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The Alvin J. Siteman Cancer Center

Venous thromboembolism (VTE) is a common, life-threatening condition in patients with cancer, which includes both deep venous thrombosis (DVT) and pulmonary embolism. The occurrence of VTE has been reported to increase the likelihood of death for cancer patients by 2- to 8-fold. Pathophysiologic explanations for VTE in cancer include known hypercoagulability, vessel wall damage, and vessel stasis from direct compression, and the incidence of VTE in cancer is increased by additional risks factors. The NCCN guidelines specifically outline strategies to prevent and treat VTE in adult cancer patients. These guidelines are characterized by evaluations of the therapeutic advantages of pharmacologic anticoagulation measures based on both perceived risk for bleeding (i.e., contraindications to anticoagulation) and cancer status. Important updates for 2008 include new work-up recommendations and changes in the recommendations for outpatient prophylaxis and diagnosis and for treatment of heparin-induced thrombocytopenia.

For the most recent version of the guidelines, please visit NCCN.org

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Roy H. Decker and Lynn D. Wilson

The role of radiotherapy in treating local and regional disease in patients with clinically localized Merkel cell carcinoma remains controversial. Given the lack of randomized evidence and patient and treatment heterogeneity in published retrospective series, sound clinical judgment is required to assess individual patient risk factors. Although many single-institution series have shown that adjuvant radiation to the primary tumor site decreases the risk for local and regional failure, evidence is emerging that there is a cohort of patients at relatively low risk for local recurrence after wide local excision alone. Node dissection, radiotherapy, and combined modality treatment may all play a role in managing occult or clinically evident nodal disease, depending on the anatomic location of draining lymphatics and the extent of microscopic or macroscopic disease. For select patients, primary radiotherapy is a reasonable option with a low risk for local or regional recurrence.

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William G. Wierda

The decision of when to start treatment for patients with chronic lymphocytic leukemia (CLL) has not markedly changed; it is triggered by parameters of active disease, such as progressive symptoms or progressive cytopenias related to bone marrow compromise from disease. How to treat patients with CLL has become less complicated, given the growing list of options for CLL, and generally depends on the patient's age, presence of comorbidities, and risk factors (such as chromosome 17 or 11 deletion). During his presentation at the NCCN 20th Annual Conference, Dr. William Wierda focused attention on many of the new kids on the therapeutic block for CLL—the CD20 monoclonal antibodies obinutuzumab and ofatumumab, the BTK inhibitor ibrutinib, the PI3K inhibitor idelalisib, and the BCL-2 inhibitor venetoclax—and reviewed some of the clinical data supporting the use of these agents in different patient populations with CLL.

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Benjamin O. Anderson, Kristine E. Calhoun, and Eric L. Rosen

Lobular neoplasia broadly defines the spectrum of changes within the lobule, ranging from atypical lobular hyperplasia (ALH) to lobular carcinoma in situ (LCIS). This continuum of lesions is associated with an increased risk for developing subsequent invasive breast cancer, with the magnitude of that risk corresponding to the degree of proliferative change. The associated risk for developing invasive breast cancer after a diagnosis of lobular neoplasia is multicentric, bilateral, and equal in both breasts. Lobular neoplasia itself may transform into invasive carcinoma, although the frequency of this occurrence is unknown. Thus, lobular neoplasia is a risk factor for invasive breast cancer and may be a precursor lesion in unusual circumstances. The management of ALH and LCIS depends on the setting in which they are encountered. When ALH and LCIS are diagnosed after core needle breast biopsy, wire localization for surgical excision is required for definitive diagnosis because rates of histologic underestimation approach those of atypical ductal hyperplasia (ADH). When diagnosed on surgical biopsy, ALH and LCIS generally do not require further intervention, even when present at a surgical margin. However, bilateral breast cancer risk must be considered, especially when patients have a family history of breast cancer. In selected situations, bilateral prophylactic mastectomy with or without reconstruction may be considered when atypical hyperplasia or LCIS is diagnosed. Although this reduces risk for developing subsequent breast carcinoma by 90%, patients selected for prophylactic mastectomy represent a small subgroup of lobular neoplasia patients and generally have other risk factors, such as strong family history or evidence of genetic predisposition.

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Brian Vicuna and Al B. Benson III

The treatment of stage II colon cancer is a controversial issue that has persisted for the past decade. Clinicians must understand that accurate assessment of risk factors is the key to identifying patients who will benefit from treatment. Pathologic staging for colon cancer is based on the American Joint Committee on Cancer 6th edition staging system. In addition, distinct pathologic factors characterize a patient at high risk for stage II disease. More recent retrospective data suggest that molecular markers and gene expression microarrays may be valuable as prognostic and predictive tests. Unfortunately, previous research studies were not powered to properly assess efficacy in stage II disease. However, 2 recent clinical trials, National Surgical Adjuvant Breast and Bowel Project C-07 and MOSAIC, have provided more insight into defining the optimal treatment approach. With the development of the newer therapeutic agents, oxaliplatin and bevacizumab, ongoing trials such as Intergroup E5202 should help determine risk versus benefit of chemotherapy in the adjuvant treatment of stage II colon cancer.

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Christopher E. Desch

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David H. Moore

When cervical cancer is beyond curative treatment with surgery or radiation therapy, the prognosis is poor and palliation is the primary objective. Early prospective studies identified cisplatin as an active drug for advanced, metastatic, or recurrent cervical cancer, and results with other platinum analogs seemed inferior to cisplatin. Several phase III trials have established the combination of cisplatin plus paclitaxel as standard therapy for comparison. Using pooled data from 3 Gynecologic Oncology Group (GOG) phase III studies, a predictive model was developed to better identify patients who are unlikely to respond to cisplatin-containing chemotherapy. The GOG is currently developing a phase III trial to investigate the impact of bevacizumab and a regimen containing topotecan instead of cisplatin in combination with paclitaxel chemotherapy and also to externally validate the predictive model. This study has the potential to radically change standard care for cervical cancer chemotherapy. Furthermore, if the predictive model is upheld, then patients with high risk factors for treatment failure may be directed to chemotherapy regimens that do not include cisplatin or to investigational trials.

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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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Vanderbilt-Ingram Cancer Center

Approximately 13,290 people will be diagnosed with acute myeloid leukemia (AML) in 2008, and 8820 patients will die of the disease. As the population ages, the incidence of AML, along with myelodysplasia, appears to be rising. Clinical trials have led to significant treatment improvements in some areas, primarily acute promyelocytic leukemia. However, recent large clinical trials have highlighted the need for new, innovative strategies, because outcomes for AML patients have not substantially changed in the past 3 decades. The NCCN AML Panel has focused on outlining reasonable treatment options based on recent clinical trials and data from basic science, which may identify new risk factors and treatment approaches. These guidelines attempt to provide a rationale for including several treatment options in some categories, as divergent opinions about the relative risks and benefits of various treatment options have surfaced. Updates for 2009 include new clarifications of some treatment recommendations as well as for defining polymerase chain reaction positivity.

For the most recent version of the guidelines, please visit NCCN.org

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Robert J. Motzer, Neeraj Agarwal, Clair Beard, Graeme B. Bolger, Barry Boston, Michael A. Carducci, Toni K. Choueiri, Robert A. Figlin, Mayer Fishman, Steven L. Hancock, Gary R. Hudes, Eric Jonasch, Anne Kessinger, Timothy M. Kuzel, Paul H. Lange, Ellis G. Levine, Kim A. Margolin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Bruce G. Redman, Cary N. Robertson, Lawrence H. Schwartz, Joel Sheinfeld, and Jue Wang