Peruvian Patients Research Articles

Carcinoma hepatocelular en Perú: una descripción molecular de un cuadro clínico atípico

IntroductionHepatocellular carcinoma (HCC) is the third most frequent cancer of digestive tract tumors in Peru, with a high mortality rate of 17.7 per 100,000 inhabitants. A significant number of HCC cases in Peru do not follow the classic clinical epidemiology of the disease described in other parts of the world. Those patients present with a distinct transcriptome profile and a singular tumor process, suggesting a particular type of hepatocarcinogenesis in a portion of the Peruvian population. AimOur aim was to understand the clinical and biologic involvement of the epigenetic profile (methylation) and gene expression (transcriptome) of HCC in Peruvian patients. MethodsHCC and liver transcriptome and DNA methylation profiles were evaluated in 74 Peruvian patients. ResultsWhen grouped by age, there was greater DNA methylation in younger patients with HCC but no differences with respect to the transcriptomic profile. A high prevalence of the hepatitis B virus (HBV) (> 90%) was also observed in the younger patients with HCC. Enrichment analyses in both molecular profiles pinpointed PRC2 as an important molecular effector of that liver tumor process in Peruvian patients. ConclusionHCC in Peruvian patients has a unique molecular profile, associated with the presence of HBV, as well as overall DNA hypermethylation related to undifferentiated liver cells or cellular reprogramming.

Alterations in the coagulation markers did not show differences with the severity of COVID-19 in Peruvian patients: A cross-sectional single-center study.

COVID-19 is a pandemic disease that can lead to altered lung function, systemic inflammatory events, and altered coagulation. During severe stages of the disease, changes in coagulation homeostasis increase, leading to thrombosis, and increased risk of death. In this cross-sectional study, we aimed to assess coagulation markers by COVID-19 severity in Peruvian adults. During the second wave of infections, we included 186 adults diagnosed with COVID-19 (mean age 53.3 ± 16.3 years). Patients were divided into mild, moderate, and severe stages of COVID-19, and coagulation markers included prothrombin time (PT), activated partial prothrombin time (aPTT), fibrinogen, d-dimer, and platelet count. Of the total, 120 (64.5%) were males and 39 (21%) were in the intensive care unit. We determine 104 (55.9%), 43 (24.7%), and 36 (19.4%) patients in mild, moderate, and severe stages of COVID-19, respectively. In the severe stage of COVID-19, patients had an average concentration of PT, aPTT, fibrinogen, d-dimer, and platelets of 13.2 ± 0.9 s, 28.9 ± 4.3 s, 679.4 ± 185.1 mg/dL, 1.9 ± 3.1 µg/mL, and 272.8 ± 88.9 cel/10 mm,3respectively. We found no differences in the concentration of each marker according to severity (p < 0.05). Patients with severe COVID-19 had altered the aPTT, fibrinogen, d-dimer, and PT in 31 (57.4%), 48 (88.9%), 37 (68.5%), and 15 (27.8%) cases, respectively. Our results showed that although there is an alteration in coagulation markers, mainly fibrinogen and d-fiber, there are no differences in concentration according to the severity of COVID-19.

PP.04 EGFR Structure-Based Classification and Presence of Commutations in Peruvian Patients With Advanced Lung Cancer

PP.04 EGFR Structure-Based Classification and Presence of Commutations in Peruvian Patients With Advanced Lung Cancer

CBCT Study of Root Apices Distance to Mandibular Canal in Peruvian Population

The purpose of this study was to compare the average distances from the root apices of the first molars, second molars, and second premolars to the mandibular canal according to sex in the Peruvian population using cone-beam computed tomography (CBCT). Eighty CBCT scans of Peruvian patients aged from 15-80 years were examined. After locating the mandibular canal, measurements of the vertical distances from the mandibular canal to the apices of the second premolars, as well as the first molars and second molars, were made. For the statistical analysis, Student’s t test was used for both paired and unpaired samples, with a significance level of p&lt;0.05. On the right side, the second molar presented a mean distance of 3.99mm for males and 2.87mm for females, showing a significant difference (p&lt;0.05). When compared bilaterally, no significant differences were found (p&gt;0.05) between the distances from the apices of the second premolars and the first and second molars to the mandibular canal. However, for the second premolars and second molars on the left side, the values were higher, with averages of 5.52mm and 3.75mm, respectively.The mesial roots of the second molars were closer to the mandibular canal. In addition, women showed shorter distances than men.

Evaluation of a functional assessment tool in patients with mild cognitive impairment or Alzheimer’s disease in Lima, Peru

AbstractBackgroundFunctional assessment screening tools are crucial for dementia evaluations. The Alzheimer’s Disease Cooperative Study‐Activities of Daily Living (ADCS‐ADL) scale is a versatile functional assessment screening tool that can be used to monitor functional decline of patients with Alzheimer’s disease (AD). We sought to evaluate the validity and reliability of the ADCS‐ADL scale in Peruvian patients with mild cognitive impairment (MCI) or AD.MethodThis was a cross‐sectional study of older adults from a multidisciplinary neurology institute in Lima, Peru in one of three groups: cognitively healthy controls, MCI or AD. ANOVA or chi‐square tests were used. Psychometric properties evaluated included reliability (intraclass correlation coefficient, ICC; internal consistency, Cronbach’s alpha) and validity (external and convergent).ResultWe included 276 patients in the analysis. Age, sex, educational level, and depressive symptoms did not vary significantly between the groups, but the Mini Mental State Examination and Addenbrooke’s Cognitive Examination scores were significantly different between groups. ICC was 0.996 and Cronbach’s alpha was 0.937 for the ADCS‐ADL. The ADCS‐ADL could not differentiate patients with MCI from cognitively healthy controls, but it accurately differentiated degrees of cognitive impairment within the AD group. The ADCS‐ADL correlated highly with all functional assessment and cognitive screening tools, except for the Alzheimer’s Disease Assessment Scale‐Cognitive subscale.ConclusionThe ADCS‐ADL scale is reliable in a population of patients with AD in Lima, Peru, and correlated with most functional assessment scales used to evaluate patients with AD.

Genomic Profiling and Clinicopathological Features in Peruvian Patients with EBV-Positive Diffuse Large B-Cell Lymphomas, NOS

Introduction: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is a newly recognized entity by the World Health Organization. EBV+ DLBCL, NOS is commonly encountered in Latin American countries and carries a dismal prognosis. It has been published studies that have evaluated the genetic profiling in EBV +DLBCL from Asian and Western countries. However, there are lacking of studies from Latin America. This study aimed to characterize and compare the genetic profiling and clinicopathological features in Peruvian EBV+ with EBV- DLBCL patients. Methods: This retrospective cohort study included patients ≥18 years from one institution in Peru from 2010 to 2020. Hematopathologists reviewed pathological samples to confirm the diagnosis of EBV+ DLBCL cases. An EBV+ case was confirmed when the EBER test had a positivity more or equal to 40%. We collected clinicopathological data by reviewing the medical records of the patients. Twenty paraffin-embedded biopsy samples were analyzed and tumor DNA was purified using silica columns (QIAGEN, Valencia, CA, USA). The quantity and quality of the purified DNA were evaluated by spectrophotometry. We compared the genetic profiling with ten EBV+ versus ten EBV- DLBCL samples. Results: Twenty-two candidate genes were selected from previous reports of exome analysis with the diagnosis of DLBC. The median age at diagnosis was similar in both groups (58 years old, range 19-89). There was a male predominance in EBV+ (57%) compared to EBV- DLBCL cases (43%). Sixty-eight percent of patients with EBV+ had advanced disease (Ann arbor stage III-IV), compared to 48% of EBV- DLBCL patients. The non-germinal center was more common in EBV+ (60%) than EBV- cases (40%). All patients received either R-CHOP-like regimens as a first-line treatment. The overall response rate was 91% for EBV- compared to 74% for EBV+ DLBCL. We found mutations in MYC (10%), NOTCH2 (5%), STAT6 (5%) , ANKRD11(5%), TP53 (5%), KMT2A (5%), YY1 (5%), CARD11 (5%), ARID1A (5%) and RHOA (5%) in EBV+ cases, meanwhile, ARID1A (10%) , CCR6 (10%), KMT2A (5%), CARD11(5%), NOTCH2 (5%), TP53 (5%), and ANKRD11(5%) in EBV - DLBCL cases. Conclusions: This is the first Latin American study that have performed the genomic pattern in Peruvian EBV+ in comparison to EBV- DLBCL patients. Overall, our data suggest that Peruvian EBV+ DLBCL have different genetic profiling compared to East and Western countries. Also, we found that EBV+ and EBV- patients share similar drive mutations. Our findings should be validated in a larger prospective cohort of Latin American patients.

Quality of Life, Anxiety, and Depression in Peruvian Patients with Acute Coronary Syndrome

The current study aims to identify the factors associated with anxiety and depression in patients with acute coronary syndrome (ACS) at hospital discharge from a Peruvian health center. Patients at discharge from the cardiology hospitalization service between November 2019 and December 2020 were evaluated using a cross-sectional study. The median time elapsed from the ACS event to the interview date was 10 months. A total of 34.1% of the population presented mild depression and 78.8% had mild anxiety. All three of our analyses indicated that patients who had attended university had significantly lower levels of both depression and anxiety, and patients with diabetes had significantly higher levels of anxiety. The lower-low socioeconomic group had 1.5 times the frequency of depression (p-value = 0.002) and 3.12 times the frequency of anxiety (p-value = 0.050). Interestingly, while a good quality of life was associated with lower levels of depression, it was also associated with higher levels of moderate/severe anxiety (p-value = 0.035). A multiple regression analysis found that hypertension was also associated with higher levels of anxiety, and patients who have had COVID-19 had 21.05 times the level of moderate/severe anxiety (p-value = 0.000). Cases of ACS are more frequent in patients with an age greater than or equal to 60 years, as well as in males. Isolation was a common feature that may have a negative impact on their quality of life and mental health.

Whole exome sequencing in a sample of Peruvian patients diagnosed with epidermolysis bullosa.

Epidermolysis bullosa (EB) is a complex and heterogeneous dermatological disease. Four main types of EB have been described, each of them with distinct characteristics: EB simplex (EBS), dystrophic EB (DEB), junctional EB (JEB) and Kindler EB (KEB). Each main type varies in its manifestations, severity, and genetic abnormality. We sought mutations in 19 genes known to cause EB and 10 genes associated with other dermatologic diseases in 35 Peruvian pediatric patients of a rich Amerindian genetic background. Whole exome sequencing and bioinformatics analysis was performed. Thirty-four of 35 families revealed an EB mutation. Dystrophic EB was the most frequently diagnosed type, with 19 (56%) patients, followed by EBS (35%), JEB (6%), and KEB (3%). We found 37 mutations in seven genes; 27 (73%) were missense mutations; 22 (59%) were novel mutations. Five cases changed their initial diagnosis of EBS. Four were reclassified as DEB and one as JEB. Inspection into other non-EB genes revealed a variant, c.7130C&gt;A, in the gene FLGR2, which was present in 31 of the 34 patients (91%). We were able to confirm and identify pathological mutations in 34 of 35 patients.

Association between PIK3CA Mutations in Blood and Tumor-Infiltrating Lymphocytes in Peruvian Breast Cancer Patients.

To evaluate the relationship between circulating tumor DNA (ctDNA) presence and tumor features including tumor-infiltrating lymphocyte (TIL) levels in Peruvian breast cancer patients. This was a prospective study conducted at the Instituto Nacional de Enfemedades Neoplasicas, Peru. We evaluated level of TIL and PIK3CA mutations in ctDNA. Clinical characteristics, including outcome data, were collected from the patient file. Survival was calculated from the date of blood sample drawn to the event time. Data collected were analyzed using SPSS software version 25. We analyzed plasma samples from 183 breast cancer patients. most cases were of Luminal-B (44.8%) phenotype and stage II (41.5%), and median stromal TIL was 30%. PIK3CA mutation in ctDNA was detected in 35% cases (most with E545K) and was associated with lower TIL level (p=0.04). PIK3CA in ctDNA tended to be associated with advanced stages (p=0.09) in the whole series and with higher recurrence rates (p=0.053) in the non-metastatic setting. Patients with presence of PIK3CA in ctDNA tended to have shorter survival (p=0.083). Presence of PIK3CA mutation in ctDNA was frequently found in our Peruvian breast cancer series, was associated with lower TIL levels and tended to predict poor outcomes.

Programmed death-ligand 1 (PD-L1) expression in Hodgkin’s lymphoma among Peruvian patients

Objective: Various studies on Hodgkin’s lymphoma (HL) have determined programmed death-ligand 1 (PD-L1) expression in Hodgkin and Reed-Sternberg (HRS) cells, with variable results. This protein has gained relevance for its role in theimmune response in malignant neoplasms. This work aimed to determine PD-L1 immunohistochemical expression in HRS cells and its relationship with age, sex, clinical stage and overall survival (OS) in a cohort of Peruvian patients. Materials and methods: Twenty-five (25) biopsies from patients diagnosed with HL were assessed, which allowed determining PD-L1 immunohistochemical expression in HRS cells in relation to OS and clinical data of the patients. Results: All cases showed PD-L1 expression in more than 1 % of tumor cells. There was no statistically significant difference in OS when two groups were compared in terms of PD-L1 expression with a cut-off point of 50 %, clinical stage (CS), age and sex. Conclusions: High PD-L1 expression was found in pre-treatment HL tumors. No association was found between PD-L1 expression, OS, age, sex or CS. Further studies with a larger number of patients are necessary to reassess the prognosticimpact of the expression of this protein in HL.

GSTT1/GSTM1 Genotype and Anti-Tuberculosis Drug-Induced Hepatotoxicity in Peruvian Patients.

In Peru, 24,581 people were diagnosed with tuberculosis (TB) in 2020. Although TB treatments are effective, 3.4–13% are associated with significant adverse drug reactions (ADRs), with drug-induced liver injury (DILI) considered the most predominant. Among the first-line antituberculosis drugs, isoniazid (INH) is the main drug responsible for the appearance of DILI. In the liver, INH is metabolized by the enzymes N-acetyltransferase-2 (NAT2), cytochrome P450 2E1 (CYP2E1), and glutathione S-transferase (GST) with two isoforms, GSTT1 and GSTM1. Based on previous studies, we hypothesized that interactions between the GSTT1 and GSTM1 null genotypes induce DILI in TB patients. In this cross-sectional study of 377 participants who completed their anti-TB treatment, we genotyped by revealing the presence or absence of 215- and 480-bp bands of GSTM1 and GSTT1, respectively. We found that the prevalence of the GSTM1 genotype was 52.79% and 47.21% for presence and null, respectively, and for GSTT1 it was 69.76% and 30.24% for presence and null, respectively. Neither genotype was prevalent in the patients who developed DILI (n = 16). We did not confirm our hypothesis; however, we found that the combination of GSTM1 present genotype, GSTT1 null genotype, fast NAT2 acetylators, and CYP2E1 c1/c1 genotype had a significant risk for the development of ADR (OR 11; p = 0.017; 95% CI: (0.54–186.35)). We propose that the presence of the GSTM1 present genotype, GSTT1 null genotype, fast NAT2 acetylators, and CYP2E1 c1/c1 genotype in the Peruvian population could be considered a risk factor for the development of ADR due to therapeutic drug intake.

Zonulin, a marker of gut permeability, is associated with mortality in a cohort of hospitalised peruvian COVID-19 patients.

Zonulin has previously been related to intestinal permeability in various inflammatory diseases, and more recently to the physiopathology of severe COVID-19 infections. We analysed serum samples from a previous study of a Peruvian cohort of hospitalised COVID-19 patients, for the quantification of zonulin by sandwich ELISA. Comparisons with clinical data, haematological and biochemical parameters and cytokine/chemokine levels were made. We found higher baseline zonulin levels in deceased patients, and zonulin was associated with fatal outcome in multivariable analyses, even after adjustment for age, gender, and obesity. There were also positive correlations between zonulin, creatinine, D-dimer values and prothrombin time, while inverse correlations were found for Sa/FiO2 ratio and CCL5 (RANTES). Further longitudinal studies are recommended to analyse the variation of zonulin levels over time as well as their relationship with long-COVID.

One-year follow-up of depression, anxiety, and quality of life of Peruvian patients who survived COVID-19.

PurposeTo assess health-related quality of life (HRQoL) and its associated factors in patients who survived COVID-19 and to assess a prospective evaluation of the prevalence and severity of their depression and anxiety symptoms.MethodsWe followed up a sample of hospitalized patients who survived COVID-19 at 3 and 12 months after discharge. We assessed HRQoL (Euroqol-5D-5L) through telephone interviews. Any problem in any dimension of Euroqol-5D-5L was considered as low HRQoL. The depression and anxiety symptoms were measured using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 tools, respectively. We estimated the adjusted prevalence ratios (aPR) to low HRQoL using Poisson regression and the changes on their depression and anxiety symptoms during the follow-up.ResultsWe included 119 patients with a mean follow-up time of 363.6 days. 74% of the participants had low HRQoL at one year after hospital discharge and were associated with being ≥ 41 years old (aPR: 1.95), having a previous history of psychiatric diagnoses before COVID-19 infection (aPR: 1.47), having any COVID-19 symptom during the follow-up at one year (aPR: 1.84), and having a family member who had died from COVID-19 during the first wave (aPR: 1.24). In addition, the clinically relevant depression symptoms were frequent, and they increased from 3 (14.3%) to 12 months (18.5%).ConclusionOne year after COVID-19 hospitalization discharge, patients had low HRQoL, and their depression symptoms increased. These findings acknowledge the need to provide services that adequately address mental health sequels and HRQoL to reduce the burden of the COVID-19.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as risk factors for mortality in Peruvian adults with chronic kidney disease

ObjectiveTo assess the association between the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with all-cause mortality in Peruvian patients with chronic kidney disease (CKD) attending a tertiary hospital.MethodsWe conducted a retrospective cohort study in adults with CKD in stages 1–5. The outcome variable was mortality and as variables of exposure to NLR and PLR. Both ratios were categorized as high with a cutoff point of 3.5 and 232.5, respectively. We carried out a Cox regression model and calculated crude and adjusted hazard ratios (HR) with their 95% confidence interval (95% CI).ResultsWe analyzed 343 participants with a mean age of 78.3 (± 11.9) years and 62.9% (n = 216) men. The median follow-up time was 2.45 years (2.08–3.08), and the frequency of deaths was 17.5% (n = 60). The mortality of patients with high NLR was 28% compared to 15.7% of the group with normal NLR, and the mortality was 35.7% in those with high PLR and 15.6% in those with normal PLR. In the crude analysis, the high NLR and PLR were significantly associated with all-cause mortality (HR = 2.01; 95% CI 1.11–3.66) and (HR = 2.58; 95% CI 1.31–5.20). In the multivariate model, after adjusting for age, sex, serum creatinine, albumin and hemoglobin, the high NLR and PLR remained as independent risk factors for all-cause mortality (aHR = 1.97; 95% CI 1.05–3.69) and (aHR = 2.62; 95% CI 1.25–5.51), respectively.ConclusionOur study suggests the relationship between high NLR and PLR with all-cause mortality in patients with CKD.

Comparative Profiling of Circulating Exosomal Small RNAs Derived From Peruvian Patients With Tuberculosis and Pulmonary Adenocarcinoma.

Tuberculosis (TB) is one of the most fatal infectious diseases, caused by the aerobic bacteria Mycobacterium tuberculosis. It is estimated that one-third of the world’s population is infected with the latent (LTB) version of this disease, with only 5-10% of infected individuals developing its active (ATB) form. Pulmonary adenocarcinoma (PA) is the most common and diverse form of primary lung carcinoma. The simultaneous or sequential occurrence of TB and lung cancer in patients has been widely reported and is known to be an issue for diagnosis and surgical treatment. Raising evidence shows that patients cured of TB represent a group at risk for developing PA. In this work, using sRNA-sequencing, we evaluated the expression patterns of circulating small RNAs available in exosomes extracted from blood samples of Peruvian patients affected by latent tuberculosis, active tuberculosis, or pulmonary adenocarcinoma. Differential expression analysis revealed a set of 24 microRNAs perturbed in these diseases, revealing potential biomarker candidates for the Peruvian population. Most of these miRNAs are normally expressed in healthy lung tissue and are potential regulators of different shared and unique KEGG pathways related to cancers, infectious diseases, and immunology.

Normal transaminases in obese patients with metabolic associated steatohepatitis (MASH): a cohort of Peruvian patients

Introduction: Metabolic associated steatohepatitis (MASH) is one of the most frequent causes of chronic liver disease. Liver transaminases are important biomarkers to measure liver injury, however, a proportion of patients with MASH may present with normal levels of transaminases. The levels of serum transaminases may not correlate with the severity of histopathological changes. Objective: We aimed to identify the frequency of normal transaminases in obese patients with MASH, as well as to describe the clinical, biochemical and histological characteristics in this specific group of patients. Materials and methods: A retrospective cross-sectional study was conducted in the bariatric surgery service of a private clinic. Obese patients older than 18 years with a body mass index (BMI) &gt;30Kg/m2 and 2 co-morbidities undergoing a gastric sleeve surgery were included. Measurement of biochemical routine laboratory exams was performed. Insulin resistance was calculated using the homeostasis evaluation model (HOMA-IR). All patients underwent liver biopsies prior to surgery and the diagnosis of MASH was based on the Brunt criteria. Results: 159 obese patients with MASH were included, of which 47.2% had normal transaminases and 52.8% elevated transaminases. Factors associated with alteration in transaminases were: being male OR=4.02 (95% CI: 2.03-7.96; p&lt;0.01), diagnosis of type 2 diabetes mellitus OR=4.86 (95% CI: 1.97- 11.95; p&lt;0.01) and levels of GGT &gt;50 IU/L OR=7.50 (95% CI: 3.40-16.56; p&lt;0.01). The values of HOMA-IR and GGT were significantly higher in the group of high transaminases (p&lt;0.01). Differences in the degree of fibrosis were not associated with transaminases levels. Conclusion: In conclusion we found that the frequency of normal transaminases was 47.2% in obese patients with MASH. Factors associated with elevation in liver enzymes were being male, diagnosis of diabetes mellitus and elevation in GGT levels. The degree of fibrosis was not associated with elevations in liver transaminases. These findings suggest that transaminases levels alone are not accurate markers to assess liver injury, as they do not necessarily correlate with histological liver damage.

NAT2 and CYP2E1 polymorphisms and antituberculosis drug-induced hepatotoxicity in Peruvian patients.

BackgroundIn Peru, 32,970 people were diagnosed with tuberculosis (TB) in 2019. Although TB treatment is effective, 3.4%–13% is associated with significant adverse drug reactions (ADR), considering drug‐induced liver injury (DILI) as the most prevalent. Among the first‐line anti‐TB drugs, isoniazid (INH) is primarily responsible for the occurrence of DILI. INH is metabolized in the liver by the enzymes N‐acetyltransferase‐2 (NAT2) and Cytochrome P450 2E1 (CYP2E1). Based on the previous studies, we hypothesized that the interactions between slow CYP2E1 genotype and NAT2 slow acetylators will induce DILI in TB patients.MethodsIn this cross‐sectional study, all 377 participants completed their anti‐TB treatment, and we genotyped SNPs: rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2 and rs3813867 and rs2031920 for CYP2E1.ResultsWe found that rapid, intermediate, and slow NAT2 acetylator were 15%, 38%, and 47%, respectively, in the general population. Intermediate NAT2 acetylator is the least prevalent among patients with adverse reactions (p = 0.024). We did not confirm our hypothesis, however, we found that the combination of intermediate NAT2 acetylators and CYP2E1 c1/c1 genotype significantly protected (OR = 0.16; p = 0.049) against the development of DILI in our population.ConclusionWe propose that the presence of NAT2 intermediate and CYP2E1 c1/c1 genotype could help in therapeutic drug monitoring, and optimize its therapeutic benefits while minimizing its risk for side effects or toxicity.

Abstract 2770: Microbiota, mutational landscape and tumor sidedness of colorrectal cancer

Abstract Background: Colorectal cancer (CRC) is one of the most common cancers in the world, and it is one of the leading causes of cancer-related death. New biomarker candidates have emerged as an important prognostic and predictive factor and genetic profile approach has been used in the choice of targeted therapies and in the prediction of drug response. The aim of this study was performed a comprehensive genomic profile and intestinal microbiota characterization in peruvian CRC patients to define biomarkers for decision making. Methods: Patients with CRC diagnosed in 2019 and treated at INEN were included. Tumor samples were collected to assessed the presence of high-risk human papillomavirus (HPV) and Epstein-Bar virus (EBV) by qPCR, microsatellite instability (MSI) by IHC and somatic genomic alterations by next generation sequencing (NGS) using Ampliseq FOCUS panel (Illumina). Fecal samples were self-collected to performed V3-V4 region 16S ribosomal RNA metagenomics sequencing (Illumina). Results: The study included 40 CRC patients with a mean age at diagnosis of 56 (28-90) years, 59.2% were men. Clinical stages were distributed, in I-II (16.5%), III (37.5%), IV (27.5%). The remaining 12.5% had an unknown tumor stage at diagnosis. The 62.5% of patients underwent tumor surgical treatment. Most tumors (85%) were adenocarcinoma NOS and moderately differentiated (65%). Tumor location was rectum (RC; 27.5%), right side colon (RCC; 42.5%) and left side colon (LCC; 30%). Chemotherapy was administered in 30%. The median follow-up period was 11.1 months (2-28). MSI was high (20%), low (10%) and stable (70%). HPV and EBV DNA was detected in 42.5% and 82.5% of CRC patients respectively. The prevalence of genomic alterations was 77.5%. KRAS alterations were found in 47.5% patients. BRAF (5%), NRAS (2.5%), PIK3CA (12.5%), APC (2.5%), and AKT1 (2.5%). All PIK3CA and BRAF variants were found in RCC. No variants were found in the NTRK or HER2 amplifications. Patients with BRAF variant had a median survival rate only 5 months (3-7). MSI-high/low was present only in colon, showing dominance on the RCC (66.7%). Verrucomicrobia, Staphylococcus, Peptostreptococcus and Clostridium were present in both RCC and LCC. Clostridium and Peptostreptococcus were highly enriched in the LCC. Campylobacter and Spirochaeta were found only in the LCC. Surprisingly, Fusobacterium was found in RCC except one patient in LCC. Bifidobacterium and Acinetobacter were present only in LCC and RC. Elusimicrobia, Shigella and WPS-2 were found only in RC. Conclusion: The current pressure to select the best treatment has generated intense interest in the evaluation of CRC molecular alterations characteristic to define prognostic and predictive biomarkers of disease and treatment in our population. This study constitutes the first integrative biomarkers research in peruvian CRC patients showing a diferent molecular signatures between RCC, LCC and RC patients. Citation Format: Bruno A. Muñante Luna, Jhoysi Casas Goñas, Manuel Chumpitaz, Juan Pablo Cerapio, Marcos Santos Chavez, Mariela Huerta-Rosario, Franco Doimi Garcia, Juan F. Olivos Gonzales, Claudia Jiménez Orosco, Daniel Valdivia Leonardo, Luis F. Barreda Bolaños, Silvia Neciosup Delgado, Victor Castro Oliden, Paola Montenegro Beltran, Luis Mas Lopez, Eduardo Payet Meza, Carolina Belmar-López. Microbiota, mutational landscape and tumor sidedness of colorrectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2770.

Clinicopathological features and management of patients with primary CNS lymphoma: Peruvian experience in two cancer centers.

e19541 Background: Primary central nervous system lymphoma (PCNSL) is an aggressive and rare extranodal non-Hodgkin lymphoma with a dismal prognosis in most patients. Outcomes in Latin population is unknown. Methods: We present a retrospective cohort of fifty-five and six newly diagnosed Peruvian patients treated at the Instituto Nacional de Enfermedades Neoplasicas from 2000-2020 and at Oncosalud from 2014-2020, respectively. Inclusion criteria were (1) histologic diagnosis of diffuse large B-cell lymphoma by two pathologists; (2) disease localized exclusively in the brain, cranial nerves, meninges, or eyes; and (3) no evidence of human immunodeficiency virus infection. Results: Median age at diagnosis was 52 years old [range 21-76]. Sixty-one percent were men. Eastern Cooperative Oncology Group performance status was ≥2 in 68% of patients. Clinical presentation was characterized by intracranial hypertension symptoms (67%), focal deficit (64%), visual disturbance (18%), and seizures (9%). elevated LDH was present in 26/46 (57%) patients, multiple lesions in 19/56 (34%) patients, and involvement of deep structures 21/62 (34%) patients. Seven patients were treated by surgery only (3, subtotal and 4, total resection), three patients received radiotherapy only, and six patients did not receive any treatment. Forty-two patients received the following chemotherapy protocols: DeAngelis (26%), high-dose methotrexate (HD-MTX) (17%), HD-MTX + high-dose ARAC (HD-ARAC) (36%) and HD- MTX + HD-ARAC + Rituximab (9%), HD-MTX + Rituximab + Temozolomide (TMZ) as induction and consolidation with etoposide (VP16) + HD-ARAC (12%), the latter was used in the private center. Clinical outcomes are described in Table. The median follow-up time was 9m (0.03-248). The median overall survival (OS) was 9.9m, 5y OS was 41.7% (95% CI, 29.2-53.9). The median OS were 6.6m and 67.3m for the public and the private institution, respectively (p=0.02). 5y OS was 34% and 100% in the public and the private center, respectively. Conclusions: Peruvian patients are 15 years younger than those reported in the literature. OS in our cohort is dismal, being poorer in those patients treated at the public center reflecting treatment disparities between the public and private health system. All patients who received HD-MTX+HD-ARAC+TMZ as induction and VP16 +HD-ARAC as consolidation achieved complete response and the median OS was not reached although this can be explained due to a short follow-up time compared to those who received DeAngelis regimen. A longer follow-up is needed to demonstrate if polychemotherapy without radiotherapy is the best treatment in this group of patients.[Table: see text]

Genomic profile by liquid biopsy of Peruvian patients with lung cancer.

e15027 Background: The optimal treatment of advanced NSCLC patients is currently led by genomic profiling with the goal of detecting actionable mutations with an approved targeted therapy. However, tissue DNA samples are not always available to perform this assays. In this context, liquid biopsy has emerged as a valuable tool for providing the best treatment option. Methods: Retrospective study held at Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima - Peru, between January 2019 and September 2021 to assess the genomic profile of 190 newly diagnosed advanced NSCLC patients through liquid biopsy. Blood samples were profiled with the FoundationOne Liquid Biopsy assay. We describe frequency of pathogenic and targetable genetic alterations, as well as the survival outcomes. Genomic and clinical data were recorded from clinical files. Results: The median age was 63 years (26-90), 66.3% were women, 15.3% smokers, 26.3% had exposure to biomass, 22.6% had a first-degree family history of cancer. The most frequent histological type was adenocarcinoma (86.8%). Regarding genomic profile, 183 patients (96.3%) had at least one pathogenic genetic alteration, the most frequent altered genes were TP53 (54.7%), EGFR (50.5%), DNMT3A (17.9%), KRAS (9.5%) and NF1 (6.8%). 116 patients (61%) had a targetable mutation: EGFR Ex19del/ins (27.4%), EGFR L858R/L861Q (17.9%), ALK rearrangements (5.8%), BRAF V600E (3.2%), RET fusions (1.6%), METex14 skipping (1.6%), KRAS G12C (1.6%), ROS 1 (1.1%), and NTRK (0.5%). Of these, 71 patients (65.5%) were able to access target therapy. For the latter, estimated median PFS and OS were 14.0 months (9.3 – 18.6) and 17.8 months (8.2 – 27.4), respectively. Conclusions: Peruvian NSCLC patients represent a population with a high frequency of pathogenic and targetable mutations, being EGFR mutations and ALK rearrangements the most prevalent ones. Despite limited access, a great proportion of patients received target therapy, achieving remarkable survival.