Clinical & experimental metastasis
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An overview of colorectal cancer discussed (Philip Paty) the good outcome after primary management with local control in 90-95 % of colon and 85 % in rectal cancer patients with major progression to metastases and to death related to hematogenous dissemination. The major disease pathways include the APC, aneuploid pathway involving mutations of P53, KRAS, SMAD 4, or the CMP/MSI pathway, mismatched repair defect as characterized by Lynch syndrome, the major hereditary form which may also have KRAS and P53 mutations. The common sporadic colorectal cancers are MS1 high, with many patients having BRAF and KRAS mutations. ⋯ An adjuvant trial of HAI at MSK in 156 patients showed an overall survival benefit at 2 year and recent long term 10yr follow-up showing a significant overall survival of 41 % with HAI versus 27 % with systemic therapy (5FU leucovorin). In the neoadjuvant Nordlinger trial for hepatic metastases, there was a significant outcome differences-the preoperative therapy group had 9.2 % increase of progression free survival versus the surgery alone group which suggests the value of combining neoadjuvant surgery in good risk liver resection candidates. Conclude the final lesson from this well presented mini symposium confirms the need for continued evaluation of the numerous discussion points by clinical trial.
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The pace of genomic discoveries in the field of cancer is revolutionizing our understanding of the biological dynamics of cancerous growth and, at the same time, fueling research for newer and smarter cancer therapies to reverse the effects of these alterations. These dynamics are driving a tremendous paradigm shift in cancer diagnostics, drug development and clinical trial design with the hope of eliminating the current structure and approach of cancer care, to one which is driven by the underlying biology of the tumor and, thus highly personalized. ⋯ Today, therapies are being rationally designed to target the precise genetic alterations with better clinical outcomes with reduced morbidity. Therefore, molecular profiling of tumors to identify the multiplicity of alterations in a tumor is an essential and necessary companion for targeted therapies.
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Clin. Exp. Metastasis · Oct 2012
Review Meta Analysis Comparative StudyThe efficacy of Tilmanocept in sentinel lymph mode mapping and identification in breast cancer patients: a comparative review and meta-analysis of the ⁹⁹mTc-labeled nanocolloid human serum albumin standard of care.
Sentinel lymph node (SLN) mapping is common, however question remains as to what the ideal imaging agent is and how such an agent might provide reliable and stable localization of SLNs. (99m)Tc-labeled nanocolloid human serum albumin (Nanocoll) is the most commonly used radio-labeled colloid in Europe and remains the standard of care (SOC). It is used in conjunction with vital blue dyes (VBDs) which relies on simple lymphatic drainage for localization. Although the exact mechanism of Nanocoll SLN localization is unknown, there is general agreement that Nanocoll exhibits the optimal size distribution and radiolabeling properties of the commercially available radiolabel colloids. [(99m)Tc]Tilmanocept is a novel radiopharmaceutical designed to address these deficiencies. ⋯ The lower bound of the confidence interval was used for comparison to Tilmanocept. Tilmanocept data included 148 patients, and pooled analysis revealed a 99.99 % (CI 0.9977-1.0000) localization rate and degree of localization of 2.16 (CI 1.964-2.3600). Tilmanocept was superior to the Nanocoll SOC for both endpoints (P < 0.0001).
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Clin. Exp. Metastasis · Oct 2012
Should ACOSOG Z0011 change practice with respect to axillary lymph node dissection for a positive sentinel lymph node biopsy in breast cancer?
While any study can be criticized, the results of Z0011 clearly show that sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection (ALND) results in extremely low locoregional recurrence and excellent overall survival comparable to completion ALND. The observed results in this trial with SLNB alone were excellent. A prospective randomized study with results such as Z0011 should alter therapy. ⋯ Currently, there are no definable criteria that completely prevent patients from benefiting from ALND in the setting of metastatic disease to the axilla. It is, therefore, clear that ALND should be strongly considered in the management of the SLN-positive axilla. SLNR has its role in the management of early stage breast cancer, but whether SLNR alone should replace ALND is yet to be determined.
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Clin. Exp. Metastasis · Oct 2012
Reduction of circulating regulatory T cells by intravenous high-dose interferon alfa-2b treatment in melanoma patients.
High-dose interferon alfa-2b (IFNα-2b) is the only approved adjuvant systemic therapy for resected, high risk melanoma in the United States (Fecher and Flaherty, in Natl Compr Cancer Netw 7:295-304, 2009). Recently, two important meta-analyses of randomized trials (Wheatley et al., in J Clin Oncol, 2007; Mocellin et al. in J Natl Cancer Inst, 2010) investigating IFNα-2b versus observation in high risk melanoma patients, showed that adjuvant IFNα-2b has an impact both on relapse-free survival (RFS) and overall survival (OS) independently by dosage, duration and route compared with observation in high risk melanoma patients. Despite of an absolute benefits of 3 % (Wheatley et al., in J Clin Oncol, 2007), this treatment is associated with significant toxicity, which impacts on patient quality of life. ⋯ The presence of Tregs in tumor-draining lymph nodes and tumors provides a potential inhibitory population that may block or balance effector cell function. Thus, depletion of Tregs or blockade of Treg function using targeted antibodies or other strategies might be able to remove Treg suppression and enhance antitumor immunity (Viguier et al., in J Immunol 173:1444-1453, 2004). We conducted an observational study to examine whether the induction phase of the FDA-approved HDI regimen administered iv in patients with stage 3-4 melanoma (20 MU/m(2) intravenously (IV) five times per week for 4 weeks) reduced the number of Treg cells in the peripheral blood.