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UFT/Methotrexate/Leucovorin for Breast Cancer Patients in Progression After HDCT/PBPC SupportTwenty-four patients with metastatic breast cancer that had progressed after high-dose chemotherapy with peripheral blood progenitor cell (PBPC) support were given intramuscular methotrexate in combination with oral
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HER2 Overexpression and Paclitaxel Sensitivity in Breast Cancer: Therapeutic ImplicationsOverexpression by the HER2 gene plays a significant role in breast cancer pathogenesis, and the phenomenon is commonly regarded as a predictor of a poor prognosis. HER2 overexpression has been linked to sensitivity and/or resistance to hormone therapy and chemotherapeutic regimens, including CMF (cyclophosphamide, methotrexate, and fluoro-uracil) and anthracyclines. Studies of patients with advanced disease demonstrate that, despite the association of HER2 overexpression with poor prognosis, the odds of HER2-positive patients responding clinically to taxanes were greater than three times those of HER2-negative patients. Further studies in preclinical models used combination therapy for breast cancer cells that overexpress HER2, and the use of agents that interfere with HER2 function plus paclitaxel (Taxol) resulted in significant antitumor effects. [ONCOLOGY 11(Suppl):43-48, 1997]
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Commentary (Botet): Management of Malignant Biliary Obstruction: Nonoperative and Palliative TechniquesThere has been a significant accumulation of collective experience with percutaneous biliary drainage (PCD) during the past 20 years. As experience with the technique has increased, its role has undergone a series of redefinitions, although early enthusiasm for percutaneous drainage has been tempered by the realities of numbers and statistics.
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The Era of Immuno-Oncology: Are We There Yet?The next few years hold great promise, as new agents emerge and others consolidate their place on our shelves. We will be forced to rethink strategies and redefine management as a new era of immuno-oncology dawns.
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Nonoperative Strategies for Rectal Cancer Following a Complete Clinical Response to Preoperative Chemoradiation: A Few ConsiderationsAlthough the current standard treatment for patients with locally advanced rectal cancer is preoperative chemoradiotherapy followed by total mesorectal excision, concerns have been raised over the functional sequelae and possible overtreatment of rectal cancer patients.
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Molecular Staging of Prostate Cancer: Dream or Reality?Dr. de la Taille and colleagues from Columbia University provide an overview of the concept of molecular staging” of prostate cancer using reverse transcriptase–polymerase chain reaction (RT-PCR). They do an admirable job of summarizing all of the currently available data on the results of this assay in the clinical staging of prostate cancer. As they note, only their group and one other have been able to demonstrate that a positive assay correlates with final pathologic stage. A limited number of other studies have suggested that the RT-PCR assay can predict prostate-specific antigen (PSA) recurrence.
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Oropharyngeal and Oral Cavity Cancer Surgical Practice GuidelinesThe Society of Surgical Oncology surgical practice guidelines focus on the signs and symptoms of primary cancer, timely evaluation of the symptomatic patient, appropriate preoperative evaluation for extent of disease, and role of the surgeon in
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The Promise of Pharmacogenomics: Gemcitabine and PemetrexedAlthough no overall differences in survival have been observed betweenthe many chemotherapy combinations in non–small-cell lungcancer, the clinical application of mRNA expression levels of amplifiedgenes may disclose many genetic influences on cytotoxic drug sensitivityand enable clinicians to tailor chemotherapy according to eachindividual’s gene profile. Specifically, the assessment of ribonucleotidereductase subunit M1 and thymidylate synthase mRNA expression levelsmight select patients who benefit from gemcitabine (Gemzar) orpemetrexed (Alimta) combinations. Until recently, clinical prognosticfactors such as performance status, weight loss, and lactate dehydrogenasewere the only parameters used to predict chemotherapy responseand survival. However, accumulated data indicate that overexpressionof genes involved in cancer glycolysis pathways plays an important role,and might be an independent mechanism of chemoresistance. Thedysregulation of glycolytic genes is affected by growth signals involvingthe PI3K/Akt pathway and downstream genes such as hypoxiainduciblefactor-1-alpha. One can thus envision that substantial improvementsin therapeutic outcome could benefit from the integrationof tailored ribonucleotide reductase-dependent chemotherapy, ribonucleotidereductase antisense therapy, and targeted therapy.
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Paraneoplastic Leukocytosis: An Unusual Manifestation of Squamous Cell Carcinoma of the Urinary BladderA 76-year-old woman with a history of dementia, hypertension, type 2 diabetes mellitus, and newly diagnosed squamous cell carcinoma of the urinary bladder was referred to Indiana University Medical Center after 3 to 4 weeks of hospitalization at two other hospitals.
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Breast Cancer Following Radiation for Hodgkin Lymphoma: Clinical Scenarios and Risk-Reducing StrategiesWe review available strategies for screening and risk reduction through chemoprevention or risk-reducing surgery, as well as challenges for management of breast cancer in patients with prior exposure to radiation for Hodgkin lymphoma.
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The Promise of Pharmacogenomics: Gemcitabine and PemetrexedAlthough no overall differences in survival have been observed betweenthe many chemotherapy combinations in non–small-cell lungcancer, the clinical application of mRNA expression levels of amplifiedgenes may disclose many genetic influences on cytotoxic drug sensitivityand enable clinicians to tailor chemotherapy according to eachindividual’s gene profile. Specifically, the assessment of ribonucleotidereductase subunit M1 and thymidylate synthase mRNA expression levelsmight select patients who benefit from gemcitabine (Gemzar) orpemetrexed (Alimta) combinations. Until recently, clinical prognosticfactors such as performance status, weight loss, and lactate dehydrogenasewere the only parameters used to predict chemotherapy responseand survival. However, accumulated data indicate that overexpressionof genes involved in cancer glycolysis pathways plays an important role,and might be an independent mechanism of chemoresistance. Thedysregulation of glycolytic genes is affected by growth signals involvingthe PI3K/Akt pathway and downstream genes such as hypoxiainduciblefactor-1-alpha. One can thus envision that substantial improvementsin therapeutic outcome could benefit from the integrationof tailored ribonucleotide reductase-dependent chemotherapy, ribonucleotidereductase antisense therapy, and targeted therapy.
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Triple-Negative Breast Cancer: Not Entirely NegativeTriple-negative breast cancer (TNBC) remains a very challenging entity today, but with the identification of new targets and further optimization of therapy, the landscape for TNBC may not look so negative. In the future, “TNBC” may be considered an antiquated misnomer, as we will have identified various breast cancer subgroups based on what they “are” rather than what they “are not.”
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Genomic Testing in Colorectal Cancer: How Much Is Enough?The identification and characterization of gene signatures, driver events, and pharmacogenomics in molecularly homogeneous subsets of patients is likely to advance effective drug development strategies in colorectal cancer.
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Further Perspectives on Treating Localized Prostate CancerStandard treatment options for prostate cancer patients include surveillance, surgery, external-beam radiotherapy, brachytherapy, the combination of external-beam and brachytherapy, and the combination of radiotheraputic modalities with hormonal therapy, for appropriately chosen patients.
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Gene Therapy for Head and Neck CancersDespite advances in surgery, radiotherapy, and chemotherapy, survival of patients with squamous cell carcinoma of the head and neck has not significantly improved over the past 30 years. Locally recurrent or refractory disease is particularly difficult to treat. Repeat surgical resection and/or radiotherapy are often not possible, and long-term results for salvage chemotherapy are poor. Recent advances in gene therapy have been applied to recurrent squamous cell carcinoma of the head and neck. Many of these techniques are now in clinical trials and have shown some efficacy. This article discusses the techniques employed in gene therapy and summarizes the ongoing protocols that are currently being evaluated in clinical trials. [ONCOLOGY 15(3):303-314, 2001]
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Management of Hot Flushes Due to Endocrine Therapy for Prostate CarcinomaEndocrine manipulation plays a crucial role in the treatment of advanced prostate carcinoma. Recent enthusiasm for earlier use of endocrine therapy has increased the significance of diminishing treatment-related side effects,
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Gene Expression Assays in Early-Stage Breast CancerDr. Sparano discusses the implications of TAILORx, the first trial to use Oncotype DX in clinical decision making.
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New SSRI Antidepressants Offer Advantages in Cancer PatientsA 43-year-old married man was referred to Memorial Sloan-Kettering Cancer Center in June, 1995, for further management of a malignant brain tumor. He was asymptomatic until April, 1994, when he suffered a generalized seizure and was admitted to a local hospital. An MRI revealed a right parietal lobe lesion. The tumor was resected and found to be a glioblastoma multiforme.
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Graft Purging in Autologous Bone Marrow Transplantation: A Promise Not Quite FulfilledClonogenic tumor cells contained within hematopoietic stem cell(HPC) grafts may contribute to relapse following autologous transplantation.Graft purging involves either in vivo or ex vivo HPC manipulationin order to reduce the level of tumor cell contamination.Some phase II trials suggest that patients who receive purged productsmay have a superior transplant outcome. Phase I trials demonstratethe feasibility of purging methods including ex vivo graft incubationwith chemotherapeutic drugs, monoclonal antibodies and complement,and CD34+ cell selection. A phase II trial in follicular non-Hodgkin’slymphoma demonstrates that patients who receive HPC products purgednegative for bcl-2 gene rearrangements have a superior outcome, comparedwith patients who receive polymerase chain reaction (PCR)-positiveproducts. This finding, however, has not been confirmed in a randomizedtrial. HPC purging has demonstrated no benefit in a phase IIItrial in myeloma. Phase II trials in acute myelogenous leukemia showcomparable outcomes for patients who receive either purged orunpurged HPC grafts. Limitations of purging include possible progenitorcell loss, delayed engraftment, and qualitative immune defects followingtransplant. Data to justify routine use of HPC graft purging areinsufficient. Phase I and II data support development of phase III trialsof both in vivo and in vitro purging methods.
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Transanal Excision of Rectal Cancer: A Work in ProgressThe exact role of combined-modality therapy and TAE of rectal cancer remains to be defined. Certainly the stakes are high, as studies have shown that the recurrence of locally excised rectal cancer is associated with worse long-term survival outcomes.
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The Prostate Cancer Intervention Versus Observation Trial (PIVOT)The Prostate Cancer Intervention Versus Observation Trial (PIVOT) is a randomized trial designed to determine whether radical prostatectomy or expectant management provides superior length and quality of life for men with clinically localized prostate cancer. Conducted at Department of Veterans Affairs and National Cancer Institute medical centers, PIVOT will enroll over 1,000 individuals less than 75 years of age. The primary study end point is all-cause mortality. Secondary outcomes include prostate cancer- and treatment-specific morbidity and mortality, health status, predictors of disease-specific outcomes, and cost-effectiveness. Within the first 3 years of enrollment, over 400 men have been randomized. Early analysis of participants' baseline characteristics indicate that enrollees are representative of men diagnosed with clinically localized prostate cancer throughout the United States. Therefore, results of PIVOT will be generalizable. These results are necessary in order to determine the preferred therapy for clinically localized prostate cancer. [ONCOLOGY 11(8):1133-1143, 1997]
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Management of Primary and Metastatic Tumors to the LiverThis comprehensive report summarizes the current management of primary liver cancer and of metastatic colorectal cancer in the liver. Numerous tests to help define the location and stage of disease have been evaluated. It now appears that spiral CT with arterial portography is superior to other nonoperative methods in evaluating liver tumors. Immunoscintography using monoclonal antibodies is currently under development and appears to be of potential great value. Subclinical, micrometastatic disease is the bane of all efforts at surgical control of cancer. An ability to detect this would have far-reaching consequences. Complete evaluation of patients with these diseases must include a medical evaluation, including liver function tests and a chest CT. Particular attention must also be paid to cardiac, pulmonary, and renal function.
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Tumor Hypoxia and the Future of Cancer ManagementThe role of hypoxia as a key determinant of outcome for human cancers has encouraged efforts to noninvasively detect and localize regions of poor oxygenation in tumors. In this review, we will summarize existing and developing techniques for imaging tumoral hypoxia. A brief review of the biology of tumor oxygenation and its effect on tumor cells will be provided initially. We will then describe existing methods for measurement of tissue oxygenation status. An overview of emerging molecular imaging techniques based on radiolabeled hypoxic markers such as misonidazole or hypoxia-related genes and proteins will then be given, and the usefulness of these approaches toward targeting hypoxia directly will be assessed. Finally, we will evaluate the clinical potential of oxygen- and molecular-specific techniques for imaging hypoxia, and discuss how these methods will individually and collectively advance oncology.
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Plastic Surgery: A Component in the Comprehensive Care of Cancer PatientsPart of the multidisciplinary approach to cancer care involves surgical intervention. This is harmoniously interwoven through the efforts of the surgical oncologist and the reconstructive surgeon. As elegantly pointed out by Drs. Hasen, Few, and Fine, the reconstructive surgeon’s role in the management of malignancy is critical, involving the restoration of form and function. Sometimes, as in breast reconstruction, quality of life is improved by the restoration of form; other times, as in head and neck reconstruction, it is improved by the restoration of form and function. In fact, due to the significant morbidity associated with major ablation of head and neck cancer, such radical surgery would not be feasible without concomitant reconstruction.
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Thromboembolism and Bleeding in Bladder CancerOverall, approximately 2% of patients with bladder cancer will experience a venous thromboembolism event, a rate five times higher than that in the overall population; also, such an event results in a threefold increased risk of death in patients with cancer.
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Palliative Radiotherapy for Prostate CancerThis review will include discussion of the role of radiation therapy for osseous metastases and metastatic spinal cord compression, as well as the use of radiopharmaceuticals for painful osseous metastases.
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Prostate CancerThis management guide covers the treatment, diagnosis, and staging of prostate cancer.
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Book Review:Wintrobe’s Clinical Hematology, 10th EditionThe 10th edition of Wintrobe’s Clinical Hematology is a two volume, multiauthored work that spans the ever-expanding discipline of hematology in over 2,600 pages. The book is appropriately introduced by an excellent short chapter written previously by Dr. Wintrobe on “The Diagnostic and Therapeutic Approach to Hematologic Problems.” There follows a valuable series of six chapters totaling 133 pages devoted to laboratory hematology, including blood and bone marrow examination, immunodiagnosis, clinical flow cytometry, cytogenetics, clusters of differentiation, and molecular genetics. These chapters contain ample illustrations, diagrams, tables, and references.
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Evaluation and Definitive Management of Medically Inoperable Early-Stage Non-Small-Cell Lung Cancer: Part 2Lung cancer is estimated to be the second most commonly diagnosed cancer in both men and women in 2006, and the leading cause of cancer mortality. Non-small-cell lung cancer represents the majority of such cases. Most of these patients have locally advanced disease at presentation and are not eligible for curative resection. For the minority of patients who are technically resectable at presentation, lobectomy or pneumonectomy and pathologic mediastinal nodal staging offer the best overall survival. The high rate of comorbid medical illness and poor baseline pulmonary function in this population, however, make many such early-stage patients medically inoperable. For these patients, conventional single-modality radiotherapy has been the primary definitive treatment option, as discussed in part 1 of this article, which appeared in last month's issue. Numerous retrospective reports demonstrate long-term disease-free and overall survival data that are modestly superior to that expected after observation, but both local and distant failure continue to be significant risks. Investigation of radiotherapy dose escalation is ongoing, in an effort to improve local control while maintaining minimal toxicity. Additionally, emerging evidence suggests that new modalities, such as stereotactic radiosurgery and radiofrequency ablation, may also be potentially curative treatment alternatives. These modalities are addressed in part 2.
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Who Should-or Should Not-Receive RT for DLBCL?As we examine the question of which patients with DLBCL do not need RT, the first step must be to confine our review to patients who have received optimal chemotherapy.
