bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Molecular Perspective: VEGF and Angiogenesis
Authors: Goodsell David S. 
Published: August 2004

Abstract

Learning Objective
After completing this course, the reader will be able to:
Gain a basic understanding of VEGF and its role in angiogenesis.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Living as a Cancer Surpriser: A Doctor Tells His Story
Authors: Knuti Kristine A. , Wharton Robert H. , Wharton Karen Levine , Chabner Bruce A. , Lynch Thomas J. , Penson Richard T. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to: Identify the unique issues confronted by caregivers who become patients.Appreciate how addressing issues of life and death affects patients, families, and caregivers.Recognize the advantages and limitations of prognostication.Better care for and communicate with patients and families who face life-threatening illnesses.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to the caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers and gain insight and support from fellow staff members.
We tell the story of one physician with incurable non-small cell lung cancer (NSCLC) who had an unexpectedly favorable response to an experimental treatment while receiving it as a part of his palliative care. His unique insight provides an opportunity to elucidate some of the issues that arise from living both as a patient-caregiver and as a cancer “surpriser.” When caregivers face their own cancer, their reflections as patient-caregivers offer an internal perspective on the illness experience and help us as fellow caregivers to better understand and support all patients who face serious illnesses, both those who are colleagues and those who are not. Just like any patient with cancer, patient-caregivers experience the dramatic changes in health, daily life, and perspective that come with serious illness. Within the context of a life-threatening illness, caregiver-patients and their families search for new meaning as they face an uncertain future and address the issues of life and death. In addition to such processes, patient-caregivers with cancer also find that their own medical knowledge and their colleagues’ reactions shape their experiences and to an extent separate them from those of other patients.
Molecular Cytogenetics in Solid Tumors: Laboratorial Tool for Diagnosis, Prognosis, and Therapy
Authors: Varella-Garcia Marileila 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Explain the basic principles supporting the FISH technology and list examples of methodology variants suitable for analysis in metaphase and interphase cells. Describe at least one advantageous and one limiting factor for the expansion of the applicability of FISH assays to solid tumors. Explain technical strategies for detection of chromosomal translocation in nondividing cells. Illustrate applications of cytogenetic markers to solid malignancies for diagnosis, prognosis, selection of therapy, and monitoring disease recurrence or response to treatment.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
The remarkable progress in the understanding of leukemogenesis was soundly sustained by methodological developments in the cytogenetic field. Nonrandom chromosomal abnormalities frequently associated with specific types of hematological disease play a major role in their diagnosis and have been demonstrated as independent prognostic indicators. Molecular pathways altered by chimeric or deregulated proteins as a consequence of chromosomal abnormalities have also significantly contributed to the development of targeted therapies, and cytogenetic assays are valuable for selecting patients for treatment and monitoring outcome. In solid tumors, significantly high levels of chromosome abnormalities have been detected, but distinction between critical and irrelevant events has been a major challenge. Consequently, the application of cytogenetic technology as diagnostic, prognostic, or therapeutic tools for these malignancies remains largely underappreciated. The emergence of molecular-based techniques such as fluorescence in situ hybridization was particularly useful for solid malignancies, and the spectrum of their application is rapidly expanding to improve efficiency and sensitivity in cancer prevention, diagnosis, prognosis, and therapy selection, alone or in combination with other diagnostic methods. This overview illustrates current uses and outlines potential applications for molecular cytogenetics in clinical oncology.
Growth Factor Receptors in Breast Cancer: Potential for Therapeutic Intervention
Authors: Nahta Rita , Hortobágyi Gabriel N. , Esteva Francisco J. 
Published: August 2004

AbstractIncreased expression and activation of receptor tyrosine kinases occurs frequently in human breast carcinomas. Several therapies targeting these receptors are currently in clinical trials. Therapeutic strategies include blockade of individual receptors with monoclonal antibodies and inhibition of tyrosine kinase function. Trastuzumab is the first of these biologic therapies to be approved for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic breast cancer. Novel trastuzumab-based combinations are being investigated in patients with advanced breast cancer. Large clinical trials have also been launched in the adjuvant setting. Small molecules that inhibit specific tyrosine kinases (e.g., epidermal growth factor receptor, HER2) are in phase I and phase II clinical trials. Other growth-factor-targeted drugs that have reached clinical development include STI571 and antibodies directed at the insulin-like growth factor pathway. Biologic therapies directed against these important receptors are promising. In this review we discuss challenges and opportunities for the development of growth-factor-targeted approaches for the treatment of breast cancer.
Current Status of Sentinel Lymph Node Mapping and Biopsy: Facts and Controversies
Authors: Jakub James W. , Pendas Solange , Reintgen Douglas S. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to: Explain the current application of lymphatic mapping and sentinel lymph node biopsy.Discuss the ability of sentinel lymph node biopsy to allow a more focused pathologic evaluation and identify tumor cells not previously detected by standard techniques.Discuss the major controversies of lymphatic mapping and sentinel lymph node biopsy as they apply to melanoma, breast cancer, and colon cancer.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Lymphatic mapping and sentinel lymph node biopsy were first reported in 1977 by Cabanas for penile cancer. Since that time, the technique has become rapidly assimilated into clinical practice. Morton first described the application of lymphatic mapping for melanoma only a decade ago, and this technique is now accepted as the standard of care. The application for lymphatic mapping and sentinel lymph node biopsy in breast cancer remains approximately 5 years behind its utilization in melanoma. This technique has the potential to be utilized in all solid tumors. The rapid assent of this technique in clinical practice is the result of multiple factors, including accuracy, decreased morbidity, and supplying the pathologist with only a few nodes to allow a more focused and sensitive pathologic evaluation. Despite the success and acceptance of lymphatic mapping, many controversies remain. We have attempted to clearly highlight these controversies in this review.
Use of Temozolomide with Other Cytotoxic Chemotherapy in the Treatment of Patients with Recurrent Brain Metastases from Lung Cancer
Authors: Ebert Benjamin L. , Niemierko Ewa , Shaffer Kitt , Salgia Ravi 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Identify appropriate treatments for patients with brain metastases from lung cancer with a consideration of the response rates of chemotherapy in phase II clinical trials. Describe the mechanism of action and the current clinical applications of temozolomide. Explain why temozolomide may have utility in combination with other cytotoxic chemotherapeutic agents for treating brain metastases from lung cancer.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
The use of chemotherapy for the treatment of brain metastases arising from lung cancer has been limited by poor efficacy and high toxicity. Temozolomide, an orally bioavailable alkylating agent that crosses the blood-brain barrier, has activity against brain metastases from both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) when used as a single agent, but response rates are low. Preclinical experiments and early clinical studies in other malignancies indicate that temozolomide may have additive or synergistic effects when used with other chemotherapeutic agents. We report a case of a patient with SCLC with recurrent brain metastases after treatment with multiple chemotherapeutic regimens and whole-brain radiation therapy (WBRT) who was treated with temozolomide (150 mg/m2 for 5 days in a 28-day cycle) and oral etoposide (50 mg/m2 for 10 days in a 28-day cycle). A second patient with NSCLC and brain metastases who progressed after treatment with chemotherapy and WBRT was treated with temozolomide (150 mg/m2 for 5 days in a 28-day cycle) and gemcitabine (1,000 mg/m2 weekly for 2 weeks in a 3- week cycle). In both patients, the temozolomide regimens were extremely well tolerated and resulted in dramatic and durable responses. The combination of temozolomide with other chemotherapeutic agents represents a promising strategy for treating patients with lung cancer and recurrent brain metastases and merits further study.
Phase I Study of Paclitaxel and Topotecan for the First-Line Treatment of Extensive-Stage Small Cell Lung Cancer
Authors: West William , Birch Robert , Schnell Frederick , Hainsworth John , Tongol Jose , Campos Luis 
Published: August 2004

Abstract
Extensive-stage small cell lung cancer (SCLC) is an aggressive disease with a median survival of approximately 8 months. Although current combination chemotherapy regimens provide high initial tumor response rates, they have not translated into large gains in survival. Topotecan and paclitaxel have nonoverlapping mechanisms of action and are active agents in SCLC. Additionally, these two agents demonstrate in vitro synergy in animal and human tumor models. We investigated the maximum tolerated dose of 3-day topotecan in combination with paclitaxel in previously untreated patients with extensive SCLC. Seventeen patients were enrolled in an open-label, phase I, dose-escalation study and were treated with intravenous paclitaxel 135-175 mg/m2 over 1 hour on day 1, followed by intravenous topotecan 1.25-1.5 mg/m2 over 30 minutes on days 1-3 of a 21-day course. Sixty-nine courses of therapy were administered with no delays due to hematologic toxicity. Prophylactic hematologic support was required for 24% of patients. The topotecan/paclitaxel combination was well tolerated, with 24%, 12%, and 6% of patients experiencing grade 3/4 neutropenia, anemia, or thrombocytopenia, respectively. Dose-limiting neutropenia was seen in three of five patients treated with topotecan 1.5 mg/m2 and paclitaxel 175 mg/m2. Therefore, topotecan 1.5 mg/m2 with paclitaxel 135 mg/m2 was determined to be the maximum tolerated dose. Of the 17 evaluable patients, 53% achieved a partial response and 18% achieved stable disease. In summary, we have identified a regimen of topotecan 1.5 mg/m2 and paclitaxel 135 mg/m2 that was well tolerated and active in this patient group. Additional studies of topotecan and paclitaxel at these dose levels are needed to fully elucidate the efficacy of this combination in extensive SCLC.
Immunotherapy for Epstein-Barr Virus-Associated Cancers in Children
Authors: Straathof Karin C.M. , Bollard Catherine M. , Rooney Cliona M. , Heslop Helen E. 
Published: August 2004

AbstractLearning ObjectivesAfter completing this course, the reader will be able to:Explain the pathogenesis of post-transplant lymphoproliferative disease.Identify patients at risk for post-transplant lymphoproliferative disease.Appreciate the rationale for using immunotherapy approaches in Epstein-Barr virus-associated malignancies.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.comLatent Epstein-Barr virus (EBV) infection is associated with several malignancies, including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disease (LPD). The presence of EBV antigens in these tumors provides a target for immunotherapy approaches, and immunotherapy with EBV-specific cytotoxic T cells (CTLs) has proved effective in post-transplant LPDs, which are highly immunogenic tumors expressing type III latency. The malignant cells in Hodgkin's disease and nasopharyngeal carcinoma express type II latency and hence a more restricted pattern of EBV antigens. Trials with autologous EBV-specific CTL responses are under way in both of these diseases, and while some activity has been seen, no patient has yet been cured. This reduced CTL efficacy may reflect either downregulation of immunodominant EBV proteins, which are major CTL targets, or the ability of these tumors to evade the immune response by secreting inhibitory cytokines. Further improvement of EBV-specific CTL therapy for these type II latency tumors will require improved methods to activate and expand CTLs specific for the subdominant EBV genes expressed and to genetically modify the expanded CTLs to render them resistant to inhibitory cytokines. If these strategies to improve the therapeutic potential of immunotherapy for EBV-associated tumors prove successful, this type of treatment may be adapted to other tumors expressing known (viral) antigens.
Baseline and Early Treatment Factors are not Clinically Useful for Predicting Individual Response to Erythropoietin in Anemic Cancer Patients
Authors: Littlewood Timothy J. , Zagari Martin , Pallister Christopher , Perkins Alan 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to: Recognize that anemia is common in patients with malignant disease.Appreciate that treatment with recombinant erythropoietin can increase the hemoglobin concentration by 2g/dL or more in 70% of patients at the usual doses and frequency.Recognize that factors that predict for a hemoglobin response lack sensitivity and specificity.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Recombinant human erythropoietin (rHuEPO) is an effective treatment for anemia in patients with cancer, and recent studies show that over two-thirds of patients can be expected to respond with a large increase (&gt;2 g/dl) in hemoglobin concentration. However, it would be helpful to identify likely responders and nonresponders before initiating treatment. Previous studies have suggested that high pretreatment endogenous erythropoietin levels are associated with a lower response to erythropoietin, especially in certain patient groups, such as patients with hematological malignancies, nonchemotherapy patients, or patients with myelodysplastic syndrome. Various algorithms have therefore been developed to predict patient response to rHuEPO using baseline serum erythropoietin levels and other baseline factors. We performed an analysis of data pooled from four randomized clinical trials of 604 patients with nonmyeloid malignancies, examining the clinical usefulness of pretreatment and early treatment factors for predicting response to erythropoietin. The analysis confirms several other reports that the most predictive models combined pretreatment and early treatment factors, including change in hemoglobin at 4 weeks, but even these models did not increase sensitivity above 85% (total response in unselected patients was 68.1%), while specificity remained poor. We conclude that clinically useful prediction of response to erythropoietin is not possible using baseline or early response variables because of poor sensitivity and specificity of prediction compared with generally accepted clinical tests.
Arsenic Trioxide (Trisenox®) Therapy for Acute Promyelocytic Leukemia in the Setting of Hematopoietic Stem Cell Transplantation
Authors: Douer Dan , Hu Wendy , Giralt Sergio , Lill Michael , DiPersio John 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Explain how to treat patients with relapsed acute promyelocytic leukemia. Describe how to use arsenic trioxide in acute promyelocytic leukemia and be familiar with drug's side effects. Identify the role of bone marrow transplantation in acute promyelocytic leukemia.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at.CME.TheOncologist.com
The relapse-free survival of patients with acute promyelocytic leukemia (APL) has significantly increased during the last decade. The introduction of all-trans retinoic acid (ATRA) doubled the survival of patients with this disease. However, despite ATRA and anthracycline-based chemotherapy, 12%–30% of patients will still relapse. Arsenic trioxide (ATO) has demonstrated efficacy and safety in patients with first and subsequent relapsed or refractory APL, regardless of the disease-free interval. Treatment of relapsed and refractory patients with this novel therapy produces complete remission in 87% of patients and molecular remission in 83%. Studies have documented the efficacy of autologous and allogeneic transplantation as salvage therapy in relapsed and refractory APL. The introduction of ATO into the treatment regimen for APL has stimulated discussion on its role in the transplantation setting. Investigators recently met to discuss the issue and make recommendations regarding ATO therapy in patients who are in their second or subsequent complete remission and are candidates for transplantation. This article describes the pivotal studies of this novel agent, discusses risk factor stratification for relapse in patients with APL, and proposes protocols for treatment incorporating ATO therapy. In addition, it describes scientific issues in ongoing and proposed clinical trials of ATO therapy for this disease.
Update on the Management of Inflammatory Breast Cancer
Authors: Cristofanilli Massimo , Buzdar Aman U. , Hortobágyi Gabriel N. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Recognize the differences in biology and clinical outcome of IBC compared with non-IBC. Summarize the standard of care for IBC. Identify molecular targets and novel agents for future treatments of IBC.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Inflammatory breast cancer (IBC) is the most aggressive manifestation of primary breast carcinoma, with the clinical and biological characteristics of a rapidly proliferating disease. The multidisciplinary management of IBC has changed in the past 3 decades and is presently clearly outlined in sequence, with preoperative or neoadjuvant chemotherapy representing the mainstay of treatment. Anthracyclines and taxanes are the most effective cytotoxic agents in the management of primary breast cancer and should be the standard of treatment for women with IBC. Locoregional treatment includes radiotherapy with or without surgery and continues to play a major role after appropriate medical treatment. The many investigations into the particular molecular determinants of IBC development have provided several interesting new therapeutic targets. Combination regimens that include angiogenic modulators, farnesyl transferase inhibitors, and p53 modulators hold great promise in the medical management of IBC. Future therapeutic approaches should focus on these discoveries so that we can improve the overall prognosis for women with IBC.
The Medical Management of Pancreatic Cancer: A Review
Authors: McKenna Sarah , Eatock Martin 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Understand the clinical problems associated with treating pancreatic cancer. Appreciate the role of chemotherapy in the treatment of pancreatic cancer. Appreciate the rational for the investigation of a number of novel agents in this disease.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Pancreatic carcinoma is a commonly occurring cancer that tends to present late in its course when potentially curative surgical treatment is not possible. The majority of patients are, therefore, candidates for systemic therapy. We review the patient and disease-related factors that contribute to the difficulties in the medical management of this condition and discuss new methods of assessing response to treatment, including the introduction of more clinically relevant novel end points such as clinical benefit response. We review the current trial literature examining the use of conventional cytotoxic agents in this disease, both as single agents and in combination. We also review the use of more novel targeted agents and examine their potential utility in this disease. The use of the farnesyl transferase inhibitors, matrix metalloproteinase inhibitors, epidermal growth factor receptor antagonists, and angiogenesis inhibitors is discussed.
Clinical Approaches to Osseous Metastases in Prostate Cancer
Authors: Morris Michael J. , Scher Howard I. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Recognize the biology underlying metastatic prostate cancer to bone. Identify the clinical risks that osseous metastases pose to prostate cancer patients. Explain the clinical management of osseous disease in prostate cancer patients.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Background. Prostate cancer is unique among solid tumors in its proclivity to metastasize primarily to bone. Osseous metastases pose a formidable health threat to patients with metastatic disease, putting them at risk for pain, marrow crowding, fracture, and other sequelae. Treatments directed against bone disease have the potential both to palliate pain and to increase survival.
Conclusions. A number of agents exist that have the potential to palliate the effects of osseous metastases and should be routinely applied in the clinical care of the patient with advanced prostate cancer. These include hormones, bone-seeking radiopharmaceuticals, chemotherapy, and bisphosphonates. Strategies under investigation aim to eradicate bone disease, and not merely palliate symptoms. These approaches combine those listed above with tumor-directed targeting of osseous disease and manipulation of the biology that underlies the cancer's relationship to bone.