabricated so that several breast CT scanners can be used in a multi-institutional clinical trial to better understand the role that this technology can bring to breast imaging.
Genomic Characterization of Gene Copy-Number Aberrations in Endometrial Carcinoma Cell Lines Derived from Endometrioid-Type Endometrial Adenocarcinoma
Authors: Wang Yingmei , Yang Da , Cogdell David , Hu Limei , Xue Fengxia , Broaddus Russell , Zhang Wei
Published: October 2014

Endometrial carcinoma is one of the most common cancers in women. A limited number of endometrial carcinoma cell lines are available for studies of signal transduction pathways and experimental therapeutics in vitro. However, these cell lines have not been comprehensively characterized. In this study, we used genome-wide microarray-based comparative genomic hybridization (aCGH) technology to characterize five of the more commonly used endometrial cancer cell lines. We detected DNA copy-number gains in chromosomal regions 2q, 3p, 3q, 5q, 7p, 17q, and 19q in all five cell lines. Other common sites of copy-number gains, which were detected in four of five cell lines, included segments of chromosomes 1, 6, 8, 9, 11, 12, and 16. In all five cell lines, we found DNA copy-number losses in regions 3p, 10p, 10q, 11q, 11p, 14q, 15q, 18p, and 21q. Other common sites of genetic aberrations included segments of chromosomes 1, 2, 4, 5, 6, 16, 20, and 22. The genes involved in the copy-number alterations included the oncogenes PIK3CA (3q26.3), K-ras (12p12.1), R-ras (19q13.3-qter), Raf-1 (3p25), EGFR (7p12), Akt1 (14q32.32), and Akt2 (19q13.1-q13.2). A pathway analysis showed that genes in the PI3K and Wnt pathways are commonly affected. Our characterization of genomic alterations in these five commonly used endometrial cancer cell lines provides valuable genomic information for research that focuses on these key oncogenic pathways in endometrial cancer.
Emerging Roles for Multimodal Optical Imaging in Early Cancer Detection: A Global Challenge
Authors: Bedard Noah , Pierce Mark , El-Naggar Adel , Anandasabapathy S. , Gillenwater Ann , Richards-Kortum R.
Published: October 2014

Medical imaging technologies have become increasingly important in the clinical management of cancer, and now play key roles in cancer screening, diagnosis, staging, and monitoring response to treatment. Standard imaging modalities such as MRI, PET, and CT require significant financial resources and infrastructure, which limits access to these modalities to those patients in high-resource settings. In contrast, optical imaging strategies, with the potential for reduced cost and enhanced portability, are emerging as additional tools to facilitate the early detection and diagnosis of cancer. This article presents a vision for an expanding role for optical imaging in global cancer management, including screening, early detection at the point-of-care, biopsy guidance, and real-time histology. Multi-modal optical imaging - the combination of widefield and high resolution imaging - has the potential to aid in the detection and management of precancer and early cancer for traditionally underserved populations. Several recent widefield and high-resolution optical imaging technologies are described, along with requirements for implementing such devices into lower-resource settings.
Automated Analysis of Fluorescent in situ Hybridization (FISH) Labeled Genetic Biomarkers in Assisting Cervical Cancer Diagnosis
Authors: Wang Xingwei , Zheng Bin , Zhang Roy R. , Li Shibo , Chen Xiaodong , Mulvihill John J. , Lu Xianglan , Pang Hui , Liu Hong
Published: October 2014

The numerical and/or structural deviation of some chromosomes ( i.e., monosomy and polysomy of chromosomes 3 and X) are routinely used as positive genetic biomarkers to diagnose cervical cancer and predict the disease progression. Among the available diagnostic methods to analyze the aneusomy of chromosomes 3 and X, fluorescence in situ hybridization (FISH) technology has demonstrated significant advantages in assisting clinicians to more accurately detect and diagnose cervical carcinoma at an early stage, in particular for the women at a high risk for progression of low-grade and high-grade squamous intraepithelium lesions (LSIL and HSIL). In order to increase the diagnostic accuracy, consistency, and efficiency from that of manual FISH analysis, this study aims to develop and test an automated FISH analysis method that includes a two-stage scheme. In the first stage, an interactive multiple-threshold algorithm is utilized to segment potential interphase nuclei candidates distributed in different intensity levels and a rule-based classifier is implemented to identify analyzable interphase cells. In the second stage, FISH labeled biomarker spots of chromosomes 3 and X are segmented by a top-hat transform. The independent FISH spots are then detected by a knowledge-based classifier, which enables recognition of the splitting and stringy FISH signals. Finally, the ratio of abnormal interphase cells with numerical changes of chromosomes 3 and X is calculated to detect positive cases. The experimental results of four test cases showed high agreement of FISH analysis results between the automated scheme and the cytogeneticist's analysis including 92.7% to 98.7% agreement in cell segmentation and 4.4% to 11.0% difference in cell classification. This preliminary study demonstrates the feasibility of potentially applying the automatic FISH analysis method to expedite the screening and detecting cervical cancer at an early stage.
A Monte Carlo Comparison of Three Different Media for Contrast Enhanced Radiotherapy of the Prostate
Authors: Garnica-Garza H. M.
Published: October 2014

Contrast-enhanced radiotherapy makes use of a kilovoltage X-ray beam, either from a diagnostic X-ray tube or modified megavoltage linear accelerator, in conjunction with a high-Z contrast medium deposited into the target volume to enhance the absorption of radiation. In this work, using the Monte Carlo code PENELOPE and the voxelized Zubal phantom to model a prostate radiotherapy treatment, a comparison between the physical absorbed dose distributions rendered by three different enhancing agents namely bismuth, gadolinium, and iodine is performed. It is assumed that there exists a concentration of 10 mg of enhancing agent per 1 g of tissue in the target volume while in the background a concentration of 1.5 mg per 1 g of tissue is present. The X-ray beam energy spectrum was obtained by means of Monte Carlo simulation of a tungsten target upon which a 220 keV mono-energetic electron pencil beam is made to impinge, and the resultant photon beam is heavily filtrated by 0.2 cm of copper. The treatment delivery is simulated as a 360° arc collimated to conform to the target from every direction. Cumulative dose-volume histograms and isodose curves are presented for the target as well as five organs-at-risk, namely rectal wall, bladder, femoral heads, skin, and bone marrow. It is shown that under these conditions clinically acceptable treatment plans are obtained for all three contrast agents. A 72 Gy dose to 100% of the target volume results in maximum absorbed doses to the above mentioned organs-at-risk of 65, 56, 44, 32 and 65 Gy respectively when bismuth is used as the contrast agent, but the results obtained with gadolinium follow closely.