Simplified, standardized methods to assess the accuracy of clinical cancer staging

Background. Hospitals lack intuitive methods to monitor their accuracy of clinical cancer staging, which is critical to treatment planning, prognosis, refinements, and registering quality data. Methods. We introduce a tabulation framework to compare clinical staging with the reference-standard pathological staging, and quantify systematic errors. As an example, we analyzed 9,644 2016 U.S. National Cancer Institute SEER surgically-treated non-small cell lung cancer (NSCLC) cases, and computed concordance with different denominators to compare with incompatible past results. Results. The concordance for clinical versus pathological lymph node N-stage is very good, 83.4 ± 1.0%, but the tumor length-location T-stage is only 58.1 ± 0.9%. There are intuitive insights to the causes of discordance. Approximately 29% of the cases are pathological T-stage greater than clinical T-stage, and 12% lower than the clinical T-stage, which is due partly to the fact that surgically-treated NSCLC are typically lower-stage cancer cases, which results in a bounded higher probability for pathological upstaging. Individual T-stage categories Tis, T1a, T1b, T2a, T2b, T3, T4 invariant percent-concordances are 85.2 ± 9.7 + 10.3%; 72.7 ± 1.6 + 11.3%; 46.6 ± 1.8 + 10.9%; 54.6 ± 1.6 – 20.5%; 41.6 ± 3.3 – 0.1%; 54.7 ± 2.8 – 24.1%; 55.2 ± 4.7 + 2.6%, respectively. Each percent-concordance is referenced to an averaged number of pathological and clinical cases. The first error number quantifies statistical fluctuations; the second quantifies clinical and pathological staging biases. Lastly, comparison of over and under staging versus clinical characteristics provides further insights. Conclusions. Clinical NSCLC staging accuracy and concordance with pathological values can improve. As a first step, the framework enables standardizing comparing staging results and detecting possible problem areas. Cancer hospitals and registries can implement the efficient framework to monitor staging accuracy

A comprehensive evaluation of polygenic score and genotype imputation performances of human SNP arrays in diverse populations

publishedVersio

The RNA-Binding Protein Musashi1 Affects Medulloblastoma Growth via a Network of Cancer- Related Genes and Is an Indicator of Poor Prognosis

Musashi1 (Msi1) is a highly conserved RNA-binding protein that is required during the development of the nervous system. Msi1 has been characterized as a stem cell marker, controlling the balance between self-renewal and differentiation, and has also been implicated in tumorigenesis, being highly expressed in multiple tumor types. We analyzed Msi1 expression in a large cohort of medulloblastoma samples and found that Msi1 is highly expressed in tumor tissue compared with normal cerebellum. Notably, high Msi1 expression levels proved to be a sign of poor prognosis. Msi1 expression was determined to be particularly high in molecular subgroups 3 and 4 of medulloblastoma. We determined that Msi1 is required for tumorigenesis because inhibition of Msi1 expression by small-interfering RNAs reduced the growth of Daoy medulloblastoma cells in xenografts. To characterize the participation of Msi1 in medulloblastoma, we conducted different high-throughput analyses. Ribonucleoprotein immunoprecipitation followed by microarray analysis (RIP-chip) was used to identify mRNA species preferentially associated with Msi1 protein in Daoy cells. We also used cluster analysis to identify genes with similar or opposite expression patterns to Msi1 in our medulloblastoma cohort. A network study identified RAC1, CTGF, SDCBP, SRC, PRL, and SHC1 as major nodes of an Msi1-associated network. Our results suggest that Msi1 functions as a regulator of multiple processes in medulloblastoma formation and could become an important therapeutic target

Protective and Enhancing HLA Alleles, HLA-DRB1*0901 and HLA-A*24, for Severe Forms of Dengue Virus Infection, Dengue Hemorrhagic Fever and Dengue Shock Syndrome

Dengue has become one of the most common viral diseases transmitted by infected mosquitoes (with any of the four dengue virus serotypes: DEN-1, -2, -3, or -4). It may present as asymptomatic or illness, ranging from mild to severe disease. Recently, the severe forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of death among children in Southern Vietnam. The pathogenesis of DHF/DSS, however, is not yet completely understood. The immune response, virus virulence, and host genetic background are considered to be risk factors contributing to disease severity. Human leucocyte antigens (HLA) expressed on the cell surface function as antigen presenting molecules and those polymorphism can change individuals' immune response. We investigated the HLA-A, -B (class I), and -DRB1 (class II) polymorphism in Vietnamese children with different severity (DHF/DSS) by a hospital-based case-control study. The study showed persons carrying HLA-A*2402/03/10 are about 2 times more likely to have severe dengue infection than others. On the other hand, HLA-DRB1*0901 persons are less likely to develop DSS with DEN-2 virus infection. These results clearly demonstrated that HLA controlled the susceptibility to severe forms of DV infection

Thelytokous Parthenogenesis in the Fungus-Gardening Ant Mycocepurus smithii (Hymenoptera: Formicidae)

The general prevalence of sexual reproduction over asexual reproduction among organisms testifies to the evolutionary benefits of recombination, such as accelerated adaptation to changing environments and elimination of deleterious mutations. Documented instances of asexual reproduction in groups otherwise dominated by sexual reproduction challenge evolutionary biologists to understand the special circumstances that might confer an advantage to asexual reproductive strategies. Here we report one such instance of asexual reproduction in the ants. We present evidence for obligate thelytoky in the asexual fungus-gardening ant, Mycocepurus smithii, in which queens produce female offspring from unfertilized eggs, workers are sterile, and males appear to be completely absent. Obligate thelytoky is implicated by reproductive physiology of queens, lack of males, absence of mating behavior, and natural history observations. An obligate thelytoky hypothesis is further supported by the absence of evidence indicating sexual reproduction or genetic recombination across the species' extensive distribution range (Mexico-Argentina). Potential conflicting evidence for sexual reproduction in this species derives from three Mycocepurus males reported in the literature, previously regarded as possible males of M. smithii. However, we show here that these specimens represent males of the congeneric species M. obsoletus, and not males of M. smithii. Mycocepurus smithii is unique among ants and among eusocial Hymenoptera, in that males seem to be completely absent and only queens (and not workers) produce diploid offspring via thelytoky. Because colonies consisting only of females can be propagated consecutively in the laboratory, M. smithii could be an adequate study organism a) to test hypotheses of the population-genetic advantages and disadvantages of asexual reproduction in a social organism and b) inform kin conflict theory

Isolated hemangioblastoma of the cervical spinal cord: A case report and literature review

Introduction: Hemangioblastomas are benign, slow growing but highly vascularized tumors of the central nervous system, with the most common location of occurrence in the posterior fossa. Hemangioblastomas usually have an associated with patients that have Von-Hippel Lindau disease, resulting a germline mutation in the VHL tumor suppressor gene. Isolated or sporadic occurrences of hemangioblastomas are much more infrequent and typically respond well after surgery. Presentation of case: We present case of a 22 year old female with worsening shoulder pain, decreased sensation in the hands and feet, and decreasing strength and was found to have a hemangioblastoma of the cervical spine. Discussion: The patient was treated with surgery and responded well to treatment. We also present a review of the literature on isolated occurrences of hemangioblastomas of the spinal cord. Conclusion: Isolated hemangioblastoma are a rare tumor of the central nervous system and can be managed with surgery

miR-551a and miR-551b-3p target GLIPR2 and promote tumor growth in high-risk head and neck cancer by modulating autophagy

The potential role for microRNA (miRNA) in the metastatic process that occurs in head and neck squamous cell carcinoma (HNSCC) was examined. miRNA was extracted from surgically excised tumor samples from 41 HNSCC cancer patients diagnosed with distant metastasis (DM) and from 53 patients who displayed no evidence of disease (NED) for a minimum of two years a minimum of two years after treatment with post-operative radiotherapy (PORT). A comparative two-way ANOVA of miRNA expression between DM and NED specimens identified 28 differentially expressed miRNAs with a false discovery rate (FDR)  1.5. Two miRNA, miR-551a and miR-551b-3p, which share the same seed sequence, were associated with the DM group and with poor survival. Cell proliferation, migration, and invasion assays using the HN5 and UMSCC-17B HNSCC cell lines were performed after transfecting mimics or inhibitors of these miRNA uncovered an oncogenic role for miR-551a and miR-551b-3p. Furthermore, it was determined that miR-551a and miR-551b-3p directly target GLIPR2 mRNA, a negative regulator of autophagy. Overexpression of GLIPR2 reduced proliferation, migration and invasion of HNSCC cells. In addition, overexpression of miR-551a and miR-551b-3p increased radioresistance while GLIPR2 overexpression increased the radiosensitivity of HNSCC cell lines. These results propose that the miR-551a, miR-551b-3p and GLIPR2 axis plays an important role in tumor growth, invasion and metastasis, at least in part by modulating autophagy and that the proliferative and pro-survival roles of miR-551a and miR-551b-3p may represent potential therapeutic targets by inhibiting autophagy through the regulation of GLIPR2 expression in HNSCC

3D printed integrated bolus/headrest for radiation therapy for malignancies involving the posterior scalp and neck

Abstract Background Malignancies of the head and neck region, encompassing cutaneous, mucosal, and sarcomatous histologies, are complex entities to manage, comprising of coordination between surgery, radiation therapy, and systemic therapy. Malignancies of the posterior scalp are particular challenging to treat with radiation therapy, given its irregular contours and anatomy as well as the superficial location of the target volume. Bolus material is commonly used in radiation therapy to ensure that the dose to the skin and subcutaneous tissue is appropriate and adequate, accounting for the buildup effect of megavoltage photon treatment. The use of commercially available bolus material on the posterior scalp potentially creates air gaps between the bolus and posterior scalp. Case presentations In this report, we created and utilized a custom 3D-printed integrated bolus and headrest for 5 patients to irradiate malignancies involving the posterior scalp, including those with cutaneous squamous cell carcinoma, melanoma, malignant peripheral nerve sheath tumor, and dermal sarcoma. Treatment setup was consistently reproducible, and patients tolerated treatment well without any unexpected adverse effects. Conclusions We found that the use of this custom 3D-printed integrated bolus/headrest allowed for comfortable, consistent, and reproducible treatment set up while minimizing the risk of creating significant air gaps and should be considered in the radiotherapeutic management of patients with posterior scalp malignancies

Clinical Non–Small Cell Lung Cancer Staging and Tumor Length Measurement Results From U.S. Cancer Hospitals

Rationale and Objectives: Examine the accuracy of clinical non–small cell lung cancer staging and tumor length measurements, which are critical to prognosis and treatment planning. Materials and Methods: Compare clinical and pathological staging and lengths using 10,320 2016 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) and 559 2010–2018 non-SEER single-institute surgically-treated cases, and analyze modifiable causes of disagreement. Results: The SEER clinical and pathological group-stages agree only 62.3% ± 0.9% over all stage categories. The lymph node N-stage agrees much better at 83.0% ± 1.0%, but the tumor length-location T-stage agrees only 57.7% ± 0.8% with approximately 29% of the cases having a greater pathology than clinical T-stage. Individual T-stage category agreements with respect to the number of pathology cases are Tis, T1a, T1b, T2a, T2b, T3, T4: 89.9% ± 10.0%; 78.7% ± 1.7%; 51.8% ± 1.9%; 46.1% ± 1.3%; 40.5% ± 3.1%; 44.1% ± 2.2%; 56.4% ± 4.7%, respectively. Most of the single-institute results statistically agree with SEER's. Excluding Tis cases, the mean difference in SEER tumor length is ∼1.18 ± 9.26 mm (confidence interval: 0.97–1.39 mm) with pathological lengths being longer than clinical lengths except for small tumors; the two measurements correlate well (Pearson-r >0.87, confidence interval: 0.86–0.87). Reasons for disagreement include the use of family-category descriptors (e.g., T1) instead of their subcategories (e.g., T1a and T1b), which worsens the T-stage agreement by over 15%. Disagreement is also associated with higher tumor grade, larger resected specimens, higher N-stage, patient age, and periodic biases in clinical and pathological tumor size measurements. Conclusions: By including preliminary non–small cell lung cancer clinical stage values in their evaluation, diagnostic radiologists can improve the accuracy of staging and standardize tumor-size measurements, which improves patient care