The impact of the variation of imaging parameters on the robustness of Computed Tomography radiomic features: A review.

The field of radiomics is at the forefront of personalized medicine. However, there is concern that high variation in imaging parameters will impact robustness of radiomic features and subsequently the performance of the predictive models built upon them. Therefore, our review aims to evaluate the impact of imaging parameters on the robustness of radiomic features. We also provide insights into the validity and discrepancy of different methodologies applied to investigate the robustness of radiomic features. We selected 47 papers based on our predefined inclusion criteria and grouped these papers by the imaging parameter under investigation: (i) scanner parameters, (ii) acquisition parameters and (iii) reconstruction parameters. Our review highlighted that most of the imaging parameters are disruptive parameters, and shape along with First order statistics were reported as the most robust radiomic features against variation in imaging parameters. This review identified inconsistencies related to the methodology of the reviewed studies such as the metrics used for robustness, the feature extraction techniques, the reporting style, and their outcome inclusion. We hope this review will aid the scientific community in conducting research in a way that is more reproducible and avoids the pitfalls of previous analyses.

The complexity of microRNAs in human cancer.

MicroRNAs (miRNAs) are small non-coding RNA molecules that have key regulatory roles in cancer, acting as both oncogenes and tumor suppressors. Due to the potential roles of miRNAs in improving cancer prognostic, predictive, diagnostic and therapeutic approaches, they have become an area of intense research focus in recent years. MiRNAs harbor attractive features allowing for translation to the clinical world, such as relatively simple extraction methods, resistance to molecular degradation, and ability to be quantified. Numerous prognostic, predictive and diagnostic miRNA signatures have been developed. To date however, miRNA analysis has not been adopted for routine clinical use. The objectives of this article are to provide an overview of miRNA research and review a selection of miRNA studies in breast cancer, cervical cancer, sarcoma, and nasopharyngeal carcinoma to highlight advances and challenges in miRNA cancer research.

Mapping the future: towards oncology curriculum reform in undergraduate medical education at a Canadian medical school.

PURPOSE: To evaluate (1) the quantity and quality of current undergraduate oncology teaching at a major Canadian medical school; and (2) curricular changes over the past decade, to enhance local oncology education and provide insight for other educators. METHODS AND MATERIALS: Relevant 2011-2012 undergraduate curricular sessions were extracted from the University of Toronto curriculum mapping database using keywords and database identifiers. Educational sessions were analyzed according to Medical Council of Canada objectives, discussion topics, instructor qualifications, teaching format, program year, and course subject. Course-related oncology research projects performed by students during 2000 to 2012 were extracted from another internal database. Elective choices of clerks during 2008-2014 were retrieved from the institution. The 2011-2012 and 2000-2001 curricula were compared using common criteria. RESULTS: The 2011-2012 curriculum covers 5 major themes (public health, cancer biology, diagnosis, principles of care, and therapy), which highlight 286 oncology teaching topics within 80 sessions. Genitourinary (10, 12.5%), gynecologic (8, 10.0%), and gastrointestinal cancers (7.9, 9.8%) were the most commonly taught cancers. A minority of sessions were taught by surgical oncologists (6.5, 8.1%), medical oncologists (2.5, 3.1%), and radiation oncologists (1, 1.2%). During 2000-2012, 9.0% of students (233 of 2578) opted to complete an oncology research project. During 2008-2014, oncology electives constituted 2.2% of all clerkship elective choices (209 of 9596). Compared with pre-2001 curricula, the 2012 oncology curriculum shows notable expansion in the coverage of epidemiology (6:1 increase), prevention (4:1), screening (3:1), and molecular biology (6:1). CONCLUSIONS: The scope of the oncology curriculum has grown over the past decade. Nevertheless, further work is needed to improve medical student knowledge of cancers, particularly those relevant to public health needs. Defining minimum curricular content, emphasizing content based on population needs, and ensuring educational delivery with the support and expertise of oncologists and non-oncologists will be essential next steps.

Correlation of dosimetric and clinical factors with the development of esophagitis and radiation pneumonitis in patients with limited-stage small-cell lung carcinoma.

BACKGROUND: The purpose of the study was to correlate clinical and dosimetric factors with the development of esophagitis and radiation pneumonitis in patients with limited-stage small-cell lung carcinoma (LS SCLC). PATIENTS AND METHODS: One hundred eighteen patients who received curative intent chemoradiotherapy for LS SCLC and had electronically archived radiation treatment plans were included. The medical charts were reviewed for clinical data. The treatment plan was reviewed for critical structure delineation and dose delivered. Treatment planning data were analyzed using Computational Environment for Radiotherapy Research (V3.3). Dosimetric parameters were correlated with the risk of toxicity using Spearman rank correlation. RESULTS: Radiotherapy dose was 40 Gy in 15 fractions (fx) (n = 80) and 45 Gy in 30 fractions twice per day (n = 38). The 6-month cumulative incidence of Grade ≥ 2 radiation pneumonitis was 6.5% and 7.9% for the 40 Gy/15 fx and 45 Gy/30 fx groups, respectively (P = .40). The 3-month cumulative incidence of Grade 3 esophagitis was 7.5% and 13.2% for the 40 Gy/15 fx and 45 Gy/30 fx groups, respectively (P = .31). Grade ≥ 3 pneumonitis was correlated with volume of lung receiving 20 Gy (V20) and mean lung dose. Grade ≥ 3 esophagitis was correlated with mean esophagus dose and minimum dose to the hottest 45% of the esophagus (D45). CONCLUSION: Mean lung dose and V20 were significant predictors of radiation pneumonitis in LS SCLC. Mean esophageal dose and D45 were significant predictors of esophagitis. These 2 treatment schedules have similar toxicity profiles.

A porphodimethene chemical inhibitor of uroporphyrinogen decarboxylase.

Uroporphyrinogen decarboxylase (UROD) catalyzes the conversion of uroporphyrinogen to coproporphyrinogen during heme biosynthesis. This enzyme was recently identified as a potential anticancer target; its inhibition leads to an increase in reactive oxygen species, likely mediated by the Fenton reaction, thereby decreasing cancer cell viability and working in cooperation with radiation and/or cisplatin. Because there is no known chemical UROD inhibitor suitable for use in translational studies, we aimed to design, synthesize, and characterize such a compound. Initial in silico-based design and docking analyses identified a potential porphyrin analogue that was subsequently synthesized. This species, a porphodimethene (named PI-16), was found to inhibit UROD in an enzymatic assay (IC50 = 9.9 µM), but did not affect porphobilinogen deaminase (at 62.5 µM), thereby exhibiting specificity. In cellular assays, PI-16 reduced the viability of FaDu and ME-180 cancer cells with half maximal effective concentrations of 22.7 µM and 26.9 µM, respectively, and only minimally affected normal oral epithelial (NOE) cells. PI-16 also combined effectively with radiation and cisplatin, with potent synergy being observed in the case of cisplatin in FaDu cells (Chou-Talalay combination index <1). This work presents the first known synthetic UROD inhibitor, and sets the foundation for the design, synthesis, and characterization of higher affinity and more effective UROD inhibitors.

Identification of genes expressed by immune cells of the colon that are regulated by colorectal cancer-associated variants.

A locus on human chromosome 11q23 tagged by marker rs3802842 was associated with colorectal cancer (CRC) in a genome-wide association study; this finding has been replicated in case-control studies worldwide. In order to identify biologic factors at this locus that are related to the etiopathology of CRC, we used microarray-based target selection methods, coupled to next-generation sequencing, to study 103 kb at the 11q23 locus. We genotyped 369 putative variants from 1,030 patients with CRC (cases) and 1,061 individuals without CRC (controls) from the Ontario Familial Colorectal Cancer Registry. Two previously uncharacterized genes, COLCA1 and COLCA2, were found to be co-regulated genes that are transcribed from opposite strands. Expression levels of COLCA1 and COLCA2 transcripts correlate with rs3802842 genotypes. In colon tissues, COLCA1 co-localizes with crystalloid granules of eosinophils and granular organelles of mast cells, neutrophils, macrophages, dendritic cells and differentiated myeloid-derived cell lines. COLCA2 is present in the cytoplasm of normal epithelial, immune and other cell lineages, as well as tumor cells. Tissue microarray analysis demonstrates the association of rs3802842 with lymphocyte density in the lamina propria (p = 0.014) and levels of COLCA1 in the lamina propria (p = 0.00016) and COLCA2 (tumor cells, p = 0.0041 and lamina propria, p = 6 × 10(-5)). In conclusion, genetic, expression and immunohistochemical data implicate COLCA1 and COLCA2 in the pathogenesis of colon cancer. Histologic analyses indicate the involvement of immune pathways.