Browsing by Author "Mas, L"

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A high number of co-occurring genomic alterations detected by NGS is associated with worse clinical outcomes in advanced EGFR-mutant lung adenocarcinoma: Data from LATAM population
(Elsevier Ireland Ltd, 2022) Heredia, D; Mas, L; Cardona, AF; Oyervides, V; Motta-Guerrero, R; Galvez-Nino, M; Lara-Mejía, L; Aliaga-Macha, C; Carracedo, C; Varela-Santoyo, E; Ramos-Ramírez, M; Davila-Dupont, D; Martínez, J; Cruz-Rico, G; Remon, J; Arrieta, O
Background: Co-occurring genomic alterations identified downstream main oncogenic drivers have become more evident since the introduction of next-generation sequencing (NGS) analyses at diagnosis and progression. Emerging evidence has stated that co-occurring genomic alterations at diagnosis might represent de novo and primary resistance mechanisms to tyrosine kinase inhibitors (TKIs) in advanced EGFR-mutant (EGFRm) non-small lung cancer (NSCLC). In this study, we assessed the prognostic role of co-occurring genomic alterations in advanced EGFRm NSCLC. Methods: A cohort of 111 patients with advanced NSCLC harboring EGFR-sensitive mutations detected by PCR was analyzed in 5 Latin American oncological centers from January 2019 to December 2020. All eligible patients received upfront therapy with EGFR-TKI. Co-occurring genomic alterations were determined at diagnosis in every patient by the NGS (FoundationOneCDx) comprehensive platform, which evaluates 324 known cancer-related genes. Results: EGFR exon19 deletion was the most frequent oncogenic driver mutation (60.4 %) detected by NGS. According to the NGS assay, 31 % and 68.3 % of patients had 1–2 and ≥ 3 co-occurring genomic alterations, respectively. The most frequent co-occurring genomic alterations were TP53 mutations (64.9 %) followed by CDKN2AB alterations (13.6 %), BRCA2 (13.6 %), and PTEN (12.7 %) mutations. Baseline central nervous system disease was present in 42.7 % of patients. First- or second-generation EGFR TKIs (gefitinib, afatinib, or erlotinib) were the most common treatment in 67.5 % of patients, while osimertinib was administered in 27.9 % of cases. The median PFS in all evaluated patients was 13.63 months (95 %CI: 11.79–15.52). Using ≥ 3 co-occurring alterations as the cut-off point, patients with ≥ 3 co-occurring genomic alterations showed a median PFS, of 12.7 months (95 %CI: 9.92–15.5) vs 21.3 months (95 %CI: 13.93-NR) in patients with 2 or less co-occurring genomic alterations [HR 3.06, (95 %CI: 1.55–5.48) p = 0.0001]. Also, patients with a TP53 mutation had a shorter PFS, 13.6 (95 %CI: 10.7–15.5) vs 19.2 months (95 %CI: 12.8-NR) in wild type TP53 [HR 2.01 (95 %CI: 1.18–3.74) p = 0.12]. In the multivariate analysis, the number (≥3) of concurrent genomic alterations and ECOG PS of 2 or more were related to a significant risk factor for progression [HR 2.79 (95 %CI: 1.49–5.23) p = 0.001 and HR 2.42 (95 %CI: 1.22–4.80) p = 0.011 respectively]. Conclusion: EGFR-mutant NSCLC is not a single oncogene-driven disease in the majority of cases, harboring a higher number of co-occurring genomic alterations. This study finds the number of co-occurring genomic alterations and the presence of TP53 mutations as negative prognostic biomarkers, which confers potentially earlier resistance mechanisms to target therapy.
[Anemia as a prognostic factor in cancer patients]
(Instituto Nacional de Salud, 2018) Paitan, V; Alcarraz, C; Leonardo, A; Valencia, G; Mantilla, R; Morante, Z; Oscanoa, TJ; Mas, L
Objective.: To determine the frequency and prognostic value of anemia in cancer patients receiving care at the National Institute of Neoplastic Diseases (Instituto Nacional de Enfermedades Neoplásicas - INEN) between January and April of 2010. Materials and methods.: Anemia was considered for men with hemoglobin levels at <13 g/dL; and for women, at <12 g/dL. Associations between qualitative features were assessed with a Chi-square test. Kaplan-Meier estimator was used for the analysis of the survival curves, and differences between the curves were performed with the log-rank test. Results.: 772 patients were included; 584 (75.7%) had solid tumors and 188 (24.3%) had hematologic malignancies. Anemia was diagnosed in 359 patients (46.5%); hematologic malignancies in 127 patients (67.6%); and solid neoplasms in 235 (40.2%). Hematologic malignancies with the highest frequency of anemia were chronic myeloid leukemia, acute leukemias, and multiple myeloma (100%, 92.5% and 60%, respectively); and were cancer of gastrointestinal, gynecological, and urological origin were in the group of solid neoplasms (62%, 52.1% and 45%, respectively). Two hundred and four (204) patients (26.4%) were transfused. In 762 patients, a significant difference in overall survival was found between groups with and without anemia, estimated at 5 years in 62% and 47% respectively (p <0.001). In the solid tumor subgroup (p = 0.002), and the hematological malignancies subgroup (p = 0.007), such association was also found. Conclusions.: Anemia is common in cancer patients, and its presence determines an independent prognostic factor in overall survival.
Breast cancer subtype and clinical characteristics in women from Peru
(Frontiers Media S.A., 2023) Zavala, VA; Casavilca-Zambrano, S; Navarro-Vasquez, J; Tamayo, LI; Castaneda, CA; Valencia, G; Morante, Z; Calderon, M; Abugattas, JE; Gomez, HL; Fuentes, HA; Liendo-Picoaga, R; Cotrina, JM; Neciosup, SP; Roque, K; Vasquez, J; Mas, L; Galvez-Nino, M; Fejerman, L; Vidaurre, T
Introduction: Breast cancer is a heterogeneous disease, and the distribution of the different subtypes varies by race/ethnic category in the United States and by country. Established breast cancer-associated factors impact subtype-specific risk; however, these included limited or no representation of Latin American diversity. To address this gap in knowledge, we report a description of demographic, reproductive, and lifestyle breast cancer-associated factors by age at diagnosis and disease subtype for The Peruvian Genetics and Genomics of Breast Cancer (PEGEN-BC) study. Methods: The PEGEN-BC study is a hospital-based breast cancer cohort that includes 1943 patients diagnosed at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru. Demographic and reproductive information, as well as lifestyle exposures, were collected with a questionnaire. Clinical data, including tumor Hormone Receptor (HR) status and Human Epidermal Growth Factor Receptor 2 (HER2) status, were abstracted from electronic medical records. Differences in proportions and mean values were tested using Chi-squared and one-way ANOVA tests, respectively. Multinomial logistic regression models were used for multivariate association analyses. Results: The distribution of subtypes was 52% HR+HER2-, 19% HR+HER2+, 16% HR-HER2-, and 13% HR-HER2+. Indigenous American (IA) genetic ancestry was higher, and height was lower among individuals with the HR-HER2+ subtype (80% IA vs. 76% overall, p=0.007; 152 cm vs. 153 cm overall, p=0.032, respectively). In multivariate models, IA ancestry was associated with HR-HER2+ subtype (OR=1.38,95%CI=1.06-1.79, p=0.017) and parous women showed increased risk for HR-HER2+ (OR=2.7,95%CI=1.5-4.8, p<0.001) and HR-HER2- tumors (OR=2.4,95%CI=1.5-4.0, p<0.001) compared to nulliparous women. Multiple patient and tumor characteristics differed by age at diagnosis (<50 vs. >=50), including ancestry, region of residence, family history, height, BMI, breastfeeding, parity, and stage at diagnosis (p<0.02 for all variables). Discussion: The characteristics of the PEGEN-BC study participants do not suggest heterogeneity by tumor subtype except for IA genetic ancestry proportion, which has been previously reported. Differences by age at diagnosis were apparent and concordant with what is known about pre- and post-menopausal-specific disease risk factors. Additional studies in Peru should be developed to further understand the main contributors to the specific age of onset and molecular disease subtypes in this population and develop population-appropriate predictive models for prevention. Copyright © 2023 Zavala, Casavilca-Zambrano, Navarro-Vásquez, Tamayo, Castañeda, Valencia, Morante, Calderón, Abugattas, Gómez, Fuentes, Liendo-Picoaga, Cotrina, Neciosup, Roque, Vásquez, Mas, Gálvez-Nino, Fejerman and Vidaurre.
Epidemiology of thymic epithelial tumors: 22-years experience from a single-institution
(International Association for the Study of Lung Cancer, 2021) Rioja, PJ; Ruiz RJ; Galvez-Nino, MJ; Lozano, SJ; Valdiviezo, NJ; Olivera, MJ; Cabero, OJ; Guillen, MEJ; De La Guerra, AJ; Amorin, EJ; Barrionuevo, CJ; Mas, L
Background: To assess the correlation of WHO histological classification and Masaoka-Koga staging system of thymic epithelial tumors (TETs) with prognosis. Methods: We retrospectively analyzed 83 patients with TETs in the Instituto Nacional de Enfermedades Neoplasicas between 1996 to 2018. We analyzed the clinical stages, histological types and treatment modalities and attempted to determine the impact on overall survival. The data was retrieved from clinical files and reviewed by a pathologist who reclassificated according to the 2004 WHO classification system. The staging was performed with the Masaoka-Koga staging system. Survival curves were constructed with Kaplan-Meir method. Results: There was a total of 83 patients with a median age of 55 years old included in the study. The histological type corresponded to thymoma (T) in 63.8% (n = 53) and to thymic carcinoma (TC) in 36.1%. T were type A, AB, B1, B2 and B3 in 14.4%, 18%, 12%, 3.6%, 7.4% of cases, respectively. The proportion of advanced disease (Masaoka stage III-IV) was high (65%). With a median follow-up of 88.4 months, median overall survival (OS) was 81.6 months for T and 12.3 months for TC (P = 0.01). Univariate analysis showed that sex, histological type, clinical stage and surgery (P = 0.01) were significant independent prognostic factors. On multivariate analysis, histology type and Masaoka-Koga staging had an effect on survival. Conclusions: The results indicates a clear association between the WHO histological classification and Masaoka-Koga staging system with survival. We found a higher proportion of TETs with advanced disease at diagnosis. Further research are required and collaboration is important to foster knowledge focused on classification and treatment.
Impact of Concurrent Genomic Alterations on Clinical Outcomes in Patients With ALK-Rearranged NSCLC
(Elsevier Inc., 2024) Lara-Mejía, L; Cardona, AF; Mas, L; Martin, C; Samtani, S; Corrales, L; Cruz-Rico, G; Remon, J; Galvez-Nino, M; Ruiz, R; Rios-Garcia, E; Tejada, F; Lozano-Vazquez, N; Rosell, R; Arrieta, O
Introduction: ALK tyrosine kinase inhibitors have exhibited promising activity against advanced ALK-rearranged NSCLC. However, co-occurring genetic alterations, such as CDKN2A/B or TP53, may negatively affect the efficacy of targeted therapies. Methods: From December 2017 to December 2022, this study cohort analyzed next-generation sequencing data of 116 patients with metastatic ALK-rearranged NSCLC from five Latin American cancer centers. Clinicopathologic and molecular features were associated with clinical outcomes and risk of brain metastasis (BrM) in patients with and without concurrent somatic alterations. Results: All patients (N = 116) received a second-generation ALK tyrosine kinase inhibitor, and alectinib was selected in 87.2% of cases. Coalterations occurred in 62% of the cases; the most frequent were TP53 mutations (27%) and CDKN2A/B loss (18%). The loss of CDKN2A/B was associated with an increased risk of BrM, with a cumulative incidence of 33.3% versus 7.4% in the non-coaltered subgroup. Compared with patients without coalterations, patients with concurrent CDKN2A/B loss (n = 21) had a shorter median progression-free survival (10.2 versus 34.2 mo, p < 0.001) and overall survival (26.2 versus 80.7 mo, p < 0.001). In the multivariate analysis, co-occurring CDKN2A/B loss was associated with poorer progression-free survival and OS despite the presence of other somatic coalterations, TP53 mutations, BrM, and Eastern Cooperative Oncology Group Performance Status. Conclusions: This study confirmed the worse prognostic value, which depicted co-occurring alterations in patients with ALK rearrangement. CDKN2A/B loss was substantially associated with worse outcomes and a higher risk of brain metastases. The evidence presented in our study may help select patients with ALK-positive tumors suitable for treatment escalation and closer brain follow-up.
Retos y avances del cáncer de pulmón de células no pequeñas metastásico EGFR mutado
(Universidad Ricardo Palma, Instituto de Investigaciones en Ciencias Biomedicas, Facultad de Medicina Humana, 2024) Castro-Mollo, M; Ruiz, R; Roque, K; Mas, L
Introduction: Tyrosine kinase inhibitors have dramatically changed the clinical outcomes for patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutations. However, there are still challenges in the management of patients with this mutation in a metastatic setting, such as intrinsic and acquired resistance to tyrosine kinase inhibitors. We will discuss the latest advances and new strategies in first-line treatment, osimertinib resistance, and exon 20 mutation treatment. © 2024 Universidad Ricardo Palma, Facultad de Medicina Humana. All rights reserved.
Update in Immunotherapy for Advanced Non-Small Cell Lung Cancer: Optimizing Treatment Sequencing and Identifying the Best Choices
(Multidisciplinary Digital Publishing Institute (MDPI), 2023) Roque, K; Ruiz, R; Mas, L; Pozza, DH; Vancini, M; Silva-Junior, JA; de-Mello, RA
The introduction of immunotherapy has brought about a paradigm shift in the management of advanced non-small cell lung cancer (NSCLC). It has not only significantly improved the prognosis of patients but has also become a cornerstone of treatment, particularly in those without oncogenic driver mutations. Immune checkpoint inhibitors (ICIs) play a crucial role in the treatment of lung cancer and can be classified into two main groups: Anti-cytotoxic T lymphocyte antigen-4 (Anti-CTLA-4) and anti-T-cell receptor programmed cell death-1 or its ligand (Anti-PD-1 and Anti-PD-L1). Certainly, the landscape of approved first line immunotherapeutic approaches has expanded to encompass monotherapy, immunotherapy-exclusive protocols, and combinations with chemotherapy. The complexity of decision-making in this realm arises due to the absence of direct prospective comparisons. However, a thorough analysis of the long-term efficacy and safety data derived from pivotal clinical trials can offer valuable insights into optimizing treatment for different patient subsets. Moreover, ongoing research is investigating emerging biomarkers and innovative therapeutic strategies that could potentially refine the current treatment approach even further. In this comprehensive review, our aim is to highlight the latest advances in immunotherapy for advanced NSCLC, including the mechanisms of action, efficacy, safety profiles, and clinical significance of ICI.