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What Is the Role of Maintenance Rituximab in Follicular NHL?Recent trials have demonstrated improvements in progression-free and overall survival with the inclusion of the chimeric anti-CD20 monoclonal antibody rituximab (Rituxan) in chemotherapy regimens for treatment-naive and relapsed patients with advanced-stage follicular non-Hodgkin's lymphoma (NHL). As rituximab therapy has significant single-agent activity in follicular NHL, is generally well tolerated, and has no dose-limiting or significant hematologic toxicity, a number of approaches evaluating maintenance therapy with extended dosing of rituximab are being tested. Trials have demonstrated prolonged progression-free survival in patients treated with maintenance rituximab using a variety of schedules following treatment with single-agent rituximab, induction or salvage chemotherapy, or salvage therapy with rituximab and chemotherapy combinations. Small increases in neutropenia and infections have been reported with extended rituximab use. Ongoing trials are evaluating the optimal use of rituximab (maintenance vs retreatment) and the benefit of rituximab maintenance following treatment of therapy-naive patients treated with rituximab-containing chemoimmunotherapy induction regimens. This article discusses the risks and benefits of maintenance rituximab for follicular NHL.
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Combining Artificial Neural Networks and Transrectal Ultrasound in the Diagnosis of Prostate CancerDrs. Porter and Crawford carefullyassess the role of artificialneural networks (ANNs)as predictive models of outcomes forinitial prostatic biopsies performed inconjunction with transrectal ultrasound(TRUS). Obviously, the treatmentof prostate cancer rests onestablishing the diagnosis via biopsy,and TRUS-guided core biopsies havebeen the standard of care since Hodgeet al reported the superiority of thistechnique in 1989.[1]
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Gynecologic Manifestations of Hereditary Nonpolyposis Colorectal CancerHereditary nonpolyposis colorectal cancer (HNPCC) is an autosomaldominant cancer susceptibility syndrome associated with inheriteddefects in the DNA mismatch repair system. HNPCC family membersare at high risk for developing colorectal, endometrial, and ovariancancers. Studies of HNPCC families have helped define the importantrole that mismatch repair genes play in the molecular pathogenesis ofendometrial and ovarian cancers. This review will describe some of theimportant clinical and molecular features of HNPCC-related endometrialand ovarian cancer and describe how genetic susceptibility can beidentified in patients with sporadic endometrial and ovarian cancers. Itis important to identify patients with HNPCC, as families of mutationcarriers may benefit from genetic counseling, testing, and intensifiedcancer surveillance.
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Commentary (Lim et al): Revisiting Induction Chemotherapy for Head and Neck CancerArgiris and colleagues report asystematic review evaluatingthe activity and potential roleof induction chemotherapy in patientswith previously untreated, locoregionallyadvanced squamous cell head andneck cancer.[1] They consider bothphase II and III published trials. Thedata reviewed in their paper, and theirthoughtful synthesis and interpretationof these data, highlight certain themes:
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Improving Childhood Cancer Survivor Care Through Web-Based PlatformsHere, we review the barriers to adherence, including those unique to childhood cancer survivors, and the rationale for distribution of a survivorship care plan. We also discuss advantages and potential limitations of delivering survivorship care plans via web-based platforms, and describe the unique features of one of these platforms, Passport for Care.
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Paclitaxel as First-Line Treatment for Metastatic Breast CancerWhen administered as a single agent in pretreated patients with advanced breast cancer, paclitaxel (Taxol) exhibits remarkable antitumor activity. This trial was undertaken to compare paclitaxel with standard
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Getting to the Heart of Improving Outcomes for Patients With Acute Promyelocytic LeukemiaThe management of patients with acute promyelocytic leukemia (APL) has been transformed over the course of the last two decades following the introduction of successful molecularly targeted therapies-all-trans retinoic acid (ATRA) and arsenic trioxide (ATO)- which act in concert to induce degradation of the PMLRARα oncoprotein formed by the chromosomal translocation t(15;17)(q22;q21).
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The Role of Intravenous Iron in Cancer-Related AnemiaPatients with cancer may have an absolute or functional iron deficiency as a result of their disease or its treatment. These conditions can lead to an insufficient supply of iron for incorporation into erythrocytes during supportive care with erythropoiesis-stimulating proteins for chemotherapy. The use of supplemental iron therapy is well established in patients with chronic kidney disease and anemia, but less well studied in the oncology/hematology setting. Furthermore, the use of oral iron formulations in patients with cancer and anemia is limited by poor absorption in the duodenum, arduous dosing requirements (three times a day), and a high likelihood of gastrointestinal side effects. Two recent studies have shown that intravenous (IV) iron (iron dextran or ferric gluconate) increases the hematopoietic response rates in cancer patients who were receiving chemotherapy and treated with epoetin alfa (Procrit) for anemia. The effects on hemoglobin levels and measures of iron metabolism were notably greater with IV iron formulations than with oral iron formulations. The results from several ongoing trials of IV iron in patients treated with epoetin alfa or darbepoetin alfa (Aranesp) for chemotherapy-induced anemia should lead to a greater understanding of the role of IV iron supplementation in improving the hematopoietic responses in these patients.
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Preoperative Therapy in Esophageal Cancer: Controversy and ConsensusDr. Krasna has written an overview of multimodality therapy in esophageal cancer, with a particular focus on aspects related to staging and surgical care. The optimal management of locally advanced esophageal cancer remains a subject of controversy and active debate. However, there is now a clear consensus that surgery alone is inadequate therapy for patients with T3 or node-positive disease.
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Commentary (Chung/Johnson): Targeting the Epidermal Growth Factor ReceptorThe epidermal growth factor receptor (EGFR) promotes the growth of different cell types and has been implicated in tumorigenesis. The EGFR comprises a family of four structurally similar tyrosine kinases with a complex link to downstream signaling molecules that ultimately regulate key cell processes. Anti-EGFR agents have been developed as promising therapeutic anticancer targets, and some have been recently approved for the treatment of non-small-cell lung cancer and colon cancer. The two anti-EGFR therapies with the greatest clinical application are monoclonal antibodies that block the binding of ligands to EGFR and small-molecule tyrosine kinase inhibitors that inhibit the binding of adenosine triphosphate to the internal tyrosine kinase receptor of EGFR. We attempt to give an overview of the EGFR function and biology, focusing on the most important clinical findings and applications of EGFR inhibitors in lung and head and neck cancer.
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ACR Appropriateness Criteria® Adjuvant Management of Early-Stage Endometrial CancerAfter a review of the published literature, the panel voted on three variants to establish best practices for the utilization of imaging, radiotherapy, and chemotherapy after primary surgery for early-stage endometrial cancer.
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Endoscopic Ultrasound Fine-Needle Aspiration in the Staging of Non‑Small‑Cell Lung CancerPrecise mediastinal staging of non-small-cell lung cancer is extremely important, as mediastinal lymph node metastases generally indicate unresectable disease. Reliance on computed tomography (CT) and positron-emission tomography (PET) alone to stage and determine resectability is limited by false-positive results. Whenever possible, pathologic confirmation of metastases is desirable. Mediastinoscopy and transbronchial fine-needle aspiration are widely established but imperfect modalities. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) has emerged as a diagnostic and staging tool because of its safety, accuracy, and patient convenience. We reviewed 13 prospective studies evaluating the comparative performance of EUS for staging lung cancer. We conclude that EUS is a valuable staging modality. Further studies of the role of EUS compared to other modalities such as integrated PET/CT and endobronchial ultrasound (EBUS) are forthcoming.
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Recent Advancements and Future Directions in Frontline Treatment of Multiple MyelomaKimberley R. Doucette, MD, MSC; and David H. Vesole, MD, PhD, discuss updates to frontline treatment in multiple myeloma.
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Current Management of Cancer-Associated Anorexia and Weight LossIn their article in this issue, Drs. Jatoi and Loprinzi review much of the data on weight loss and anorexia in cancer patients from the standpoint of the impact of nutrition and various pharmacologic agents on management, and they make some sound recommendations for therapy. The benefit of nutritional interventions in this area are often overhwhelmed by the patient’s complex disease course and, therefore, are difficult to demonstrate.
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The Evolving Approach to Management of Cancer CachexiaCancer patients are often referred for cachexia intervention treatments late in their disease trajectory-that is, at a point where attempts to reverse the weight loss process may be less beneficial. In addition, healthcare professionals frequently under-recognize the prevalence of cancer cachexia, and this may contribute to delayed treatment of weight loss, often until the refractory stage.
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The Current Clinical Value of the DCIS ScoreThe DCIS Score provides clinically relevant information about personal risk that can guide patient discussions and facilitate shared decision making.
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The Role of Neck Dissection Following Definitive ChemoradiationThe presence of regional nodal metastases represents a significantadverse prognostic factor for patients with squamous cell carcinoma ofthe head and neck. Early-stage head and neck cancers, localized to theprimary site without regional lymph node metastases have excellentcure rates with either surgery or radiation therapy. The presence ofregional metastases results in cure rates that are approximately half ofthose obtainable in early-stage disease. Therefore, due to the significantadverse impact of neck metastases on prognosis, the treatment ofthe neck remains a vital part of the decision-making process in determiningtherapy for head and neck cancer.
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Salvage Chemotherapy for Refractory Germ Cell TumorsWhen relapse occurs in patients with germ cell tumors, two salvage treatment paradigms exist: standard-dose chemotherapy, or high-dose chemotherapy with autologous stem cell rescue.
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New Drugs Bring New QuestionsThe treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.
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Postoperative Radiation Therapy for Rectal Cancer Combined With UFT/LeucovorinPostoperative combined-modality therapy with fluorouracil (5-FU) and radiation therapy is accepted practice for high-risk rectal cancer. Postoperative pelvic radiotherapy alone may improve pelvic control, but is not associated with an improvement in survival.
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Commentary (Adelstein): The Role of Neck Dissection Following Definitive ChemoradiationThe recent recognition that theaddition of concurrent chemotherapyto definitive radiationcan improve locoregional control, organpreservation, and survival in patientswith squamous cell head andneck cancer has had a significant impacton our management choices.Chemoradiotherapy data from metaanalyses,cooperative group trials, andlarge tertiary care institutions now suggestthat there is a realistic potentialfor cure in almost all patients withlocoregionally confined disease, and thefocus has increasingly shifted towardthe impact of our treatments on longtermfunction. In the past, control ofneck node involvement often requireda comprehensive neck dissection, a procedureassociated with some degree oflong-term morbidity. In this review,Kutler, Patel, and Shah address the importantquestion of whether the neckdissection should be a planned componentin the management of patientstreated with definitive concurrentchemoradiotherapy.
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Proton Radiotherapy: The Good, the Bad, and the UncertainProton radiotherapy is here to stay. Despite the high initial cost, the number of proton therapy machines in the United States and elsewhere is increasing rapidly.[1] The major questions now relate to defining and optimizing their appropriate use.
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Do Families Understand "Do Not Resuscitate" Orders?Do not resuscitate (DNR) orders have become an integral part of the care of the terminally ill patient. Often, the decision whether or not to resuscitate a patient in the event of cardiopulmonary arrest must be made by the patient's family members. This is a difficult decision that is made at an emotionally trying time. Our study investigated the satisfaction, understanding, and feelings of families who sign DNR orders for their relatives. We are not aware of any other studies that have evaluated this aspect of the DNR order.
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Patterns of Chemotherapy Administration in Patients With Intermediate-Grade Non-Hodgkin’s LymphomaRecords from 653 patients treated between 1991 and 1998 in the Oncology Practice Patterns Study (OPPS) were analyzed to determine contemporary chemotherapy delivery patterns in patients with intermediate-grade non-
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Genome-Wide Association Studies of Cancer: Principles and Potential UtilityGenome-wide association studies (GWAS) have emerged as a new approach for investigating the genetic basis of complex diseases. In oncology, genome-wide studies of nearly all common malignancies have been performed and more than 100 genetic variants associated with increased risks have been identified. GWAS approaches are powerful research tools that are revealing novel pathways important in carcinogenesis and promise to further enhance our understanding of the basis of inherited cancer susceptibility. However, “personal genomic tests” based on cancer GWAS results that are currently being offered by for-profit commercial companies for cancer risk prediction have unproven clinical utility and may risk false conveyance of reassurance or alarm.
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Commentary (Hewitt): An Alternative Algorithm for Dosing Transdermal Fentanyl for Cancer-Related PainThe inadequate treatment of pain associated with malignancy remains a significant clinical problem.[1-4] Despite published guidelines on the appropriate management of cancer pain, 50% of dying patients experience moderate to severe pain.[1,5-8] One of the greatest barriers to the proper treatment of cancer pain remains health care professionals’ lack of knowledge regarding the appropriate use of analgesic medications.[9-11] The failure to refer to and limited availability of knowledgeable specialists in pain and palliative care also contribute to this pervasive problem.[12]
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Capecitabine/Irinotecan Combination Regimens in Colorectal CancerCapecitabine (Xeloda) and irinotecan (CPT-11, Camptosar) both have demonstrated single-agent activity in patients with colorectal cancer.
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Managing Thrombocytopenia Associated With Cancer ChemotherapyThis review will focus on the general approach to, and treatment of, thrombocytopenia in cancer patients, including thrombopoietin treatment in patients receiving non-myeloablative chemotherapy.
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Mohs Micrographic Surgery: Established Uses and Emerging TrendsMohs surgery has been well-established as the gold standard for the treatment of BCCs and SCCs. And, as described in this article, preliminary reports suggest that it may play an equally important role in the management of several other cutaneous malignancies.
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The Challenges of Treating Cancer Patients on Hemodialysis, or With Chronic Kidney DiseaseIt is challenging to diagnose, manage, and treat patients who have kidney disease in addition to cancer. Second to cardiovascular disease, cancer represents a major cause of mortality and morbidity in the kidney disease population.
