Rodgersgriffith2993

may still be the preferred treatment when there are surgical indications after recurrence.

In patients with STS of the extremity and abdominothoracic wall, ELR after R0 resection indicated a worse prognosis than those with LLR, and TLR can be considered an independent prognostic factor for OS and SAR. Furthermore, local recurrence was significantly influenced by the depth and the histopathological grading of the primary tumor, and reoperation after local recurrence could improve survival, which means salvage surgery may still be the preferred treatment when there are surgical indications after recurrence.

Neutrophil-lymphocyte ratio (NLR) has been associated with mortality in non-small cell lung cancer (NSCLC), but its association with recurrence in locally advanced NSCLC (LA-NSCLC), specifically, is less established. We hypothesized pre- and posttreatment NLR would be associated with recurrence and mortality.

We studied the association of pretreatment NLR (pre-NLR) and posttreatment NLR at 1 (post-NLR

) and 3 months (post-NLR

) with outcomes in patients with LA-NSCLC treated with chemoradiation. Pre-NLR was dichotomized by 5, an

cutoff previously shown to be prognostic in LA-NSCLC. Post-NLR

and post-NLR

were dichotomized by their medians.

We identified 135 patients treated with chemoradiation for LA-NSCLC between 2007 and 2016. Median follow-up for living patients was 61.1 months. On multivariable analysis, pre-NLR ≥ 5 was associated with worse overall survival (HR = 1.82; 95% CI 1.15 - 2.88; p = 0.011), but not with any recurrence, locoregional recurrence, or distant recurrence. Post-NLR

≥ 6.3 was not associated with recurrence or survival. Post-NLR

≥ 6.6 was associated with worse overall survival (HR = 3.27; 95% CI 2.01- 5.31; p < 0.001), any recurrence (HR = 2.50; 95% CI 1.53 - 4.08; p < 0.001), locoregional recurrence (HR = 2.50; 95% CI 1.40 - 4.46; p = 0.002), and distant recurrence (HR = 2.53; 95% CI 1.49 - 4.30; p < 0.001).

Pretreatment NLR is associated with worse overall survival and posttreatment NLR is associated with worse survival and recurrence. These findings should be validated independently and prospectively studied.

Pretreatment NLR is associated with worse overall survival and posttreatment NLR is associated with worse survival and recurrence. These findings should be validated independently and prospectively studied.Lymphomas represent a diverse group of malignancies that emerge from lymphocytes. Despite improvements in diagnosis and treatment of lymphomas of B-cell origin, relapsed and refractory disease represents an unmet clinical need. Therefore, it is of utmost importance to better understand the lymphomas' intrinsic features as well as the interactions with their cellular microenvironment for developing novel therapeutic strategies. In fact, the role of immune-based approaches is steadily increasing and involves amongst others the use of monoclonal antibodies against tumor antigens, inhibitors of immunological checkpoints, and even genetically modified T-cells. Metabolic reprogramming and immune escape both represent well established cancer hallmarks. Tumor metabolism as introduced by Otto Warburg in the early 20th century promotes survival, proliferation, and therapeutic resistance. Simultaneously, malignant cells employ a plethora of mechanisms to evade immune surveillance. Increasing evidence suggests that metabolic reprogramming does not only confer cell intrinsic growth and survival advantages to tumor cells but also impacts local as well as systemic anti-tumor immunity. Tumor and immune cells compete over nutrients such as carbohydrates or amino acids that are critical for the immune cell function. Moreover, skewed metabolic pathways in malignant cells can result in abundant production and release of bioactive metabolites such as lactic acid, kynurenine or reactive oxygen species (ROS) that affect immune cell fitness and function. This "metabolic re-modeling" of the tumor microenvironment shifts anti-tumor immune reactivity toward tolerance. Here, we will review molecular events leading to metabolic alterations in B-cell lymphomas and their impact on anti-tumor immunity.Metastases are a major cause of cancer-related death and despite the fact that they have been focus of intense research over the last two decades, effective therapies for patients with distant secondary lesions are still very limited. In addition, in some tumor types metastases can grow years after the patients have been declared clinically cured, indicating that disseminated cancer cells (DCCs) persist undetected for years, even decades in a quiescent state. Clinical and experimental data highlight the importance of the immune system in shaping the fitness and behaviour of DCCs. Here, we review mechanisms of survival, quiescence and outgrowth of DCCs with a special focus on immune-regulation and we highlight the latest cutting-edge techniques for modelling the biology of DCCs in vitro and for studying the metastatic niche in vivo. We believe that a wide dissemination of those techniques will boost scientific findings towards new therapies to defeat metastatic relapses in cancer patients.Pericentromeric heterochromatin is maintained in a condensed structure by repressive epigenetic control mechanisms and perturbation of these may cause diseases. The chromosome 1q12 region harbors the largest pericentromeric heterochromatin domain in the genome and is among the most common breakpoints in both solid and hematopoietic cancers. Furthermore, the 1q arm is frequently amplified in cancer and this may support tumorigenesis by increasing the dosage of the many oncogenes of this genomic region. Recent studies have provided insight into the mechanisms leading to loss of 1q12 stability and 1q amplification and DNA hypomethylation seems to play a prominent role. This may be the result of decreased activity of DNA methyltransferases and instrumental for 1q12 destabilization or arise secondary to perturbation of other important epigenetic mechanisms that control repression of pericentromeric heterochromatin. Polycomb proteins were recently demonstrated to epigenetically reprogram demethylated 1q12 pericentromeric heterochromatin in premalignant and malignant cells to form large subnuclear structures known as polycomb bodies. This may influence the regulation and stability of 1q12 pericentromeric heterochromatin and/or the distribution of polycomb factors to support tumorigenesis. This review will discuss recent insight into the epigenetic perturbations causing the destabilization of 1q12 pericentromeric heterochromatin and its possible implications for tumor biology.

This study was designed to explore the progression patterns of IDH-wildtype glioblastoma (GBM) at first recurrence after chemoradiotherapy.

Records from 247 patients who underwent progression after diagnosis of IDH-wildtype GBM was retrospectively reviewed. Progression patterns were classified as either local, distant, subependymal or leptomeningeal dissemination based on the preoperative and serial postoperative radiographic images. The clinical and molecular characteristics of different progression patterns were analyzed.

A total of 186 (75.3%) patients had local progression, 15 (6.1%) patients had distant progression, 33 (13.3%) patients had subependymal dissemination, and 13 (5.3%) patients had leptomeningeal dissemination. The most favorable survival occurred in patients with local progression, while no significant difference of survival was found among patients with distant progression, subependymal or leptomeningeal dissemination who were thereby reclassified into non-local group. Multivariable ainct clinical and molecular characteristics. Our nomograms could provide theoretical references for physicians to make more personalized and precise treatment decisions.Novel oncology drugs often fail to progress from preclinical experiments to FDA approval. Therefore, determining which preclinical or clinical factors associate with drug activity could accelerate development of effective therapies. We investigated whether preclinical metrics and patient characteristics are associated with objective response rate (ORR) in phase II clinical trials of targeted therapies for non-small cell lung cancer (NSCLC). We developed a reproducible process to select a single phase II trial and supporting preclinical publication for a given drug-indication pair, which we defined as the pairing of a small molecule inhibitor (e.g., crizotinib) with the specific patient population for which it was designed to work (e.g., patients with an ALK aberration). We demonstrated that robust drug activity in mice, as measured by change in tumor size, is independently associated with improved ORR in phase II clinical trials. The number of mice utilized in experiments, the number of publications referencing the drug for NSCLC before the phase II clinical trial, and whether the drug was approved for a cancer other than NSCLC also significantly correlated with ORR. Among clinical characteristics, sex, race, histology, and smoking history were significantly associated with ORR. Further research into metrics that correlate with drug activity has the potential to optimize selection of novel therapies for clinical trials and enrich the drug development pipeline, particularly for patients with targetable genetic aberrations and rare cancers.B cell lymphoma 2 (BCL-2) family proteins play an important role in intrinsic apoptosis. Overexpression of BCL-2 proteins in acute myeloid leukemia can circumvent resistance to apoptosis and chemotherapy. Considering this effect, the exploration of anti-apoptotic BCL-2 inhibitors is considered to have tremendous potential for the discovery of novel pharmacological modulators in cancer. This review outlines the impact of BCL-2 family proteins on intrinsic apoptosis and the development of acute myeloid leukemia (AML). Furthermore, we will also review the new combination therapy with venetoclax that overcomes resistance to venetoclax and discuss biomarkers of treatment response identified in early-phase clinical trials.Hepatocellular carcinoma (HCC) is a highly malignant and aggressive cancer with high recurrence rates and mortality. Some studies have illustrated that RNA binding proteins (RBPs) were involved in the carcinogenesis and development of multiple cancers, but the roles in HCC were still unclear. We downloaded the RNA-seq and corresponding clinical information of HCC from The Cancer Genome Atlas (TCGA) database, and 330 differentially expressed RBPs were identified between normal and HCC tissues. Through series of the univariate, the least absolute shrinkage selection operator (LASSO), and the stepwise multivariate Cox regression analyses, six prognosis-related key RBPs (CNOT6, UPF3B, MRPL54, ZC3H13, IFIT5, and PPARGC1A) were screened out from DE RBPs, and a six-RBP gene risk score signature was constructed in training set. Survival analysis indicated that HCC patients with high-risk scores had significantly worse overall survival than low-risk patients, and furthermore, the signature can be used as an independent prognostic indicator. The good accuracy of this prognostic signature was confirmed by the ROC curve analysis and was further validated in the International Cancer Genome Consortium (ICGC) HCC cohort. Besides, a nomogram based on six RBP genes was established and internally validated in the TCGA cohort. Gene set enrichment analysis demonstrated some cancer-related phenotypes were significantly gathered in the high-risk group. Overall, our study first identified an RBP-related six-gene prognostic signature, which could serve as a promising prognostic biomarker and provide some potential therapeutic targets for HCC.