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Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Jean-Luc Harousseau

Edited by Kerrin G. Robinson

The introduction of novel agents (thalidomide, bortezomib, lenalidomide) is changing the management of patients with multiple myeloma who are candidates for stem cell transplantation. Bortezomib-dexamethasone given as induction treatment before autologous stem cell transplantation is significantly superior to the classical vincristine-doxorubicin-dexamethasone regimen in terms of complete response and very good partial response, both before and after transplantation. Triple combinations with thalidomide and bortezomib plus either cyclophosphamide or doxorubicin also yield excellent response rates, with the combination of bortezomib with thalidomide and dexamethasone seeming to be the most promising. Postautologous transplantation maintenance with thalidomide improves the response rate, progression-free survival, and, in some subgroups, overall survival. However, the optimal dose and duration of administration of thalidomide is not known. Both lenalidomide and bortezomib are being evaluated in this setting. The addition of novel agents before and after autotransplant yields a very high complete response rate and prolonged progression-free and overall survival. However, outstanding results have also been achieved with novel agents without transplantation. Therefore, randomized trials comparing novel agents with and without early transplantation are awaited. Tandem autologous plus reduced-intensity conditioning allogeneic transplantation have replaced myeloablative conditioning allogeneic transplantation. Despite improved results and decreased toxic death rate, this approach still carries the risk for morbidity and mortality related to graft-versus-host disease and should not be proposed in front-line therapy, especially in patients with no adverse prognostic features.

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Strategy for Incorporating Molecular and Cytogenetic Markers into Acute Myeloid Leukemia Therapy

Mark G. Frattini and Peter G. Maslak

Edited by Kerrin G. Robinson

Acute myeloid leukemia is a heterogeneous disease. Standard treatments may be applied to biologically distinct subgroups, resulting in different treatment outcomes. The concept of risk-adapted therapy allows for recognition of this biologic diversity by incorporating key biologic features, such as cytogenetic and molecular markers, when formulating treatment regimens and investigating emerging targeted therapies based on disease characteristics.

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Neoadjuvant Chemotherapy in Stage III NSCLC

Jeffrey Allen and Mohammad Jahanzeb

Edited by Kerrin G. Robinson

Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related mortality in the United States. Current standard care for treating NSCLC is surgical resection, when feasible, followed by adjuvant chemotherapy in stages II and III. Neoadjuvant or induction chemotherapy may have several potential advantages compared with adjuvant chemotherapy and has been evaluated in randomized and nonrandomized clinical trials in NSCLC. This article reviews the data for neoadjuvant chemotherapy in NSCLC with a particular focus on regionally advanced disease (stage III) that is still amenable to surgical resection.

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Intravenous Iron in Oncology

Michael Auerbach and Harold Ballard

Edited by Kerrin G. Robinson

Intravenous iron (IV Fe) as an adjunct to therapy with erythropoiesis-stimulatory agents (ESAs) is standard care in dialysis-associated anemia, adding huge increments in hemoglobin and hematopoietic responses and decreased transfusions without significant toxicity. Cost savings, decreased exposure to ESAs, and decreased times to reach target hemoglobins are realized. Although similar benefits have been seen in all studies performed in patients with chemotherapy-induced anemia (CIA), experts are reluctant to incorporate routine use of IV Fe into treatment, largely because of misinterpretation and misunderstanding of the clinical nature of adverse events reportedly associated with its administration. IV Fe is therefore underused in oncology patients with anemia. Published experience with more than 1000 patients in clinical trials involving the use of IV Fe suggests minimal toxicity and substantial benefit are experienced when high molecular weight iron dextran is avoided. This article presents evidence recommending routine incorporation of IV Fe into treatment for CIA.

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The Role of Inhibitors of the Epidermal Growth Factor in Management of Head and Neck Cancer

Bruce Brockstein, Mario Lacouture, and Mark Agulnik

Edited by Kerrin G. Robinson

Epidermal growth factor receptor (EGFR) is overexpressed in most head and neck cancers and correlates with poor prognosis. In the past few years, numerous clinical trials for head and neck cancer have tested monoclonal antibodies against EGFRs and small molecule inhibitors of EGFR tyrosine kinase. Results led to FDA approval of cetuximab with concomitant radiotherapy for treating locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN), and as a single agent in patients with recurrent or metastatic SCCHN for whom prior platinum-based therapy failed. This article reviews the biology of EGFR as it pertains to head and neck cancer, including the important clinical trials of EGFR monoclonal antibodies and tyrosine kinase inhibitors in SCCHN, alone and with concomitant radiotherapy. Molecular and clinical markers of response and outcome are also discussed.

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Combined Modality Therapy of Esophageal Cancer

Rosalyn A. Juergens and Arlene Forastiere

Edited by Kerrin G. Robinson

Esophageal cancer is a deadly disease. Only one third of patients with localized disease experience long-term survival. Over the past 20 years, investigators have evaluated neoadjuvant strategies to improve the outcomes of surgical management. Chemotherapy and radiation have been evaluated individually and in combination for preoperative management of patients with localized esophageal cancer. This article provides a critical review of the data on multimodality approaches to the management of esophageal cancer.

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Review of Evidence-Based Support for Pretreatment Imaging in Melanoma

Michael S. Sabel and Sandra L. Wong

Edited by Kerrin G. Robinson

When making a new diagnosis of melanoma, clinicians often obtain imaging studies to rule out clinically occult distant disease. These studies range from inexpensive tests, such as chest radiographs, to more expensive studies, such as PET/CT. The impetus for ordering these studies is usually the desire to identify potentially resectable distant disease, avoid surgery when curative resection is not possible, and assuage patient anxiety by showing that no evidence of distant disease is present. However, some detrimental aspects to these studies are less apparent, including cost and potential for false-positive findings. Although routine use seems reasonable, the true benefit of these studies depends on the probability of clinically occult disease being present, likelihood that disease will be detected with the available technology, and impact of earlier detection on outcome. Contrary to current practice patterns, available evidence suggests that preoperative imaging studies are associated with significant costs and minimal benefit in most patients with melanoma. This article reviews available literature on the role of pretreatment imaging in patients with newly diagnosed cutaneous melanoma.

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Transplantation for Hepatocellular Carcinoma and Cholangiocarcinoma

B. Daniel Campos and Jean F. Botha

Edited by Kerrin G. Robinson

Hepatocellular carcinoma (HCC) and cholangiocarcinoma represent more than 95% of primary hepatic malignancies in adults. The incidence of both seems to be rising. Any form of cirrhosis and primary sclerosing cholangitis represent independent risk factors for the development of HCC and cholangiocarcinoma, respectively. The surgical treatment of these malignancies has evolved significantly in the past decade, and liver transplantation (LT) has revolutionized the prognosis of these conditions. Provided both malignancies are diagnosed early in their natural history, LT offers a greater than 75% chance of survival at 4 years. This is a remarkable improvement in the treatment of primary hepatic malignancies and compares favorably with any other form of treatment, including partial liver resection. The application of specific pretransplantation staging criteria, along with the addition of neoadjuvant chemoradiation therapy for cholangiocarcinoma, has made these results possible. The development of living donor LT further expands the treatment horizon for both diseases. It also lessens the impact of the scarcity of available deceased donor organs available for transplantation. The future challenge is to better characterize biologic staging/prognostic indicators that could expand the understanding and success in treating both malignancies.

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Carcinosarcomas (Malignant Mixed Müllerian Tumor) of the Uterus: Advances in Elucidation of Biologic and Clinical Characteristics

Lauren E. Kernochan and Rochelle L. Garcia

Edited by Kerrin G. Robinson

Carcinosarcoma of the uterus (malignant mixed Müllerian tumor [MMMT]) is an uncommon, typically extremely aggressive neoplasm histologically composed of malignant epithelial and mesenchymal (stromal) elements. Although the literature contains some debate, most authors now agree that most MMMTs derive from sarcomatous differentiation in a high-grade carcinoma. This article reviews the clinical and histopathologic features of this interesting neoplasm, with particular emphasis on recent data supporting MMMTs as primarily epithelial malignant neoplasms with areas of mesenchymal/spindle cell differentiation.

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Optimal Management of Localized Renal Cell Carcinoma: Surgery, Ablation, or Active Surveillance

David Y. T. Chen and Robert G. Uzzo

Edited by Kerrin G. Robinson

Radical nephrectomy is historically accepted as standard treatment for localized renal cell carcinoma (RCC). However, the presentation of RCC has changed dramatically over the past 3 decades. Newer alternative interventions aim to reduce the negative impact of open radical nephrectomy, with the natural history of RCC now better understood. This article discusses current surgical and management options for localized kidney cancer.