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Sondak V.K.,H. Lee Moffitt Cancer Center and Research Institute | King D.W.,STATKING Clinical Services | Zager J.S.,H. Lee Moffitt Cancer Center and Research Institute | Schneebaum S.,Sourasky Medical Center | And 9 more authors.
Annals of Surgical Oncology | Year: 2013

Background: [99mTc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared [99mTc] tilmanocept to vital blue dye. Methods: Patients received [99mTc] tilmanocept and blue dye. SLNs identified intraoperatively as radioactive and/or blue were excised and histologically examined. The primary end point, concordance, was the proportion of blue nodes detected by [99mTc] tilmanocept; 90 % concordance was the prespecified minimum concordance level. Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated. The prospective statistical plan combined the data from both trials. Results: Fifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated. Intraoperatively, 232 of 235 blue nodes were detected by [99mTc] tilmanocept, for 98.7 % concordance (p < 0.001). [99mTc] Tilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes). [99mTc]Tilmanocept detected at least one node in more patients (n = 150) than blue dye (n = 138, p = 0.002). In 135 of 138 patients with at least one blue node, all blue nodes were radioactive. Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by [99mTc]tilmanocept, whereas blue dye detected only 36 (80 %) of 45 (p = 0.004). No positive SLNs were detected exclusively by blue dye. Four of 34 node-positive patients were identified only by [ 99mTc]tilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by [99mTc]tilmanocept. No serious adverse events were attributed to [99mTc]tilmanocept. Conclusions: [99mTc] Tilmanocept met the prespecified concordance primary end point, identifying 98.7 % of blue nodes. It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye. © 2012 The Author(s).

CLEVELAND: A researcher from University Hospitals Seidman Cancer Center will discuss his upcoming immunotherapy clinical trial for triple-negative breast cancer at the 2016 San Antonio Breast Cancer Symposium. The annual symposium is the premier meeting for more than 7,500 physicians and scientists dedicated to breast cancer treatment, featuring state-of-the-art breast cancer research such as experimental biology, etiology, prevention, diagnosis, and therapy of both breast cancer and premalignant breast disease. Joseph Baar, MD, PhD, Director of Breast Cancer Research at UH Seidman Cancer Center and Associate Professor at Case Western Reserve University School of Medicine, will share details about a phase II clinical trial testing the effectiveness of combining the chemotherapy drugs carboplatin and nab-paclitaxel with an immunotherapeutic agent called pembrolizumab (Keytruda) for use in patients with metastatic triple-negative breast cancer. Dr. Baar's poster presentation will be part of the Ongoing Trials-Targeted Therapy session on December 8, 2016 from 5 pm to 7 pm. "Up until now, women with triple-negative breast cancer have only had one treatment option, which is chemotherapy. However, more recently, we've seen that the immune modulator pembrolizumab improves outcomes in patients with metastatic triple-negative breast cancer," said Dr. Baar. "As a result, it is now critical to explore how the addition of pembrolizumab to chemotherapy might improve survival in patients with this type of breast cancer." Triple-negative breast cancer is a highly aggressive form which comprises 10-15 percent of newly diagnosed early-stage breast cancer. Most triple-negative tumors are high grade and have a high incidence of recurrence and metastases (spreading to other organs). Unlike other types of breast cancer, there is no standard follow-up treatment for triple-negative breast cancer to prevent recurrence. As triple-negative breast cancer progresses, tumor cells express a protein ligand called PD-L1, which interacts with the PD-1 receptor on T-cells. T-cells are the immune system's primary mechanism for fighting back against harmful foreign invaders. The PD-L1 to PD-1 interaction prevents the T-cell from responding to the tumor as a threat. Pembrolizumab binds to the T-cell's PD-1 receptors and therefore blocks the PD-1 to PD-L1 interaction, allowing the T-cells to be activated against the tumor cells. The research team hypothesizes that the addition of such an immunotherapeutic agent to chemotherapy will allow the body's natural immune response to reduce disease recurrence to a greater extent than either modality alone. This is the first phase II trial to study the effectiveness of combining these two chemotherapeutic agents with the immunotherapeutic agent pembrolizumab for this type of cancer. The trial will enroll approximately 30 patients beginning in early 2017. Eligible patients must have radiologically measurable and documented metastatic triple negative breast cancer, be mostly functional day to day as measured by an ECOG performance status of between zero and one, must not have received more than two prior therapies for this disease, and must be willing to undergo a preliminary biopsy for research purposes. The trial is sponsored by Merck, which produces pembrolizumab as Keytruda. "Trials our faculty members present at SABCS and other research meetings around the world illustrate the remarkable advances in oncology taking place today," says Neal J. Meropol, MD, Chief, Division of Hematology and Oncology, University Hospitals Seidman Cancer Center and Associate Director for Clinical Research, Case Comprehensive Cancer Center at Case Western Reserve. The symposium takes place December 6-10, 2016, and is hosted by The Cancer Therapy & Research Center at the University of Texas Health Science Center at San Antonio, the American Association for Cancer Research, and Baylor College of Medicine. Founded in 1866, University Hospitals serves the needs of over 1 million patients per year through an integrated network of 18 hospitals, more than 40 outpatient health centers and 200 physician offices in 15 counties throughout northern Ohio. The system's flagship academic medical center, University Hospitals Cleveland Medical Center, located on a 35-acre campus in Cleveland's University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; University Hospitals MacDonald Women's Hospital, Ohio's only hospital for women; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women's health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, dermatology, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including "America's Best Hospitals" from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals - part of The Harrington Project for Discovery & Development. UH is the second largest employer in northern Ohio with 26,000 employees. For more information, go to

Marten K.A.,Des Moines University | Gudena V.K.,University Hospitals Seidman Cancer Center
Cancer Biology and Therapy | Year: 2015

Anaplastic thyroid carcinoma (ATC) is a rare, poorly differentiated type of thyroid cancer occurring in less than 5% of all thyroid cancers. Patients typically have a poor prognosis with very few options for treatment.2 With current therapy of surgery, chemotherapy, and radiation, median survival is only 6 months from the time of diagnosis. Several mutations in cell cycle regulation have been discovered in ATC that contribute to its undifferentiated state, one of which is the BRAF kinase mutation. This mutation results in activation of the MAPK pathway and uncontrolled cell proliferation. In this case report, a 51 y old male presented with a 2-week history of hoarseness and was diagnosed with ATC. Genetic analysis revealed a mutation in BRAF kinase; the patient subsequently began therapy with vemurafenib, a BRAF kinase inhibitor indicated for melanoma. After an initial response, the patient quickly declined and consequently died from his disease. Anaplastic thyroid carcinoma is a deadly cancer without an effective treatment. Inhibiting mutated enzymes that drive the development of this cancer is a potential drug target that may improve outcomes in patients with ATC. © 2015 Taylor & Francis Group, LLC.

Mohile S.G.,University of Rochester | Hardt M.,University of California at Los Angeles | Tew W.,Sloan Kettering Cancer Center | Owusu C.,University Hospitals Seidman Cancer Center | And 10 more authors.
Oncologist | Year: 2013

Background. Bevacizumab leads to improved survival for patients with metastatic colorectal cancer (CRC) or non-small cell lung cancer (NSCLC) when added to chemotherapy. Little is known about factors associated with receipt of bevacizumab, or whether bevacizamab is associated with increased toxicity when added to chemotherapy. Patients and Methods. We conducted a prospective study of patients aged ≥65 years, which evaluated the association between geriatric assessment (GA) metrics and chemotherapy toxicity. We examined differences in characteristics and outcomes of patients with CRC and NSCLC cancers who received bevacizumab with chemotherapy versus chemotherapy alone. Results. From a total of 207 patients, 27 (13%) received bevacizumab plus chemotherapy and 180 (87%) received chemotherapy alone. Groups were similar in sociodemographic and cancer characteristics. There were no baseline differences in GA domains except that patients with heart disease were less likely to receive bevacizumab (4% vs. 26%, p<.01). Seventyeight percent of patientswhohadbevacizumabhadgrade3-5 toxicity compared to only 57% who received chemotherapy alone (p =.06). Patients receiving bevacizumab were more likely to develop grade 3 hypertension than those who receivedchemotherapyalone(15%vs.2%, p<.01). In multivariable analysis, factors associated with grade 3 or more toxicity included: bevacizumab (OR: 2.86, p =.04), CRC (OR: 2.54, p<.01), and baseline anemia (OR: 2.58, p=.03). Conclusion. Heart diseasewasmorecommonin thosewhodid not receive bevacizumab. Older patients who receive bevacizumab with chemotherapy have a higher odds of developing a grade 3-5 toxicity compared with those who receive chemotherapy alone. © AlphaMed Press 2013.

Siroy A.,University Hospitals Seidman Cancer Center | Abdul-Karim F.W.,Cleveland Clinic | Miedler J.,University Hospitals Seidman Cancer Center | Fong N.,Fairview Hospital | And 3 more authors.
Human Pathology | Year: 2013

Summary Triple-negative breast cancer comprises 10% to 15% of newly diagnosed breast cancer and lacks expression of the estrogen, progesterone, and human epidermal growth factor receptor 2/neu receptors. Many such tumors are basal like, a molecular intrinsic subtype of breast cancer associated with poor clinical outcomes. Patients with early-stage basal-like triple-negative breast cancer are at a high risk for relapse and may, therefore, benefit from novel therapies, including immunotherapy. MUC1 is a tumor antigen expressed on adenocarcinomas and represents an ideal target for MUC1-based vaccination. We evaluated 52 cases of early-stage basal-like triple-negative breast cancer for MUC1 expression by immunohistochemistry. The intensity of staining was graded according to the intensity (negative [0], positive [1], or strongly positive [2]) and percentage (0%-100%) of tumor cells staining for MUC1. An overall score of 0 to 2.0 was calculated for each case by multiplying the intensity of staining by the percentage of tumor cells staining positively. Four staining patterns for MUC1 were identified: apical, cytoplasmic, membranous, and combination. Of the 52 cases of basal-like triple-negative breast cancers, 49 (94%) were positive for MUC1 expression. The mean score was 0.90 (range, 0-1.9). Cases were evenly distributed over this range, where most (67%) exhibited moderate to strong MUC1 expression (score, 0.5-1.90), 27% demonstrated weak MUC1 expression, and 6% lacked MUC1 expression. There was a significant difference in MUC1 score and percent MUC1+ cells in favor of the combination pattern. This study indicates that a large proportion of early-stage basal-like triple-negative breast cancer expresses MUC1 and provides a rationale for MUC1-based immunotherapy in this high-risk patient cohort. © 2013 Elsevier Inc.

Lo S.S.,University Hospitals Seidman Cancer Center | Sahgal A.,University of Toronto | Chang E.L.,University of Southern California | Mayr N.A.,Ohio State University | And 7 more authors.
Clinical Oncology | Year: 2013

The clinical applications of stereotactic body radiotherapy or stereotactic ablative radiotherapy (SABR) for the treatment of primary and metastatic tumours of different organ sites have been expanding rapidly in the recent decade. SABR requires advanced technology in radiotherapy planning and image guidance to deliver a highly conformal ablative dose precisely to targets (or tumours) in the body. Although this treatment modality has shown promising results with regard to tumour control, some serious complications have been observed and reported. In order to achieve a favourable therapeutic ratio, strategies to mitigate the risk of complications must be in place. This overview will summarise the reported serious complications caused by SABR and strategies to mitigate the risk will be discussed. © 2013 The Royal College of Radiologists.

Warrell G.,University of Toledo | Warrell G.,University Hospitals Seidman Cancer Center | Shvydka D.,University of Toledo | Parsai E.I.,University of Toledo
Medical Physics | Year: 2016

Purpose: A practical means of delivering both therapeutic radiation and hyperthermia to a deepseated target has been identified in the literature as highly desirable, provided it is capable of generating sufficient temperatures over the defined target volume. The authors present continued development of a dual-modality thermobrachytherapy (TB) seed, investigating its capabilities in delivering prescribed hyperthermia to realistic deep-seated targets. Methods: The TB seed is based on the ubiquitous low dose-rate (LDR) brachytherapy permanent implant. Heat is generated by incorporating a ferromagnetic core within the seed and placing the patient in an oscillating external magnetic field, producing eddy currents within the core and hence Joule heating. A strategically selected Curie temperature results in thermal self-regulation. The magnetic and thermal properties of the TB seed were studied experimentally by means of seed prototypes placed in a tissue-mimicking phantom and heated with an industrial induction heater, as well as computationally in the finite element analysis solver COMSOL Multiphysics. Patient-specific seed distributions derived from LDR permanent prostate implants previously conducted at their institution were modeled in COMSOL to evaluate their ability to adequately cover a defined target volume and to overcome the loss of heat due to blood perfusion within tissue. The calculated temperature distributions were analyzed by generating temperature-volume histograms, which were used to quantify coverage and temperature homogeneity for varied blood perfusion rates, seed Curie temperatures, and thermal power production rates. Use of additional hyperthermia-only (HT-only) seeds in unused spots within the implantation needles was investigated, as was an increase in these seeds' core size to increase their power. The impact of the interseed attenuation and scatter (ISA) effect on radiation dose distributions of this seed was also quantified by Monte Carlo studies in the software package Monte Carlo N-Particle Version 5. Results: Increasing the power production of the seeds, as well as increasing their Curie point, would increase the maximum blood perfusion rate that a given seed distribution could overcome to obtain an acceptable temperature distribution. However, this would also increase the maximum temperatures generated at the seed surfaces. Auxiliary HT-only seeds serve to improve the temperature uniformity within the target, as well as decrease the seed power generation requirements. Both an increase in their core size and an increase in both seed types' Curie temperatures enhance the resulting temperature coverage. The interseed and scatter effect caused by both the TB and HT-only seeds was found to reduce the dose to 90% of the target volume (D90) by a factor of 1.10±0.02. Conclusions: A systematic approach of combining LDR prostate brachytherapy with hyperthermia is described, and its ability to provide sufficient and uniform temperature distributions in realistic patient-specific implants evaluated. A combination of TB and HT-only seeds may be used to produce a uniform temperature distribution in a defined target. Various modeled changes to their design, such as optimization of their Curie temperature, improve their ability to overcome the thermal effects of blood perfusion. The enhanced ISA of the TB and HT-only seeds must be taken into account for dose calculations, but is manageable. © 2016 American Association of Physicists in Medicine.

Palma D.A.,London Health Sciences Center | Salama J.K.,Duke University | Lo S.S.,University Hospitals Seidman Cancer Center | Senan S.,VU University Amsterdam | And 3 more authors.
Nature Reviews Clinical Oncology | Year: 2014

The oligometastatic paradigm implies that patients who develop a small number of metastatic lesions might achieve long-term survival if all these lesions are ablated with surgery or stereotactic radiotherapy. Clinical data indicate that the number of patients with oligometastatic disease receiving aggressive treatment is increasing rapidly. We examine the key evidence supporting or refuting the existence of an oligometastatic state. Numerous single-arm studies suggest that long-term survival is 'better-than-expected' after ablative treatment. However, the few studies with adequate controls raise the possibility that this long-term survival might not be due to the treatments themselves, but rather to the selection of patients based on favourable inclusion criteria. Furthermore, ablative treatments carry a risk of harming healthy tissue, yet the risk-benefit ratio cannot be quantified if the benefits are unmeasured. If the strategy of treating oligometastases is to gain widespread acceptance as routine clinical practice, there should be stronger evidence supporting its efficacy. © 2014 Macmillan Publishers Limited.

Wallace C.R.,University Hospitals Seidman Cancer Center
Orthopaedic Nursing | Year: 2012

Individuals with Type 1 and Type 2 diabetes who are managed with insulin are at risk for developing hypoglycemia, a significant consequence of insulin therapy. Symptoms of hypoglycemia develop rapidly and the condition can be life threatening. It is imperative that the inpatient team, including the orthopaedic nurse, is able to recognize the signs and symptoms, respond appropriately, and prevent hypoglycemia. It is equally important to provide the patient with education to prevent, identify, and self-manage hypoglycemia at home. A case study example is included that addresses an elderly patient with Type 2 diabetes who had a total hip arthroplasty and developed hypoglycemia postoperatively while on an orthopaedic unit. Assessment, treatment, prevention, and patient self-management education of hypoglycemia are reviewed. © 2012 by National Association of Orthopaedic Nurses.

Beatty K.,University Hospitals Seidman Cancer Center
AACN advanced critical care | Year: 2011

The start of the 21st century has produced advances in cancer care that have improved both survival rates and quality of life for many persons diagnosed with cancer. Targeted therapy has given new hope for controlling cancer as a chronic illness. Alone, or in combination with traditional therapies such as surgery, radiation, and/or chemotherapy, this new form of therapy targets malignant cells, halting tumor growth and the potential metastatic spread of disease. Toxicities are limited, but some are serious and may require intensive care. It is imperative for the experienced critical care nurse to have an understanding of these new treatment options and those on the horizon, as these therapies are the future of cancer care. Whereas in previous decades, patients with cancer may not have survived an intensive care admission for treatment complications or advanced disease, many patients now are recovering from life-threatening events, continuing treatment for their disease, and going on to live meaningful, good-quality lives.

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