The ability to reliably distinguish synchronous primary non-small-cell lung cancer (NSCLC) from intrapulmonary metastatic spread affects staging and treatment decisions in resected NSCLC. Adjuvant therapy for early-stage NSCLC is complicated and recommendations are primarily based on older data from trials that used now-outdated staging systems. Patients found to have 2 tumors with similar morphology in the same lobe are currently staged as pathologic T3 (pT3) but such cases represent a minority of patients in adjuvant lung cancer trials. Potentially more precise than tumor morphology alone, comprehensive genomic profiling technologies have the power to discriminate whether tumors in the same lobe represent 2 separate primary lesions or localized spread of a single lesion. In addition to lineage insights, tumor profiling simultaneously provides information on actionable genomic alterations. In this review we discuss the data that support the ability of molecular technologies to distinguish synchronous primary tumors from intrapulmonary metastases and discuss the use of molecular assays as an adjunct to current staging systems. Two cases are presented to highlight the potential immediate clinical implications of comprehensive genomic profiling.
Copyright © 2015 Elsevier Inc. All rights reserved.

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In the phase III, LUX-Lung 6 trial, afatinib prolonged progression-free survival (PFS) versus cisplatin/gemcitabine in Asian patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). This article provides detailed assessments of patient-reported outcomes (PROs), a LUX-Lung 6 secondary end point, and explores the relationship between PFS and health-related quality of life (QoL) in these patients.
Patients (n = 364) were randomized (2:1) to oral afatinib (40 mg/day) or up to six cycles of cisplatin/gemcitabine (21-day cycle; cisplatin 75 mg/m(2) [d1]; gemcitabine 1000 mg/m(2) [d1,8]). QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and its lung cancer-specific module. The relationship between PFS (investigator assessment and independent review) and QoL was evaluated using analysis of covariance and a longitudinal model.
More patients treated with afatinib versus cisplatin/gemcitabine showed improvements in global health status/QoL (p < 0.0001) and physical (p < 0.0001), role (p = 0.013), and social (p < 0.001) functioning scales. Delayed symptom deterioration and better QoL over time was also observed with afatinib. QoL measured before tumor assessment was considerably poorer for patients with progression than those without progression, with significant differences in mean scores at multiple assessment time points. Results from the longitudinal analysis consistently demonstrated a significant negative impact of progression on QoL (p < 0.0001).
Afatinib improved PFS and PROs versus chemotherapy in EGFR mutation-positive NSCLC patients. Progression was associated with statistically significant worsening in QoL measured before tumor assessment, underscoring the value of PFS as a clinically relevant end point.

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Seven compounds were extracted and purified from the roots of Michelia compressa var. lanyuensis. These compounds are liriodenine, (-)-N-acetylanonaine, pressalanine A, p-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic acid, (-)-bornesitol and β-sitostenone. These compounds were screened for anti-proliferation and anti-tyrosinase activities in B16F10 cells. Liriodenine, pressalanine A, (-)-bornesitol and β-sitostenone displayed cytotoxicity at high concentration (100 μM), but liriodenine (5 μM), (-)-N-acetylanonaine (10 μM), and β-sitostenone (5 μM) inhibit tyrosinase activity and reduce the melanin content in B16F10 cells without cytotoxicity, suggesting that liriodenine and β-sitostenone could be safe and potentially used in cosmetic skin whitening.

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Melanoma is one of the major cancer types for which new immune-based cancer treatments have achieved promising results. However, anti-PD-1 and anti-CTLA-4 therapies are effective only in some patients. Hence, predictive molecular markers for the development of clinical strategies targeting immune checkpoints are needed. Using the Cancer Genome Atlas (TCGA) RNAseq data, we found expression of ESRP1, encoding a master splicing regulator in the epithelial-to-mesenchymal transition (EMT), was inversely correlated with tumor-associated immune cytolytic activity. That association holds up across multiple TCGA tumor types, suggesting a link between tumor EMT status and infiltrating lymphocyte activity. In melanoma, ESRP1 mainly exists in a melanocyte-specific truncated form transcribed from exon 13. This was validated by analyzing CCLE cell line data, public CAGE data, and RT-PCR in primary cultured melanoma cell lines. Based on ESRP1 expression, we divided TCGA melanoma cases into ESRP1 low, truncated, and full-length groups. ESRP1-truncated tumors comprise approximately two-thirds of melanoma samples and reside in an apparent transitional state between epithelial and mesenchymal phenotypes. ESRP1 full-length tumors express epithelial markers and constitute about five percent of melanoma samples. In contrast, ESRP1-low tumors express mesenchymal markers and are high in immune cytolytic activity as well as PD-L2 and CTLA-4 expression. Those tumors are associated with better patient survival. Results from our study suggest a path toward the use of ESRP1 and other EMT markers as informative biomarkers for immunotherapy.
Copyright ©2016, American Association for Cancer Research (AACR) (Free AACR Whitepaper).

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Breast cancer screening and presurgical diagnosis are currently based on mammography, ultrasound and more sensitive imaging technologies; however, noninvasive biomarkers represent both a challenge and an opportunity for early detection of cancer. An extensive number of potential breast cancer biomarkers have been discovered by microarray hybridization or sequencing of circulating DNA, noncoding RNA and blood cell RNA; multiplex analysis of immune-related molecules and mass spectrometry-based approaches for high-throughput detection of protein, endogenous peptides, circulating and volatile metabolites. However, their medical relevance and their translation to clinics remain to be exploited. Once they will be fully validated, cancer biomarkers, used in combination with the current and emerging imaging technologies, represent an avenue to a personalized breast cancer diagnosis.

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