Tumor antigen-independent and cell size variation-inclusive enrichment of viable circulating tumor cells.

Isolation of circulating tumor cells (CTCs) from blood provides a minimally-invasive alternative for basic understanding, diagnosis, and prognosis of metastatic cancer. The roles and clinical values of CTCs are under intensive investigation, yet most studies are limited by technical challenges in the comprehensive enrichment of intact and viable CTCs with minimal white blood cell (WBC) contamination. Here, we report a novel method based on contrast of cell magnetization in biocompatible ferrofluids (a colloidal magnetic nanoparticle suspension), termed as integrated ferrohydrodynamic cell separation (iFCS), that enriches CTCs in a tumor antigen-independent and cell size variation-inclusive manner, achieves a high throughput (12 mL h-1), high recovery rate (99.08% at down to ∼10 cells per mL spike ratio), and low WBC contamination (533 cells for every one milliliter blood processed) and is biocompatible. This method will enable large cohort research to define the clinical and diagnostic value of CTC subtypes.

nab-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.PS2 Study in Patients With NSCLC and a Performance Status of 2.

INTRODUCTION: The phase II ABOUND.PS2 study (NCT02289456) assessed safety/tolerability of a first-line modified nab-paclitaxel/carboplatin regimen for patients with advanced non-small cell lung cancer (NSCLC) and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2. METHODS: Chemotherapy-naive patients with stage IIIB/IV NSCLC and ECOG PS 2 received four cycles of nab-paclitaxel 100 mg/m2 days 1 and 8 plus carboplatin area under the curve 5 day 1 q3w (induction). Patients without progression received nab-paclitaxel monotherapy (100 mg/m2 days 1 and 8 q3w) until progression/unacceptable toxicity. Primary endpoint: percentage of patients discontinuing induction due to treatment-emergent adverse events (TEAEs). RESULTS: 11/40 treated patients (27.5%; 95% CI, 14.60-43.89) discontinued chemotherapy induction due to TEAEs; 16/40 (40.0%) continued nab-paclitaxel monotherapy. Median progression-free and overall survival were 4.4 (95% CI, 2.99-7.00) and 7.7 (95% CI, 4.93-13.17) months. Grade 3/4 TEAEs during induction included neutropenia (22.5%), anemia (17.5%), thrombocytopenia (5.0%), and peripheral neuropathy (2.5%). CONCLUSION: This nab-paclitaxel-based regimen was tolerable in patients with advanced NSCLC and ECOG PS 2, with efficacy comparable to historical chemotherapy data.

Harnessing a Different Dependency: How to Identify and Target Androgen Receptor-Positive Versus Quadruple-Negative Breast Cancer.

The androgen receptor (AR) is a promising therapeutic target for a subset of triple-negative breast cancers (TNBCs) in which AR is expressed. However, the mechanistic action of AR and the degree to which primary and metastatic tumors depend on AR, both before and after conventional treatment, remain to be defined. We discuss preclinical and clinical data for AR+ TNBC, the difficulties in monitoring AR protein levels, new methods for determining AR status, the influence of AR on "stemness" in the context of TNBC, the role of combined inhibition of sex steroid production and AR, and the role of AR in regulation of the immune system. Although the exact role of AR in subsets of TNBC is still being characterized, new therapies that target AR and the production of androgens may provide additional options for patients with TNBC for whom chemotherapy is currently the sole treatment option.

Associations between use of the 21-gene recurrence score assay and chemotherapy regimen selection in a statewide registry.

BACKGROUND: The 21-gene recurrence score (RS) assay predicts response to adjuvant chemotherapy in patients with early-stage, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer, but to the authors' knowledge, the role of the assay in guiding the selection of chemotherapy regimen has not been established. The current study was conducted to examine patterns of use of the RS assay for selecting chemotherapy regimens across a statewide registry from 2006 through 2013. METHODS: Demographic, pathologic, and treatment data were abstracted from medical records for 16,666 women with breast cancer who were treated at 25 hospital systems across Michigan that were participating in the Michigan Breast Oncology Quality Initiative. Treatment patterns were examined based on the RS assay test result. RESULTS: Approximately 25% of patients with lymph node-negative disease who underwent testing with the RS assay and who were treated with chemotherapy received an anthracycline-based regimen, compared with 49% of patients with lymph node-negative disease who were treated with chemotherapy and who had not undergone testing with the RS assay. Of those patients with lymph node-positive disease who underwent testing with the RS assay and who received chemotherapy, 31% received an anthracycline-based regimen. In comparison, 71% of patients with lymph node-positive, chemotherapy-treated disease who did not undergo testing received an anthracycline. From 2006 through 2013, there was a statistically significant decrease in the use of anthracycline-containing regimens in both patients with lymph node-negative and lymph node-positive disease. CONCLUSIONS: Use of anthracycline-containing chemotherapy regimens in eligible patients appears to vary with use of the RS assay, despite the lack of evidence supporting use of the assay to guide regimen selection. Results of ongoing prospective trials should help to define the role of the RS assay in this setting. Cancer 2017;123:948-56. © 2016 American Cancer Society.