Correlation of PD-L1 Expression with Tumor Mutation Burden and Gene Signatures for Prognosis in Early-Stage Squamous Cell Lung Carcinoma

Objectives

Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.

Increasing Rate of Noninterventional Treatment Management in Localized Prostate Cancer Candidates for Active Surveillance: A North American Population-Based Study

Background

The rate of noninterventional treatment (NIT) in prostate cancer (PCa) active surveillance (AS) candidates is on the rise. However, contemporary data are unavailable. We described community-based NIT rates within 16 Surveillance Epidemiology and End Results (SEER) registries between 2010 and 2014.

Radiologic Considerations and Standardization of Malignant Pleural Mesothelioma Imaging Within Clinical Trials: Consensus Statement from the NCI Thoracic Malignancy Steering Committee – International Association for the Study of Lung Cancer – Mesothelioma Applied Research Foundation Clinical Trials Planning Meeting

Detailed guidelines pertaining to radiological assessment of malignant pleural mesothelioma are currently lacking due to the rarity of the disease, complex morphology, propensity to invade multiple planes simultaneously, and lack of specific recommendations within the radiology community about assessment, reporting, and follow-up. In March 2017, a multidisciplinary meeting of mesothelioma experts was co-sponsored by the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and the Mesothelioma Applied Research Foundation. One of the outcomes of this conference was the foundation of detailed, multidisciplinary consensus imaging and management guidelines. Here, we present the recommendations for radiologic assessment of malignant pleural mesothelioma in the setting of clinical trial enrollment. We discuss optimization of imaging parameters across modalities, standardized reporting, and response assessment within clinical trials.     

Prognosis and prognostic factors of running-related injuries in novice runners: A prospective cohort study

Objectives

To investigate the prognosis and possible prognostic factors of running-related injuries (RRIs) in novice runners.

Unmarried status is a barrier for access to treatment in patients with metastatic renal cell carcinoma

International Urology and Nephrology - We tested the effect of marital status on cytoreductive nephrectomy, metastasectomy, and systemic therapy rates, as well as on cancer-specific mortality (CSM)...     

Reasons and predictors of discontinuation of running after a running program for novice runners

Objectives

To determine the proportion of participants of a running program for novice runners that discontinued running and investigate the main reasons to discontinue and characteristics associated with discontinuation.

Validity of injury self-reports by novice runners: comparison with reports by sports medicine physicians

This study examined the criterion validity of self-reported running-related injuries (RRI) by novice runners. Fifty-eight participants (41 females; age 46 ± 11 yrs) of the “Start-to-Run” program provided self-reports on their RRIs using an online questionnaire. Subsequently, they attended injury consultations with sports medicine physicians who provided physician-reports (blinded for the self-reports) as a reference standard. Self-reports and physician-reports included information on injury location (i.e., hip/groin, upper leg, knee, lower leg, and ankle/foot) and injury type (i.e., muscle-tendon unit, joint, ligament, or bone). Sensitivity, specificity, and positive predictive values were 100% for all five injury locations. For injury type, sensitivity was low (66% for muscle-tendon unit, 50% for ligament, and 40% for bone) and lowest for joint injuries (17%). In conclusion, the validity of self-reported RRIs by novice runners is good for injury locations but not for injury types. In particular for joint injuries, the validity of novice runners’ self-reports is low.

Abbreviations: RRI: Running Related Injury; SMC: Sports Medicine Centre; MTU: Muscle Tendon Unit; PPV: Positive Predictive Value     

The subthalamic nucleus‐external globus pallidus loop biases exploratory decisions towards known alternatives: a neuro‐computational study

Theories and models of the basal ganglia have mainly focused on the role of three different corticothalamic pathways: direct, indirect and hyperdirect. Although the indirect and the hyperdirect pathways are linked through the bidirectional connections between the subthalamic nucleus (STN) and the external globus pallidus (GPe), the role of their interactions has been mainly discussed in the context of a dysfunction (abnormal oscillations in Parkinson's disease) and not of its function. We here propose a novel role for the loop formed by the STN and the GPe. We show, through a neuro‐computational model, that this loop can bias the selection of actions during the exploratory period after a change in the environmental conditions towards alternative responses. Testing well‐known alternative solutions before completely random actions can reduce the time required for the search of a new response after a rule change. Our simulations further show that the knowledge acquired by the indirect pathway can be transferred into a stable memory via learning in the hyperdirect pathway to establish the blocking of unwanted responses. After a rule switch, first the indirect pathway learns to inhibit the previously correct actions. Once the new correct association is learned, the inhibition is transferred to the hyperdirect pathway through synaptic plasticity.     

Changes in DNA Damage Repair Gene Expression and Cell Cycle Gene Expression Do Not Explain Radioresistance in Tamoxifen-Resistant Breast Cancer

Tamoxifen-induced radioresistance, reported in vitro, might pose a problem for patients who receive neoadjuvant tamoxifen treatment and subsequently receive radiotherapy after surgery. Previous studies suggested that DNA damage repair or cell cycle genes are involved, and could therefore be targeted to preclude the occurrence of cross-resistance. We aimed to characterize the observed cross-resistance by investigating gene expression of DNA damage repair genes and cell cycle genes in estrogen receptor-positive MCF-7 breast cancer cells that were cultured to tamoxifen resistance. RNA sequencing was performed, and expression of genes characteristic for several DNA damage repair pathways was investigated, as well as expression of genes involved in different phases of the cell cycle. The association of differentially expressed genes with outcome after radiotherapy was assessed in silico in a large breast cancer cohort. None of the DNA damage repair pathways showed differential gene expression in tamoxifen-resistant cells compared to wild-type cells. Two DNA damage repair genes were more than two times upregulated (NEIL1 and EME2), and three DNA damage repair genes were more than two times downregulated (PCNA, BRIP1, and BARD1). However, these were not associated with outcome after radiotherapy in the TCGA breast cancer cohort. Genes involved in G₁, G₁/S, G₂, and G₂/M phases were lower expressed in tamoxifen-resistant cells compared to wild-type cells. Individual genes that were more than two times upregulated (MAPK13) or downregulated (E2F2, CKS2, GINS2, PCNA, MCM5, and EIF5A2) were not associated with response to radiotherapy in the patient cohort investigated. We assessed the expression of DNA damage repair genes and cell cycle genes in tamoxifen-resistant breast cancer cells. Though several genes in both pathways were differentially expressed, these could not explain the cross-resistance for irradiation in these cells, since no association to response to radiotherapy in the TCGA breast cancer cohort was found.