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Research shows that chemotherapy for inoperable non-small-cell lung cancer (NSCLC) improves survival. The economic implications of this treatment choice may be substantial. This paper reviews studies examining the cost-

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Exciting advances in understanding the biology of lung cancer have occurred over the last few years.

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The optimal management of opioid-related side effects is hampered by a lack of comparative studies of management strategies. The prevalence of such side effects is influenced by the extent of disease, the patient’s

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In the conclusion to the article “Proton Radiation Therapy for Lung Cancer: Is There Enough Evidence?” Dr. David Bush puts his finger on the critical issue underlying most debates about the value of new medical technologies. He notes that “The evidence required to bring new technology into clinical practice is poorly defined.”[1] In the specific context of this article, the answer to the question of whether or not there is enough evidence depends entirely on how one chooses to define “enough.” Some experts believe that biological modeling based on dose distributions is sufficient to conclude that proton therapy improves health outcomes. Others have argued that the evidence is only adequate once randomized clinical trials have been completed to directly compare alternative interventions. Whatever one’s position on this issue, the lack of clarity on the question of adequacy of evidence is a major contributor to the gaps in knowledge about the comparative effectiveness of many widely used clinical interventions. Accelerating the rate at which this knowledge is generated will require a serious and sustained effort to define these evidence thresholds. This would allow more energy to be channeled into generating the needed evidence and less energy to be devoted to debating whether or not the evidence we have today is good enough.

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Although the optimal route of administration of opioids is by mouth, some patients may require alternative routes during the course of their illnesses for several reasons. These include bowel obstruction, severe emesis, or severe

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Results from the ECOG-ACRIN E4112 trial appear to support the use of DCIS scores for identifying patients with breast cancer who may be eligible to omit radiotherapy following MRI-guided surgery.

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Supportive care remains the mainstay of therapy for patients withmyelodysplastic syndrome (MDS). Although allogeneic bone marrowtransplantation is the only known curative therapy for MDS, its risksmake this treatment prohibitive in many patients, who tend to be olderand have other medical problems. With advances in hematopoietic stemcell transplantation (HSCT), we can offer transplant to an increasingnumber of patients. It is, however, necessary to assess each patient andhis or her disease individually and evaluate prognostic factors, treatmentoptions, appropriateness of HSCT, and, if appropriate, type andtiming of HSCT. We will review the data on HSCT in MDS in order toexamine each of these issues and clarify the decision-making process.

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Although data are anecdotal, there is no question that the increased numbers of patients with insurance resulted in cancer patients receiving care they previously could not.

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Although 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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Gastric cancer is a major clinical challenge, with poor overall prognosisand limited life expectancy for patients with advanced disease.Even with surgery and other modalities, palliation is often difficult.Improvement of response rates has evolved with the development ofstandard regimens and those incorporating newer chemotherapy agents,such as oral fluoropyrimidines, the taxanes, camptothecins, novel platinums(eg, oxaliplatin [Eloxatin]), and antifolates (eg, pemetrexed[Alimta]). Ongoing trials with these regimens aim toward improvingsurvival, as well as improving the safety profile. It is hoped that in conjunctionwith molecular research in the pathogenesis of gastric cancerand development of targeted therapies in this disease, these trial datamight lead to the evolution of treatment strategies that could prove effective.

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The review by Beth Peshkin andClaudine Isaacs in this issue ofONCOLOGY is an excellentoverview of the recognition, evaluation,and clinical management ofwomen with BRCA1 and BRCA2mutations. It is comprehensive andpractical, and emphasizes the approachthat a risk assessment and clinicalgenetics program might take tothe evaluation of an individual concernedabout the possibility thathereditary breast/ovarian cancer predispositionmight be present in herkindred. The authors clearly and conciselypresent the risks of breast, ovarian,and other cancers associated withBRCA1 and BRCA2 mutation carrierstatus, as well as some of the issues thathave arisen in the estimation of thoserisks. They provide a review of factorsthat may modify gene penetrance(cancer risks), and devote the finalsegment of their article to a clear andrational discussion of the surveillanceand preventive options available forthe management of the associatedbreast and ovarian cancer risks.

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Shabason et al have written a thoughtful review of an exciting new class of agents, histone deacetylase (HDAC) inhibitors. While the authors focus primarily on the role of HDAC inhibitors in combination with radiation therapy, we would like to highlight some potential strategies combining these agents with systemic therapies for the treatment of cancer.

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High-dose myeloablative therapy with allogeneic hematopoietictransplantation is an effective treatment for hematologic malignancies,but this approach is associated with a high risk of complications.The use of relatively nontoxic, nonmyeloablative, or reduced-intensitypreparative regimens still allows engraftment and the generation ofgraft-vs-malignancy effects, is potentially curative for susceptiblemalignancies, and reduces the risk of treatment-related morbidity.Two general strategies along these lines have emerged, based on theuse of (1) immunosuppressive chemotherapeutic drugs, usually apurine analog in combination with an alkylating agent, and (2) lowdosetotal body irradiation, alone or in combination with fludarabine(Fludara).

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A 68-year-old man is referred for further evaluation and treatment of jaundice. He describes pruritus, intermittent mild midabdominal discomfort, and progressive weight loss. There is no history of fever. His history is significant for renal cell carcinoma with pulmonary metastasis.

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Management of ductal carcinoma in situ (DCIS) commonly involves excision, radiotherapy, and hormonal therapy. Radiotherapy is employed for local control in breast conservation. Evidence is evolving for several radiotherapy techniques exist beyond standard whole-breast irradiation.

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Complication rates in 1,000 consecutive patients who underwent radical retropubic prostatectomy for clinically localized prostate cancer between November 1989 and January 1992 were assessed and compared to complication rates in a historical group of patients operated on by primarily the same surgeons prior to 1987. In the contemporary series, there were no operative deaths, only 22% of patients required blood transfusion, and only six (0.6%) patients suffered rectal injuries. Early complications, including myocardial infarction, pulmonary embolism, bacteremia, and wound infection, occurred in less than 1% of patients. Vesical neck contracture, the most common late complication, developed in 87 patients (8.7%). At 1 year post-surgery, 80% of patients were completely continent, and fewer than 1% were totally incontinent. [ONCOLOGY 9(5):379-389, 1995]

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Sentinel node surgery potentially increases the accuracy of identifyinglymph nodes that contain breast cancer and decreases morbiditycompared to conventional axillary lymph node resection. However, nolong-term comparisons of the two modalities have been carried out,and the survival benefit associated with one protocol vs the other remainsunknown. Although sentinel node surgery is not expected to increasethe cure rate of breast cancer patients, a significant reduction inthe incidence of permanent side effects associated with axillary noderesection will be a considerable advance. The completion of clinicaltrials establishing that no meaningful reduction in survival is associatedwith the decrease in side effects is important.

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Occult distant micrometastasis at the time of radical cystectomy leads predominantly to distant failures in patients with locally advanced muscle-invasive transitional cell carcinoma of the bladder. Cisplatin-based combination chemotherapy enhances survival in patients with metastatic urothelial cancer. Studies evaluating adjuvant chemotherapy have been limited by inadequate statistical power. However, randomized clinical trials have demonstrated a survival benefit for neoadjvuant cisplatin-based combination chemotherapy, which should be considered a standard of care. In addition, neoadjuvant therapy may assist in the rapid development of novel systemic therapy regimens, since pathologic complete remission appears to be a powerful prognostic factor for long-term outcomes. Patients who are either unfit for or refuse radical cystectomy may benefit from neoadjuvant chemotherapy with or without radiation to enable bladder preservation.

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In February 21, I presented testimony on behalf of the Society before the Senate Labor and Human Resources Committee during a hearing on Food and Drug

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The article by Bhatia and colleagues focuses on the treatment of patients with metastatic melanoma using standard therapies, but it also includes a brief outline of recent treatment approaches using investigational agents. In addition, the authors describe prognostic factors for metastatic melanoma, highlighting the impact of the extent of tumor and the site of metastasis (eg, soft-tissue vs visceral metastases) on survival.

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A 60-year-old man presented with lower limb claudication and a painful mass on his left buttock. Physical examination revealed a firm round mass, fixed to deep planes. A biopsy was performed and revealed a chordoma.

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In this review, we critically analyze clinical trials that were specifically designed for the very elderly, and we discuss the challenges encountered by investigators who are conducting studies in this patient population. We conclude by proposing an algorithm to help clinicians determine the optimal therapeutic strategy for treatment of DLBCL in very elderly patients.

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The review by Gururangan andFriedman takes an interestingand informative approach to pediatricbrain tumors in emphasizingthe possible biologic bases for chemotherapyfailure in these neoplasmsin general, and focusing on newer, asyet largely unproven, strategies employing“biologic” therapies to circumventsuch mechanisms of tumor resistance.Many of these newer treatment strategiesare drawn from the work of theauthors and others in the field of adultmalignant gliomas. To date, minimalprogress has been achieved in improvingoutcome for children with malignantsupratentorial gliomas andbrainstem tumors. Hopefully, these newstrategies will have significant benefitin pediatric as well as adult patients.

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APBI is a technique that offers women with early-stage breast cancer a choice. The preponderance of evidence supports the efficacy and safety of this technique, and it should continue to be offered to appropriately selected patients on and off protocol.

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Given the current rate of progress in this field, it may not be completely unlikely that women with hormone receptor–positive breast cancer will be cured of this disease in the foreseeable future.

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This review will focus on properties of cancer stem cells; will compare and contrast the cancer stem cell model with the clonal evolution model of tumorigenesis; will discuss the role of cancer stem cells in the development of resistance to chemotherapy; and will review the therapeutic implications and challenges of targeting cancer stem cells, with an assessment of the potential such an approach holds for improving outcomes for patients with cancer.

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Most physicians are less aware of clinical presentations of the various heavy chain diseases, due in great part to their low incidence and highly variable clinical course. Heavy chain diseases are rare lymphoproliferative B-cell disorders whose hallmark is the accumulation and secretion of truncated constant heavy chains without the associated light chains.

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Conventional histopathologic evaluation of bladder cancer, encompassing tumor grade and stage, is inadequate to accurately predict the behavior of most bladder tumors. Intense research efforts are under way to identify and