Seminars in oncology
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The mainstay of screening for breast cancer is the mammogram. There are several randomized control trials that demonstrate a significant decrease in breast cancer mortality when compared to women without screening mammography included in their care. ⋯ With the introduction of digital mammography, other novel techniques such as stereo digital mammography (SDM) and tomosynthesis can reduce recall significantly without a negative effect on cancer detection. Magnetic resonance imaging (MRI) and ultrasound added to mammography can improve cancer detection for high-risk women but can have false positive consequences.
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In the last decades discoveries of adrenal masses incidentally during the course of diagnostic procedures for unrelated disorders (incidentalomas) have become progressively more frequent. The clinician in this position must answer two main questions: Is the mass benign or malignant?, and To what extent is the adrenal secretion altered? To come to a clinical decision, several diagnostic tools need to be engaged, starting with an accurate and correct radiological evaluation and a hormonal assessment of the adrenal function. When necessary, other diagnostic procedures such as functional imaging and fine-needle biopsy (FNB) can be considered in selected cases. ⋯ Follow-up criteria have not been established. Laparoscopic surgery is the recommended procedure to remove benign masses. The surgical procedure for adrenal malignancies is still debated.
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Seminars in oncology · Oct 2010
ReviewDevelopment of ipilimumab: contribution to a new paradigm for cancer immunotherapy.
Identification of cytotoxic T-lymphocyte antigen-4 (CTLA-4) as a key negative regulator of T-cell activity led to development of the fully human, monoclonal antibody ipilimumab to block CTLA-4 and potentiate antitumor T-cell responses. Animal studies first provided insight into the ability of an anti-CTLA-4 antibody to cause tumor regression, particularly in combination regimens. Early clinical studies defined ipilimumab pharmacokinetics and possibilities for combinability. ⋯ Ipilimumab monotherapy exhibits conventional and new patterns of activity in advanced melanoma, with a delayed separation of Kaplan-Meier survival curves. The observation of some new response patterns with ipilimumab, which are not captured by standard response criteria, led to novel criteria for the evaluation of immunotherapy in solid tumors. Overall, lessons from the development of ipilimumab contributed to a new clinical paradigm for cancer immunotherapy evolved by the Cancer Immunotherapy Consortium.
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Seminars in oncology · Oct 2010
ReviewImmune checkpoint proteins: a new therapeutic paradigm for cancer--preclinical background: CTLA-4 and PD-1 blockade.
Much of the recent excitement in the translational field of tumor immunology and immunotherapy has been generated by the recognition that immune checkpoint proteins can be blocked by human antibodies with profound effects in vitro, in animal tumor systems, and in patients. Promising clinical data have already been generated in melanoma and other tumor types with human antibodies directed against cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1). The preclinical data that supported the clinical development of these two antibodies will be discussed in detail in this review, showing that many of the therapeutic effects of these two agents were predicted by the animal models, as were the immune-related side effects noted with these drugs. ⋯ The clinical development of anti-PD-1 antibody so far has shown that it has a potent effect when administered alone, and trials of vaccines with anti-PD-1 are just being initiated to test the idea that the predicted effects of that antibody observed in animal systems also would be seen in patients. These observations support the idea that animal preclinical therapeutic experiments are an important guide to the conduct of trials employing abrogation of immune checkpoint proteins in T cells in patients. Nonetheless, clinical investigators must be flexible and prepared to find that the biology of those systems may be very different in humans compared to mice.
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Seminars in oncology · Oct 2010
ReviewUpdate on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management.
Immune-modifying monoclonal antibodies may induce or enhance the natural immune response against tumor cells. The complex interaction between antigen-presenting cells and T lymphocytes as an immune response is strongly affected by anti-CD152 (cytotoxic T-lymphocyte antigen-4, CTLA-4)-antibodies. However, specific CTLA-4 antibodies can block the CTLA-4 receptor and thus induce an unrestrained T-cell activation. ⋯ The results of a phase III trial in patients with advanced disease treated with ipilimumab alone or in combination with a peptide vaccination (gp100) recently presented at the 2010 annual meeting of the Ameircan Society of Clinical Oncology (ASCO) made groundbreaking news as ipilimumab was demonstrated to be the first drug in melanoma treatment to show a significant prolongation of survival time. Patients undergoing treatment with CTLA-4 antibodies may experience immune-related phenomena and adverse events (irAEs) that differ greatly from the well-known adverse events of cytotoxic drugs and which are due to the CTLA-4 antibodies' specific mode of action. This review gives a condensed overview on the mechanisms of action, an update on clinical data of the two CTLA-4 antibodies, ipilimumab and tremelimumab, and detailed recommendations for adverse event management strategies.