bluuebunny/crossref_metadata_2025 huggingface dataset:
Cervical Cancer Screening: From Molecular Basis to Diagnostic Practice, Going through New Technologies
Authors: Zappacosta Roberta , Rosini Sandra
Published: October 2014

In the era of Human Papillomavirus (HPV) vaccination, a lot of misunderstanding still exists among healthcare professionals and patients regarding HPV infection. The purpose of this review is to synthesize the clinical molecular mechanisms that contribute to HPV-mediated cervical carcinogenesis, as well as to appraise the current status of new biomarkers and technologies in terms of available data on clinical applications and future promises.
Benefits of Six Degrees of Freedom for Optically Driven Patient Set-up Correction in SBRT
Authors: Spadea Maria Francesca , Baroni Guido , Riboldi Marco , Luraschi Rosa , Tagaste Barbara , Garibaldi Cristina , Catalano Gianpiero , Orecchia Roberto , Pedotti Antonio
Published: October 2014

To quantify the advantages of a 6 degrees of freedom (dof) versus the conventional 3- or 4-dof correction modality for stereotactic body radiation therapy (SBRT) treatments. Eighty-five patients were fitted with 5–7 infra-red passive markers for optical localization. Data, acquired during the treatment, were analyzed retrospectively to simulate and evaluate the best approach for correcting patient misalignments. After the implementation of each correction, the new position of the target (tumor's center of mass) was estimated by means of a dedicated stereotactic algorithm. The Euclidean distance between the corrected and the planned location of target point was calculated and compared to the initial mismatching. Initial and after correction median±quartile displacements affecting external control points were 3.74±2.55 mm (initial), 2.45±0.91 mm (3-dof), 2.37±0.95 mm (4-dof), and 2.03±1.47 mm (6-dof). The benefit of a six-parameter adjustment was particularly evident when evaluating the results relative to the target position before and after the re-alignment. In this context, the Euclidean distance between the planned and the current target point turned to 0.82±1.12mm (median±quartile values) after the roto-translation versus the initial displacement of 2.98±2.32mm. No statistical improvements were found after 3- and 4-dof correction (2.73±1.22 mm and 2.60±1.31 mm, respectively). Angular errors were 0.09±0.93° (mean±std). Pitch rotation in abdomen site showed the most relevant deviation, being − 0.46±1.27° with a peak value of 5.46°. Translational misalignments were −0.68±2.60 mm (mean±std) with the maximum value of 12 mm along the cranio-caudal direction. We conclude that positioning system platforms featuring 6-dof are preferred for high precision radiation therapy. Data are in line with previous results relative to other sites and represent a relevant record in the framework of SBRT.
Clinical Implementation of Prostate Image Guided Radiation Therapy: A Prospective Study to Define the Optimal Field of Interest and Image Registration Technique Using Automated X-Ray Volumetric Imaging Software
Authors: Moran Meena S. , Lund Molly W. , Ahmad Munir , Moseley Douglas , Waldron Kathryn , Gregory Jayne , Friedman Franklin P. , Wilson Lynn D.
Published: October 2014

Alignment of the CBCT with the reference CT is called image registration (IR). The parameters for utilizing the automated Elekta XVI IR software for IGRT of the prostate still remain to be defined. In this study, we compare several automated XVI IR parameters to manual registration to identify the optimal automated IR technique for the prostate gland. 280 prostate IRs were conducted as follows: 210 automated, and 70 manual IR were performed using 70 CBCT scans of seven patients. The three arms of the automated registrations were: (i) extended FOI/Bone + grey scale (double IR); (ii) limited FOI/GS (single IR); and (iii) extended FOI/GS (single IR). Automated IRs were compared to manual IRs; x, y, z shifts, failures, and errors recorded for off-line analysis. Based on the most successful parameters, a departmental protocol was developed and 432 automated IR were performed (on 20 patients) for analysis. Automated IR were classified as: Successful, failed, error, or unregistered. In arm 1, the rate of successful, failed, error, and unregistered IR were 52.8%, 1.5%, 8.6%, 37.1%, respectively, arm 2: 90% successful, 10% failed, arm 3: 100% successful. Using the arm 3 parameters for the 432 automated IRs, the incidence of unregistered scans was 0%, rescanning was required in 1% of treatments, and the time for performing the auto IR was < 5.5 minutes. We found that extended FOI + single (GS) IR results in shifts comparable to manual IR using automated XVI software. We experienced multiple unsuccessful registrations with the other methods. We conclude that when utilizing the Elekta XVI automated IR software, the extended FOI/single IR results in successful registrations most often. In addition, it is currently effectively used in our clinical practice.
Comparison of Helical Tomotherapy versus Conventional Radiation to Deliver Craniospinal Radiation
Authors: Kunos Charles A. , Dobbins Donald C. , Kulasekere Ravi , Latimer Bruce , Kinsella Timothy J.
Published: October 2014

The purpose of this study was to investigate whether helical tomotherapy would better dose-limit growing vertebral ring apophyses during craniospinal radiation as compared to conventional techniques. Four pediatric patients with M0 medulloblastoma received tomotherapy craniospinal radiation (23.4 Gy, 1.8 Gy/fx) by continuous helical delivery of 6 MV photons. Weekly blood counts were monitored. For comparison, conventional craniospinal radiation plans were generated. To assist in tomotherapy planning, a cross-sectional growth study of 52 children and young adults was completed to evaluate spine growth and maturation. Vertebral ring apophyses first fused along the posterolateral body-pedicle synostosis, proceeding circumferentially toward the anterior vertebral body such that the cervical and lumbar vertebrae fused early and mid-thoracic vertebrae fused late. For the four pediatric patients, tomotherapy resulted between 2% and 14% vertebral volume exceeding 23 Gy. Conventional craniospinal radiation predicted between 33% and 44% exceeding 23 Gy. Cumulative body radiation doses exceeding 4 Gy were between 50% and 57% for tomotherapy and between 25% and 37% for conventional craniospinal radiation. Tomotherapy radiation reduced neutrophil, platelet, and erythrocyte hemoglobin levels during treatment. Tomotherapy provides improved dose avoidance to growing vertebrae as compared to conventional craniospinal radiation. However, the long-term effects of tomotherapy dose avoidance on spine growth and large volume low dose radiation in children are not yet known.
Present Trend in the Primary Treatment of Aggressive Malignant Glioma: Glioblastoma Multiforme
Authors: Parvez Tariq
Published: October 2014

The standard treatment for glioblastoma multiforme is surgery, radiation, and chemotherapy. Yet this aggressive therapy has only a modest effect on survival with most patients surviving less than 1 year after diagnosis. This poor prognosis has lead scientists to seek alternative molecular approaches for the treatment of glioblastoma multiforme. Among these, gene therapy, vaccine therapy, and immunotherapy are all approaches that are currently being investigated. While these molecular approaches may not herald an immediate change in the prognosis of these aggressive tumors, combining them with existing approaches may bring some progress in the standard of care. This paper reviews current treatments and several newer therapies in preclinical and early clinical studies.
A Cell- Surface Polymer Reptation Mechanism for Tumor Transendothelial Transport of Macromolecules
Authors: Uzgiris Egidijus E.
Published: October 2014

Polymer reptation is a process by which flexible linear polymers can migrate around obstacles and through pores and around other polymer molecules. It has successfully described quantitative behavior of polymer melts and has been invoked in explaining DNA separation according to length in sequencing gels. This mechanism may therefore be useful in delivering contrast agents or therapeutic drugs to tumors as these must traverse from the intravascular space through the tumor endothelial junction gaps and into the tumor. In this work, we show that polymers capable of weak interactions with tumor endothelium can translocate into the tumor interstitium at up to 9 times the rate of polymers without such cell-surface interactions. We propose a new mechanism by which the polymers diffuse along the cell surface and through cell junction gaps that occur in the tumor endothelium. This process can be halted in a number of ways that demonstrate that the surface interaction is essential for the higher transport rate. Alternative transport mechanisms are ruled out by further tests of polymer length scaling dependence, and by comparison of transport rates to those for globular constructs. Polymers of Gd-DTPA-polylysine and related backbones were investigated in an animal model of breast cancer and prostate cancer. Polymer lengths ranged from 30 nm to 300nm, (from 100 to 700 lysine residues) and the polymer constructs had a cross section of approximately 1.2 nm in radius. Polymer uptake rate into tumors for an equivalent hydrodynamic size globular macromolecule was some 135 times larger demonstrating the importance of this transport mechanism compared to free diffusion of globular macromolecules through the endothelium junction pores. The polymer length scaling, with monomer number N, on rate of tumor transport goes as N−1, which rejects alternative transport processes such as pinocytosis, active transport, and particle like center of mass diffusion through pores. This N−1 scaling implies a cell-surface assisted polymer reptation process. This new transport mechanism allows very strong discrimination of aggressive tumors from nonaggressive tumors in animal model studies.
Photodynamic Therapy for Treatment of Solid Tumors — Potential and Technical Challenges
Authors: Huang Zheng , Xu Heping , Meyers Arlen D. , Musani Ali I. , Wang Luowei , Tagg Randall , Barqawi Al B. , Chen Yang K.
Published: October 2014

Photodynamic therapy (PDT) involves the administration of photosensitizer followed by local illumination with visible light of specific wavelength(s). In the presence of oxygen molecules, the light illumination of photosensitizer can lead to a series of photochemical reactions and consequently the generation of cytotoxic species. The quantity and location of PDT-induced cytotoxic species determine the nature and consequence of PDT. Much progress has been seen in both basic research and clinical application in recent years. Although the majority of approved PDT clinical protocols have primarily been used for the treatment of superficial lesions of both malignant and non-malignant diseases, interstitial PDT for the ablation of deep-seated solid tumors are now being investigated worldwide. The complexity of the geometry and non-homogeneity of solid tumor pose a great challenge on the implementation of minimally invasive interstitial PDT and the estimation of PDT dosimetry. This review will discuss the recent progress and technical challenges of various forms of interstitial PDT for the treatment of parenchymal and/or stromal tissues of solid tumors.
A New Preclinical 3-Dimensional Agarose Colony Formation Assay
Authors: Kajiwara Yoshinori , Panchabhai Sonali , Levin Victor A.
Published: October 2014

The evaluation of new drug treatments and combination treatments for gliomas and other cancers requires a robust means to interrogate wide dose ranges and varying times of drug exposure without stain-inactivation of the cells (colonies). To this end, we developed a 3-dimensional (3D) colony formation assay that makes use of GelCount™ technology, a new cell colony counter for gels and soft agars.

We used U251MG, SNB19, and LNZ308 glioma cell lines and MiaPaCa pancreas adenocarcinoma and SW480 colon adenocarcinoma cell lines. Colonies were grown in a two-tiered agarose that had 0.7% agarose on the bottom and 0.3% agarose on top. We then studied the effects of DFMO, carboplatin, and SAHA over a 3-log dose range and over multiple days of drug exposure. Using GelCount we approximated the area under the curve (AUC) of colony volumes as the sum of colony volumes (μm2 × OD) in each plate to calculate IC50 values.

Adenocarcinoma colonies were recognized by GelCount™ scanning at 3–4 days, while it took 6–7 days to detect glioma colonies. The growth rate of MiaPaCa and SW480 cells was rapid, with 100 colonies counted in 5–6 days; glioma cells grew more slowly, with 100 colonies counted in 9–10 days. Reliable log dose versus AUC curves were observed for all drugs studied.

In conclusion, the GelCount™ method that we describe is more quantitative than traditional colony assays and allows precise study of drug effects with respect to both dose and time of exposure using fewer culture plates.
The Secret Marriage between Calcium and Tumor Angiogenesis
Authors: Munaron Luca , Tomatis Cristiana , Pla Alessandra Fiorio
Published: October 2014

Endothelial cell biochemistry and responsiveness to a wide variety of external stimula are regulated by intracellular calcium concentration.

During the last twenty years, electrophysiology and functional imaging based on the use of fluorescent probes provided several informations about the dynamics and role of calcium at the single cell level: highly diverse extracellular agonists, such as proangiogenic growth factors and vasoactive compounds, trigger increases in intracellular calcium and specific informations are transduced for proliferation, differentiation, death, movement in physiological and pathological conditions.

Obviously, the investigation at multicellular and tissutal levels is much more complex. In this review we discuss the potential specific roles of calcium signaling in tumor angiogenesis progression trying to address two key questions: (i) how can this ion play specific roles in the angiogenesis regulation; and (ii) could it be used as a target to interfere with or prevent tumor vascularization?
MRI-based Treatment Planning with Electron Density Information Mapped from CT Images: A Preliminary Study
Authors: Wang C. , Chao M. , Lee L. , Xing L.
Published: October 2014

Nowadays magnetic resonance imaging (MRI) has been profoundly used in radiotherapy (RT) planning to aid the contouring of targets and critical organs in brain and intracranial cases, which is attributable to its excellent soft tissue contrast and multi-planar imaging capability. However, the lack of electron density information in MRI, together with the image distortion issues, precludes its use as the sole image set for RT planning and dose calculation. The purpose of this preliminary study is to probe the feasibility and evaluate an MRI-based radiation dose calculation process by providing MR images the necessary electron density (ED) information from a patient's readily available diagnostic/staging computed tomography (CT) images using an image registration model. To evaluate the dosimetric accuracy of the proposed approach, three brain and three intracranial cases were selected retrospectively for this study. For each patient, the MR images were registered to the CT images, and the ED information was then mapped onto the MR images by in-house developed software generating a modified set of MR images. Another set of MR images with voxel values assigned with the density of water was also generated. The original intensity modulated radiation treatment (IMRT) plan was then applied to the two sets of MR images and the doses were calculated. The dose distributions from the MRI-based calculations were compared to that of the original CT-based calculation. In all cases, the MRI-based calculations with mapped ED yielded dose values very close (within 2%) to that of the CT-based calculations. The MRI-based calculations with voxel values assigned with water density indicated a dosimetric error of 3–5%, depending on the treatment site. The present approach offers a means of utilizing MR images for accurate dose calculation and affords a potential to eliminate the redundant simulation CT by planning a patient's treatment with only simulation MRI and any available diagnostic/staging CT data.
Development of a Streamlined, Non-invasive Robotic Radiosurgery Method for Treatment of Uveal Melanoma
Authors: Muacevic Alexander , Nentwich Martin , Wowra Berndt , Staerk Sibylle , Kampik Anselm , Schaller Ulrich
Published: October 2014

To analyze the feasibility and safety of frameless, image-guided robotic radiosurgery against uveal melanoma, we developed a streamlined procedure that is completed within 3 hours under retrobulbar anesthesia without immobilization. Twenty patients (10 men and 10 women) with medium (3–5-mm prominence) and large (>5-mm prominence) unilateral uveal melanomas were treated with a frameless robotic radiosurgery system. Median age was 61 years (range 32–78 years). All patients underwent a single-session procedure beginning with retrobulbar anaesthesia, followed by computerized tomography (CT) scanning that was used in the generation of a treatment plan, and then the delivery of a radiosurgical tumor dose between 18 and 22 Gy to the 70% isodose line. Three-dimensional treatment planning was aimed at securing the optical lens and the optic disc as much as possible. Follow-up occurred at 3, 6, 12, and 18 months after the radiosurgery with clinical, ultrasound, and CT studies.

We were able to treat all patients in the frameless setup within 3 hours. In five patients with lateral and dorsal tumors, the dose to the optic lens could be kept below 2 Gy. The clinical response was evaluated for the first seven patients treated with a follow-up of at least 6 months. No local recurrences occurred with any of the clinically evaluated patients for a mean 13-month follow-up (range 6–22 months). Maximum median apical tumor height according to standardized A-scan ultrasound evaluations decreased from 7.7 to 5.6 mm (p < 0.1). The median reflectivity increased from 41% to 70% (p < 0.01). None of the patients developed a secondary glaucoma during the short-term follow-up period. Frameless, single-session, image-guided robotic radiosurgery is a feasible, safe and comfortable treatment option for patients with uveal melanoma. Longer follow-up and analysis of a larger patient series is required for definitive clinical recommendations.
Cyberknife Radiosurgery for Squamous Cell Carcinoma of Vulva after Prior Pelvic Radiation Therapy
Authors: Kunos Charles , von Gruenigen Vivian , Waggoner Steven , Brindle James , Zhang Yuxia , Myers Brenda , Funkhouser Gary , Wessels Barry , Einstein Douglas
Published: October 2014

Limited options exist for patients experiencing a local recurrence of vulvar malignancies after surgery and pelvic radiation. These recurrences often are associated with cancer-related skin desquamation and poor clinical outcomes. A new radiotherapeutic treatment modality for the previously irradiated patient is cyberknife radiosurgery, which uses a linear accelerator mounted on an industrial robotic arm to allow non-coplanar radiation therapy delivery with sub-millimeter precision. This study describes the first reported use of cyberknife radiosurgery for the treatment of recurrent vulvar cancer in three women.
The Benefits and Challenges of Using Computer-Assisted Symptom Assessments in Oncology Clinics: Results of a Qualitative Assessment
Authors: Mark Tami L. , Johnson Gina , Fortner Barry , Ryan Katheryn
Published: October 2014

Developed for clinical use in oncology settings, the Patient Assessment, Care & Education (PACE) System™ is a computer technology tool designed to address the under-identification and treatment of chemotherapy-related symptoms. This system includes general core questions together with the Patient Care Monitor™ (PCM), a validated questionnaire that assesses patient-reported problems, six symptom burden indices, and one global quality of life index. The system automatically scores the PCM and generates a written report. The objective of this study was to assess the manner in which clinicians use this system and identify the benefits and challenges that oncology clinics may face when adopting this system. The study was part of a larger evaluation of the system that included standardized surveys and chart review. Sixteen providers (physicians, nurses, and physician assistants) at 13 community oncology clinics participated in a 30-minute interview. Responses were coded according to common phrases or concepts. Clinicians indicated that they use the system mainly for symptom assessment or review of systems. The most common benefits identified included the improved ability to identify under-reported symptoms, enhanced communication with patients; increased efficiency; and its ability to highlight patients' most bothersome symptoms. Challenges included patient burden from the frequent need to answer the questionnaires, issues with the wording and formatting of the screening questionnaire, and technical difficulties. In sum, these interviews suggest that electronic symptom assessments offer potential advantages in terms improving the integration of routine assessment of patients' symptoms and health-related quality of life into the daily flow of an oncology clinic. The approach should receive additional research and development attention.
Multimodal Cancer Treatment: Real Time Monitoring, Optimization, and Synergistic Effects
Authors: Myhr Gunnar
Published: October 2014

The primary objective of this analysis is to provide the theoretical framework for a novel multimodal cancer treatment system emphasizing the use of ultrasound as a synergistic drug release mechanism, real time monitoring by MRI of hyperthermic, pO2, and ultrasound induced released effects. The aim is to provide a cure for the 20% of cancer victims who will die of complications from local solid tumors. Adjuvant therapy usually refers to surgery preceding or following chemotherapy and/or ionizing radiation treatment to decrease the risk of recurrence, but the absolute benefit for survival obtained with adjuvant therapy compared to control is only approximately 6%.

Tumor hypoxia represents a primary therapeutic concern, besides multi-drug resistance (MDR), because it can reduce the effectiveness of drugs and radiotherapy; well-oxygenated cells require one-third the dose of hypoxic cells to achieve a given level of cell killing.

The era of systemic and indiscriminate chemotherapeutic drug delivery into both healthy and pathologic tissues is near an end. Targeted drug delivery using nanoparticles is emerging as the new vehicle, either as a single treatment option, as part of adjuvant procedures or as a component of a multimodal cancer treatment system. There are more than 100 nanosized liposomes or particles, and conjugated anticancer agents in various stages of preclinical and clinical development. Active targeting can be achieved by site-specific delivery or site-specific triggering. Ultrasound can be utilized as both a site triggering and synergistic mechanism in drug release. The process can be monitored using MRI by a physical process called cavitation. An analysis of low frequency ultrasound exposure in combination with liposomally encapsulated doxorubicin (Caelyx) on Balb/c nude mice inoculated with a WiDr (human colon cancer) tumor cell line provided tumor growth inhibition of 30–40%. Mild hyperthermia causes mean intratumor pO2 to increase by 25% and enhances tumor radiosensitization. Hyperthermia causes the extravasation of liposome nanoparticles in deep tumor regions. Ionizing radiation improves the distribution and uptake of drugs. Liposomally encapsulated drugs and ultrasound mediated hyperthermia have been proven to circumvent MDR effects. Hyperthermic effects and pO2 monitoring of bodily fluid have been performed by MRI. It is hypothesized that increased vascularization and subsequent increase in pO2 levels to hypoxic regions, and monitoring of drug release through cavitation, can facilitate optimized real time concomitant or sequential treatments of drug therapy, hyperthermia, ionizing radiation, etc., before or after surgery.

An improved therapeutic index with the use of the outlined system seems probable.
Helical Tomotherapy for Brain Metastases: Dosimetric Evaluation of Treatment Plans and Early Clinical Results
Authors: Tomita Natsuo , Kodaira Takeshi , Tachibana Hiroyuki , Nakamura Tatsuya , Nakahara Rie , Inokuchi Haruo , Shibamoto Yuta
Published: October 2014

The purpose of this study was to evaluate the feasibility and treatment plans of intensity-modulated radiation therapy using helical tomotherapy (HT) for brain metastases. Twenty-three patients with 1 to 4 brain metastases were treated with H T. In combination with whole-brain radiotherapy ( simultaneous plans), metastatic lesions, and the whole brain were treated with 50 Gy and 30 Gy, respectively, in 10 fractions, with a simultaneous integrated boost technique. In patients treated for brain metastases alone ( focal plans), metastatic lesions were treated with 35 or 37.5 Gy in 5 fractions. The treatment plans were compared regarding the conformation number (CN) and homogeneity index (HI), and differences in these indexes between simultaneous and focal plans were examined by Student's t-test. Seven and 16 patients were treated with simultaneous plans and focal plans, respectively. The mean ± SD of CN and HI values were 0.75 ± 0.13 and 0.063 ± 0.042, respectively, for simultaneous plans, and 0.73 ± 0.12 and 0.052 ± 0.023, respectively, for focal plans. The CN and HI between the two plans were not significantly different. Response rates in 13 patients with follow-up imaging were approximately 90% for both plans and the local control rate at 1 year was 69%. One patient with a huge tumor (34.0 cc) and WHO performance status 3 treated with focal plans experienced severe headache, requiring prolongation of the treatment time, and died at 8 days after completion of treatment. The exact cause of deterioration was uncertain as no radiological investigation was performed in this patient. No late complications were observed during follow-up periods up to 20 months. HT is a viable non-invasive technique for treatment of brain metastases and achieves high accuracy in terms of dose conformity and homogeneity.
Consistency Check of Planned Adaptive® Option on Helical Tomotherapy
Authors: Schirm Maximilien , Yartsev Slav , Bauman Glenn , Battista Jerry , Van Dyk Jake
Published: October 2014

This study aims to evaluate a new Planned Adaptive® software (TomoTherapy Inc., Madison, WI) of the helical tomotherapy system by retrospective verification and adaptive re-planning of radiation treatment. Four patients with different disease sites (brain, nasal cavity, lungs, prostate) were planned in duplicate using the diagnostic planning kVCT data set and MVCT studies of the first treatment fraction with the same optimization parameters for both plan types. The dosimetric characteristics of minimum, maximum, and mean dose to the targets as well as to organs at risk were compared. Both sets of plans were used for calculation of dose distributions in a water-equivalent phantom. Corresponding measurements of these plans in phantom were carried out with the use of radiographic film and ion chamber. In the case of the lung and prostate cancer patients, changes in dosimetric parameters compared to data generated with the kVCT study alone were less than 2%. Certain changes for the nasal cavity and brain cancer patients were greater than 2%, but they were explained in part by anatomy changes that occurred during the time between kVCT and MVCT studies. The Planned Adaptive software allows for adaptive radiotherapy planning using the MVCT studies obtained by the helical tomotherapy imaging system.
Dose Escalated, Hypofractionated Radiotherapy Using Helical Tomotherapy for Inoperable Non-Small Cell Lung Cancer: Preliminary Results of a Risk-Stratified Phase I Dose Escalation Study
Authors: Adkison Jarrod B. , Khuntia Deepak , Bentzen Søren M. , Cannon George M. , Tome Wolfgang A. , Jaradat Hazim , Walker Wendy , Traynor Anne M. , Weigel Tracey , Mehta Minesh P.
Published: October 2014

To improve local control for inoperable non-small cell lung cancer (NSCLC), a phase I dose escalation study for locally advanced and medically inoperable patients was devised to escalate tumor dose while limiting the dose to organs at risk including the esophagus, spinal cord, and residual lung. Helical tomotherapy provided image-guided IMRT, delivered in a 5-week hypofractionated schedule to minimize the effect of accelerated repopulation.

Forty-six patients judged not to be surgical candidates with Stage I-IV NSCLC were treated. Concurrent chemotherapy was not allowed. Radiotherapy was delivered via helical tomotherapy and limited to the primary site and clinically proven or suspicious nodal regions without elective nodal irradiation. Patients were placed in 1 of 5 dose bins, all treated for 25 fractions, with dose per fraction ranging from 2.28 to 3.22 Gy. The bin doses of 57 to 80.5 Gy result in 2 Gy/fraction normalized tissue dose (NTD) equivalents of 60 to 100 Gy. In each bin, the starting dose was determined by the relative normalized tissue mean dose modeled to cause < 20% Grade 2 pneumonitis. Dose constraints included spinal cord maximum NTD of 50 Gy, esophageal maximum NTD < 64 Gy to ≤ 0.5 cc volume, and esophageal effective volume of 30%.

No grade 3 RTOG acute pneumonitis (NCI-CTC v.3) or esophageal toxicities (CTCAE v.3.0 and RTOG) were observed at median follow-up of 8.1 months. Pneumonitis rates were 70% grade 1 and 13% grade 2. Multivariate analysis identified lung NTDmean (p=0.012) and administration of adjuvant chemotherapy following radiotherapy (p=0.015) to be independent risk factors for grade 2 pneumonitis. Only seven patients (15%) required narcotic analgesics (RTOG grade 2 toxicity) for esophagitis, with only 2.3% average weight loss during treatment. Best in-field gross response rates were 17% complete response, 43% partial response, 26% stable disease, and 6.5% in-field thoracic progression. The out-of-field thoracic failure rate was 13%, and distal failure rate was 28%. The median survival was 18 months with 2-year overall survival of 46.8% ± 9.7% for this cohort, 50% of whom were stage IIIB and 30% stage IIIA.

Dose escalation can be safely achieved in NSCLC with lower than expected rates of pneumonitis and esophagitis using hypofractionated image-guided IMRT. The maximum tolerated dose has yet to be reached.
Review: Optical Micrometer Resolution Scanning for Non-invasive Grading of Precancer in the Human Uterine Cervix
Authors: Bazant-Hegemark Florian , Edey Katharine , Swingler Gordon R. , Read Mike D. , Stone Nicholas
Published: October 2014

Management of cervical precancer is archetypal for other cancer prevention programmes but has to consider diagnostic and logistic challenges. Numerous optical tools are emerging for non-destructive near real-time early diagnosis of precancerous lesions of the cervix. Non-destructive, real-time imaging modalities have reached pre-commercial status, but high resolution mapping tools are not yet introduced in clinical settings. The NCBI PubMed web page was searched using the keywords ‘CIN diagnosis’ and the combinations of ‘cervix {confocal, optical coherence tomography, ftir, infrared, Raman, vibrational, spectroscopy}’. Suitable titles were identified and their relevant references followed. Challenges in precancer management are discussed. The following tools capable of non-destructive high resolution mapping in a clinical environment were selected: confocal microscopy, optical coherence tomography, IR spectroscopy, and Raman spectroscopy. Findings on the clinical performance of these techniques are put into context in order to assist the reader in judging the likely performance of these methods as diagnostic tools. Rationale for carrying out research under the prospect of the HPV vaccine is given.
Comparison of the Helical Tomotherapy and MLC-based IMRT Radiation Modalities in Treating Brain and Cranio-spinal Tumors
Authors: Mavroidis Panayiotis , Ferreira Brigida Costa , Shi Chengyu , Delichas Miltiadis G. , Lind Bengt K. , Papanikolaou Nikos
Published: October 2014

The investigation of the clinical efficacy and effectiveness of Intensity Modulated Radiotherapy (IMRT) using Multileaf Collimators (MLC) and Helical Tomotherapy (HT) has been an issue of increasing interest over the past few years. In order to assess the suitability of a treatment plan, dosimetric criteria such as dose-volume histograms (DVH), maximum, minimum, mean, and standard deviation of the dose distribution are typically used. Nevertheless, the radiobiological parameters of the different tumors and normal tissues are often not taken into account. The use of the biologically effective uniform dose (D̿) together with the complication-free tumor control probability ( P+) were applied to evaluate the two radiation modalities.

Two different clinical cases of brain and cranio-spinal axis cancers have been investigated by developing a linac MLC-based step-and-shoot IMRT plan and a Helical Tomotherapy plan. The treatment plans of the MLC-based IMRT were developed on the Philips treatment planning station using the Pinnacle 7.6 software release while the dedicated Tomotherapy treatment planning station was used for the HT plan. With the use of the P+ index and the D̿ concept as the common prescription point, the different treatment plans were compared based on radiobiological measures. The tissue response probabilities were plotted against D̿ for a range of prescription doses.

The applied plan evaluation method shows that in the brain cancer, the HT treatment gives slightly better results than the MLC-based IMRT in terms of optimum expected clinical outcome ( P+ of 66.1% and 63.5% for a D̿ to the PTV of 63.0 Gy and 62.0 Gy, respectively). In the cranio-spinal axis cancer, the HT plan is significantly better compared to the MLC-based IMRT plan over the clinically useful dose prescription range ( P+ of 84.1% and 28.3% for a D̿ to the PTV of 50.6 Gy and 44.0 Gy, respectively). If a higher than 5% risk for complications could be allowed, the complication-free tumor control could be increased by almost 30% compared to the initial dose prescription.

In comparison to MLC based-IMRT, HT can better encompass the often large PTV while minimizing the volume of the OARs receiving high dose. A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose-response relations of the irradiated tumors and normal tissues. The use of P — D̿ diagrams can complement the traditional tools of evaluation such as DVHs, in order to compare and effectively evaluate different treatment plans.
Megavoltage Computed Tomography Image-based Low-dose Rate Intracavitary Brachytherapy Planning for Cervical Carcinoma
Authors: Wagner Thomas H. , Langen Katja M. , Meeks Sanford L. , Willoughby Twyla R. , Zeidan Omar A. , Staton Robert J. , Shah Amish P. , Manon Rafael R. , Kupelian Patrick A.
Published: October 2014

Initial results of megavoltage computed tomography (MVCT) brachytherapy treatment planning are presented, using a commercially available helical tomotherapy treatment unit and standard low dose rate (LDR) brachytherapy applicators used for treatment of cervical carcinoma. The accuracy of MVCT imaging techniques, and dosimetric accuracy of the CT based plans were tested with in-house and commercially-available phantoms. Three dimensional (3D) dose distributions were computed and compared to the two dimensional (2D) dosimetry results. Minimal doses received by the 2 cm3 of bladder and rectum receiving the highest doses (DB2cc and DR2cc, respectively) were computed from dose-volume histograms and compared to the doses computed for the standard ICRU bladder and rectal reference dose points. Phantom test objects in MVCT image sets were localized with sub-millimetric accuracy, and the accuracy of the MVCT-based dose calculation was verified. Fifteen brachytherapy insertions were also analyzed. The ICRU rectal point dose did not differ significantly from DR2cc (p=0.749, mean difference was 24 cGy ± 283 cGy). The ICRU bladder point dose was significantly lower than the DB2cc (p=0.024, mean difference was 291 cGy ± 444 cGy). The median volumes of bladder and rectum receiving at least the corresponding ICRU reference point dose were 6.1 cm3 and 2.0 cm3, respectively. Our initial experience in using MVCT imaging for clinical LDR gynecological brachytherapy indicates that the MVCT images are of sufficient quality for use in 3D, MVCT-based dose planning.
Assessing Four-dimensional Radiotherapy Planning and Respiratory Motion-induced Dose Difference Based on Biologically Effective Uniform Dose
Authors: Su Fan-Chi , Shi Chengyu , Mavroidis Panayiotis , Goytia Virginia , Crownover Richard , Rassiah-Szegedi Prema , Papanikolaou Niko
Published: October 2014

Four-dimensional (4D) radiotherapy is considered as a feasible and ideal solution to accommodate intra-fractional respiratory motion during conformal radiation therapy. With explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy, 4D treatment planning in principle provides better dose conformity. However, the clinical benefits of developing 4D treatment plans in terms of tumor control rate and normal tissue complication probability as compared to other treatment plans based on CT images of a fixed respiratory phase remains mostly unproven. The aim of our study is to comprehensively evaluate 4D treatment planning for nine lung tumor cases with both physical and biological measures using biologically effective uniform dose (D̿) together with complication-free tumor control probability, P+. Based on the examined lung cancer patients and PTV margin applied, we found similar but not identical curves of DVH, and slightly different mean doses in tumor (up to 1.5%) and normal tissue in all cases when comparing 4D, P0%, and P50% plans. When it comes to biological evaluations, we did not observe definitively PTV size dependence in P+ among these nine lung cancer patients with various sizes of PTV. Moreover, it is not necessary that 4D plans would have better target coverage or higher P+ as compared to a fixed phase IMRT plan. However, on the contrary to significant deviations in P+ (up to 14.7%) observed if delivering the IMRT plan made at end-inhalation incorrectly at end-exhalation phase, we estimated the overall P+, PB, and PI for 4D composite plans that have accounted for intra-fractional respiratory motion.
Biochemical Control and Toxicity after Intensity-Modulated Radiation Therapy for Prostate Cancer
Authors: Liauw Stanley L. , Weichselbaum Ralph R. , Rash Carla , Correa David , Al-Hallaq Hania A. , Pelizzari Charles A. , Jani Ashesh B.
Published: October 2014

Intensity modulated radiation therapy (IMRT) has achieved widespread use for prostate cancer; however, in relation to this use, outcomes studies are still relatively sparse. We report a single-institutional experience in outcomes analysis with the use of IMRT for the primary management of prostate cancer. One hundred thirty consecutive patients with adenocarcinoma of the prostate were treated at a single institution using IMRT with curative intent. Thirty-six (28%) patients were classified as low-risk, 69 (53%) as intermediate-risk, and 25 (19%) as high-risk. The median dose prescription was 76 Gy to the planning target volume. Sixty-five (50%) patients received androgen deprivation therapy (ADT) for a median 4 months, starting 2 months prior to IMRT. Biochemical failure was defined as PSA > post-treatment nadir+2. Gastrointestinal (GI) and Genitourinary (GU) toxicity were defined by RTOG criteria. Median follow-up was 53 months. By NCCN risk category, 4-year biochemical control was 97%, 94%, and 87% for low, intermediate, and high-risk patients, respectively. Among disease factors, multivariable analysis demonstrated the strongest association between biochemical control and Gleason score ≤6 (p=0.0371). Therapy was well tolerated with no Grade 4 toxicity and limited grade 3 GI or GU toxicity. Acute Grade 3+ GI and GU toxicity rates were 0% and 2%, and maximal late Grade 3+ GI and GU toxicity rates were 5% and 6%, respectively. Late rectal toxicity was associated with higher volumes of RT to the rectum. By last follow-up late Grade 3+ toxicity was 2% for both GI and GU systems. In conclusion, patients treated with IMRT for prostate cancer have excellent rates of biochemical control and low rates of severe toxicity of treatment.
The Correlation between GPR30 and Clinicopathologic Variables in Breast Carcinomas
Authors: Tu Gang , Hu Dingrong , Yang Guanglun , Yu Tinghe
Published: October 2014

The G-protein-coupled-receptor 30 (GPR30) is a new membrane estrogen receptor. The aim of the present study was to determine the correlations among GPR30, ERα, PR, C-erbB-2, p53, TNM stage, and pathologic grade in breast carcinomas. Two hundred forty-one biopsy specimens were evaluated with immunohistochemical assays, and then correlations were analyzed. Low negative correlations of GPR30 with ERα ( r = −0.144, P<0.05) and PR ( r = −0.214, P<0.01) were observed. Associations of GPR30 with C-erbB-2, p53, TNM stage, and pathologic grade were not confirmed. These findings indicated that GPR30 might be an independent prognostic factor in breast carcinomas.
A Comparison of Treatment Plans using Linac-Based Intensity-Modulated Radiation Therapy and Helical Tomotherapy for Maxillary Sinus Carcinoma
Authors: Kim Songyih , Lee Ik Jae , Kim Yong Bae , Koom Woong Sub , Jeon Byeong Chul , Lee Chang Geol , Kim Gwi Eon , Keum Ki Chang
Published: October 2014

This study evaluated whether helical tomotherapy (TOMO) planning could achieve better isodose distribution for the maxillary sinus while concomitantly sparing the adjacent critical normal organs than linac-based step-and-shoot IMRT (s-IMRT) planning. TOMO and s-IMRT were established for 10 patients with maxillary sinus cancer. The prescription (66 Gy, 30 fractions) was used to cover the planning target volume (PTV) with a 95% isodose line. Each plan was independently optimized using the CORVUS planning system and Tomotherapy Hi-Art system. The treatment plans were compared using dose volume histogram (DVH), a dose homogeneity index (DHI) of the PTV, and equivalent uniform dose (EUD) and DVH of organs at risk (OARs). The TOMO plans demonstrated better dose homogeneity compared to the s-IMRT plans. The average V95% of the TOMO plans was similar to that of the s-IMRT (92.92% vs. 95.07%, respectively), but the average V107% was 0% for TOMO compared with 18.74% for s-IMRT. The average maximum dose reduction was 7 Gy, and DHI increased by 8% for PTV1 in TOMO compared with s-IMRT (79 Gy vs. 71 Gy and, 89% vs. 97%, respectively). The average EUD reduction for the optic nerve was 17%. In summary, planning with TOMO was superior to s-IMRT planning with respect to dose homogeneity within the PTV and sparing of the optic nerve.
Stereotactic Body Radiosurgery for Pelvic Relapse of Gynecologic Malignancies
Authors: Kunos Charles , Chen William , DeBernardo Robert , Waggoner Steven , Brindle James , Zhang Yuxia , Williams Jordanna , Einstein Douglas
Published: October 2014

Clinical management of pelvic relapses from gynecologic malignancies remains challenging. Bulky pelvic relapses often lead to symptomatic cancer-related complications and poor clinical outcomes. Options may be limited by prior surgical, chemotherapeutic, and radiation treatment. Stereotactic body radiosurgery is a novel treatment modality which allows high radiation dose delivery in a non-coplanar fashion with sub-millimeter precision utilizing a linear accelerator mounted on a robotic arm. This study details our clinical experience with stereotactic body radiosurgery for treatment of patients with pelvic relapses of gynecologic malignancies after prior pelvic radiation.
On the Estimation of the Location of the Hippocampus in the Context of Hippocampal Avoidance Whole Brain Radiotherapy Treatment Planning
Authors: Bender Edward T. , Mehta Minesh P. , Tomé Wolfgang A.
Published: October 2014

We demonstrate a technique for estimating the location of the hippocampus in MRI and CT images for use in radiotherapy treatment planning, using both rigid and contour based deformable image registration. The automatically generated contours can be subsequently modified for a given patient. By mapping the hippocampi from several patients into a template image set, a population-based average hippocampal atlas was generated. Approximate hippocampal contours can be automatically generated in a given image set by mapping this atlas onto it. The performance and accuracy of several atlases generated in different ways was tested on 10 MRI images and 7 CT images. Auto-contouring based on deformable registration significantly outperformed that based on rigid registration alone, with an average Dice similarity score of 0.62 (range .40–.76) for methods utilizing deformation. Comparable results were achieved in auto-contouring CT images when deformable registration was used, demonstrating that the methodology is robust with respect to imaging modality.
Combined PET/MR Imaging — Technology and Applications
Authors: Wehrl H. F. , Sauter A. W. , Judenhofer M. S. , Pichler B. J.
Published: October 2014

The combination of PET and MR in one imaging device has certain advantages over conventional imaging modalities. These include: no additional radiation dose from the MR, superior soft tissue contrast and a multitude of tracers for PET. Certain technical challenges exist when designing a PET/MR system. On the one hand these stem from the presence of the strong MR magnetic field and the addition of PET components to the MR system. Different approaches are presented to overcome these technical obstacles ranging from long optical fibers to systems that use semiconductor light detectors for photon counting. The applications of combined PET/MR are profound in the field of oncology and allow imaging of the four main processes in cancer formation: apoptosis resistance, angiogenesis, proliferation and metastasis. PET/MR has also many clinical and research applications in neurology and cardiology. Alternative techniques such as image fusion, hyperpolarized imaging, 17 O imaging and whole body diffusion are discussed in respect to their relevance regarding PET/MR. Simultaneous multifunctional and anatomical imaging using PET/MR has a great potential to impact biomedical imaging in research and clinic.
Initial Investigation of Preclinical Integrated SPECT and MR Imaging
Authors: Hamamura Mark J. , Ha Seunghoon , Roeck Werner W. , Wagenaar Douglas J. , Meier Dirk , Patt Bradley E. , Nalcioglu Orhan
Published: October 2014

Single-photon emission computed tomography (SPECT) can provide specific functional information while magnetic resonance imaging (MRI) can provide high-spatial resolution anatomical information as well as complementary functional information. In this study, we utilized a dual modality SPECT/MRI (MRSPECT) system to investigate the integration of SPECT and MRI for improved image accuracy. The MRSPECT system consisted of a cadmiumzinc-telluride (CZT) nuclear radiation detector interfaced with a specialized radiofrequency (RF) coil that was placed within a whole-body 4 T MRI system. The importance of proper corrections for non-uniform detector sensitivity and Lorentz force effects was demonstrated. MRI data were utilized for attenuation correction (AC) of the nuclear projection data and optimized Wiener filtering of the SPECT reconstruction for improved image accuracy. Finally, simultaneous dual-imaging of a nude mouse was performed to demonstrated the utility of co-registration for accurate localization of a radioactive source.