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PURPOSE The objective of this study was to determine whether pretreatment neutrophil-to-lymphocyte ratio (NLR) could predict survival outcomes and liver toxicity in hepatocellular carcinoma (HCC) patients treated with stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS In this retrospective study we collected pretreatment NLR of HCC patients treated with SABR between December 2007 and August 2018 and determined its association with overall survival (OS), progression-free survival, and radiation-related liver toxicity defined as an increase in the Child-Turcotte-Pugh score by ≥2 within 3 months after SABR in the absence of disease progression. RESULTS A total of 153 patients with a median follow-up of 13.3 months were included. Receiver operating characteristic curve analysis found that an NLR ≥2.4 was optimum (area under the curve, 0.762; 95% confidence interval [CI], 0.682-0.841, P < .001) for predicting poor 1-year OS (38.2% vs 83.6%, P < .001). Multivariable analysis demonstrated that NLR was significantly associated with OS, both as a continuous (P = .006) and a binary variable (NLR set at 2.4; P = .003). Multiple tumors (P = .003), macrovascular invasion (P = .024), extrahepatic spread (P = .002), and albumin-bilirubin score (P = .020) were also significant predictors of OS. Elevated NLR independently prognosticated poor progression-free survival (P = .016). Liver toxicity was seen in 22 evaluable patients (15.4%). Receiver operating characteristic curve analysis found NLR ≥4.0 was optimum at predicting liver toxicity (31.4% vs 10.2%, P = .005). A higher NLR (P = .049) and albumin-bilirubin score (P = .002) were independent risk factors for liver toxicity. CONCLUSIONS NLR is an objective and ubiquitous inflammatory marker that can predict OS and liver toxicity in HCC patients undergoing SABR. NLR could be a useful biomarker for patient risk stratification and therapeutic decision-making.

The level histogram is used with the K-means algorithm for clustering data.The fast K-means algorithm was effectively applied to image database sets.The fast K-means algorithm improved the efficiency of the traditional K-means algorithm.The fast K-means algorithm processed images efficiently as images increases.The selection of the initial cluster centers affected the performance. In image retrieval, the image feature is the main factor determining accuracy; the color feature is the most important feature and is most commonly used with a K-means algorithm. To create a fast K-means algorithm for this study, first a level histogram of statistics for the image database is made. The level histogram is used with the K-means algorithm for clustering data. A fast K-means algorithm not only shortens the length of time spent on training the image database cluster centers, but it also overcomes the cluster center re-training problem since large numbers of images are continuously added into the database. For the experiment, we use gray and color image database sets for performance comparisons and analyzes, respectively. The results show that the fast K-means algorithm is more effective, faster, and more convenient than the traditional K-means algorithm. Moreover, it overcomes the problem of spending excessive amounts of time on re-training caused by the continuous addition of images to the image database. Selection of initial cluster centers also affects the performance of cluster center training.

Background KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

Purpose/Objective(s): The purpose of this study was to identify the predictive factors of skeletal-related events (SREs) in NSCLC patients with bone metastases. Materials/Methods: Time-to-the first SRE and SRE-free survival and their associations with the patient characteristics were evaluated retrospectively in 416 patients in NSCLC with bone metastatic. Univariate and multivariate statistical methods were used to determine significant risk factors for SRE-free survival. Results: The overall median survival time was 11.5 (9.9-13.2) months from bone metastases. The median observation period for SREs was 8.9 (7.9-9.9) months. Out of 416 patients with bone metastases, 159 (38.2%) developed at least one SRE during or after the initial treatment. On univariate analysis, patients with characteristics such as male, nonadenocarcinoma, ever-smoking, bone metastases with soft-tissue extension and no history of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) therapy had a shorter median time from bone metastasis to first SRE. The results of multivariate analysis revealed that male, bone metastases with soft-tissue extension, no history of EGFR-TKI therapy risk factors for the first SRE, with hazard ratios (HRs) (95% confidence interval [CI]) 1.414 (1.050-1.905), 1.225 (1.030-1.457), 1.731 (1.327-2.259), respectively. Conclusions: The presence of bone metastases with soft-tissue extension was significantly associated with the development of SREs in patients with advanced NSCLC. Male sex and no history of EGFR-TKI therapy were also independent risk factor of development of SREs throughout the course of disease.