bluuebunny/crossref_metadata_2025 huggingface dataset:
Intensity-Modulated Radiation Therapy (IMRT) for Newly Diagnosed and Recurrent Intracranial Meningiomas: Preliminary Results
Authors: Sajja Ratna , Barnett Gene H. , Lee Shih-Yuan , Harnisch Gayle , Stevens Glen H. J. , Lee Joung , Suh John H.
Published: October 2014

The purpose of this study was to evaluate tumor control, complications, and outcome from intensity-modulated radiation therapy (IMRT) for intracranial meningiomas. Between July 1997 and November 2003, patients with intracranial meningiomas were treated at our institution with the NOMOS Peacock system utilizing the Multileaf Intensity Modulating Collimator (MIMiC). Thirty-five patients with 37 lesions (35 benign and two atypical histology) were identified with a minimum of six months of radiologic follow-up for this retrospective review. The median age of the patients was 65 years with a median KPS of 90 prior to treatment with IMRT. The median MRI/CT follow-up for the 37 treated lesions was 19.1 months (range 6.4–62.4 months). Twenty meningiomas (54%) were previously treated with surgery/radiosurgery prior to IMRT, and 17 meningiomas (46%) were treated with IMRT primarily after diagnosis was established by MRI/CT. The median time from previous surgery to treatment with IMRT was 18.1 months. The median tumor dose was 50.4 Gy prescribed to the 87% isodose line providing a median target coverage of 95%. Local control was at 97% three years after treatment with IMRT. Only three patients exhibited local failure after treatment. Although local control was slightly better in the upfront-IMRT lesions as compared to the lesions treated with prior surgery/radiosurgery (100% vs 95%), this difference was not statistically significant. On univariate analysis, the IMRT prescription dose and maximum dose were found to be predictors for local control (p=0.05). On multivariate analysis, these factors did not remain significant for influencing local control. No long-term complications from IMRT were documented among the 35 patients. In conclusion, intensity-modulated radiation therapy is a safe and effective treatment for some intracranial meningiomas. A greater number of patients with longer follow-up after treatment may be needed to determine treatment variables predicting for long-term tumor control.
The Use of Tyrosine Kinase Inhibitors in Modifying the Response of Tumor Microvasculature to Radiotherapy
Authors: Lu Bo , Shinohara Eric T. , Edwards Eric , Geng Ling , Tan Jiahuai , Hallahan Dennis E.
Published: October 2014

The response of the tumor microvasculature to ionizing radiation can be modified to improve tumor control in preclinical mouse models of cancer. Recent studies have shown that a variety of cancer drugs can improve the response of cancers to radiotherapy. Protein tyrosine kinase inhibitors (TKIs) have been shown to enhance radiation-induced destruction of tumor blood vessels. Among these compounds are inhibitors of a broad spectrum of receptor tyrosine kinases (RTKs). Inhibition of RTKs attenuates downstream signaling from various angiogenic growth factors, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). RTK inhibitors with various specificities against the receptors for VEGF, PDGF, and FGF manifest significant antiangiogenic activities as well. We have shown using tumor vascular window model and tumor growth delay assays that these compounds can enhance tumor radiation response by attacking tumor microvasculature. Furthermore, we have shown that radiation and RTK inhibitors exert their antiangiogenic effect through inhibition of the PI3K/Akt signaling pathway, which results in induction of apoptosis. Our studies have provided a basis for future clinical investigations of combining radiotherapy and RTK inhibitors.
Ultrasound: A Chemotherapy Sensitizer
Authors: Yu Tinghe , Li Shugang , Zhao Jie , Mason Timothy J.
Published: October 2014

Chemotherapy plays a very important role in cancer treatment. However, there are still some barriers in the successful use of such therapies, mainly because of the adverse side effects of the anticancer agents and due to the development of chemoresistance. This paper focuses on the use of ultrasound to enhance chemotherapy and to overcome drug resistance. The action of many anticancer agents can be improved with the use of ultrasonic exposure either in vitro or in vivo. Drug resistance can be circumvented using ultrasound alone. Furthermore, the reversal attributable to chemoresistance modifiers, such as verapamil and PSC 833, is augmented by ultrasound. Ultrasound-mediated chemosensitization is usually achieved via increasing intracellular drug accumulation, although other mechanisms are also involved. Ultrasound also can play a role in targeted chemotherapy, releasing anticancer chemicals directly and efficiently into the lesions. However, this promising modality has not been clinically adopted so far and the reasons are discussed.
Clinical Applications of Proton Radiation Treatment at Loma Linda University: Review of a Fifteen-year Experience
Authors: Slater Jerry D.
Published: October 2014

Proton radiation therapy has been used at Loma Linda University Medical Center for 15 years, sometimes in combination with photon irradiation, surgery, and chemotherapy, but often as the sole modality. Our initial experience was based on established studies showing the utility of protons for certain management problems, but since then we have engaged in a planned program to exploit the capabilities of proton radiation and expand its applications in accordance with progressively accumulating clinical data. Our cumulative experience has confirmed that protons are a superb tool for delivering conformal radiation treatments, enabling delivery of effective doses of radiation and sparing normal tissues from radiation exposure.
Issues Critical to the Successful Application of Cryosurgical Ablation of the Prostate
Authors: Baust J. G. , Gage A. A. , Klossner D. , Clarke D. , Miller R. , Cohen J. , Katz A. , Polascik T. , Clarke H. , Baust J. M.
Published: October 2014

The techniques of present-day cryosurgery performed with multiprobe freezing apparatus and advanced imaging techniques yield predictable and encouraging results in the treatment of prostatic and renal cancers. Nevertheless, and not unique to cryosurgical treatment, the rates of persistent disease demonstrate the need for improvement in technique and emphasize the need for proper management of the therapeutic margin. The causes of persistent disease often relate to a range of factors including selection of patients, understanding of the extent of the tumor, limitations of the imaging techniques, and failure to freeze the tumor periphery in an efficacious manner. Of these diverse factors, the one most readily managed, but subject to therapeutic error, is the technique of freezing the tumor and appropriate margin to a lethal temperature [Baust, J. G., Gage, A. A. The Molecular Basis of Cryosurgery. BJU Int 95, 1187–1191 (2005)]. This article describes the recent experiments that examine the molecular basis of cryosurgery, clarifies the actions of the components of the freeze-thaw cycle, and defines the resultant effect on the cryogenic lesion from a clinical perspective. Further, this review addresses the important issue of management of the margin of the tumor through adjunctive therapy. Accordingly, a goal of this review is to identify the technical and future adjunctive therapeutic practices that should improve the efficacy of cryoablative techniques for the treatment of malignant lesions.
Imaging Guided Percutaneous Irreversible Electroporation: Ultrasound and Immunohistological Correlation
Authors: Lee Edward W. , Loh Christopher T. , Kee Stephen T.
Published: October 2014

Preliminary results of percutaneous irreversible electroporation (PIE) on swine liver as a novel non-thermal ablation are presented. The goal of this study was to evaluate the feasibility of using irreversible electroporation in more clinically applicable manner, a percutaneous method, and to investigate a possible role of apoptosis in PIE-induced cell death. We performed PIE on four swine livers under real-time ultrasound guidance. The lesions created by PIE were imaged with ultrasound and were correlated with histology data, including pro-apoptotic marker. A total of 11 lesions were created with a mean size of 16.8 cm3 in 8.4 ± 1.8 minutes. Real-time monitoring was performed and a correlation of (+) 2 ± 3.2 mm in measurement comparison between ultrasound and gross pathologic measurements was demonstrated. Complete hepatic cell death without structural destruction, unaffected by heat-sink effect, and with a sharp demarcation between the ablated zone and the non-ablated zone were observed. Immunohistological analysis confirmed complete apoptotic cell death by PIE on Von Kossa, BAX, and H&E staining. In summary, PIE can provide a novel and unique ablative method with real-time monitoring capability, ultra-short procedure time, non-thermal ablation, and well-controlled and focused apoptotic cell death.
Irreversible Electroporation: Implications for Prostate Ablation
Authors: Onik Gary , Mikus Paul , Rubinsky Boris
Published: October 2014

Percutaneous prostate cryo-ablation has become an accepted treatment for primary prostate cancer. Thermal tissue ablation based on cold, however, does have some distinct limitations. These include, variable damage at the cryo lesions margin, injury to adjacent structures such as rectum, urethra and NVB (neurovascular bundle), and long procedure time due to the need for multiple freeze thaw cycles, that have limited the acceptance of this modality. Irreversible electroporation IRE, is a new non-thermal ablation modality that uses short pulses of DC electric current to create irreversible pore in the cell membrane, thus, causing cell death. This method theoretically should have significant advantages in ablating prostate tissue.

Six males dogs had their prostates treated using IRE. Pulses were applied using a DC generator that delivered pulses in the microsecond range of duration, with a variable pulse interval and voltage range. IRE probes were placed percutaneously or trans-rectally using trans-rectal ultrasound guidance. In one of the dogs, the lesions were made purposely to include the rectum, urethra, and neurovascular bundle (NVB). Subjects were followed for 1 to 14 days before sacrifice.

IRE lesions in the prostate had unique characteristics compared to thermal lesions. The margins of the IRE lesions was very distinct with a narrow zone of transition from normal to complete necrosis, there was complete destruction within the IRE lesion, and rapid resolution of the lesions with marked shrinkage within two weeks. Structures such as urethra, vessels, nerves, and rectum were unaffected by the IRE application.

IRE lesions have characteristics that are distinctly different than thermal lesions. The differences could be very advantageous in a clinical setting, improving the results and acceptance of prostate ablation.
Potential Value of MR Spectroscopic Imaging for the Radiosurgical Management of Patients with Recurrent High-Grade Gliomas
Authors: Chuang Cynthia F. , Chan Antoinette A. , Larson David , Verhey Lynn J. , McDermott Michael , Nelson Sarah J. , Pirzkall Andrea
Published: October 2014

Previous studies have shown that metabolic information provided by 3D Magnetic Resonance Spectroscopy Imaging (MRSI) could affect the definition of target volumes for radiation treatments (RT). This study aimed to (i) investigate the effect of incorporating spectroscopic volumes as determined by MRSI on target volume definition, patient selection eligibility, and dose prescription for stereotactic radiosurgery treatment planning; (ii) correlate the spatial extent of pre-SRS spectroscopic abnormality and treatment volumes with areas of focal recurrence as defined by changes in contrast enhancement; and (iii) examine the metabolic changes following SRS to assess treatment response. Twenty-six patients treated with Gamma Knife radiosurgery for recurrent glioblastoma multiforme (GBM) were retrospectively evaluated. All patients underwent both MRI and MRSI studies prior to SRS. Follow-up MRI exams were available for all 26 patients, with MRI/MRSI available in only 15/26 patients. We observed that the initial CNI 2 contours extended beyond the pre-SRS CE in 25/26 patients ranging in volume from 0.8 cc to 18.8 cc (median 5.6 cc). The inclusion of the volume of CNI 2 extending beyond the CE would have increased the SRS target volume by 5–165% (median 23.4%). This would have necessitated decreasing the SRS prescription dose in 19/26 patients to avoid increased toxicity; the resultant treatment volume would have exceeded 20cc in five patients, thus possibly excluding those from RS treatment per our institutional practice. MRSI follow-up studies showed a decrease in Choline, stable Creatine, and increased NAA indicative of response to SRS in the majority of patients. When combined with patient survival data, metabolic information obtained during follow-up MRSI studies seemed to indicate the potential to help to distinguish necrosis from new/recurrent tumor; however, this should be further verified by biopsy studies.
Validity of Sentinel Lymph Node (SLN) Detection following Adjuvant Radiochemotherapy (RCT) in Head and Neck Squamous Cell Carcinoma (HNSCC)
Authors: Wagner Arne , Kermer Christian , Zettinig Georg , Lang Susanna , Schicho Kurt , Noebauer Iris , Kainberger Franz , Selzer Edgar , Leitha Thomas
Published: October 2014

The effect of preoperative radio chemotherapy on lymphatic drainage and intraoperative gamma probe-guided sentinel lymph node detection has yet not been investigated. In this study, we study 13 patients with SCC. Sentinel lymph node (SLN) imaging of the patients was performed using SPECT-CT. Special care was taken to use identical injection sites for both studies. Imaging comprised planar and SPECT, iterative reconstruction and were viewed with the co-registered CT image. The results were validated by comparison with the histological results of intraoperative gamma probe detection and histology of the completed neck dissection. Identical SLNs were found in 6/13 patients. In 2/13 cases SLN biopsies were false-negative. In 4/13 patients preoperative SLN imaging identified more/additional nodes than the initial imaging, whereas fewer nodes were seen in 3/13 patients. Neither the primary tumor site nor the TNM stage was predictive for changes in the lymphatic drainage pattern. No constant effect of irradiation could be demonstrated. Preoperative radio chemotherapy has an unpredictable influence on the lymphatic drainage pattern in HNSCC. Consequently, the intraoperative gamma probe-guided sentinel lymph node detection after radio chemotherapy does not reveal the SLN of carcinogenesis. Thus, we advise fused functional/anatomical imaging (SPECT-CT) before and after radiochemotherapy if the SLN concept is utilized in HNSCC.
The Effect of Respiratory Motion on Forward Intensity Modulated Radiotherapy for Breast Cancer
Authors: Song Taesoo , Suh Chang-Ok , Lee Ikjae , Jeong Kyoungkeun , Keum Kichang , Lee Chang Geol , Seong Jinsil , Cho Jae Ho
Published: October 2014

This study evaluated the effect of respiratory movement on field-in-field (FIF) forward intensity-modulated radiotherapy (IMRT) for the treatment of breast cancer. FIF forward IMRT was performed on ten patients receiving radiotherapy to the whole breast after conservation surgery. Assuming that breast motion follows a sophisticated cyclic function, the changes in hot and cold region, dose homogeneity index (DHI), and skin dose were examined at different respiration amplitudes of 1 cm, 2 cm, and 3 cm. FIF forward IMRT significantly improved the hot region, DHI, and skin dose, but slightly worsened the cold region, compared to the two wedged tangential technique (TWT). Interestingly, we found that the respiration amplitude affected the DHI and cold region but had no effect on the hot region and skin dose. The DHI was slightly improved at 1 cm of amplitude probably due to the blurring effect, remained unchanged at 2 cm of amplitude, and was worsened at 3 cm of amplitude. FIF forward IMRT significantly increased the cold region at 2 cm and 3 cm of respiration amplitude compared to the TWT. At 3 cm of respiration amplitude, an average cold region of 3.27 cm3 was observed. In summary, our data indicate that during FIF forward IMRT, respiration movement has an important effect on various endpoints depending on the respiration amplitude of the patient.
Survival following CyberKnife Radiosurgery and Hypofractionated Radiotherapy for Newly Diagnosed Glioblastoma Multiforme
Authors: Lipani John D. , Jackson Paul S. , Soltys Scott G. , Sato Kengo , Adler John R.
Published: October 2014

Current therapeutic goals for treatment of Glioblastoma Multiforme (GBM) involve gross total resection followed by multifractionated focal external beam radiation therapy (EBRT). Patients treated with optimal therapy have a median survival of approximately 12–15 months. In the present study, we sought to determine whether a hypofractionated dosing schedule using CyberKnife is at least as effective as multifractionated focal EBRT. A retrospective analysis was conducted on 20 histopathologically confirmed GBM patients treated with CyberKnife at Okayama Kyokuto Hospital in Japan after gross total resection (n=11), subtotal resection (n=8), or biopsy (n=1). Eight patients also received adjuvant ACNU and Vincrisitine chemotherapy according to local protocol; however, no patient received any other form of radiation besides post surgical/biopsy CyberKnife treatment. The treated tumor volumes ranged from 9.62 cm3− 185.81 cm3 (mean: 86.08 cm3). The marginal dose (D90) ranged from 19.99 Gy-41.47 Gy (mean: 34.58 Gy) with a maximum mean dose of 43.99 Gy (range: 23.33 Gy-56.89 Gy). The prescribed isodose line ranged from 50.38%–85.68% with a mean of 79.25%. Treatment was delivered in 1–8 fractions (mean: 5.65). Patients were followed from 2–36 months (mean: 16.45 months). Overall median survival was 16 months with 55% of patients alive at 12 months and 34% of patients alive at 24 months. Median survival of patients in Recursive Partitioning Analysis (RPA) classes III or IV was 32 months versus 12 months for those in RPA class V. Median survival for patients who received gross total resection was 36 months versus 8 months for those who underwent subtotal resection or biopsy. The results of this study using CyberKnife stereotactic radiosurgery (SRS) and hypofractionated radiotherapy compared favorably to historic data using focal EBRT in newly diagnosed post surgical GBM patients. A larger prospective analysis that compares CyberKnife SRS and hypofractionated radiotherapy to focal EBRT is warranted.
The Performance of 17-gauge Cryoprobes In Vitro
Authors: Beemster Patricia W.T. , Lagerveld Brunolf W. , Witte Lambertus P. W. , de la Rosette Jean J. M. C. H. , Pes M. Pilar Laguna , Wijkstra Hessel
Published: October 2014

In cryosurgery it is crucial that the performance of cryoprobes is predictable and constant. In this study we tested the intra- and interneedle variation between 17-gauge cryoprobes in two homogeneous mediums. Also, a multiprobe setup was tested. Cryoprobe performance was defined as the time it takes one cryoprobe to lower the temperature from 0 to −20 °C as measured by four thermosensors each at 3 mm distance from the cryoprobe. In agar eight cryoprobes were tested during six freeze cycles, and in gel four cryoprobes during four freeze cycles; each freeze cycle in a different cup of agar or gel. Using more accurate ‘bare’ thermosensors three cryoprobes were tested in gel during two freeze cycles. A multiprobe configuration with four cryoprobes was tested during two freeze cycles in both agar and gel. Statistical analyses were done using ANOVA for repeated measures.

There was no significant intraneedle variation, whereas both in agar and gel there was a significant interneedle variation (p<0.05). Mean performance in gel was better than in agar (p<0.001). Also, there was a significant variation between the four thermosensors (p< 0.001). Using bare thermosensors mean performance was 2.7 times faster compared to measurements by regular thermosensors (p<0.001). In a multiprobe configuration, overall performance seems less variable and more reproducible compared to a single cryoprobe.

In conclusion, the performance of cryoprobes differs depending on the medium and measuring device used. Cryoprobes deliver reproducible freeze cycles, although there is variation between different cryoprobes. In a multiprobe configuration performance seems less variable.
Stereotactic Radiosurgery for a Cardiac Sarcoma: A Case Report
Authors: Soltys Scott G. , Kalani M. Yashar S. , Cheshier Samuel H. , Szabo Katalin A. , Lo Anthony , Chang Steven D.
Published: October 2014

Pulmonary artery intimal sarcoma is an uncommon tumor with a poor prognosis. We report a case of a 75-year-old man with a pulmonary artery sarcoma, recurrent following surgical resection. To palliate symptoms of this recurrence, he underwent CyberKnife stereotactic radiosurgery with a clinical and radiographic response of his treated disease. No acute or sub-acute toxicity was seen until the patient's death due to metastatic disease 10 weeks following treatment. The feasibility and short-term safety of this technique are reviewed, with emphasis on the stereotactic planning considerations, such as mediastinal organ movement and radiation tolerance.
A Monte Carlo Model for Independent Dose Verification in Serial Tomotherapy
Authors: Sarkar Vikren , Stathakis Sotirios , Papanikolaou Nikos
Published: October 2014

Due to the very high complexity of IMRT treatment plans, it is imperative to perform dose verification, preferably before patient delivery. The aim of this project is to develop a Monte-Carlo-based model to verify the final dose distributions of plans developed using the Peacock system (CORVUS Treatment Planning System and MIMiC collimator). The system delivers radiation through arc therapy and uses sinogram files to determine the state of each of the multileaf collimator leaves. In-house software was developed using Matlab to decode the sinograms and create blocklets that are used as input in an MCSIM model of the MIMiC collimator attached to a Varian Clinac 600C. After validating the model, a prostate and head and neck case were simulated. The CORVUS-predicted dose distributions were compared with the Monte Carlo dose distributions. As expected, the results agreed very closely for the homogeneous case of the prostate but there were large discrepancies observed for the more heterogeneous head and neck case.
Evaluation of Inter-fractional Setup Shifts for Site-specific Helical Tomotherapy Treatments
Authors: Lin Lan , Shi Chengyu , Eng Tony , Swanson Gregory , Fuss Martin , Papanikolaou Niko
Published: October 2014

This paper proposes to summarize and analyze the daily patient setup shifts based on megavoltage computed tomography (MVCT) image registration results for Helical TomoTherapy® (HT) treatment. One hundred and fifty-five consecutive treatment plans for a total of 137 patients delivered by the HT unit through one year were collected in this study. The patient data included pelvis (26%), abdomen (23%), lung (21%), head and neck (10%), prostate (8%), and others (12%). All the translational and roll rotational shifts made via auto MVCT and kilovoltage computed tomography (kVCT) image registration were recorded at each fraction. Manual fine-tuning was followed if automatic registration result was not satisfactory. The mean shift ± one standard deviation (1 SD) was calculated for each patient based on the entire treatment course. For each treatment site, the average shift was analyzed as well as displacement in 3D vector. Statistical tests were performed to analyze the relationship of patient-specific, tumor site-specific, and fraction number association with the patient setup shifts. For all the treatment sites, the largest average shift was found in the anterior-posterior direction. The population standard deviations were between 1.2 and 5.6 mm for the X, Y, and Z directions and ranged from 0.2 to 0.6 degrees for the roll rotational correction. The largest standard deviations of the setup reproducibility in X, Y, and Z directions were found in lung patients (4.2 mm), abdomen, lung and spine patients (4.4 mm), and prostate patients (5.6 mm), respectively. The maximum 3D displacement was 10.9 mm for prostate patients' setup. ANOVA tests demonstrated the setup shifts were statistically different between patients even for those that were treated at the same tumor site in the translational directions. No strong correlation between the setup and the fraction number was found. In conclusion, the MVCT guided function in the HT treatment enables us to generate relatively accurate daily setup through registration with KVCT data sets. Our results indicate that lung, prostate, and abdominal patients are more prone to setup uncertainty and should be carefully evaluated.
Technical Aspects of the Integration of Three-Dimensional Treatment Planning Dose Parameters (GEC-ESTRO Working Group) into Pre-implant Planning for LDR Gynecological Interstitial Brachytherapy
Authors: Chi Alexander , Gao Mingcheng , Nguyen Nam P. , Albuquerque Kevin
Published: October 2014

This study investigates the technical feasibility of pre-implant image-based treatment planning for LDR GYN interstitial brachytherapy(IB) based on the GEC-ESTRO guidelines. Initially, a virtual plan is generated based on the prescription dose and GEC-ESTRO defined OAR dose constraints with a pre-implant CT. After the actual implant, a regular diagnostic CT was obtained and fused with our pre-implant scan/initial treatment plan in our planning software. The Flexi-needle position changes, and treatment plan modifications were made if needed. Dose values were normalized to equivalent doses in 2 Gy fractions (LQED 2 Gy) derived from the linear-quadratic model with α/β of 3 for late responding tissues and α/β of 10 for early responding tissues. D90 to the CTV, which was gross tumor (GTV) at the time of brachytherapy with a margin to count for microscopic disease, was 84.7 ± 4.9% of the prescribed dose. The OAR doses were evaluated by D2cc (EBRT+IB). Mean D2cc values (LQED2Gy) for the rectum, bladder, sigmoid, and small bowel were the following: 63.7 ± 8.4 Gy, 61.2 ± 6.9 Gy, 48.0 ± 3.5 Gy, and 49.9 ± 4.2 Gy. This study confirms the feasibility of applying the GEC-ESTRO recommended dose parameters in pre-implant CT-based treatment planning in GYN IB. In the process, this pre-implant technique also demonstrates a good approximation of the target volume dose coverage, and doses to the OARs.
Sequential Treatment of Superior Vena Cava Syndrome Caused by of Non-small Cell Carcinoma Lung Cancer (NSCLC) with Vascular Stenting and Iodine-125 Implantation
Authors: Xiao Lianxiang , Li Zhenjia , Wu Lebin , Sun Zengtao , Yu Xianghong
Published: October 2014

Feasibility and efficacy of sequentially performed endovascular stenting and Iodine-125 brachytherapy for malignant superior vena cava syndrome (SVCS) were evaluated. Thirty-four patients with malignant SVCS caused by NSCLC underwent sequential treatment of endovascular stenting and Iodine-125 brachytherapy. SVCS was diagnosed in all patients by CT images or vena-cavography. Pathology diagnosis was acquired by image guided biopsy. Endovascular stent placement was performed as first-line treatment for symptom relief. CT-guided Iodine-125 seed implantation performed 24hr after stenting. Clinical end points were resolution of symptoms and local efficacy of primary malignancy regression. Symptom relief rate was >90% after 24hr and 97% after 3 months. No migration of seeds or restenosis occurred in any patient. The local efficacy (defined as either partial or complete response) was 53%, 79%, 88% and 74% after 1, 3, 6 and 12months, respectively. Mean SVCS-free survival time was 305 days (range 120–960 days). Two patients were still alive at the time of this writing, Thirty-one died from progression and one died from acute heart disease. Sequentially performed endovascular stenting and Iodine-125 brachytherapy provides a safe and effective alternative for malignant SVCS caused by NSCLC.
Stereotactic Radiosurgery for Trigeminal Neuralgia Utilizing the BrainLAB Novalis System
Authors: Zahra Hadi , Teh Bin S. , Paulino Arnold C. , Yoshor Daniel , Trask Todd , Baskin David , Butler E Brian
Published: October 2014

Stereotactic radiosurgery (SRS) is one of the least invasive treatments for trigeminal neuralgia (TN). To date, most reports have been about Cobalt-based treatments ( i.e., Gamma Knife) with limited data on image-guided stereotactic linear accelerator treatments. We describe our initial experience of using BrainLAB Novalis stereotactic system for the radiosurgical treatment of TN.

A total of 20 patients were treated between July 2004 and February 2007. Each SRS procedure was performed using the BrainLAB Novalis System. Thin cuts MRI images of 1.5 mm thickness were acquired and fused with the simulation CT of each patient. Majority of the patients received a maximum dose of 90 Gy. The median brainstem dose to 1.0 cc and 0.1 cc was 2.3 Gy and 13.5 Gy, respectively. In addition, specially acquired three-dimensional fast imaging sequence employing steady-state acquisition (FIESTA) MRI was utilized to improve target delineation of the trigeminal proximal nerve root entry zone. Barrow Neurological Index (BNI) pain scale for TN was used for assessing treatment outcome. At a median follow-up time of 14.2 months, 19 patients (95%) reported at least some improvement in pain. Eight (40%) patients were completely pain-free and stopped all medications (BNI Grade I) while another 2 (10%) patients also stopped medications but reported occasional pain (BNI Grade II). Another 2 (10%) patients reported no pain and 7 (35%) patients only occasional pain while continuing medications, BNI Grade IIIA and IIIB, respectively. Median time to pain control was 8.5 days (range: 1–70 days). No patient reported severe pain, worsening pain or any pain not controlled on their previously taken medication. Intermittent or persistent facial numbness following treatments occurred in 35% of patients. No other complications were reported. Stereotactic radiosurgery using the BrainLAB Novalis system is a safe and effective treatment for TN. This information is important as more centers are obtaining image-guided stereotactic-based linear accelerators capable of performing radiosurgery.
Using Artificial Neural Networks and Model Predictive Control to Optimize Acoustically Assisted Doxorubicin Release from Polymeric Micelles
Authors: Husseini Ghaleb A. , Mjalli Farouq S. , Pitt William G. , Abdel-Jabbar Nabil M.
Published: October 2014

We have been developing a drug delivery system that uses Pluronic P105 micelles to sequester a chemotherapeutic drug - namely, Doxorubicin (Dox) - until it reaches the cancer site. Ultrasound is then applied to release the drug directly to the tumor and in the process minimize the adverse side effects of chemotherapy on non-tumor tissues. Here, we present an artificial neural network (ANN) model that attempts to model the dynamic release of Dox from P105 micelles under different ultrasonic power intensities at two frequencies. The developed ANN model is then utilized to optimize the ultrasound application to achieve a target drug release at the tumor site via an ANN-based model predictive control. The parameters of the controller are then tuned to achieve good reference signal tracking. We were successful in designing and testing a controller capable of adjusting the ultrasound frequency, intensity, and pulse length to sustain constant Dox release.
Dual-Contrast Dynamic MRI-DOT for Small Animal Imaging
Authors: Thayer David , Unlu Mehmet Burcin , Lin Yuting , Yan Kevin , Nalcioglu Orhan , Gulsen Gultekin
Published: October 2014

In this paper we present first-of-its-kind spatially resolved enhancement kinetics of optical and magnetic resonance (MR) agents obtained by a combined MR and Diffuse Optical Tomography (MR-DOT) animal imaging system. A unique MR compatible fiber optic interface allows co-registration of MR and DOT data in space and time. High temporal resolution of the hybrid system permits acquisition of data in dynamic mode. Rats bearing a R3230 AC breast cancer tumor model are used for in vivo studies. Thirty-two optical and thirty MR images are acquired during a single imaging session that lasts nearly ten minutes. Both optical, indocyanine green (ICG), and MR contrast agents, gadolinium-DTPA (Gd-DTPA), are injected simultaneously after the acquisition of several baseline frames. Contrast enhancement time curves obtained by MR and DOT systems both indicate higher average enhancement in tumor regions, up to ten-fold for MRI and 3-fold for DOT, compared to close by non-tumor regions. This feasibility study is the first step towards clinical translation of this hybrid imaging platform. The ultimate aim is to use the enhancement kinetics of the optical agent ICG, which binds to plasma proteins, as complementary information to the kinetics of the MR agent Gd-DTPA, a small molecular agent that does not bind to plasma proteins, to better differentiate benign and malignant lesions.
Non-coding RNAs: Identification of Cancer-Associated microRNAs by Gene Profiling
Authors: Ferdin Jana , Kunej Tanja , Calin George A.
Published: October 2014

MicroRNAs (miRNAs) belong to the heterogeneous class of non-coding RNAs (ncRNAs), which are by definition RNA molecules that do not encode for proteins, but have instead important structural, catalytic or regulatory functions. In this review we first provide an overview of the different ncRNA families, focusing in particular on miRNAs and their relevance in tumour development and progression. Second we shortly describe the available ncRNA expression profiling methods, which comprise microarray, bead-based hybridization methods, in situ hybridization, quantitative real-time polymerase chain reaction, cloning and deep sequencing methods. Finally, we used the PubMed database to perform an extensive literature search for miRNA expression profiling research articles in cancer and identified 58 studies that were published between 2004 and 2009; we identified 70 miRNAs that were reported in at least five studies as being either up- or downregulated, depending on the type of cancer, and 192 miRNAs that were reported to be up- or downregulated in at least two reports. MiRNA expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis, and response to treatment. Based on the most important findings we discuss the possible use of miRNAs as clinical biomarkers in the management of cancer patients for diagnosis, prognosis, and response to therapy.
An Automatic Method for PET Target Segmentation Using a Lookup Table Based on Volume and Concentration Ratio
Authors: Zheng Yiran , Syh Joseph , Yao Min , Wessels Barry W.
Published: October 2014

Accurate evaluation of functionally significant target volumes in combination with anatomic imaging is of primary importance for effective radiation therapy treatment planning. In this study, a method for rapid and accurate PET image segmentation and volumetrics based on phantom measurements and independent of scanner calibration was developed. A series of spheres ranging in volume from 0.5 mL to 95 mL were imaged in an anthropomorphic phantom of human thorax using two commercial PET and CT/PET scanners. The target to background radioactivity concentration ratio ranged from 3:1 to 12:1 in 11 separate phantom scanning experiments. The results confirmed that optimal segmentation thresholding depends on target volume and radioactivity concentration ratio. This information can be derived from a generalized pre-determined “lookup table” of volume and contrast dependent threshold values instead of using fitted curves derived from machine specific information. A three-step method based on the PET image intensity information alone was used to delineate volumes of interest. First, a mean intensity segmentation method was used to generate an initial estimate of target volume, and the radioactivity concentration ratio was computed by a family of recovery coefficient curves to compensate for the partial volume effect. Next, the appropriate threshold value was obtained from a phantom-generated threshold lookup table. Lastly, a threshold level set method was performed on the threshold value to further refine the target contour by reducing the limitation of global thresholding. The segmentation results were consistent for spheres greater than 2.5 mL which yielded volume average uncertainty of 11.2% in phantom studies. The results of segmented volumes were comparable to those determined by contrast-oriented method and iterative threshold method (ITM). In addition, the new volume segmentation method was applied clinically to ten patients undergoing PET/CT volume analysis for radiation therapy treatment planning of solitary lung metastases. For these patients, the average PET segmented volumes were within 8.0% of the CT volumes and were highly dependent on the extension of functionally inactive tumor volume. In summary, the current method does not require fitted threshold curves or a priori knowledge of the CT/MRI target volume. This threshold method can be universally applied to radiation therapy treatment planning with comparable accuracy, and may be useful in the rapid identification and assessment of plans containing multiple targets.
Intracranial Radiosurgery in the Netherlands. A Planning Comparison of Available Systems with Regard to Physical Aspects and Workload
Authors: Schoonbeek A. , Monshouwer R. , Hanssens P. , Raaijmakers E. , Nowak P. , Marijnissen J. P. A. , Lagerwaard F. J. , Cuijpers J. P. , Vonk E. J. A. , van der Maazen R. W. M.
Published: October 2014

Different planning and treatment systems for intracranial stereotactic radiosurgery available in the Netherlands are compared. The systems for intracranial radiosurgery include: Gamma Knife, Cyberknife, Novalis, and Tomotherapy. Electronic data of 5 patients was transferred to all participating centres and treatment plans were generated according to 2 different prescription protocols. For this study, plans were also generated for a conventional linac. Even systems with a high resolution (Gammaknife and Novalis) have conformity indices in violation with RTOG guidelines (CI > 2.5) when target volumes of <0.5 cc are treated. For medium sized targets (0.5–1 cc) all systems performed reasonably well, but for the different systems a large range of conformity indices was seen (1.1 to 3.7). The differences are partly system dependent but depend also on specific planning choices made. For larger target volumes (>1 cc), all systems perform well. The workload of the different techniques was comparable although the treatment times were usually longer for Gamma Knife radiosurgery. We conclude that small targets should be treated by dedicated systems, larger volumes (>0.5–1 cc) can also be treated using conventional treatment systems equipped with a MLC.
Histopathologic Effects of Hypofractionated Robotic Radiation Therapy on Malignant and Benign Prostate Tissue
Authors: Suy Simeng , Oermann Eric , Hanscom Heather , Lei Sue , Vahdat Saloomeh , Yu Xia , Park Hyeon U , Chen Viola , Collins Brian T , McGeagh Kevin , Dawson Nancy , Jha Reena , Azumi Norio , Dritschilo Anatoly , Lynch John , Collins Sean P
Published: October 2014

We describe the first histopathologic analysis of prostatic tissue following hypofractionated robotic radiation therapy. A 66 year-old man presented with stage II, low risk adenocarcinoma of the prostate and underwent elective conformal hypofractionated radiation therapy. His pretreatment evaluation revealed T1c adenocarcinoma, Gleason's grade 3 + 3 = 6 and a prostate specific antigen (PSA) level of 4.87 ng/ml. Hypofractionated radiation therapy (37.5 Gy in five daily fractions of 7.5 Gy) was completed on an Internal Review Board approved protocol. One year later, he developed progressive urinary retention. Transurethral prostatic resection was performed to alleviate obstructive symptoms. Bilobar hypertrophy was observed without evidence of stricture. Histolopathologic analyses of resected prostate tissues revealed changes consistent with radiation treatment, including cellular changes, inflammation, glandular atrophy and hyperplasia. There was no evidence of residual cancer, fibrosis or necrosis. The patient's postoperative course was uneventful with post-treatment PSA of 0.5 ng/ml and residual grade 1 stress incontinence.
Tumor Bed Radiosurgery following Resection of Brain Metastases: A Review
Authors: Roberge David , Souhami Luis
Published: October 2014

There is a growing interest in adjuvant radiosurgery following resection of hematogenous brain metastases. We have identified 12 series reporting on a total of 480 patients treated to a tumor bed following microsurgery. These cases fall into 3 paradigms: adjuvant radiosurgery as an alternative to whole-brain radiotherapy (WBRT), radiosurgery as an intensification of adjuvant WBRT and adjuvant radiosurgery for patients having failed prior WBRT. For these paradigms the reported crude local control rates are 79%, 92% and 95%, respectively. The procedure appears well tolerate with approximately a 5% risk of late radiation necrosis. Prospective data is lagging behind clinical practice and plans for prospective trials are discussed.
Hypofractionated Stereotactic Body Radiotherapy for Primary and Metastatic Liver Tumors Using the Novalis Image-Guided System: Preliminary Results regarding Efficacy and Toxicity
Authors: Iwata Hiromitsu , Shibamoto Yuta , Hashizume Chisa , Mori Yoshimasa , Kobayashi Tatsuya , Hayashi Naoki , Kosaki Katsura , Ishikawa Tetsuya , Kuzuya Teiji , Utsunomiya Setsuo
Published: October 2014

The purpose of this study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for primary and metastatic liver tumors using the Novalis image-guided radiotherapy system. After preliminarily treating liver tumors using the Novalis system from July 2006, we started a protocol-based study in February 2008. Eighteen patients (6 with primary hepatocellular carcinoma and 12 with metastatic liver tumor) were treated with 55 or 50 Gy, depending upon their planned dose distribution and liver function, delivered in 10 fractions over 2 weeks. Four non-coplanar and three coplanar static beams were used. Patient age ranged from 54 to 84 years (median: 72 years). The Child-Pugh classification was Grade A in 17 patients and Grade B in 1. Tumor diameter ranged from 12 to 35 mm (median: 23 mm). Toxicities were evaluated according to the Common Terminology Criteria of Adverse Events version 4.0, and radiation-induced liver disease (RILD) was defined by Lawrence's criterion. The median follow-up period was 14.5 months. For all patients, the 1-year overall survival and local control rates were 94% and 86%, respectively. A Grade 1 liver enzyme change was observed in 5 patients, but no RILD or chronic liver dysfunction was observed. SBRT using the Novalis image-guided system is safe and effective for treating primary and metastatic liver tumors. Further investigation of SBRT for liver tumors is warranted. In view of the acceptable toxicity observed with this protocol, we have moved to a new protocol to shorten the overall treatment time and escalate the dose.
Rectal Planning Risk Volume Correlation with Acute and Late Toxicity in 3-Dimensional Conformal Radiation Therapy for Prostate Cancer
Authors: Dias R. S. , Giordani A. J. , Souhami L. , Segreto R. A. , Segreto H. R. C.
Published: October 2014

The purpose of this study was to evaluate rectum motion during 3-Dimensional conformal radiation therapy (3D-CRT) in prostate cancer patients, to derive a planning volume at risk (PRV) and to correlate the PRV dose-volume histograms (DVH) with treatment complications. This study was conducted in two phases. Initially, the PRV was defined prospectively in 50 consecutive prostate cancer patients (Group 1) who received a radical course of 3-D CRT. Then, the obtained PRV was used in the radiotherapy planning of these same 50 patients plus another 59 prostate cancer patients (Group 2) previously treated between 2004 and 2008. All these patients' data, including the rectum and PRV DVHs, were correlated to acute and late complications, according to the Common Toxicity Criteria (CTC) v4.0. The largest displacement occurred in the anterior axis. Long-term gastrointestinal (GI) complications grade ≥2 were seen in 9.2% of the cases. Factors that influenced acute GI reactions were: doses at 25% (p = 0.011) and 40% (p = 0.005) of the rectum volume and at 40% of the PRV (p = 0.012). The dose at 25% of the rectum volume (p = 0.033) and acute complications ≥grade 2 (p = 0.018) were prognostic factors for long-term complications. The PRV DVH did not correlate with late toxicity. The rectum showed a significant inter-fraction motion during 3D-CRT for prostate cancer. PRV dose correlated with acute gastrointestinal complications and may be a useful tool to predict and reduce their occurrence.
The Impact of a Research Ethics Training Program
Authors: Loue Sana
Published: October 2014

Case Western Reserve University’s (CWRU) Training Program in International Research Ethics, funded by the Fogarty International Center, has been ongoing in Romania since 2000. The program consists of multiple components: a U.S.-based MA degree program for long-term trainees, Romania-based short courses, a U.S.-based opportunity for mid-and senior-level personnel to develop collaborative writing or research projects and present lectures, and a newsletter and various Internet-based activities. We evaluated the impact of the training program on bioethics in Romania through a survey of the training program’s long-term trainees, a literature search for trainee publications, interviews with key informants, and identification of key events during the course of the program. Findings indicate that the program has had a considerable impact in the field of bioethics through trainee authorship of peer-reviewed publications, books, and chapters; trainee career trajectories that encompass activities related to research ethics; and the development of a Romania-based master’s degree program in bioethics and a Center of Bioethics and Health Policy. We attribute these achievements to the establishment of strong relationships between CWRU in Cleveland and the University of Medicine and Pharmacy Gr. T. Popa in Iasi, Romania, prior to the initiation of the training program; collaboration with key Romania-based institutional partners that are equally invested in the program’s success; reliance of the program on a solid theoretical framework; ongoing program responsiveness to trainee and country needs; and a sustained commitment of time, expertise, and funding by the funders, sponsors, and in-country collaborators.
Congenital thyroid hemiagenesis with multinodular goiter
Authors: Bhartiya SK , Verma A , Basu S , Shukla VK
Published: October 2014

Thyroid hemiagenesis is a rare form of thyroid dysgenesis characterized by an absence of half of the thyroid gland. Developmental hemi-thyroid anomalies can result from either an abnormal descent or an agenesis of one lobe of the thyroid gland. We report a case of a 40-year-old woman with history of a longstanding gradually progressive thyroid swelling without any complication. An ultrasonographic examination diagnosed the absence of the left thyroid lobe and enlargement of the right lobe, which was confirmed on a computed tomography (CT) angiogram and a radionuclide scan of the neck. A cytological examination showed nodular goiter with cystic degeneration. Right subtotal thyroidectomy was performed and histopathological examination confirmed adenomatous goiter with degenerative changes. We report the rarity of the condition and emphasize the role of a comprehensive radiological, cytological, and radionuclide algorithm for an accurate preoperative diagnosis and subsequent management.