Insights for clinical management from the real-life data of the centralized West of Scotland biliary cancer clinic.

BACKGROUND: With the increasing of novel therapeutics for the treatment of Biliary Tract Cancers (BTC), and the need to assess their socio-economic impacts for national licence approvals, it is as important as ever to have real-life data in national populations. METHODS AND RESULTS: We performed an audit of the first 2 year-activity (Sep 2019-Sep 2021) of the centralized West-of-Scotland-BTC clinic. 122 patients accessed the service, including 68% with cholangiocarcinoma (CCA), 27% with gallbladder cancer (GBC), and 5% with ampulla of Vater carcinoma with biliary phenotype (AVC). Median age at diagnosis was 66 (28-84), with 30% of newly diagnosed patients being younger than 60 years-old. Thirty-five cases (29%) underwent surgery, followed by adjuvant-chemotherapy in 66%. 60% had recurrent disease (80% with distant relapse). Sixty-four patients (58%) started first-line Systemic-AntiCancer-Treatment (SACT). Of these, 37% received second line SACT, the majority of which had iCCA and GBC. Thirty-% of those who progressed received third line SACT. CONCLUSIONS: About 30% of BTC were eligible for curative surgery. Fifty-eight and twenty% of the overall cohort of advanced BTC patients received first and second line SACT. Our data suggest that reflex genomic profiling may not be cost-effective until molecularly driven strategies are limited to second line setting.

PLA2G12A as a Novel Biomarker for Colorectal Cancer with Prognostic Relevance.

Metastasis is the leading cause of colorectal cancer (CRC)-related deaths. Therefore, the identification of accurate biomarkers predictive of metastasis is needed to better stratify high-risk patients to provide preferred management and reduce mortality. In this study, we identified 13 new genes that modified circulating tumor cell numbers using a genome-wide genetic screen in a whole animal CRC model. Candidate genes were subsequently evaluated at the gene expression level in both an internal human CRC cohort of 153 patients and an independent cohort from the TCGA including 592 patients. Interestingly, the expression of one candidate, PLA2G12A, significantly correlated with both the time to recurrence and overall survival in our CRC cohort, with its low expression being an indicator of a poor clinical outcome. By examining the TCGA cohort, we also found that low expression of PLA2G12A was significantly enriched in epithelial-mesenchymal transition signatures. Finally, the candidate functionality was validated in vitro using three different colon cancer cell lines, revealing that PLA2G12A deficiency increases cell proliferation, migration, and invasion. Overall, our study identifies PLA2G12A as a prognostic biomarker of early-stage CRC, providing evidence that its deficiency promotes tumor growth and dissemination.

Ninety-day mortality and clinical outcomes of patients with solid tumours and COVID-19 infection during the first pandemic outbreak in Catalonia, Spain: A multicentre retrospective study.

To describe the clinical outcomes and risk factors for 90-day mortality in patients with solid tumours (ST) and coronavirus disease 2019 (COVID-19) during the first outbreak in Catalonia. This is a multicentre retrospective study including adults with ST and COVID-19 confirmed by real time reverse transcription polymerase chain reaction between 13 March and 30 April 2020. Clinical and survival data were collected. Follow-up ended on 30 July 2020. Multivariate and survival analysis were performed. A hundred and fifteen patients were included. In all, 42.6% had advanced disease and were receiving anticancer treatment; 7% were admitted to the ICU and 22.6% died during hospitalisation. Thirty-day mortality was 27.8%, which increased to 33.9% at 90 days. Ninety-day mortality was associated with current smoker status (hazard ratio [HR]: 2.91, 95% CI [confidence interval]: 1.03-8.33, P = .044), baseline ECOG-PS 2 to 3 (HR: 3.88, 95% CI: 1.77-8.46, P < .001]), dyspnoea (HR: 3.02, 95% CI: 1.31-6.96, P = .009), a respiratory rate ≥ 24 (HR: 2.24, 95% CI: 1.02-4.92, P = .046) and sepsis (HR: 3.97, 95% CI: 1.78-8.88, P < .001). Of the 76 survivors, 73.6% had a follow-up visit. Of those, 33.9% had their cancer controlled and 23.2% had progressed. Thirty-five survivors were receiving anticancer treatment before COVID-19 diagnosis though 14 had to discontinue the treatment. Eight survivors without previous anticancer therapy started therapy. The median time to start anticancer therapy after COVID-19 was 45 days (interquartile range: 28-61). In conclusion, 90-day mortality in patients with ST and COVID-19 was 33.9%; current smoker status, poor ECOG-PS, dyspnoea, respiratory rate ≥24 and sepsis were independent risk factors for mortality; and survivors did not restart their anticancer treatment until 1.5 months after COVID-19 diagnosis.

Microenvironmental Reactive Oxygen Species in Colorectal Cancer: Involved Processes and Therapeutic Opportunities.

Colorectal cancer (CRC) is the fourth most common cause of cancer deaths worldwide. Although screening programs have reduced mortality rates, there is a need for research focused on finding the main factors that lead primary CRC to progress and metastasize. During tumor progression, malignant cells modify their habitat, corrupting or transforming cells of different origins and creating the tumor microenvironment (TME). Cells forming the TME like macrophages, neutrophils, and fibroblasts generate reactive oxygen species (ROS) that modify the cancer niche. The effects of ROS in cancer are very diverse: they promote cellular proliferation, epithelial-to-mesenchymal transition (EMT), evasion of cell death programs, migration, and angiogenesis. Due to the multifaceted role of ROS in cancer cell survival and function, ROS-modulating agents such as antioxidants or pro-oxidants could have therapeutic potential in cancer prevention and/or as a complement to systemic treatments. In this review, we will examine the main ROS producer cells and their effects on cancer progression and metastasis. Furthermore, we will enumerate the latest clinical trials where pro-oxidants and antioxidants have therapeutic uses in CRC.