Functional proteomics of colon cancer Consensus Molecular Subtypes.

BACKGROUND: The Colorectal Cancer Subtyping Consortium established four Consensus Molecular Subtypes (CMS) in colorectal cancer: CMS1 (microsatellite-instability [MSI], Immune), CMS2 (Canonical, epithelial), CMS3 (Metabolic), and CMS4 (Mesenchymal). However, only MSI tumour patients have seen a change in their disease management in clinical practice. This study aims to characterise the proteome of colon cancer CMS and broaden CMS's clinical utility. METHODS: One-hundred fifty-eight paraffin samples from stage II-III colon cancer patients treated with adjuvant chemotherapy were analysed through DIA-based mass-spectrometry proteomics. RESULTS: CMS1 exhibited overexpression of immune-related proteins, specifically related to neutrophils, phagocytosis, antimicrobial response, and a glycolytic profile. These findings suggested potential therapeutic strategies involving immunotherapy and glycolytic inhibitors. CMS3 showed overexpression of metabolic proteins. CMS2 displayed a heterogeneous protein profile. Notably, two proteomics subtypes within CMS2, with different protein characteristics and prognoses, were identified. CMS4 emerged as the most distinct group, featuring overexpression of proteins related to angiogenesis, extracellular matrix, focal adhesion, and complement activation. CMS4 showed a high metastatic profile and suggested possible chemoresistance that may explain its worse prognosis. CONCLUSIONS: DIA proteomics revealed new features for each colon cancer CMS subtype. These findings provide valuable insights into potential therapeutic targets for colorectal cancer subtypes in the future.

Is there a preferred platinum and fluoropyrimidine regimen for advanced HER2-negative esophagogastric adenocarcinoma? Insights from 1293 patients in AGAMENON-SEOM registry.

BACKGROUND: The optimal chemotherapy backbone for HER2-negative advanced esophagogastric cancer, either in combination with targeted therapies or as a comparator in clinical trials, is uncertain. The subtle yet crucial differences in platinum-based regimens' safety and synergy with combination treatments need consideration. METHODS: We analyzed cases from the AGAMENON-SEOM Spanish registry of HER2-negative advanced esophagogastric adenocarcinoma treated with platinum and fluoropyrimidine from 2008 to 2021. This study focused exclusively on patients receiving one of the four regimens: FOLFOX (5-FU and oxaliplatin), CAPOX (capecitabine and oxaliplatin), CP (capecitabine and cisplatin) and FP (5-FU and cisplatin). The aim was to determine the most effective and tolerable platinum and fluoropyrimidine-based chemotherapy regimen and to identify any prognostic factors. RESULTS: Among 1293 patients, 36% received either FOLFOX (n = 468) or CAPOX (n = 466), 20% CP (n = 252), and 8% FP (n = 107). FOLFOX significantly increased PFS (progression free survival) compared to CP, with a hazard ratio of 0.73 (95% CI 0.58-0.92, p = 0.009). The duration of treatment was similar across all groups. Survival outcomes among regimens were similar, but analysis revealed worse ECOG-PS (Eastern Cooperative Oncology Group-Performance Status), > 2 metastatic sites, bone metastases, hypoalbuminemia, higher NLR (neutrophil-to-lymphocyte ratio), and CP regimen as predictors of poor PFS. Fatigue was common in all treatments, with the highest incidence in FOLFOX (77%), followed by FP (72%), CAPOX (68%), and CP (60%). Other notable toxicities included neuropathy (FOLFOX 69%, CAPOX 62%), neutropenia (FOLFOX 52%, FP 55%), hand-foot syndrome in CP (46%), and thromboembolic events (FP 12%, CP 11%). CONCLUSIONS: FOLFOX shown better PFS than CP. Adverse effects varied: neuropathy was more common with oxaliplatin, while thromboembolism was more frequent with cisplatin.

Efficacy and safety of chemotherapy in young patients with advanced gastroesophageal adenocarcinoma: data from the Spanish AGAMENON-SEOM registry.

BACKGROUND: Gastroesophageal adenocarcinoma in young adults (GCYA) counts for 10-15% of diagnoses. Previous studies have mainly focused on surgical outcomes in patients with resectable tumors; however, systemic therapy for advanced GCYA remains under-evaluated. This study aims to assess the efficacy-related outcomes and safety of first-line chemotherapy (CT) in younger versus older patients with advanced gastroesophageal adenocarcinoma. METHODS: Patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry treated with first-line polychemotherapy between January 2008 and October 2022 were included. We compared clinicopathological features, therapies received, efficacy-related outcomes, and toxicity between individuals aged < and ≥ 45 years. RESULTS: Out of 3386 patients, 263 (7.8%) were < 45 years. Young patients exhibited a higher proportion of females affected, lower ECOG-PS ≥ 2, fewer comorbidities, and more aggressive disease-related features, such as higher proportion of diffuse subtype, signet-ring cells, plastic linitis, grade 3, peritoneal metastases and metastatic disease at diagnosis. They received more triple-agent combinations and underwent more surgeries in metastatic setting. No significant differences were observed between groups in overall response rate (53.1% vs. 52.3% in < and ≥ 45 years, respectively, p = 0.579), progression-free survival (6.1 vs. 6.83 months, p = 0.158) and overall survival (11.07 vs. 10.81 months, p = 0.82), even after adjusting for potential confounding factors. Grade 3-4 adverse events were comparable in both groups, although toxicity leading to treatment discontinuation was more frequent in older patients. CONCLUSIONS: In the AGAMENON-SEOM registry, younger patients with GCYA exhibited more aggressive clinicopathological features, and despite receiving more aggressive treatments, similar efficacy outcomes and toxicity profiles were achieved compared to their older counterparts. In the AGAMENON-SEOM registry, GEAC in < 45 years showed more aggressive clinicopathological features and, although treated with more intense first-line CT regimens, similar efficacy outcomes and toxicity were achieved compared to older patients.

Metabolomic profile of neuroendocrine tumors identifies methionine, porphyrin, and tryptophan metabolisms as key dysregulated pathways associated with patient survival.

OBJECTIVE: Metabolic profiling is a valuable tool to characterize tumor biology but remains largely unexplored in neuroendocrine tumors (NETs). Our aim was to comprehensively assess the metabolomic profile of NETs and identify novel prognostic biomarkers and dysregulated molecular pathways. DESIGN AND METHODS: Multiplatform untargeted metabolomic profiling (GC-MS, CE-MS, and LC-MS) was performed in plasma from 77 patients with G1-2 extra-pancreatic NETs enrolled in the AXINET trial (NCT01744249) (study cohort) and from 68 non-cancer individuals (control). The prognostic value of each differential metabolite (n = 155) in NET patients (P < .05) was analyzed by univariate and multivariate analyses adjusted for multiple testing and other confounding factors. Related pathways were explored by Metabolite Set Enrichment Analysis (MSEA) and Metabolite Pathway Analysis (MPA). RESULTS: Thirty-four metabolites were significantly associated with progression-free survival (PFS) (n = 16) and/or overall survival (OS) (n = 27). Thirteen metabolites remained significant independent prognostic factors in multivariate analysis, 3 of them with a significant impact on both PFS and OS. Unsupervised clustering of these 3 metabolites stratified patients in 3 distinct prognostic groups (1-year PFS of 71.1%, 47.7%, and 15.4% (P = .012); 5-year OS of 69.7%, 32.5%, and 27.7% (P = .003), respectively). The MSEA and MPA of the 13-metablolite signature identified methionine, porphyrin, and tryptophan metabolisms as the 3 most relevant dysregulated pathways associated with the prognosis of NETs. CONCLUSIONS: We identified a metabolomic signature that improves prognostic stratification of NET patients beyond classical prognostic factors for clinical decisions. The enriched metabolic pathways identified reveal novel tumor vulnerabilities that may foster the development of new therapeutic strategies for these patients.

The spatial, climatic and temporal factors influencing roadkill change according to the taxonomic level.

Roads are the second largest anthropogenic cause of mortality for most vertebrates. Previous research has analyzed the factors influencing roadkill either by species or by group of species based on some species-specific characteristics. However, to gain a comprehensive understanding on the consistency of findings within and between taxa, it is necessary to conduct an analysis that encompasses both individual species and group of species. This study aims to assess the role of taxonomic level in determining the spatial, climatic and temporal drivers using roadkill data for 70 species. We used generalized linear models to examine the association between roadkill and land cover and climate across 26 individual species and groups of reptiles, birds and mammals. Temporal patterns were evaluated using circular statistics. Our study revealed variations in spatial, climatic and temporal factors among taxa. For reptiles, spatial patterns differed between the class/order and species level, while climatic and temporal patterns remained consistent among these taxonomic levels. Spatial and climatic patterns were not consistent between class, order and associated species for birds and mammals. Temporal patterns, on the other hand, were consistent between each order and its associated species. In general, we found that roadkill incidence was positively associated with silviculture and agriculture cover as well as proximity of rivers. Accumulated insolation and mean minimum temperature were positively associated with roadkill, while mean temperature exhibited a negative association. Our study emphasizes the importance of analyzing roadkill variables on a species-specific basis. In the case of endangered species with low roadkill rates, it is essential to consider their assessment alongside other species exhibiting similar behavior and ecological needs.

Clinico-Pathological Features, Outcomes and Impacts of COVID-19 Pandemic on Patients with Early-Onset Colorectal Cancer: A Single-Institution Experience.

BACKGROUND: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic. METHODS: We included all patients with pathologically confirmed diagnoses of CRC at Hospital Universitario La Paz from October 2016 to December 2021. The EOCRC cut-off age was 50 years old. RESULTS: A total of 1475 patients diagnosed with CRC were included, eighty (5.4%) of whom had EOCRC. Significant differences were found between EOCRC and later-onset patients regarding T, N stage and metastatic presentation at diagnosis; perineural invasion; tumor budding; high-grade tumors; and signet ring cell histology, with all issues having higher prevalence in the early-onset group. More EOCRC patients had the RAS/ BRAF wild type. Chemotherapy was administered more frequently to patients with EOCRC. In the metastatic setting, the EOCRC group presented a significantly longer median OS. Regarding the COVID-19 pandemic, more patients with COVID-19 were diagnosed with metastatic disease (61%) in the year after the lockdown (14 March 2020) than in the pre-pandemic EOCRC group (29%). CONCLUSIONS: EOCRC is diagnosed at a more advanced stage and with worse survival features in localized patients. More patients with EOCRC were diagnosed with metastatic disease in the year after the COVID-19 pandemic lockdown. The long-term consequences of COVID-19 are yet to be determined.

Predicting Risk of Severe Toxicity and Early Death in Older Adult Patients Treated with Chemotherapy.

BACKGROUND: Determining the risk of grade 3-5 toxicity and early death (ED) is important to plan chemotherapy in older adult patients with cancer. Our objective was to identify factors predicting these complications at the time of treatment initiation. METHODS: 234 patients aged ≥70 were subjected to a geriatric assessment and variables related to the tumor and the treatment were also collected. Logistic regression multivariable analysis was used to relate these factors with the appearance of grade 3-5 toxicity and ED. Predictive scores for both toxicity and ED were then developed. RESULTS: Factors related to grade 3-5 toxicity were hemoglobin, MAX2 index, ADL, and the CONUT score. Factors related to ED were tumor stage and the GNRI score. Two predictive scores were developed using these variables. ROC curves for the prediction of toxicity and ED were 0.71 (95% CI: 0.64-0.78) and 0.73 (95% CI: 0.68-0.79), respectively. CONCLUSIONS: Two simple and reliable scores were developed to predict grade 3-5 toxicity and ED in older adult patients with cancer. This may be helpful in treatment planning.

The AGAMENON-SEOM model for prediction of survival in patients with advanced HER2-positive oesophagogastric adenocarcinoma receiving first-line trastuzumab-based therapy.

Background: Trastuzumab and chemotherapy is the standard first-line treatment in human epidermal growth factor receptor 2 (HER2)-positive advanced gastro-oesophageal cancer. The objective was to develop a predictive model for overall survival (OS) and progression-free survival (PFS) in patients treated with trastuzumab. Methods: Patients with HER2-positive advanced gastro-oesophageal adenocarcinoma (AGA) from the Spanish Society of Medical Oncology (SEOM)-AGAMENON registry and treated first line with trastuzumab and chemotherapy between 2008 and 2021 were included. The model was externally validated in an independent series (The Christie NHS Foundation Trust, Manchester, UK). Results: In all, 737 patients were recruited (AGAMENON-SEOM, n = 654; Manchester, n = 83). Median PFS and OS in the training cohort were 7.76 [95% confidence interval (CI), 7.13-8.25] and 14.0 months (95% CI, 13.0-14.9), respectively. Six covariates were significantly associated with OS: neutrophil-to-lymphocyte ratio, Eastern Cooperative Oncology Group performance status, Lauren subtype, HER2 expression, histological grade and tumour burden. The AGAMENON-HER2 model demonstrated adequate calibration and fair discriminatory ability with a c-index for corrected PFS/OS of 0.606 (95% CI, 0.578-0.636) and 0.623 (95% CI, 0.594-0.655), respectively. In the validation cohort, the model is well calibrated, with a c-index of 0.650 and 0.683 for PFS and OS, respectively. Conclusion: The AGAMENON-HER2 prognostic tool stratifies HER2-positive AGA patients receiving trastuzumab and chemotherapy according to their estimated survival endpoints.

Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs). Nevertheless, its role in certain tumor sites remains unclear. This study sought to elucidate the efficacy and safety of [177Lu]Lu-DOTATATE in NENs with different locations and evaluate the effect of the tumor origin, bearing in mind other prognostic variables. Advanced NENs overexpressing somatostatin receptors (SSTRs) on functional imaging, of any grade or location, treated at 24 centers were enrolled. The protocol consisted of four cycles of 177Lu-DOTATATE 7.4 GBq iv every 8 weeks (NCT04949282). RESULTS: The sample comprised 522 subjects with pancreatic (35%), midgut (28%), bronchopulmonary (11%), pheochromocytoma/ paraganglioma (PPGL) (6%), other gastroenteropancreatic (GEP) (11%), and other non-gastroenteropancreatic (NGEP) (9%) NENs. The best RECIST 1.1 responses were complete response, 0.7%; partial response, 33.2%; stable disease, 52.1%; and tumor progression, 14%, with activity conditioned by the tumor subtype, but with benefit in all strata. Median progression-free survival (PFS) was 31.3 months (95% CI, 25.7-not reached [NR]) in midgut, 30.6 months (14.4-NR) in PPGL, 24.3 months (18.0-NR) in other GEP, 20.5 months (11.8-NR) in other NGEP, 19.8 months (16.8-28.1) in pancreatic, and 17.6 months (14.4-33.1) in bronchopulmonary NENs. [177Lu]Lu-DOTATATE exhibited scant severe toxicity. CONCLUSION: This study confirms the efficacy and safety of [177Lu]Lu-DOTATATE in a wide range of SSTR-expressing NENs, regardless of location, with clinical benefit and superimposable survival outcomes between pNENs and other GEP and NGEP tumor subtypes different from midgut NENs.

Does HER2 status influence in the benefit of ramucirumab and paclitaxel as second line treatment of advanced gastro-esophageal adenocarcinoma? Data from the AGAMENON-SEOM registry.

PURPOSE: This study aimed to compare ramucirumab-paclitaxel versus chemotherapy in second-line (2L) advanced gastroesophageal cancer (aGEC) based on HER2 status and analyze prognostic factors. METHODS: The study includes patients from the AGAMENON-SEOM registry with aGEC and known HER2 status who received 2L between 2016 and 2021. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) and multivariable Cox regression analysis was done to adjust for confounding variables. RESULTS: Of the 552 patients who met the selection criteria, 149 (26.9%) had HER2-positive aGEC, 89 were treated with chemotherapy, and 60 with ramucirumab-paclitaxel, and 403 had an HER2-negative aGEC, 259 were treated with chemotherapy, and 144 with ramucirumab-paclitaxel. In the whole sample, 2L PFS was 3.0 months (95% CI 2.8-3.2), 2L OS, 5.7 months (5.2-6.3), and ramucirumab-paclitaxel versus chemotherapy was associated with increased PFS (HR 0.64, 95% CI 0.53-0.78, p < 0.0001) and OS (HR 0.68, 0.55-0.83, p = 0.0002). Median PFS of ramucirumab- paclitaxel versus chemotherapy was 3.5 vs 2.8 months (HR 0.67, 0.54-0.83, p = 0.0004) in HER2-negative, and 4.7 vs 2.7 months (HR 0.57, 0.40-0.82, p = 0.0031) in HER2-positive aGEC, respectively. Median OS for ramucirumab-paclitaxel versus chemotherapy was 6.6 vs 5 months (HR 0.67, 0.53-0.85, p = 0.0007) in HER2-negative, and 7.4 vs 5.6 months (HR 0.70, 0.53-1.04, p = 0.083) in HER2-positive aGEC, respectively. ECOG-PS, tumor burden, Lauren subtype, and neutrophil-lymphocyte ratio were prognostic factors. CONCLUSIONS: In patients with an aGEC from the AGAMENON-SEOM registry, 2L treatment with ramucirumab-paclitaxel was superior to chemotherapy in PFS, OS and response rate, independent of HER2 status.

Clinical Score to Predict Recurrence in Patients with Stage II and Stage III Colon Cancer.

Background: The prognosis of patients with stage II and stage III colon cancer is heterogeneous. Clinical and pathological characteristics, such as tumor budding, may help to further refine the recurrence risk. Methods: We included all the patients with localized colon cancer at Hospital Universitario La Paz from October 2016 to October 2021. We built a prognostic score for recurrence in the training cohort based on multivariate cox regression analysis and categorized the patients into two risk groups. Results: A total of 440 patients were included in the training cohort. After a median follow-up of 45 months, 81 (18%) patients had a first tumor recurrence. T4, N2, and high tumor budding remained with a p value <0.05 at the last step of the multivariate cox regression model for time to recurrence (TTR). We assigned 2 points to T4 and 1 point to N2 and high tumor budding. Forty-five percent of the patients were assigned to the low-risk group (score = 0). Compared to the high-risk group (score 1−4), patients in the low-risk group had a significantly longer TTR (hazard ratio for disease recurrence of 0.14 (95%CI: 0.00 to 0.90; p < 0.045)). The results were confirmed in the validation cohort. Conclusions: In our study, we built a simple score to predict tumor recurrence based on T4, N2, and high tumor budding. Patients in the low-risk group, that comprised 44% of the cohort, had an excellent prognosis.

Completeness of notifications of severe acute respiratory syndrome at the national level and in a regional health care in the state of Minas Gerais, during the COVID-19 pandemic, 2020. / Completude das notificações de síndrome respiratória aguda grave no âmbito nacional e em uma regional de saúde de Minas Gerais, durante a pandemia de COVID-19, 2020.

OBJECTIVE: To analyze the completeness of notifications of severe acute respiratory syndrome cases on the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe) during the COVID-19 pandemic, on the national database and on the Regional Health Center database of the state of Minas Gerais, Brazil, in 2020. METHODS: This was a descriptive study of the completeness of sociodemographic variables and those related to etiology, clinical condition, evolution and diagnostic criteria of SIVEP-Gripe. The level of completeness was classified as excellent (> 95%), good (90% to 95%), regular (80% to 90%), poor (50% to 80%) or very poor (< 50%). RESULTS: The percentage of variables with excellent completeness was only 18.1% on the national database, and 27.8% on the regional database. CONCLUSION: Both SIVEP-Gripe databases presented low completeness, making it necessary to improve the work process and routine training of professionals aimed at the correct filling.

Completeness of notifications of severe acute respiratory syndrome nationally and of a regional health in Minas Gerais, Brazil, during the COVID-19 pandemic, 2020 / Completitud de notificaciones de síndrome respiratorio agudo severo a nivel nacional y de salud regional en Minas Gerais, Brasil, durante la pandemia COVID-19, 2020 / Completude das notificações de síndrome respiratória aguda grave no âmbito nacional e em uma regional de saúde de Minas Gerais, durante a pandemia de COVID-19, 2020

Objective: To analyze the completeness of notifications of cases of severe acute respiratory illness from the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe) during the COVID-19 pandemic, in the national database and in a regional database in the state of Minas Gerais, Brazil, in 2020. Methods: Descriptive study of the completeness of sociodemographic variables and those related to the etiology, clinical condition, evolution and diagnostic criteria of SIVEP-Influenza. Completeness was classified as excellent (greater than 95%), good (90 to 95%), fair (80 to 90%), poor (50 to 80%), and very poor (less than 50%). Results: The percentage of variables with excellent completeness was only 18.1% in the national database and 27.8% in the regional database. Conclusion: Low completeness of both SIVEP-Gripe databases was evidenced, making it necessary to improve the work process and routine training of professionals for the correct completion.

Objetivo: Analizar la completitud de las notificaciones de casos de síndrome respiratorio agudo severo del Sistema de Información de Vigilancia Epidemiológica de Influenza (SIVEP-Gripe) durante la pandemia de COVID-19, en la base de datos nacional y en una base de datos regional de salud en el estado de Minas Gerais, Brasil, en 2020. Métodos: Estudio descriptivo de la completitud de las variables sociodemográficas y las relacionadas con la etiología, cuadro clínico, evolución y criterios diagnósticos del SIVEP-Influenza. La exhaustividad se clasificó como excelente (más grande que 95%), buena (90 a 95%), regular (80 a 90%), mala (50 a 80%) y muy mala (menos que 50%). Resultados: El porcentaje de variables con excelente completitud fue solo del 18,1% en la base de datos nacional y del 27,8% en la base de datos regional. Conclusión: Se evidenció la baja completitud de ambas bases de datos SIVEP-Gripe, siendo necesario mejorar el proceso de trabajo y la rutina de capacitación de los profesionales para el correcto llenado.

Objetivo: Analisar a completude das notificações de casos de síndrome respiratória aguda grave no Sistema de Informação de Vigilência Epidemiológica da Gripo (SIVEP Gripe) durante a pandemia de COVID-19, na base de dados nacional e na base da Unidade Regional de Saúde do estado de Minas Gerais, Brasil, em 2020. Métodos: Estudo descritivo da completude das variáveis sociodemográficas e das relativas à etiologia, condição clínica, evolução e critérios diagnósticos do SIVEP-Gripe. O nível de completude foi classificado como excelente (>95%), bom (90 a 95%), regular (80 a 90%), ruim (50 a 80%) ou muito ruim (<50%). Resultados: O percentual de variáveis com completudo excelente foi de apenas 18,1% na base de dados nacional, e de 27,8% na base de dados regional. Conclusão: Evidenciou-se baixa completude de ambas bases dados do SIVEP-Gripe, tornando-se necessários aperfeiçoamentos no processo de trabalho e capacitações rotineiras dos profissionais para o correto preenchimento.

SEOM-GEMCAD-TTD Clinical Guideline for the diagnosis and treatment of esophageal cancer (2021)

Esophageal cancer is an aggressive tumor, and is the sixth-leading cause of death from cancer. Incidence is rising in Spain, particularly among men. Two main pathological different subtypes have been described: squamous cell carcinoma and adenocarcinoma. Growing evidence of their epidemiology and molecular differences explains their different response to novel treatments, and they are therefore likely to be treated as two separate entities in the near future. The best results are obtained with a multidisciplinary therapeutic strategy, and the introduction of immunotherapy is a promising new approach that will improve prognosis. In these guidelines, we review the evidence for the different methods of diagnosis and therapeutic strategies that form the basis of our standard of care.

SEOM-GEMCAD-TTD Clinical Guideline for the diagnosis and treatment of esophageal cancer (2021).

Esophageal cancer is an aggressive tumor, and is the sixth-leading cause of death from cancer. Incidence is rising in Spain, particularly among men. Two main pathological different subtypes have been described: squamous cell carcinoma and adenocarcinoma. Growing evidence of their epidemiology and molecular differences explains their different response to novel treatments, and they are therefore likely to be treated as two separate entities in the near future. The best results are obtained with a multidisciplinary therapeutic strategy, and the introduction of immunotherapy is a promising new approach that will improve prognosis. In these guidelines, we review the evidence for the different methods of diagnosis and therapeutic strategies that form the basis of our standard of care.

Identification of Thrombosis-Related Genes in Patients with Advanced Gastric Cancer: Data from AGAMENON-SEOM Registry.

Advanced gastric cancer is one of the most thrombogenic neoplasms. However, genetic mechanisms underlying this complication remain obscure, and the molecular and histological heterogeneity of this neoplasm hinder the identification of thrombotic biomarkers. Therefore, our main objective was to identify genes related to thrombosis regardless of Lauren subtypes. Furthermore, in a secondary exploratory study, we seek to discover thrombosis-associated genes that were specific to each TCGA molecular subtype. We designed a nested case-control study using the cohort of the AGAMENON national advanced gastric cancer registry. Ninety-seven patients were selected-48 with and 49 without venous thromboembolism (using propensity score matching to adjust for confounding factors)-and a differential gene expression array stratified by Lauren histopathological subtypes was carried out in primary tumor samples. For the secondary objective, the aforementioned differential expression analysis was conducted for each TCGA group. Fifteen genes were determined to be associated with thrombosis with the same expression trend in both the intestinal and diffuse subtypes. In thrombotic subjects, CRELD1, KCNH8, CRYGN, MAGEB16, SAA1, ARL11, CCDC169, TRMT61A, RIPPLY3 and PLA2G6 were underexpressed (adjusted-p < 0.05), while PRKD3, MIR5683, SDCBP, EPS8 and CDC45 were overexpressed (adjusted-p < 0.05), and correlated, by logistic regression, with lower or higher thrombotic risk, respectively, in the overall cohort. In each TCGA molecular subtype, we identified a series of genes differentially expressed in thrombosis that appear to be subtype-specific. We have identified several genes associated with venous thromboembolism in advanced gastric cancer that are common to Lauren intestinal and diffuse subtypes. Should these genetic factors be validated in the future, they could be complemented with existing clinical models to bolster the ability to predict thrombotic risk in individuals with advanced gastric adenocarcinoma.

External Validity of Somatostatin Analogs Trials in Advanced Neuroendocrine Neoplasms: The GETNE-TRASGU Study.

INTRODUCTION: Somatostatin analogs (SSA) prolong progression-free survival (PFS) in patients with well-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, the eligibility criteria in randomized clinical trials (RCTs) have been restricted, which contrasts with the vast heterogeneity found in NENs. METHODS: We identified patients with well-differentiated (Ki-67% ≤20%), metastatic GEP-NENs treated in first line with SSA monotherapy from the Spanish R-GETNE registry. The therapeutic effect was evaluated using a Bayesian Cox model. The objective was to compare survival-based outcomes from real-world clinical practice versus RCTs. RESULTS: The dataset contained 535 patients with a median age of 62 years (range: 26-89). The median Ki-67% was 4 (range: 0-20). The most common primary tumor sites were as follows: midgut, 46%; pancreas, 34%; unknown primary, 10%; and colorectal, 10%. Half of the patients received octreotide LAR (n = 266) and half, lanreotide autogel (n = 269). The median PFS was 28.0 months (95% CI: 22.1-32.0) for octreotide versus 30.1 months (95% CI: 23.1-38.0) for lanreotide. The overall hazard ratio for lanreotide versus octreotide was 0.90 (95% credible interval: 0.71-1.12). The probability of effect sizes >30% with lanreotide versus octreotide was 2 and 6% for midgut and foregut NENs, respectively. CONCLUSION: Our study evaluated the external validity of RCTs examining SSAs in the real world, as well as the main effect-modifying factors (progression status, symptoms, tumor site, specific metastases, and analytical data). Our results indicate that both octreotide LAR and lanreotide autogel had a similar effect on PFS. Consequently, both represent valid alternatives in patients with well-differentiated, metastatic GEP-NENs.

Factors associated with the lethality of patients hospitalized with severe acute respiratory syndrome due to COVID-19 in Brazil.

Due to the high rates of transmission and deaths due to COVID-19, understanding the factors associated with its occurrence, as well as monitoring and implementing control measures should be priority actions in health surveillance, highlighting the use of epidemiological surveillance information systems as an important ally. Thus, the objectives of this study were to calculate the mortality rate of hospitalized patients with severe acute respiratory syndrome due to COVID-19 and to identify factors associated with death, in the period corresponding to epidemiological weeks 01 to 53 of the year 2020. This was a longitudinal study, using the national influenza epidemiological surveillance information system database, routinely collected by healthcare services. The sociodemographic and clinical characteristics of 563,051 hospitalized patients with severe acute respiratory syndrome due to COVID-19 in the five regions of Brazil were analyzed. Cox regression was performed to assess factors associated with patient death during hospitalization. The national lethality rate was 35.7%, and the highest rates of lethality occurred in the Northeast (44.3%) and North (41.2%) regions. During the hospital stay, death was associated with older age (Hazard Ratio-HR = 1.026; p<0.001); male sex (HR = 1.052; p<0.001); living in the North (HR = 1.429; p<0.001), Northeast (HR = 1.271; p<0.001) or Southeast regions of Brazil (HR = 1.040; p<0.001), presenting any risk factor (HR = 1.129; p< 0.001), the use of invasive (HR = 2.865; p<0.001) or noninvasive (HR = 1.401; p<0.001) mechanical ventilation devices. A high case lethality rate was evidenced in patients with severe acute respiratory syndrome due to COVID-19, however, deaths were not evenly distributed across the country's regions, being heavily concentrated in the Northeast and North regions. Older male patients living in the North, Northeast, or Southeast regions of Brazil, who presented any risk factor and were submitted to the use of invasive or noninvasive mechanical ventilation devices, presented a higher risk of evolving to death.

Completude das notificações de síndrome respiratória aguda grave no âmbito nacional e em uma regional de saúde de Minas Gerais, durante a pandemia de COVID-19, 2020 / Completitud de notificaciones de síndrome respiratorio agudo severo a nivel nacional y en una regional de salud en Minas Gerais, Brasil, durante la pandemia de COVID-19, 2020 / Completeness of notifications of severe acute respiratory syndrome at the national level and in a regional health care in the state of Minas Gerais, during the COVID-19 pandemic, 2020

Objetivo: Analisar a completude das notificações de casos de síndrome respiratória aguda grave no Sistema de Informação de Vigilância Epidemiológica da Gripe (SIVEP-Gripe) durante a pandemia de COVID-19, na base de dados nacional e na base da Unidade Regional de Saúde do estado de Minas Gerais, Brasil, em 2020. Métodos: Estudo descritivo da completude das variáveis sociodemográficas e das relativas à etiologia, condição clínica, evolução e critérios diagnósticos do SIVEP-Gripe. O nível de completude foi classificado como excelente (> 95%), bom (90% a 95%), regular (80% a 90%), ruim (50% a 80%) ou muito ruim (< 50%). Resultados: O percentual de variáveis com completude excelente foi de apenas 18,1% na base de dados nacional, e de 27,8% na base de dados regional. Conclusão: Evidenciou-se baixa completude de ambas as bases de dados do SIVEP-Gripe, tornando-se necessários aperfeiçoamentos no processo de trabalho e capacitações rotineiras dos profissionais para o correto preenchimento.

Resumen Objetivo: Analizar la completitud de las notificaciones de casos de síndrome respiratorio agudo severo del Sistema de Información de Vigilancia Epidemiológica de la Gripe (SIVEP-Gripe) durante la pandemia de COVID-19, en la base de datos nacional y en una base de datos regional de salud en el estado de Minas Gerais, Brasil, en 2020. Métodos: Estudio descriptivo de la completitud de las variables sociodemográficas y las relacionadas con la etiología, cuadro clínico, evolución y criterios diagnósticos del SIVEP-Gripe. El nivel de completitud se clasificó como excelente (> 95%), bueno (90% a 95%), regular (80% a 90%), malo a (50% a 80%) y muy malo (< 50%). Resultados: El porcentaje de variables con excelente completitud fue solo del 18,1% en la base de datos nacional y del 27,8% en la base de datos regional. Conclusión: Se evidenció la baja completitud de ambas bases de datos SIVEP-Gripe, lo que hace necesario mejorar el proceso de trabajo y la rutina de capacitación de los profesionales.

Objective: To analyze the completeness of notifications of severe acute respiratory syndrome cases on the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe) during the COVID-19 pandemic, on the national database and on the Regional Health Center database of the state of Minas Gerais, Brazil, in 2020. Methods: This was a descriptive study of the completeness of sociodemographic variables and those related to etiology, clinical condition, evolution and diagnostic criteria of SIVEP-Gripe. The level of completeness was classified as excellent (> 95%), good (90% to 95%), regular (80% to 90%), poor (50% to 80%) or very poor (< 50%). Results: The percentage of variables with excellent completeness was only 18.1% on the national database, and 27.8% on the regional database. Conclusion: Both SIVEP-Gripe databases presented low completeness, making it necessary to improve the work process and routine training of professionals aimed at the correct filling.

Hospitalizations and mortality by severe acute respiratory syndrome: comparison between the pre-pandemic and pandemic periods.

OBJECTIVE: To analyze the characteristics and the factors associated with mortality of cases hospitalized for severe acute respiratory syndrome in a health region, in pre-pandemic and pandemic periods. METHODS: A retrospective documentary study of epidemiological surveillance carried out with secondary data from the Influenza Epidemiological Surveillance Information System, regarding the cases of patients belonging to a health region of Minas Gerais, Brazil. RESULTS: During the pandemic period, there was an increase in the number of hospitalizations and deaths due to severe acute respiratory syndrome, in addition to differences between sociodemographic and clinical-epidemiological characteristics. In both periods, the age and the use of invasive ventilatory support were the predictors of hospital mortality. The mortality in the pandemic period was also associated with male gender, presence of risk factors, admission to an intensive care unit, use of non-invasive ventilatory support, and infection by COVID-19. CONCLUSIONS: In 2020, the detection rate of severe acute respiratory syndrome was 21 times higher than in 2019 and new symptoms, such as anosmia and ageusia, were included in their investigation. In both periods evaluated, elderly patients and patients on invasive mechanical ventilation had a higher risk of mortality. With the pandemic, there was a greater number of hospitalizations and factors associated with mortality.