Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study

Background Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations. Methods A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of low-frequency EGFR-T790M mutated alleles at baseline). Results The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18–21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs) agents, had a significantly longer survival in comparison to those without (p < 0.0001); conversely, KRAS mutations were associated with a significantly lower survival (p = 0.0058). Among LAC patients with additional tissue section available for next-generation sequencing (NGS)-based analysis, 26/193 (13.5%) patients found positive for even low-rate EGFR-T790M mutated alleles at baseline were associated with a highly significant lower survival in comparison to those without (8.7 vs. 47.4 months, p < 0.0001). Conclusions In addition to its predictive value for addressing targeted therapy approaches, the assessment of as more inclusive mutation analysis at baseline may provide clues about factors significantly impacting on global survival in advanced LAC patients.

INFLUENCE OF THE PERITUMORAL MATRIX ON COLON CANCER

INTRODUCTION Several publications have highlighted the importance of the peritumoral matrix in various epithelial tumors. Our team has pointed out the value of ColXIα1 in the stroma of breast, colon and pancreatic cancer. The possible prognostic factor of the stroma in colon cancer is debated. Our aim is to analyze the prognostic role of the stroma and ColXIα1 in colon adenocarcinoma. MATERIAL AND METHODS Samples of 189 patients with colon cancer were studied by image analysis. The matrix was stained with Gomori green trichrome and the CAFs with the mouse monoclonal anti-proColXIα1 antibody. The samples were evaluated with an optical microscope, obtaining data from the area stained with proColXIα1, the area stained with Gomori and the number of pro ColXIα1 positive cells. 35 Gb of images were analyzed with Image J-FIJI, which measures the number of cells and the total area of marked regions, and also quantifies the number and area of unlabeled cells. Statistical analysis by MedCalc v1o and SpSS v15. RESULTS Colon cancer stages (%): I, 13; II, 40; III, 29; IV, 18. Recurrences (%), 32; by stages: I, 0; II, 21; III, 44; IV, 86. Global survival: median, 28 months; S5, 33%. Total stromal cells, number of CAFs and its area: higher in early stages. Gomori area, smaller in early stages and in cases without recurrences. CONCLUSIONS The number of CAFs and the extension of the stromal area could have influence in the development of the cancer colon, and may be related to the prognosis of disease.

Ocular toxicity with TKI therapy in CML

Tyrosine kinase inhibitors are the standard treatment for Chronic Myeloid Leukemia. They have significantly improved the response rate and global survival in the long term for CML patients, but also added relevant and diverse toxicity. The authors report a clinical case of ocular toxicity connected to the TKIs.

Stressors at work and elsewhere: a global survival approach

The United Nations´ “Agenda 2030” aims, in an integrated manner, to address the entire multitude of major global risks – e.g., to end poverty and hunger, realize the human rights of all, and ensure the lasting protection of the planet and its natural resources. However, recent political changes put this bold initiative at risk. To increase the likelihood of success, higher education institutions worldwide should teach and train today´s students – tomorrow´s decision makers – to think both critically and ethically, to learn to cope with ethical dilemmas, and to apply systems-thinking approaches to serious and complex societal problems. The Covid-19 pandemic provides just one example of a complex and serious challenge necessitating such approaches. Promoting decent work, full employment and economic growth is one of the other major challenges. And neither of them can be successfully dealt with in a piecemeal manner

Approaching glioblastoma during COVID-19 pandemic: current recommendations and considerations in Brazil

ABSTRACT Background: Cancer patients in general and glioblastoma patients, in particular, have an increased risk of developing complications from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and reaching a balance between the risk of exposure to infection and the clinical benefit of their treatment is ideal. The aggressive behavior of this group of tumors justifies the need for a multidisciplinary team to assist in clinical decisions during the current pandemic. Brazil is now ranked #2 in the number of cases and deaths from COVID-19 pandemic, and existing disparities in the treatment of neuro-oncology patients in Brazil will challenge the clinical and surgical decisions of this population, possibly affecting global survival. Objective: To search the literature about the management of glioblastomas during COVID-19 pandemic to guide surgical and clinical decisions in this population of patients in Brazil. Methods: We performed a systematic search on the PubMed electronic database targeting consensus statements concerning glioblastoma approaches during COVID-19 pandemic up to July 18, 2020. Results: When approaching glioblastoma during the COVID-19 pandemic, important parameters that help in the decision-making process are age, performance status, tumor molecular profile, and patient consent. Younger patients should follow the standard protocol after maximal safe resection, mainly those with MGMT methylated tumors. Aged and underperforming patients should be carefully evaluated, and probably a monotherapy scheme is to be considered. Centers are advised to engage in telemedicine and to elaborate means to reduce local infection. Conclusion: Approaching glioblastoma during the COVID-19 pandemic will be challenging worldwide, but particularly in Brazil, where a significant inequality of healthcare exists.

Uterine Endometrial Sarcoma with Carcinomatosis Treated with Iterative Surgery Associated with Systemic and Intraperitoneal Chemotherapy

Introduction: Endometrial sarcoma is a rare condition, affecting women in their 60s. If total hysterectomy associated with bilateral adnexectomy is the standard treatment and can control the disease when it is localized in the uterus, at the peritoneal localization stage its prognosis becomes more negative with reduced possibilities of resection and overall survival at 5 years, therefore, the same with rates close to 30%. We report two cases of endometrial sarcoma with peritoneal localizations managed with a multidisciplinary approach and in several steps or multimodal approach associating a cytoreduction preceded or associated with systemic chemotherapy and intraperitoneal chemotherapy. These two advanced tumours were cured with this approach and at the final step, no deposit tumor were present. The global survival is respectively of 28 months and 63 months. Conclusion: this approach seems to be efficient in front of the advanced stage of endometrial sarcoma and we think that it must be adopted for a great number of patients to improve the survival and quality of life.

DETERMINANTS OF THE SUSTAINABLE DEVELOPMENT OF THE MODERN WORLD

Paradigm of sustainable development is not a stationary state but a global resolution of problem in a peacefully manner across the planetary boundaries. It is a normative (ethical) concept, an analytical concept, the science about complex systems, and at the same time a saving formula of the global survival of the world and the most complex human challenge in the 21st century. As an ideal this is a utopian concept, there are no reliable scientific arguments in support of its realisation and predictable time proximity. As an idea, it is a call to mobilizs the whole of mankind. The basic thesis and problem, whether and to what extent sustainable development is achievable or if it remains a fiction and a real danger of excessive technological mind and ecological degradation of the world of life.

SUN-218 Analysis of ATRX and ZNRF3 Expression and Copy Number Variation in a Pediatric and Adult Cohort with Adrenocortical Tumors

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 1 to 2 cases per million/year in adults and with a global survival rate of less than 40% in 5 years. ACC diagnosis was based on Weiss criteria for adult patients. Pediatric patients with adrenocortical tumors (PAT), in general, are associated with better survival in most cases, and the malignant disease is established when local or distant metastases are found. The integrated and extensive genomic-molecular characterization of ACC has resulted in a better understanding of its pathophysiology. Some studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenal tumorigenesis in pediatric and adult patients with PAT and ACC, respectively. However, these data have not been validated in a Brazilian cohort with a high prevalence of the TP53 germline R337H mutation. Objectives: We aimed to evaluate the ATRX and ZNRF3 expression and copy number variation in a Brazilian cohort of patients with PAT and adults with ACC from a tertiary center. Patients and Methods: 34 adults (19 women - 56%) with median age 49 years old (range 18-83) and twelve pediatric patients (7 girls - 58%) with median age three years old (0.8-15 years old) were included in this study. The epidemiological data, clinical presentation, hormonal data, radiological imaging, and genetic background for TP53 were retrospectively evaluated. MLPA and RT-PCR were employed to evaluate the copy number variation and the gene expression, respectively, of ATRX and ZNRF3 in tumor tissues. Results: Adult group: Seven patients out of 27 (25.9%) presented the pathogenic germline mutation pR337H onTP53. 20 patients (58.8%) presented metastasis, and 19 (55%) had a fatal outcome. The median global survival was 17.23 months (0.6-185.8 m). Pediatric group: 10 patients (83.3%) presented the pathogenic germline mutation p.R337H on TP53. Four patients presented metastasis and only two had a fatal outcome. The median global survival was 42.4months (6.63-125.5m). All tumors were functional. Molecular results: Three out of 33 adult patients (9%), and 2 out of 12 (16.6%) pediatric patients presented deletion on ATRX. Four out of 25 adults (16%) and 2 out of 12 pediatric (16.6%) patients showed deletion on ZNRF3. There was no correlation between ATRX and ZNRF3 expressions or deletions with the overall survival rate (p&gt;0.05). The decrease in the ATRX expression was associated with the presence of TP53 germline mutation in pediatric and adult cohorts (p 0.028). Conclusion: We confirmed the presence of alterations on ATRX and ZNRF3 genes in both cohort (adult and pediatric tumors). These results differ from the previous studies, which demonstrated ATRX and ZNRF3 alterations were present in pediatric and adult tumors, respectively. However, prospective studies with larger cohorts are necessary to confirm the prognostic value of ATRX and ZNRF3 genes in PAT and adults with ACC.