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Anti-angiogenic agents in metastatic colorectal cancer

Konda, Bhavana; Shum, Helen; Rajdev, Lakshmi
Colorectal cancer (CRC) is a major public health concern being the third leading cause of cancer mortality in the United States. The availability of better therapeutic options has led to a decline in cancer mortality in these patients. Surgical resection should be considered in all stages of the disease. The use of conversion therapy has made surgery a potentially curative option even in patients with initially unresectable metastatic disease. In this review we discuss the role of various anti-angiogenic agents in patients with metastatic CRC (mCRC). We describe the mechanism of action of these agents, and the rationale for their use in combination with chemotherapy. We also review important clinical studies that have evaluated the safety and efficacy of these agents in mCRC patients. Despite the discovery of several promising anti-angiogenic agents, mCRC remains an incurable disease with a median overall survival of just over 2 years in patients exposed to all available treatment regimens. Further insights into tumor biology and tumor microenvironment may help improve outcomes in these patients.
PMCID:4501927
PMID: 26191351
ISSN: 1948-5204
CID: 5274502

Multimodality management of resectable gastric cancer: A review

Shum, Helen; Rajdev, Lakshmi
Adenocarcinoma of the stomach carries a poor prognosis and is the second most common cause of cancer death worldwide. It is recommended that surgical resection with a D1 or a modified D2 gastrectomy (with at least 15 lymph nodes removed for examination) be performed in the United States, though D2 lymphadenectomies should be performed at experienced centers. A D2 lymphadenectomy is the recommended procedure in Asia. Although surgical resection is considered the definitive treatment, rates of recurrences are high, necessitating the need for neoadjuvant or adjuvant therapy. This review article aims to outline and summarize some of the pivotal trials that have defined optimal treatment options for non-metastatic non-cardia gastric cancer. Some of the most notable trials include the INT-0116 trial, which established a benefit in concurrent chemoradiation and adjuvant chemotherapy. This was again confirmed in the ARTIST trial, especially in patients with nodal involvement. Later, the Medical Research Council Adjuvant Gastric Infusional Chemotherapy trial provided evidence for the use of perioperative chemotherapy. Targeted agents such as ramucirumab and trastuzumab are also being investigated for use in locally advanced gastric cancers after demonstrating a benefit in the metastatic setting. Given the poor response rate of this difficult disease to various treatment modalities, numerous studies are currently ongoing in an attempt to define a more effective therapy, some of which are briefly introduced in this review as well.
PMCID:4197430
PMID: 25320655
ISSN: 1948-5204
CID: 5274492

Prognosis in primary effusion lymphoma is associated with the number of body cavities involved

Castillo, Jorge J; Shum, Helen; Lahijani, Majid; Winer, Eric S; Butera, James N
Primary effusion lymphoma (PEL) is a rare lymphoma associated with Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), and characterized by a malignant body cavity effusion without solid organ or nodal involvement. Prognostic factors in patients with PEL have not been systematically studied. We conducted a literature search for patients with HHV8-positive PEL to identify potential prognostic factors for survival. Our search identified 147 patients, among which 104 patients were HHV8-positive. The median overall survival was 9 months. The median age was 57 years with a male predominance (6:1). Pathologically, 33% of the patients expressed CD20 and 69% expressed CD30. Patients with PEL with > 1 body cavity involved had a median overall survival (OS) of 4 months compared with 18 months in patients with only one cavity involved (p = 0.003). Additionally, in patients with one involved body cavity, pericardial involvement was associated with a longer median OS than pleural followed by peritoneal involvement (40, 27 and 5 months, respectively; p = 0.04). In conclusion, our study suggests that the number and location of body cavities involved are prognostic in patients with PEL.
PMID: 22591071
ISSN: 1029-2403
CID: 5274482

Meta-analysis of the association between cigarette smoking and incidence of Hodgkin's Lymphoma

Castillo, Jorge J; Dalia, Samir; Shum, Helen
INTRODUCTION/BACKGROUND:Previous studies have suggested a relationship between smoking and Hodgkin's lymphoma (HL). The main objective of this study was to evaluate this potential association with a meta-analysis of observational studies. PATIENTS AND METHODS/METHODS:A literature search was undertaken through December 2010 looking for observational studies evaluating the association between smoking and HL. From 714 articles, 17 were included in this study. Outcome was calculated and reported as odds ratio (OR). Heterogeneity was assessed by using the I(2) index. Publication bias was evaluated by trim-and-fill analysis. Quality assessment was performed with the Newcastle-Ottawa scale. RESULTS:Our analysis showed an OR of developing HL of 1.35 (95% CI, 1.17 to 1.56; P < .001) in current smokers. Former smokers did not have an increased risk of HL. In subset analyses of current smokers, men and older individuals had ORs of HL of 1.78 (95% CI, 1.46 to 2.17; P < .001) and 1.77 (95% CI, 1.23 to 2.54; P = .002), respectively. In addition, the OR of HL was increased in individuals who smoke more than 20 cigarettes per day, have smoked more than 20 years, or have smoked more than 15 pack-years at 1.51 (95% CI, 1.16 to 1.98; P = .002), 1.84 (95% CI, 1.47 to 2.32; P < .001), and 1.97 (1.53 to 2.54; P < .001), respectively. Meta-regression analyses showed a relative OR of HL of 1.007 (95% CI, 1.001 to 1.013; P = .025) per cigarette per day and of 1.013 (95% CI, 1.006 to 1.019; P < .001) per year of smoking. CONCLUSION/CONCLUSIONS:Smoking seems to increase the odds of developing HL in current smokers. The risk of HL is higher in men and older individuals and increases with higher intensity and longer duration of smoking.
PMID: 21911724
ISSN: 1527-7755
CID: 5274472