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Management of Anal Cancer in the HIV-Positive Population

Squamous cell anal cancer remains an uncommon entity; however,the incidence appears to be increasing in at-risk populations, especiallythose infected with human papillomavirus (HPV) and human immunodeficiencyvirus (HIV). Given the ability to cure this cancer using synchronouschemoradiotherapy, management practices of this disease arecritical. This article considers treatment strategies for HIV-positive patientswith anal cancer, including the impact on chemoradiation-inducedtoxicities and the role of highly active antiretroviral therapy in the treatmentof this patient population. The standard treatment has beenfluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agentsplus radiation. Consideration to modifying the standard treatment regimeis based on the fact that patients with HIV tend to experience greatertoxicity, especially when CD4 counts are below 200; these patients alsorequire longer treatment breaks. Additional changes to the chemotherapydosing, such as giving 5-FU continuously and decreasing mitomycin dose,are evaluated and considered in relation to radiation field sizes in an effortto reduce toxicity, maintain local tumor control, and limit need forcolostomy. The opportunity for decreasing the radiation field size andusing intensity-modulated radiation therapy (IMRT) is also considered,particularly in light of the fact that IMRT provides dose-sparing whilemaximizing target volume dose to involved areas. The impact of the immunesystem in patients with HIV and squamous cell carcinoma of theanus and the associated response to therapy remains unknown. Continuedstudies and phase III trials will be needed to test new treatment strategiesin HIV-infected patients with squamous cell cancer of the anus todetermine which treatment protocols provide the greatest benefits.

Latest Article

Molecular Targets on Blood Vessels for Cancer Therapies in Clinical Trials

This review covers progress to date in the identification of molecular targets on blood vessels in cancers, as well as agents that act on those targets, with emphasis on those currently in clinical trials. Current vascular-targeting therapies comprise two general types—antiangiogenic therapy and antivascular therapy. Advances in antiangiogenic therapies, particularly inhibitors of vascular endothelial growth factors and their receptors, have clarified the capacity of these inhibitors to change tumor-associated vessel structure to a more normal state, thereby improving the ability of chemotherapeutics to access the tumors. The responses of other antiangiogenesis target molecules in humans are more complicated; for example, αvβ3 integrins are known to stimulate as well as inhibit angiogenesis, and cleavage of various extracellular proteins/proteoglycans by matrix metalloproteinases produces potent regulators of the angiogenic process. Antivascular therapies disrupt established blood vessels in solid tumors and often involve the use of ligand-based or small-molecule agents. Ligand-based agents, irrespective of the antiangiogenic capacity of the ligand, target antivascular effectors to molecules expressed specifically on blood vessels, such as aminopeptidase N, fibronectin extra-domain B, and prostate-specific membrane antigen. Small-molecule antivascular agents, which are not targeted to molecules on blood vessels, rely on physical differences between the vasculatures in tumors and those in normal tissues.

Latest Article

Dendritic Cell Function in Sentinel Nodes

Intraoperative lymphatic mapping and sentinel lymphadenectomy has become an increasingly popular technique for staging the regional lymph nodes in early-stage melanoma. This operative technique allows for detailed pathologic analysis of the first (or sentinel) lymph node in direct connection with the primary tumor, and provides a unique opportunity for assessing potential immunologic interactions between the primary tumor and regional lymph node basin. We performed lymphatic mapping and sentinel lymphadenectomy on 25 patients with early-stage melanoma and resected an additional nonsentinel node in each case. Sentinel and nonsentinel nodes were evaluated by routine pathologic analysis. A portion of each node was processed for expression of the dendritic markers of activation CD80, CD86, and CD40, and their corresponding T-cell receptors CTLA-4 and CD28. Of 25 patients undergoing lymphatic mapping and sentinel lymphadenectomy, 20 (80%) had matched sentinel and nonsentinel nodes. A total of 26 matched lymph node sets were obtained: three pairs from one patient and two from an additional two patients. Reverse transcription polymerase chain reaction analyses of corresponding sections of the sentinel and nonsentinel nodes demonstrated a marked reduction in semiquantitative expression of CD80 (77%), CD86 (77%), and CD40 (85%), as well as CTLA-4 (88%) and CD28 (85%) in sentinel as compared to nonsentinel nodes. The diminished expression of the dendritic cell markers appeared to be unrelated to the B-cell (CD20) and T-cell (CD2) expression. Lymphatic mapping and sentinel lymphadenectomy allows for detailed pathologic and molecular characterization of sentinel nodes. Our results suggest a quantitative reduction in dendritic cell markers in sentinel as compared to nonsentinel nodes, which may be important in the immunologic interaction between the primary site and regional lymph node basin and may also serve as useful criteria for identifying sentinel nodes. [ONCOLOGY 16(Suppl 1):27-31, 2002]