- An expert consensus to standardise the assessment of histological disease activity in Crohn's disease clinical trialsby Ahmed Almradi on 2021-01-07
CONCLUSION: We evaluated the appropriateness of items for assessing histological disease activity in CD clinical trials. These items will be used to develop a novel histological index.
- Tumor infiltrating neutrophils and gland formation predict overall survival and molecular subgroups in pancreatic ductal adenocarcinomaby Julia R Naso on 2020-12-29
CONCLUSIONS: The assessment of gland formation and neutrophil infiltration on routine histological sections can aid in prognostication and allow inferences to be made about molecular subtype, which may help guide patient management decisions and contribute to our understanding of heterogeneity in treatment response.
- Reproducibility of tumor budding assessment in pancreatic cancer based on a multicenter interobserver studyby Eva Karamitopoulou on 2020-12-17
Tumor budding has been reported to be an independent prognostic factor in pancreatic ductal adenocarcinoma (PDAC). Its use in daily diagnostics would improve the prognostic stratification of patients. We performed a multicenter interobserver study to test various budding assessment methods for their reproducibility. Two serial sections of 50 resected, treatment-naïve PDACs were stained for Hematoxylin and Eosin (H&E) and pancytokeratin. Tumor budding was scored by independent observers at five...
- Overcoming Adaptive Resistance to KRAS and MEK Inhibitors by Co-targeting mTORC1/2 Complexes in Pancreatic Cancerby Wells S Brown on 2020-12-09
Activating KRAS mutations are found in over 90% of pancreatic ductal adenocarcinomas (PDACs), yet KRAS has remained a difficult target to inhibit pharmacologically. Here, we demonstrate, using several human and mouse models of PDACs, rapid acquisition of tumor resistance in response to targeting KRAS or MEK, associated with integrin-linked kinase (ILK)-mediated increased phosphorylation of the mTORC2 component Rictor, and AKT. Although inhibition of mTORC1/2 results in a compensatory increase in...
- Uncovering Clinically Relevant Gene Fusions with Integrated Genomic and Transcriptomic Profiling of Metastatic Cancersby Erica S Tsang on 2020-11-05
CONCLUSIONS: Utilizing WGS/RNA-seq facilitates identification of novel fusions in clinically relevant genes, and detected a greater proportion than commercially available panels are expected to find. A significant benefit of WGS and RNA-seq is the innate ability to retrospectively identify variants that becomes clinically relevant over time, without the need for additional testing, which is not possible with panel-based approaches.
- The significance of histological activity measurements in immune checkpoint inhibitor colitisby Rish K Pai on 2020-11-04
CONCLUSION: Histological activity as measured by RHI is the only factor independently associated with biological use and adverse colitis outcomes. Prospective studies are needed to validate these findings to determine if histological activity should be incorporated into therapeutic algorithms.
- Subtype-Discordant Pancreatic Ductal Adenocarcinoma Tumors Show Intermediate Clinical and Molecular Characteristicsby James T Topham on 2020-10-14
CONCLUSIONS: Nearly 1 in 6 patients with PDAC have tumors that fail to reliably fall into the classical or basal-like PDAC subtype categories, based on two regression tools aimed toward clinical practice. Rather, these patient tumors show intermediate prognostic and molecular traits. We propose close consideration of the non-binary nature of PDAC subtypes for future incorporation of subtyping into clinical practice.
- Colorectal adenocarcinomas diagnosed following a negative FIT show high-risk pathologic features in a colon screening programby Michael J Steel on 2020-10-10
CONCLUSION: FIT-interval cancers are associated with high-risk pathologic features; the possibility that more aggressive, fast-growing lesions which arise in the interval after truly negative FITs cannot be ruled out. Further study of a larger cohort of FIT-interval cancers controlling for interaction amongst the different pathologic parameters will be undertaken.
- Delving into Early-onset Pancreatic Ductal Adenocarcinoma: How Does Age Fit In?by Erica S Tsang on 2020-09-22
CONCLUSIONS: Our comprehensive analysis of sequencing data generated from a large cohort of PDAC patient samples highlights a distinctive pattern of biallelic CDKN2A mutation in EOPC tumors. Increased expression of FOXC2 in EOPC, with the correlation between FOXC2 and EMT pathways, represents novel molecular characteristics of EOPC.See related commentary by Lou, p. 8.
- Stroma vs epithelium-enhanced prognostics through histologic stratification in pancreatic ductal adenocarcinomaby Steve E Kalloger on 2020-09-21
The mixture of epithelial and stromal components in pancreatic ductal adenocarcinoma (PDAC) may confound sequencing-based studies of tumor gene expression. Virtual microdissection has been suggested as a bioinformatics approach to segment the aforementioned components, and subsequent prognostic gene sets have emerged from this research. We examined the prognostic signature from the epithelial gene set of one such study using laser capture microdissected (LCM) epithelial samples. We also examined...
- Clinical and genomic characterisation of mismatch repair deficient pancreatic adenocarcinomaby Robert C Grant on 2020-09-16
CONCLUSIONS: MMRD pancreatic cancers have distinct clinical, pathological and genomic profiles. Patients with MMRD pancreatic cancer should be considered for basket trials targeting enhanced immunogenicity or the unique genomic drivers in these malignancies.
- Variability in Synoptic Reporting of Colorectal Cancer pT4a Category and Lymphovascular Invasionby Julia R Naso on 2020-09-04
CONCLUSIONS.—: Real-world reporting of pT4a category and lymphovascular invasion shows substantial variability at both local and regional levels. Our study underscores the need to address these features in quality initiatives, and provides a novel method through which existing synoptic data can be harnessed to monitor reporting patterns and provide individualized feedback.
- Evaluating the impact of universal Lynch syndrome screening in a publicly funded healthcare systemby Petra W C Lee on 2020-07-24
CONCLUSION: The implementation of universal screening in a publicly funded system will increase efficiency in detecting patients with LS. The resources available for genetic testing and counseling may be more limited in public systems, thus inclusion of secondary screening with BRAF and MLH1 promoter hypermethylation testing is key to further optimizing efficiency.
- Improved structural variant interpretation for hereditary cancer susceptibility using long-read sequencingby My Linh Thibodeau on 2020-07-07
CONCLUSION: Our findings demonstrate that long-read sequencing can improve the validation, resolution, and classification of germline SVs. This has important implications for return of results, cascade carrier testing, cancer screening, and prophylactic interventions.
- Population-based Screening for BRAF V600E in Metastatic Colorectal Cancer Reveals Increased Prevalence and Poor Prognosisby Jenny E Chu on 2020-06-24
CONCLUSIONS: Patients with BRAF ^(V600E)-mutated mCRC have a worse prognosis than previously suggested, potentially arising from referral bias for testing. High attrition between lines of therapy suggests efficacious therapies need to be prioritized early for patients to benefit.