An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

The Impact of Mixing Modes on Reliability in Longitudinal Studies

Mixed-mode designs are increasingly important in surveys, and large longitudinal studies are progressively moving to or considering such a design. In this context, our knowledge regarding the impact of mixing modes on data quality indicators in longitudinal studies is sparse. This study tries to ameliorate this situation by taking advantage of a quasi-experimental design in a longitudinal survey. Using models that estimate reliability for repeated measures, quasi-simplex models, 33 variables are analyzed by comparing a single-mode CAPI design to a sequential CATI-CAPI design. Results show no differences in reliabilities and stabilities across mixed modes either in the wave when the switch was made or in the subsequent waves. Implications and limitations are discussed. </jats:p

Measurement Equivalence in Sequential Mixed-Mode Surveys

Many surveys collect data using a mixture of modes administered in sequential order. Although the impacts of mixed-mode designs on measurement quality have been extensively studied, their impacts on the measurement quality of unobservable (or latent) constructs is still an understudied area of research. In particular, it is unclear whether latent constructs derived from multi-item scales are measured equivalently across different sequentially-administered modes—an assumption that is often made by analysts, but rarely tested in practice. In this study, we assess the measurement equivalence of several commonly-used multi-item scales collected in a sequential mixed-mode (Web-telephone-face-to-face) survey: the Age 25 wave of the Next Steps cohort study. After controlling for selection via an extensive data-driven weighting procedure, a multi-group confirmatory factor analysis was performed to assess measurement equivalence across the three modes. We show that cross-mode measurement equivalence is achieved for nearly all scales, with partial equivalence established for the remaining. Although measurement equivalence was achieved, some differences in the latent means were observed between the modes, particularly between the interviewer-administered and selfadministered modes. We conclude with a discussion of these findings, their potential causes, and implications for survey practice

Estimating stochastic survey response errors using the multitrait‐multierror model

Surveys are well known to contain response errors of different types, including acquiescence, social desirability, common method variance and random error simultaneously. Nevertheless, a single error source at a time is all that most methods developed to estimate and correct for such errors consider in practice. Consequently, estimation of response errors is inefficient, their relative importance is unknown and the optimal question format may not be discoverable. To remedy this situation, we demonstrate how multiple types of errors can be estimated concurrently with the recently introduced ‘multitrait-multierror’ (MTME) approach. MTME combines the theory of design of experiments with latent variable modelling to estimate response error variances of different error types simultaneously. This allows researchers to evaluate which errors are most impactful, and aids in the discovery of optimal question formats. We apply this approach using representative data from the United Kingdom to six survey items measuring attitudes towards immigrants that are commonly used across public opinion studies

The role of oophorectomy as adjuvant complex therapy for patients with breast cancer (preliminary assessment)

Catedra de oncologie, hematologie și radioterapie, USMF „Nicolae Testemițanu”, Institutul Oncologic, Chișinău, Republica Moldova, Conferința stiințifică „Nicolae Anestiadi – nume etern al chirurgiei basarabene” consacrată centenarului de la nașterea profesorului Nicolae Anestiadi 26 august 2016Introducere. Cea mai eficientă metodă de stopare a producerii de estrogeni la femeile cu cancer mamar (CM) în pre-/perimenopauză o reprezintă ablația ovariană. Ablația funcției ovariene poate fi realizată prin ovariectomie bilaterală sau prin utilizarea hormonului eliberator de gonadotropină (GnRH). Scop. Analiza rezultatelor imediate ale ovariectomiei în tratamentul complex adjuvant al pacientelor cu CM. Materiale și metode. Au fost studiate rezultatele la 61 paciente cu CM tratate în faza reproductivă cu vârsta între 22-48 de ani, care au fost supuse tratamentului hormonal, chimioterapic și ovariectomie. Rezultate. Pacientele cu tipul luminal A (RE+RP+Her2/neu-) au fost divizate în 3 loturi în dependență de metoda de tratament adjuvant: lotul I – chimio-/radioterapie + ovariectomie + tamoxifen – 31 paciente (50,81%); lotul II - chimio-/radioterapie + GnRH – 22 paciente (36,06%); lotul III - chimio-/radioterapie + tamoxifen – 8 paciente (13,11%). Dintre cele 31 de paciente din lotul I, date de progresare loco-regională în primii 2 ani nu s-au înregistrat la 29 de paciente, ceea ce constituie 93,54%; pentru lotul II – 19 din 22 (86,36%); lotul III – la 5 din 8 (62,5%). Concluzii. Ovariectomia în tratamentul complex adjuvant al pacientelor cu CM tip luminal A reprezintă metoda cu rata cea mai înaltă de reducere a cazurilor de progresare loco-regională comparativ cu alte metode de tratament hormonal.Introduction. The most effective method to stop the production of estrogen for patients in reproductive and perimenopausal phases presents ovarian ablation. Ovarian function ablation may be achieved by bilateral oophorectomy which leads to irreversible ablation of ovarian function with Gonadotropin releasing hormone analogues (GnRHAs). Purpose. Analysis of the immediate results of oophorectomy as adjuvant complex therapy for patients with breast cancer (BC). Material and methods. There were 61 patients with BC treated during the reproductive phases, aged 22-48 years, who were admitted within the Mastology Research Laboratory, Chemotherapy and Radiotherapy Departments of the Oncological Institute. Results. Patients with luminal A type (ER+PR+Her2/neu-) was were divided into 3 groups: group I – chemo-/ radiotherapy + oophorectomy + tamoxifen - 31 cases (50,81%); group II - chemo-/radiotherapy + GnRH - 22 cases (36,06%); group III - chemo-/radiotherapy + tamoxifen - 8 cases (13,11%). Of the 31 patients in group I, loco-regional progression data in the first 2 years have not been recorded in 29 patients, which is 93,54%; for group II - 19 cases (86,36%) of 22; for group III – 5 cases (62,5%) of 8. Conclusions. The role of oophorectomy in the adjuvant complex therapy for patients with luminal A type it is the method with the highest rate of reduction of cases of loco-regional progression comparated with other methods of hormonal treatment

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Synchronous gastrointestinal stromal tumor and gastric carcinoma

Secția chirurgie gastrică, IMSP Institutul Oncologic, Catedra Chirurgie nr.1 „Nicolae Anestiadi” şi Laboratorul Chirurgie Hepato-Pancreato-Biliară, Universitatea de Stat de Medicină şi Farmacie ”Nicolae Testemiţanu”, IMSP Institutul de Medicină Urgentă, Chișinău, Republica Moldova, Al XIII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” și al III-lea Congres al Societății de Endoscopie, Chirurgie miniminvazivă și Ultrasonografie ”V.M.Guțu” din Republica MoldovaIntroducere: Apariția sincronă a tumorilor în stomac, mai ales coexistența carcinomului gastric (CG) și a tumorii gastrointestinale stromale (TGIS) gastrice, este rar întîlnită, în literatură fiind descrise doar cazuri sporadice. Prezentăm un caz clinic de asociere sincronă a adenocarcinomului gastric slab diferenţiat cu celule „în inel cu pecete” cu o TGIS la un pacient de gen masculin. Materiale şi metode: Pacient, bărbat, 78 de ani, se internează pentru un discomfort postalimentar în regiunea epigastrului, grețuri și scădere ponderală circa 10 kg în ultima lună anterior internării. Examenul obiectiv și analizele de laborator nu au depistat devieri semnificative, cu excepția unei anemii moderate. Diagnosticul a fost stabilit endoscopic, fiind depistată o formațiune submucoasă de 5,0 x 3,5 cm în treimia inferioară a corpului gastric și o formațiune protruzivă de circa 1,5 x 2,0 cm în regiunea gastrică antrală, cu aspect de cancer gastric incipient tip IIa, confirmată morfologic, preoperator, drept adenocarcinom cu celule tip ”inel cu pecete”. S-a suspectat asocierea adenocarcinomului gastric cu o tumoră stromală gastrică. Rezultate: Pacientul a fost supus rezecției gastrice subtotale tip Billroth II. Histopatologic, postoperator, a fost confirmat: adenocarcinom gastric pT1bN0M0 și TGIS de 5,5 cm, constituită din celule fusiforme, imunohistochimic pozitivă pentru markerii CD117(c-KIT) și CD34, cu 4 mitoze la 50 câmpuri de înaltă rezoluție – grup pronostic 3a și risc redus de progresare a bolii. Evoluția postoperatorie imediată a fost favorabilă. Pacientul nu a necesitat tratament adjuvant și a fost programat pentru TC abdomenului în dinamică. Concluzii: Apariția sincronă a adenocarcinomului gastric cu TGIS este foarte rară și poate fi detectată incidental în timpul investigațiilor sau laparotomiilor pentru alte patologii. Explorarea chirurgicală completă intraoperatorie a fiecărui pacient își păstrează valoarea. Tratamentul chirurgical este unica metodă curativă.Introduction: Synchronous gastric tumors, especially collision of a gastric carcinoma (GC) and gastrointestinal stromal tumor (GIST), are very rare, a few cases being reported in the literature. We present a case of a signet-ring cell adenocarcinoma associated with GIST in a male patient. Material and methods: Pacient, 78 y.o. male, admitted for postprandial discomfort in the epigastric region of abdomen, nausea, and weight loss about 10 kg in the last month prior to admission. Physical examination and laboratory data were unremarkable, except for a moderate anemia. Positive diagnostic was established by upper endoscopy with biopsy which revealed a submucosal tumor of 5,0 x 3,5 cm in the lower third of gastric body and a protrusive tumor of 1,5 x 2,0 cm in the gastric antrum, resembling type IIa early gastric cancer. Preoperative histopathological report showed signet-ring cell adenocarcinoma. Association of GC and GIST was suspected. Results: The patient undergone a subtotal Billroth II gastrectomy. Postoperative histological examination reported a GC pT1bN0M0 and a spindle-cell type GIST, CD117(c-KIT) and CD34 positive, with mitosis of 4/50 HPF and a low risk of progression. The patient had an uneventful postoperative period. No adjuvant treatment was needed and a follow-up abdominal CT was scheduled. Conclusions: Synchronous occurrence of GC and GIST is very rare and can be accidentally found during instrumental work-up or laparotomy for other pathology. Intraoperative complete surgical exploration of each patient is imperative. Surgical treatment is the only curative option