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Knowing the genetic makeup of patient tumors permits the development of new DNA-based diagnostics, such as BEAMing and PARE. By incorporating these new tools into future trials, we should be able to concurrently learn about drug resistance and significantly improve patient responses.

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This review describes the achievements in therapeutic and molecular diagnostics, details evolving molecular platforms, and highlights the challenges for the translation of these developments to daily clinical practice.

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In populations in whom there has been a focus on the important components of rectal cancer management, 5-year survival is better in rectal cancer than in colon cancer, which was not the case in the past. Total mesorectal excision (TME) is one of many important components of current management.

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Benjamin A. Teply, MD, considers the optimal treatment of renal cell carcinoma in a peer perspective accompanying an article by Tiffany Y. Shaw, MD, and colleagues.

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ABSTRACT: Colorectal cancer (CRC) is a commonly diagnosed malignancy. Although chemotherapy remains the backbone of treatment, the landscape of treating metastatic CRC (mCRC) is changing with the understanding of its heterogeneity and molecular blueprint. Colon cancer sidedness has proven to hold prognostic implications, with right-sided tumors having higher incidence of BRAF and KRAS mutations and being microsatellite instability–high (MSI-H); overall, they have a worse prognosis compared with left sided-tumors. Results of molecular research have demonstrated the need to profile each mCRC patient for RAS and BRAF mutations, MSI-H status, HER2 amplifications, and NTRK fusions. Ongoing clinical trials using targeted agents aim to further improve survival outcomes. We emphasize the epidemiology, knowledge of primary tumor location, and mutational landscape of mCRC, as well as novel treatment options for patients harboring unique subtypes of these characteristics.

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Despite aggressive surgical management, 5-year survival rates of non–small-cell lung cancer (NSCLC) patients range from 73% for those with pathologic stage IA to 25% for those with stage IIIA.[1] Clinical or preoperative staging often underestimates the extent of the disease (particularly if positron-emission tomography and mediastinoscopy are not used), and the estimated survival rates for a given clinical stage are much lower than those for the corresponding surgical/pathologic stage.[1]

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This review summarizes promising new targets and immunotherapy combination strategies currently under clinical development.

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Personalized cancer care is generally thought of as using molecular information from tumors in order to identify which therapeutic agents will be most effective in a given patient.

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Patients aged 65 years and older represent 12% of the US population yet account for approximately 56% of cancer cases and 69% of all cancer mortalities. The overall cost of cancer in 2005 was $209.9 billion—$74 billion for direct medical costs and $118.4 billion for indirect mortality costs. This paper considers the direct, indirect, and out-of-pocket expenditures incurred by cancer patients ‚â • 50 years of age. Several major empirical studies on supportive care for older patients and cancer-related costs were reviewed. Insurance coverage, hematologic malignancies, squamous cell carcinoma of the head and neck, and cancers of the breast, prostate, colorectum, and lung were evaluated. Major sources of direct medical expenditures covered by third-party insurers for patients aged 65 years and older include extended length of hospital stay, home health assistance following hospital discharge, adjuvant prescription medications, lower-risk treatment (for prostate cancer), and advent of new pharmaceuticals (for colorectal cancer). The mean total direct medical cost for breast cancer is $35,164, and the cumulative cost for prostate cancer is $42,570. Emerging targeted cancer drug costs range from $20,000 to $50,000 annually per patient. Additional clinical trials and cost-effective treatments are needed for older patients to ameliorate the disproportionate economic burden among older individuals with cancer. Additional research about cancer costs may also lead to reforms in cancer care reimbursement, and therefore provide access to affordable health care for older patients.

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The first issue deserving comment is the heterogeneity of stage III disease. Stage IIIA N2 non–small-cell lung cancer (NSCLC) includes patients with at least one “incidental” N2 node detected at the time of surgical resection in patients who had a negative mediastinal evaluation (including mediastinoscopy) preoperatively. It also includes patients whose initial computed tomography (CT) and positron-emission tomography (PET) scans show multiple bulky (> 2 cm) nodes that are confirmed by either mediastinoscopy or endobronchial ultrasound-guided bronchoscopy.

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Adrenocortical carcinoma is a rare disease, with an annual incidence rate ranging from 0.5 to 2.0 cases per million individuals.

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A case report is followed by a review of the diagnosis and treatment of other cutaneous paraneoplastic syndromes that are associated with hematologic malignancies.

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A recent retrospective study found that adding chemotherapy to postoperative treatment of craniospinal radiation for adults with medulloblastoma improves survival.

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Bcl-2 protein is upregulated in a wide variety of lymphoid malignancies,including chronic lymphocytic leukemia (CLL). The proteinis thought to be responsible for maintaining the viability of malignantlymphoid cells and may contribute to chemotherapy and radiotherapyresistance. Previous studies have shown that reduction of bcl-2 expressionby antisense therapy sensitizes cells to chemotherapy-inducedapoptosis. In vitro, the Bcl-2 antisense drug oblimersen sodium(Genasense, previously known as G3139) enhances the apoptotic responsein CLL cells to fludarabine (Fludara), corticosteroids,alemtuzumab (Campath), and rituximab (Rituxan). A phase I trial inpatients with refractory/relapsed CLL showed that patients with CLLwere more sensitive to oblimersen than patients with solid tumors. Themaximum tolerated oblimersen dose was 3 mg/kg/d, and the most commondose-limiting reaction was hypotension, frequently in associationwith high spiking fever. In this study, oblimersen displayed limited singleagentactivity, including tumor lysis syndrome, transient decreases incirculating CLL cells, and reduction of splenomegaly and size of lymphnodes. Major responses were observed in 9% of patients. Subsequently,a phase III trial evaluating fludarabine and cyclophosphamide with orwithout oblimersen (3 mg/kg/d for 7 days) was initiated in patients withrelapsed or refractory CLL. This trial recently completed accrual of241 patients.

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Here we review some of the most significant changes in the surgical management of melanoma that have reduced morbidity and thereby improved patient outcomes.

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In this interview we discuss how quality-of-life information from patients with lung cancer can be used to help guide treatment and inform outcomes.

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Few areas in breast disease elicit as much controversy as the management of DCIS. The review by Sanders and Simpson, “Can We Know What to Do When DCIS Is Diagnosed?”

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Panelists discuss how thoracic oncologists are adapting to a rapidly evolving treatment landscape for lung cancer, focusing on the integration of novel therapies and the importance of biomarker-driven approaches in patient care.

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Early clinical studies combining irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) have yielded encouraging results. Gemcitabine administered via a twice-weekly schedule results in an enhanced radiation-sensitizing effect.

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Because of the high rate of distant disease recurrence, the 5-yearsurvival of patients who have undergone complete surgical resectionof localized non–small-cell lung cancer (NSCLC) is approximately 50%.Initial results from early studies of adjuvant postoperative chemotherapyreported an adverse effect of alkylating agent and older chemotherapyregimens on survival. Cisplatin-based combinations were the first toshow a survival advantage. A 1995 meta-analysis of these studies suggesteda 13% reduction in the hazard ratio for death (HR = 0.87), leadingto a 5% survival benefit at 5 years. Still, these trials involved limitednumbers of patients (N = 1,394), and the results failed to reach statisticalsignificance (P = .08). Of the five largest subsequent randomizedtrials of platinum-based adjuvant therapy, three showed a significantsurvival advantage. Although it is impossible to determine the reasonsfor the differing outcomes of these studies, several key features distinguishthem, and the data suggest that medically fit patients with resectedstage IB or II NSCLC should be offered chemotherapy with a platinum/new drug combination.

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The review by Drs. Boumber and Issa of epigenetic drugs that target human cancers nicely summarizes recent progress in this hot area and points out future lines of investigation.

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Locally advanced adenocarcinoma of the prostate (American Urological Association stages B2, C; American Joint Committee on Cancer stages T2c, T3) has been difficult to control by either external-beam irradiation or

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A 74-year-old man presented with a 2.5-cm ulcerated mass occupying the middle third of his left outer ear, approximating the helical rim.

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Drs. Bystryn and Reynoldspresent an overview of melanomavaccines, including atheoretical rationale to support the approach,criteria for an effective vaccine,and a discussion of the challengesto optimal vaccine design. Results ofclinical trials where vaccine-inducedimmune responses correlated withimproved clinical outcome are discussed,as well as limitations of monitoringvaccine-induced immuneresponses. A series of randomized, concurrentlycontrolled trials with complex,polyvalent whole-cell vaccines,extracts, lysates, or shed antigens arereviewed. The authors conclude thatmelanoma vaccines' "potentially mostsignificant application" may be the preventionof melanoma in individuals athigh risk of developing the disease.Their review discusses the generallyaccepted rationale for selecting vaccineantigens and does a thoughtfuljob of reviewing the current state ofcomplex melanoma vaccines.

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Thousands of practice guidelines/practice parameters have been published by various professional organizations. The American Medical Association,[1] American College of Physicians,[2,3] and others[4-6] have written extensively about

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Patient selection based on a much more comprehensive biologic assessment of both host and tumor is likely the key to further advances in the treatment of all bladder cancer patients. Until such time, there can be no compromise in the careful application of the rigorous therapy required to optimize outcomes.

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The relationships between psychological variables and the presence of cancer, its prediction, and the prediction of cancer mortality and course of disease have been studied extensively. From a limited list of about 50 such

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The article by Posadas and Figlin on systemic therapy in advanced renal cell carcinoma (RCC) provides a very interesting and comprehensive review of our current knowledge concerning the treatment of RCC.

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Nearly 150,000 people will be diagnosed with colorectal cancer in the United States in 2006. The impact of this diagnosis will be felt by countless family members, coworkers, and friends. Although screening tests for colorectal cancer have been available and encouraged by medical associations such as the American Cancer Society (ACS) and others, public awareness and compliance has been dismal.