Comparison of Eight Technologies to Determine Genotype at the UGT1A1 (TA) Repeat Polymorphism: Potential Clinical Consequences of Genotyping Errors?

To ensure accuracy of (rs3064744) genotyping for use in pharmacogenomics-based irinotecan dosing, we tested the concordance of several commonly used genotyping technologies. Heuristic genotype groupings and principal component analysis demonstrated concordance for Illumina sequencing, fragment analysis, and fluorescent PCR. However, Illumina sequencing and fragment analysis returned a range of fragment sizes, likely arising due to PCR "slippage".

Twenty-five-Year Follow-up of a Prospective Randomized Trial Comparing Preoperative Versus Postoperative FLAC/Granulocyte Colony-Stimulating Factor Chemotherapy for Stage II Breast Cancer.

Background: Preoperative chemotherapy is important in the management of women with breast cancer, with the ability to downstage the breast primary tumor and axillary lymph nodes. Long-term studies are needed to identify late toxicities, recurrence patterns, and equivalency with postoperative chemotherapy for recurrence-free survival (RFS) and overall survival (OS).

Patients And Methods: We conducted a single-institution prospective randomized control trial comparing preoperative or postoperative fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamides/granulocyte colony-stimulating factor chemotherapy for women with untreated clinical stage II (T1N1, T2N0, and T2N1) breast cancer.

Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma.

Background: Thymic epithelial tumors are PD-L1-expressing tumors of thymic epithelial origin characterized by varying degrees of lymphocytic infiltration and a predisposition towards development of paraneoplastic autoimmunity. PD-1-targeting antibodies have been evaluated, largely in patients with thymic carcinoma. We sought to evaluate the efficacy and safety of the anti-PD-L1 antibody, avelumab (MSB0010718C), in patients with relapsed, advanced thymic epithelial tumors and conduct correlative immunological studies.

Reproducibility of pharmacogenetics findings for paclitaxel in a heterogeneous population of patients with lung cancer.

Pharmacogenetics studies have identified several allelic variants with the potential to reduce toxicity and improve treatment outcome. The present study was designed to determine if such findings are reproducible in a heterogenous population of patients with lung cancer undergoing therapy with paclitaxel. We designed a prospective multi-institutional study that recruited n = 103 patients receiving paclitaxel therapy with a 5-year follow up.

Thymic epithelial tumors and metastasis to the brain: a case series and systematic review.

Background: Thymic epithelial tumors (TETs) rarely metastasize to the brain. Clinico-pathologic features of TET patients with brain metastasis are not well described.

Methods: TET patients referred for consultation or screening for clinical trials are included.

Expression of mesothelin in thymic carcinoma and its potential therapeutic significance.

Objectives: Advanced thymic epithelial tumors (TETs) lack adequate treatment options in part due to absence of well characterized tumor-specific antigens. Mesothelin, a cell surface antigen, has been used successfully as a target for tumor-directed therapy. We sought to determine tumor expression and serum levels of mesothelin in patients with TETs.

Alterations of immune cell subsets in relapsed, thymoma-associated minimal change disease: A case report.

The most frequently described glomerulopathy in patients with thymoma is minimal change disease (MCD). The present study reports the case of a 63-year-old female with recurrent thymoma and poorly-controlled paraneoplastic MCD, who was enrolled on a phase I/II clinical trial (no. NCT01100944) and treated with the histone deacetylase inhibitor, belinostat, in combination with cisplatin, doxorubicin and cyclophosphamide.

Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial.

Background: No standard treatments are available for advanced thymic epithelial tumours after failure of platinum-based chemotherapy. We investigated the activity of sunitinib, an orally administered tyrosine kinase inhibitor.

Methods: Between May 15, 2012, and Oct 2, 2013, we did an open-label phase 2 trial in patients with histologically confirmed chemotherapy-refractory thymic epithelial tumours.

Cixutumumab for patients with recurrent or refractory advanced thymic epithelial tumours: a multicentre, open-label, phase 2 trial.

Background: No standard treatment exists for refractory or relapsed advanced thymic epithelial tumours. We investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody targeting the insulin-like growth factor 1 receptor in thymic epithelial tumours after failure of previous chemotherapy.

Methods: Between Aug 25, 2009, and March 27, 2012, we did a multicentre, open-label, phase 2 trial in patients aged 18 years or older with histologically confirmed recurrent or refractory thymic epithelial tumours.

18F-fluorodeoxyglucose positron emission tomography in the management of patients with thymic epithelial tumors.

Purpose: There are limited data regarding the role of (18)F-fluorodeoxyglucose positron emission tomography ([(18)F]-FDG PET) imaging in management of patients with thymic epithelial tumors (TET). The primary objective of this study was to assess the usefulness of early [(18)F]-FDG PET to monitor treatment efficacy and its correlation with Response Evaluation Criteria in Solid Tumors (RECIST) in patients with TETs.

Experimental Design: [(18)F]-FDG PET/computed tomographic (CT) scans were conducted at baseline and after 6 weeks of treatment in patients enrolled in two phase II and one phase I/II clinical trials.

Characterization and management of cardiac involvement of thymic epithelial tumors.

Introduction: Although thymic epithelial tumors (TETs) commonly infiltrate mediastinal structures, cardiac involvement is uncommon and has not been systematically studied. The purpose of this study was to describe our single-institution experience of the clinical presentation, treatment, and follow-up of cardiac involvement in patients with TETs.

Methods: A single-institution retrospective review of cardiac involvement among patients with TETs from 2008 to 2012.

EGFR and KRAS mutation analysis in cytologic samples of lung adenocarcinoma enabled by laser capture microdissection.

The discovery of activating mutations in EGFR and KRAS in a subset of lung adenocarcinomas was a major advance in our understanding of lung adenocarcinoma biology, and has led to groundbreaking studies that have demonstrated the efficacy of tyrosine kinase inhibitor therapy. Fine-needle aspirates and other cytologic procedures have become increasingly popular for obtaining diagnostic material in lung carcinomas. However, frequently the small amount of material or sparseness of tumor cells obtained from cytologic preparations limit the number of specialized studies, such as mutation analysis, that can be performed.

Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors.

Purpose: Thymic epithelial tumors are rare malignancies, and there is no standard treatment for patients with advanced disease in whom chemotherapy has failed. Antitumor activity of histone deacetylase (HDAC) inhibitors in this disease has been documented, including one patient with thymoma treated with the pan-HDAC inhibitor belinostat.

Patients And Methods: Patients with advanced thymic epithelial malignancies in whom at least one line of platinum-containing chemotherapy had failed were eligible for this study.

Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia.

Patients with thymic malignancy have high rates of autoimmunity leading to a variety of autoimmune diseases, most commonly myasthenia gravis caused by anti-acetylcholine receptor autoantibodies. High rates of autoantibodies to cytokines have also been described, although prevalence, spectrum, and functionality of these anti-cytokine autoantibodies are poorly defined. To better understand the presence and function of anti-cytokine autoantibodies, we created a luciferase immunoprecipitation system panel to search for autoantibodies against 39 different cytokines and examined plasma from controls (n = 30) and patients with thymic neoplasia (n = 17).

Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with [corrected] human epidermal growth factor receptor 2-positive metastatic breast cancer.

Purpose: To evaluate safety and efficacy of trastuzumab with pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who had progressive disease on trastuzumab-based therapy.

Experimental Design: Patients with measurable HER2(+) metastatic breast cancer, < or = 3 trastuzumab-based regimens, and left ventricular ejection fraction (LVEF) > or = 55% received 8 or 6 mg/kg trastuzumab and 840 mg pertuzumab i.v.

Circulating biomarkers of bevacizumab activity in patients with breast cancer.

Purpose: Noninvasive markers of anti-vascular endothelial growth factor (VEGF) therapy are needed. Soluble vascular cell adhesion molecule (sVCAM-1), soluble VEGF receptor-2 (sVEGFR-2), and plasma VEGF levels were assessed as potential biomarkers of therapy with bevacizumab. Tumor samples were evaluated for VEGFR-2 mutations before and after bevacizumab.

A novel case of bisphosphonate-related osteonecrosis of the torus palatinus in a patient with metastatic breast cancer.

Bisphosphonates administered orally and intravenously are used for a variety of endocrine and oncologic indications. Long-term intravenous use of bisphosphonates has been shown to cause osteonecrosis of the jaw. We report a case in which a 58-year-old woman with metastatic breast cancer received 18 doses of 4 mg intravenous zoledronic acid over a period of 16 months and developed a region of osteonecrosis on the posterior edge of a large, lobular torus palatinus.

Phase II trial of ixabepilone, an epothilone B analog, in patients with metastatic breast cancer previously untreated with taxanes.

Purpose: Ixabepilone is an epothilone B analog that binds to microtubules and results in microtubule stabilization and mitotic arrest. Ixabepilone was evaluated for efficacy and safety in a phase II clinical trial for women with metastatic breast cancer.

Patients And Methods: Patients were eligible if they had not previously received treatment with a taxane and had measurable metastatic breast cancer.

A prospective study of adjuvant CMF in males with node positive breast cancer: 20-year follow-up.

Purpose: To determine the long-term overall survival of male patients with stage II node positive breast cancer treated with adjuvant chemotherapy.

Patients And Methods: Between 1974 and 1988, 31 male breast cancer patients were prospectively enrolled on study MB-82 in the National Cancer Institute. Following mastectomy, patients were treated with 12 cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy.

Phase II trial of ixabepilone, an epothilone B analog, given daily for three days every three weeks, in metastatic breast cancer.

Twelve patients with metastatic breast cancer previously exposed to taxanes were treated on a Phase II trial with ixabepilone. Eligible patients had histologically confirmed metastatic breast cancer with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST), and adequate hematopoietic, renal, and hepatic function. Ixabepilone 8 mg/m(2)/day was given intravenously daily for 3 days for the first 3-week cycle and increased to 10 mg/m(2)/day for subsequent cycles if patients did not have hematologic or other toxicity after the first cycle.

Changes in neurologic function tests may predict neurotoxicity caused by ixabepilone.

Purpose: To investigate baseline factors and neurologic function tests (NFTs) that may predict the development of grade 2 or higher peripheral neuropathy (PN) after treatment with ixabepilone, an epothilone microtubule-stabilizing agent with antitumor activity.

Patients And Methods: Advanced breast cancer patients were treated with ixabepilone (6 mg/m2) for 5 consecutive days every 3 weeks in a phase II clinical trial. Physical examinations, questionnaires, nerve conduction studies, and NFTs, including the Jebsen Test of Hand Function (JTH) and the Grooved Pegboard Test (GPT), were performed at baseline and during subsequent cycles.