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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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Christopher E. Desch

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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

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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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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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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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Weijia Wang, Edward Li, Kim Campbell, and Ali McBride

Network guidelines recognize that the risk of developing FN is based on a regimen’s risk (high, intermediate, low) and patient-related risk factors. This study aims to estimate the association of demographics, comorbidities, chemotherapy regimen and FN

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Michael J. Baine, Richard Sleightholm, Beth K. Neilsen, David Oupický, Lynette M. Smith, Vivek Verma, and Chi Lin

Background: Despite the fact that stereotactic body radiation therapy (SBRT) is the only recommended first-line therapy for inoperable early-stage non–small cell lung cancer (NSCLC), several thermal ablative procedures (TAPs; defined herein as laser/cryoablation and electrocautery) are available. Studies showing outcomes of these procedures and how they compare with SBRT are scarce. We sought to evaluate the comparative efficacy of SBRT versus TAPs using the National Cancer Database (NCDB). Methods: The NCDB was queried for patients with early-stage NSCLC who did not undergo surgical resection. Treatment-specific inclusion criteria were applied to select for patients receiving either TAPs or SBRT. Univariate logistic regression and Cox proportional hazards modeling were performed, and Kaplan-Meier curves were generated. Serial propensity matches were performed using a modified greedy 8→n matching 1:1 algorithm. Results: A total of 27,734 patients were analyzed; 26,725 underwent SBRT and 1,009 underwent TAPs. Patients who received SBRT were older and more likely to have clinical stage IB (vs IA) disease. Despite this, SBRT was associated with longer median overall survival (mOS; 37.7 vs 33.5 months; P=.001) and 1-, 2-, and 5-year OS rates compared with the TAPs cohort (86.7% vs 83.1%, 67.5% vs 62.7%, and 30.6% vs 26.9%, respectively; P=.001). Upon propensity matching, improved OS with SBRT remained, with a mOS of 40.4 versus 33.4 months and 1-, 2-, and 5-year OS rates of 89.0% versus 82.9%, 69.7% versus 62.7%, and 34.4% versus 26.4%, respectively (P=.003). Conclusions: Despite being associated with more higher-risk factors, SBRT was associated with higher OS compared with TAPs for treatment of nonoperative patients diagnosed with early-stage NSCLC. However, causation cannot be implied owing to the inherent limitations of large heterogeneous datasets such as the NCDB.

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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