Emerging therapies in the treatment of locally advanced squamous cell cancers of head and neck.

Head and neck squamous cell cancers (HNSCCs) represent 4 to 5% of all solid malignancies. Despite improvements in diagnostic techniques, 60% of patients will present with locally advanced HNSCCs with a median survival of about 12 months and 5-year overall survival of approximately 10-40%. Recent clinical trials have altered the treatment landscape by refining existing forms of radiation, incorporation of IMRT, choice of chemotherapeutic agents, introduction of biological and targeted therapy, immunotherapy and gene therapy. Cetuximab, a monoclonal antibody directed against the human epidermal growth factor receptor (EGFR), has recently been approved in combination with RT in patients with locally advanced HNSCCs. Antiangiogenic therapies and tyrosine kinase inhibitors (gefitinib and erlotinib) have also shown promise in the clinical trials. Vandetanib, an antagonist of both vascular endothelial growth factor receptor (VEGFR) and the EGFR is currently being tested in phase II trial. New patents on hypoxia-inducible factor 1 alpha, mesenchymal-epithelial transition factor, insulin-like growth factor or the PI3K/AKT/mTOR pathway, farnesyl transferase inhibitors have shown promise in the management of HNSCCs. Nevertheless, identification of predictive biomarkers of resistance or sensitivity to these therapies remains a fundamental challenge in the optimal selection of patients most likely to benefit from them. However, increase in efficacy comes at the cost of increased toxicity. The current review focuses on insight into recent patents and updates on the clinical trials using new investigational agents in the management for HNSCCs.

Dual-Positive (CD4+/CD8+) Acute Adult T-Cell Leukemia/Lymphoma Associated with Complex Karyotype and Refractory Hypercalcemia: Case Report and Literature Review.

We describe a rare case of adult T-cell leukemia characterized by an expansion of CD4+ CD8+ double-positive lymphocytes associated with human T-lymphotropic virus type 1 (HTLV-1) and a complex karyotype in a 43-year-old Caribbean male who was initially admitted to our hospital with significant lethargy, visual disturbances, dysphagia, right facial palsy and numbness in both feet for 3 days. He was found to have severe hypercalcemia (15.6 mg/dl). Peripheral blood smear showed multilobulated clover-shaped nuclei. Bone marrow and CSF flow cytometries revealed abnormal monoclonal expansion of T cells positive for CD4, CD5, CD8 and CD25 but negative for CD7, CD20, CD56, CD68 and terminal deoxynucleotidyl transferase. The polymerase chain reaction analysis showed a distinct band of the T-cell receptor γ gene, revealing T-cell clonal integration of the proviral DNA of HTLV-1, thus confirming the diagnosis of acute adult T-cell leukemia/lymphoma. Cytogenetic study revealed a male karyotype with monosomy 12, unbalanced translocation 5q and 13q and additional material on 5q, 7q, 14q and 17q. The patient underwent prednisone (EPOCH) chemotherapy followed by autologous transplantation with BEAM regimen. Although patients with a rare mixed CD4+ CD8+ immunophenotype usually present with an aggressive clinical course and have a poor prognosis, our patient was able to survive for 2.5 years.