bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Cytogenetics in Solid Tumors: Laboratorial Tool for Diagnosis, Prognosis, and Therapy
Authors: Varella-Garcia Marileila
Published: August 2004

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

Increased 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

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

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.

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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

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

Learning Objectives

After 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.com

Latent 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

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.

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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 (>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

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

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

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

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.
Advances in the Diagnosis, Molecular Genetics, and Treatment of Pediatric Embryonal CNS Tumors
Authors: MacDonald Tobey J. , Rood Brian R. , Santi Maria R. , Vezina Gilbert , Bingaman Kimberly , Cogen Philip H. , Packer Roger J.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Recognize the classification, clinical presentation, and diagnosis of embryonal CNS tumors. Explain the important molecular genetic alterations identified in embryonal CNS tumors. Describe the current management and novel treatment strategies for embryonal CNS tumors.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Embryonal central nervous system (CNS) tumors are the most common group of malignant brain tumors in children. The diagnosis and classification of tumors belonging to this family have been controversial; however, utilization of molecular genetics is helping to refine traditional histopathologic and clinical classification schemes. Currently, this group of tumors includes medulloblastomas, supratentorial primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, ependymoblastomas, and medulloepitheliomas. While the survival of older children with nonmetastatic medulloblastomas has improved considerably within the past two decades, the outcomes for infants and for those with metastatic medulloblastomas or other high-risk embryonal CNS tumors remain poor. It is anticipated that the emerging field of molecular biology will greatly aid in the future stratification and therapy for pediatric patients with malignant embryonal tumors. In this review, recent advances in the diagnosis, molecular genetics, and treatment of the most common pediatric embryonal CNS tumors are discussed.
Chemotherapy-Induced Nausea and Vomiting: The Importance of Acute Antiemetic Control
Authors: Schnell Frederick M.
Published: August 2004

Nausea and vomiting are two of the most feared side effects of cancer chemotherapy and radiotherapy. Chemotherapy-induced nausea and vomiting can be broadly categorized as acute (occurring within 24 hours of therapy), delayed (persisting for 6–7 days after therapy), or anticipatory (occurring prior to chemotherapy administration). Breakthrough and refractory nausea and vomiting describe the symptoms of uncontrolled emesis. Evidence suggests that good control of nausea and vomiting during the acute period correlates with the control of delayed emesis. Conversely, protection failure during the first 24 hours has a high predictive value for delayed emesis in the same cycle.

The 5-HT3-receptor antagonists, regarded as the ‘gold standard’ in antiemetic therapy, are the first-line treatment for moderately and highly emetogenic chemotherapy and radiotherapy regimens in adults and children. Evidence suggests that the 5-HT3-receptor antagonists administered in combination with corticosteroids afford the best protection from symptoms of acute emesis and, by extrapolation, the most effective prevention of delayed emesis.

Antiemetic therapeutic guidelines stress that the goal of therapy is to prevent cytostatic-induced nausea and vomiting. Therefore, the prophylactic use of the most effective antiemetic regimen—taking into consideration the emetogenicity of the chemotherapy and individual patient characteristics—must be adhered to in order to prevent acute, delayed, and anticipatory nausea and vomiting.
Trust Violated: Analgesics for Addicts
Authors: Penson Richard T. , Nunn Catherine , Younger Jerry , Schaeffer Nancy J. , Chabner Bruce A. , Fricchione Gregory L. , Quinn Thomas E. , Lynch Thomas J.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Explore the complexities of addictive behavior in cancer patients with pain. Learn treatment and management strategies for cancer patients with pain. Develop an informed approach to difficult cancer pain patients.

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 at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages 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.

Addiction among cancer patients on strong analgesics is a rare but difficult management challenge. The case is presented of a 28-year-old woman with breast cancer and painful bone metastases, suffering with dysfunctional social chaos and addicted to Percocet® (oxycodone and acetaminophen). Having broken the trust of her health care team, trust was rebuilt by incorporating the substance abuse clinic and enforcing a contractual agreement. With open and honest support, the team was able to both care for and empower the patient. Issues of trust, liability, opioid tolerance, and barriers to optimal analgesia for cancer pain are discussed.
Population-Based Pharmacoeconomic Model for Adopting Capecitabine/Docetaxel Combination Treatment for Anthracycline-Pretreated Metastatic Breast Cancer
Authors: Verma Shailendra , Ilersich A. Lane
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Evaluate the combination of docetaxel and capecitabine compared with docetaxel alone for cost effectiveness. Categorize cost differences according to the costs of drugs, hospitalizations, consultations, and other expenditures. Appreciate how combining efficacy quality of life and cost to effectiveness data can be used to support decisions on health care.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Purpose. To model the cost-effectiveness of adopting capecitabine/docetaxel combination therapy in place of single-agent taxane therapy for women in the province of Ontario, Canada, receiving treatment for anthracycline-pretreated metastatic breast cancer.

Methods. Clinical effectiveness and economic data were combined in a population model, from the perspective of a universal health care system. Estimates of clinical effectiveness and medical resource utilization were derived prospectively during a phase III randomized controlled trial comparing single-agent docetaxel with capecitabine/docetaxel combination therapy. Population data were obtained from the Cancer Care Ontario Registry and provincial prescription claims data.

Results. During 1999–2000, 542 patients were eligible for taxane monotherapy. As capecitabine/docetaxel treatment confers a median 3-month survival benefit compared with docetaxel monotherapy, the projected survival gain in these patients was 136 life-years. The results of the cost-effectiveness analysis demonstrate that the survival benefit provided by the addition of capecitabine to single-agent docetaxel is afforded at a small incremental cost of Canadian $3,691 per life-year gained. Hospitalization costs for treatment of adverse events were less for patients receiving capecitabine/docetaxel combination therapy than for those receiving docetaxel monotherapy. The results were robust for adjustments in treatment costs and adverse effects costs.

Conclusion. Due to its 3-month survival gain and small incremental treatment cost, capecitabine/docetaxel is judged to be a highly cost-effective treatment in anthracycline-pretreated advanced breast cancer. From the perspective of the Ontario health care system, the addition of capecitabine to docetaxel in this patient population is a clinically appropriate and economically acceptable treatment strategy.
A Role for Curative Surgery in the Treatment of Selected Patients with Metastatic Breast Cancer
Authors: Singletary S. Eva , Walsh Garrett , Vauthey Jean-Nicolas , Curley Steven , Sawaya Raymond , Weber Kristin L. , Meric Funda , Hortobágyi Gabriel N.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Explain how surgery in combination with systemic therapy may offer significantly improved survival outcomes in selected patients with metastatic breast cancer. Appreciate the value of chest x-rays in follow-up to identify patients with pulmonary or sternal metastases who may be candidates for surgical resection. Recognize that the concept of a “cure” in breast cancer is evolving to mean a prolonged period of survival without significant symptoms.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Although metastatic breast cancer is widely believed to carry a grim prognosis, treatment developments over the past 25 years have greatly improved survival outcomes in these patients. In selected cases, aggressive treatment approaches may occasionally result in long-term survival of 15 years or more. This review considers the role of surgery in the treatment of single or multiple metastatic lesions restricted to one site. For each site, available literature from 1992–2002 was assessed to determine the role of surgery on survival outcomes and to determine appropriate criteria for selecting the best candidates for surgery. For lung, liver, brain, and sternum metastases, the use of surgery with or without adjuvant therapy resulted in greater median survival times and 5-year survival rates. The best candidate for surgery had no evidence of additional metastatic disease, good performance status, and a long disease-free interval after treatment of the primary tumor. Current treatment standards for breast cancer follow-up do not include imaging studies other than mammography. The addition of chest x-rays as part of routine follow-up should be considered as a cost-effective approach for early assessment of metastases to the lung or sternum that may be appropriate for surgical excision.
Clinical Application of cDNA Microarrays in Oncology
Authors: Pusztai Lajos , Ayers Mark , Stec James , Hortobágyi Gabriel N.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Appreciate how future DNA microarray-based tests will be different from other diagnostic tests. Discuss the potential clinical applications of DNA microarray technology. Define limitations of the technology.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

DNA microarrays represent an important new tool to analyze human tissues. The technology enables investigators to measure the expression of several thousand mRNA species simultaneously in a biological specimen. This process, called transcriptional profiling, represents a technological breakthrough in the analysis of biological specimens. It may be used to screen for individual genes that are differentially expressed between normal and diseased tissues in the hope of finding novel targets for drug development or finding new single-gene markers of clinical outcome. Microarrays are also applied to learn about the complex biology of cancer by simultaneously monitoring interactions between hundreds of genes during experimental conditions in vitro or during therapy in vivo. Analysis of gene expression patterns may also be used as a classification tool to sort cancer into various clinically relevant subgroups that is not currently possible with other methods. The first clinically important applications of this technology will likely be its use as a tool to refine diagnosis and improve the accuracy of predictions of prognosis and response to therapy. DNA microarrays in several “proof-of-principle” experiments have demonstrated that they can predict important clinical outcomes, including outcomes that cannot currently be predicted with other methods, but the true clinical utility and the limits of this exciting new technology are yet to be established. This paper reviews the current methodology and applications of this technique as they relate to clinical oncology.
Management of High-Risk Populations with Locally Advanced Prostate Cancer
Authors: Khan Masood A. , Partin Alan W.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Recognize the clinical and pathological characteristics of a prostate tumor that is at high risk of having spread beyond the gland. Be familiar with novel markers for detection of high-risk prostate cancers. Explain the management strategy for high-risk prostate cancer.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Prostate cancer that extends beyond the confines of the prostatic gland on clinical and/or radiographic assessment, without evidence of lymph node or distant metastases, is regarded as locally advanced. The locally advanced prostate cancer patient population consists of a heterogeneous group of men, some of whom have tumors that may be amenable to primary curative intent with local definitive therapy associated with acceptable long-term cancer control rates. In order to optimally manage this group of patients, it is important to be able to recognize who is at a high risk of tumor recurrence after primary local therapy. In this brief review, we discuss the factors that contribute to the prediction of high risk in populations with locally advanced disease and the treatment options available.
Chemotherapy Options for the Elderly Patient with Advanced Non-Small Cell Lung Cancer
Authors: Hennessy B.T. , Hanrahan E.O. , Breathnach O.S.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Describe the available clinical trial data of chemotherapy for advanced non-small cell lung cancer in elderly patients. Compare older chemotherapy combinations with newer single agents in the treatment of advanced non-small cell lung cancer. Identify reasons why elderly patients with lung cancer have been excluded from clinical trials.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Combination chemotherapy has been shown to improve overall survival compared with best supportive care in patients with advanced non-small cell lung cancer (NSCLC). The survival advantage is modest and was initially demonstrated with cisplatin-containing regimens in a large meta-analysis of randomized trials reported in 1995. Newer chemotherapy combinations have been shown to be better tolerated than older cisplatin-based combinations, and some trials have also shown greater efficacy and survival benefits with these newer combinations. Combination chemotherapy is, therefore, the currently accepted standard of care for patients with good performance statuses aged less than 70 years with advanced NSCLC. However, there are limited data from clinical trials to support the use of combination chemotherapy in elderly patients over 70 years of age with advanced NSCLC. Subgroup analyses of large randomized phase III trials suggest that elderly patients with good performance statuses do as well as younger patients treated with combination chemotherapy. There are few randomized trials reported that evaluate chemotherapy in patients aged greater than 70 years only. Based on data from trials performed by an Italian group, single-agent vinorelbine has been shown to have significant activity in elderly patients with advanced NSCLC and to be well tolerated by those patients with Eastern Cooperative Oncology Group performance statuses of two or less, with associated improvements in measures of global health.
Advances in the Diagnosis and Treatment of Neuroblastoma
Authors: Weinstein Joanna L. , Katzenstein Howard M. , Cohn Susan L.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Appreciate the heterogeneity of neuroblastoma and identify clinical and biological prognostic factors. Explain the determinants and the clinical significance of the neuroblastoma risk stratification system. Select appropriate treatment regimens for neuroblastoma patients that are tailored according to risk stratification.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

Neuroblastoma, a childhood neoplasm arising from neural crest cells, is characterized by a diversity of clinical behavior ranging from spontaneous remission to rapid tumor progression and death. To a large extent, outcome can be predicted by the stage of disease and the age at diagnosis. However, the molecular events responsible for the variability in response to treatment and the rate of tumor growth remain largely unknown. Over the past decade, transformation-linked genetic changes have been identified in neuroblastoma tumors that have contributed to the understanding of tumor predisposition, metastasis, treatment responsiveness, and prognosis. The Children's Oncology Group recently developed a Neuroblastoma Risk Stratification System that is currently in use for treatment stratification purposes, based on clinical and biologic factors that are strongly predictive of outcome. This review discusses the current risk-based treatment approaches for children with neuroblastoma and recent advances in biologic therapy.
The Molecular Perspective: Ubiquitin and the Proteosome
Authors: Goodsell David S.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Gain a basic understanding of the structure and function of ubiquitin and the proteosome and their role in cancer.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
FDA Drug Approval Summary: Gefitinib (ZD1839) (Iressa®) Tablets
Authors: Cohen Martin H. , Williams Grant A. , Sridhara Rajeshwari , Chen Gang , Pazdur Richard
Published: August 2004

On May 5, 2003, gefitinib (Iressa®, ZD1839) 250-mg tablets received accelerated approval by the U.S. Food and Drug Administration as monotherapy treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of both platinum-based and docetaxel chemotherapies. Information provided in this summary includes efficacy and safety results of relevant clinical trials. Effectiveness was demonstrated in a randomized, double-blind, phase II, multicenter trial comparing two oral doses of gefitinib (250 mg/day versus 500 mg/day). Two hundred sixteen patients were enrolled. The 142 patients who were refractory to or intolerant of a platinum and docetaxel comprised the evaluable population for the efficacy analysis. A partial tumor response occurred in 14% (9 of 66) of patients receiving gefitinib 250 mg/day and in 8% (6 of 76) of patients receiving gefitinib 500 mg/day. The overall objective response rate for both doses combined was 10.6% (15 of 142 patients) (95% confidence interval 6.0%–16.8%). Responses were more frequent in females and in nonsmokers. The median duration of response was 7.0 months (range 4.6–18.6+ months).

Other submitted data included the results of two large trials conducted in chemotherapy-naive, stage III and IV NSCLC patients. Patients were randomized to receive gefitinib (250 mg or 500 mg daily) or placebo, in combination with either gemcitabine plus cisplatin (n = 1,093) or carboplatin plus paclitaxel (n = 1,037). Results from those studies showed no benefit (response rate, time to progression, or survival) from adding gefitinib to chemotherapy. Consequently, gefinitib is only recommended for use as monotherapy. Common adverse events associated with gefitinib treatment included diarrhea, rash, acne, dry skin, nausea, and vomiting. Most toxicities were Common Toxicity Criteria grade 1 or 2. Interstitial lung disease (ILD) has been observed in patients receiving gefitinib. Worldwide, the incidence of ILD is about 1% (2% in the Japanese postmarketing experience and about 0.3% in a U.S. expanded access program). Approximately one-third of the cases were fatal. Physicians should promptly evaluate new or worsening pulmonary symptoms. If ILD is confirmed, appropriate management includes discontinuation of gefitinib. Gefitinib was approved under accelerated approval regulations on the basis of a surrogate end point response rate. No controlled gefitinib trials, to date, demonstrate a clinical benefit, such as improvement in disease-related symptoms or greater survival. Accelerated approval regulations require the sponsor to conduct further studies to verify that gefitinib therapy produces such a benefit.
The HER-2/neu Gene and Protein in Breast Cancer 2003: Biomarker and Target of Therapy
Authors: Ross Jeffrey S. , Fletcher Jonathan A. , Linette Gerald P. , Stec James , Clark Edward , Ayers Mark , Symmans W. Fraser , Pusztai Lajos , Bloom Kenneth J.
Published: August 2004

Learning Objectives

After completing this course, the reader will be able to:

Define the historical background and biological basis of the discovery of the HER-2/neu gene and its first use as a prognostic factor in breast cancer. Recall the uses of HER-2/neu testing prior to the approval of trastuzumab including the impact on anthracycline adjuvant and first-line chemotherapy responses. Explain the basic principles of all the HER-2/neu tests in clinical practice: IHC, FISH, Southern blot, PCR, tissue ELISA, and serum ELISA. Contrast the pros and cons and uses and limitations of the IHC versus the FISH approach to HER-2/neu testing. Critique the most recent data comparing IHC with FISH for the prediction of response to single-agent trastuzumab and trastuzumab in combination with standard chemotherapy for advanced metastatic breast cancer. Describe the HER-2/neu expression patterns in all types of breast conditions, including in situ carcinoma, lobular versus ductal carcinoma, Paget's disease, male breast cancer, breast sarcomas, and benign breast disorders.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com

The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor. In this review, the association of HER-2/neu gene and protein abnormalities with prognosis and response to therapy with trastuzumab and to other therapies in breast cancer is presented. By considering a series of 80 published studies encompassing more than 25,000 patients, the relative advantages and disadvantages of Southern blotting, polymerase chain reaction amplification, and fluorescence in situ hybridization assays designed to detect HER-2/neu gene amplification are compared with HER-2/neu protein overexpression assays performed by immunohistochemical techniques applied to frozen and paraffin-embedded tissues and enzyme immunoassays performed on tumor cytosols. The significance of HER-2/neu overexpression in ductal carcinoma in situ and the HER-2/neu status in uncommon female breast conditions and male breast cancer are also considered. The role of HER-2/neu testing for the prediction of response to trastuzumab therapy in breast cancer is presented as well as its potential impact on responses to standard and newer hormonal therapies, cytotoxic chemotherapy, and radiation. The review also evaluates the status of serum-based testing for circulating HER-2/neu receptor protein and its ability to predict disease outcome and therapy response.
Behavioral Risk Factors in Breast Cancer: Can Risk Be Modified?
Authors: McTiernan Anne
Published: August 2004

The International Agency for Research on Cancer estimates that 25% of breast cancer cases worldwide are due to overweight/obesity and a sedentary lifestyle. The preponderance of epidemiologic studies indicates that women who engage in 3–4 hours per week of moderate to vigorous levels of exercise have a 30%-40% lower risk for breast cancer than sedentary women. Women who are overweight or obese have a 50%-250% greater risk for postmenopausal breast cancer. Alcohol use, even at moderate levels (two drinks per day) increases risk for both premenopausal and postmenopausal breast cancer. Certain dietary patterns, such as high fat, low vegetables/fruits, low fiber, and high simple carbohydrates, may increase risk, but definitive data are lacking. These lifestyle factors are likely associated with breast cancer etiology through hormonal mechanisms. The worldwide trends of increasing overweight and obesity and decreasing physical activity may lead to an increasing incidence of breast cancer unless other means of risk reduction counteract these effects. Thus, adoption of lifestyle changes by individuals and populations may have a large impact on the future incidence of this disease.