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Impact of KRASG12D subtype and concurrent pathogenic mutations on advanced non-small cell lung cancer outcomes / Impacto del subtipo KRASG12D y mutaciones patogénicas concurrentes en los resultados del cáncer de pulmón de células no pequeñas avanzado
Caballé-Perez, Enrique; Hernández-Pedro, Norma; Ramos-Ramírez, Maritza; Barrios-Bernal, Pedro; Romero-Núñez, Eunice; Lucio-Lozada, José; Ávila-Ríos, Santiago; Reyes-Terán, Gustavo; Cardona, Andrés F; Arrieta, Oscar.
Affiliation
  • Caballé-Perez, Enrique; Instituto Nacional de Cancerología. Thoracic Oncology Unit. Mexico City. Mexico
  • Hernández-Pedro, Norma; Instituto Nacional de Cancerología. Personalized Medicine Laboratory. Mexico City. Mexico
  • Ramos-Ramírez, Maritza; Instituto Nacional de Cancerología. Thoracic Oncology Unit. Mexico City. Mexico
  • Barrios-Bernal, Pedro; Instituto Nacional de Cancerología. Personalized Medicine Laboratory. Mexico City. Mexico
  • Romero-Núñez, Eunice; Instituto Nacional de Cancerología. Personalized Medicine Laboratory. Mexico City. Mexico
  • Lucio-Lozada, José; Instituto Nacional de Cancerología. Personalized Medicine Laboratory. Mexico City. Mexico
  • Ávila-Ríos, Santiago; Instituto Nacional de Cancerología. Personalized Medicine Laboratory. Mexico City. Mexico
  • Reyes-Terán, Gustavo; Instituto Nacional de Enfermedades Respiratorias. Mexico City. Mexico
  • Cardona, Andrés F; Universidad El Bosque. Molecular Oncology and Biology Systems Research Group. Bogotá. Colombia
  • Arrieta, Oscar; Instituto Nacional de Cancerología. Thoracic Oncology Unit. Mexico City. Mexico
Clin. transl. oncol. (Print) ; 26(4): 836-850, Abr. 2024. graf
Article in English | IBECS | ID: ibc-VR-47
Responsible library: ES1.1
Localization: ES15.1 - BNCS
ABSTRACT

Purpose:

Mutations in the Kirsten rat sarcoma viral (KRAS) oncogene constitute a significant driver of lung adenocarcinoma, present in 10–40% of patients, which exhibit heterogeneous clinical outcomes, mainly driven by concurrent genetic alterations. However, characterization of KRAS mutational subtypes and their impact on clinical outcomes in Latin America is limited.

Methods:

A cohort study was conducted at the National Cancer Institute (INCan) of Mexico. Individuals with advance-staged of adenocarcinoma and KRAS mutations, detected by next-generation sequencing, having undergone at least one line of therapy were included for analysis. Clinical and pathological characteristics were retrieved from institutional database from June 2014 to March 2023.

Results:

KRAS was identified in fifty-four (15.6%) of 346 patients, among which 50 cases were included for analysis. KRASG12D (n = 16, 32%) and KRASG12C (n = 16, 32%) represented the most prevalent subtypes. KRASG12D mutations were associated with female (p = 0.018), never smokers (p = 0.108), and concurrences with EGFR (25.0% vs. 17.6%, p = 0.124) and CDKN2A (18.8% vs. 14.7%, p = 0.157). KRASG12D patients showed a better ORR (66.6% vs. 30.0%; OR 4.66, 95% CI 1.23–17.60, p = 0.023) and on multivariate analysis was significantly associated with better PFS (HR 0.36, 95% CI 0.16–0.80; p = 0.012) and OS (HR 0.24, 95% CI 0.08–0.70; p = 0.009).

Conclusions:

To our knowledge, this study represents the first effort to comprehensively characterize the molecular heterogeneity of KRAS-mutant NSCLC in Latin American patients. Our data reinforce the current view that KRAS-mutated NSCLC is not a single oncogene-driven disease and emphasizes the prognostic impact of diverse molecular profiles in this genomically defined subset of NSCLC. Further validation is warranted in larger multicenter Latin American cohorts to confirm our findings.(AU)
Subject(s)


Full text: Available Collection: National databases / Spain Health context: SDG3 - Target 3C: Increase health financing and the recruitment, development, training and retention of the health workforce / Sustainable Health Agenda for the Americas / SDG3 - Health and Well-Being / SDG3 - Target 3.3 End transmission of communicable diseases / SDG3 - Target 3.4 Reduce premature mortality due to noncommunicable diseases / SDG3 -Target 3.5 Prevention and treatment of consumption of psychoactive substances Health problem: Authority and Accountability for Healthcare Workers / Goal 10: Communicable diseases / Goal 3 Human resources for health / Target 3.3: End transmission of communicable diseases / Antimicrobial Resistance / Leishmaniasis / Congenital and Chromosomal Anomalies / Alcohol Database: IBECS Main subject: Skin / Hip / Osteoarthritis / Pediatrics / Physical Examination / Professional Competence / Prostheses and Implants / Quality of Life / Reoperation / Speech Type of study: Diagnostic study / Evaluation study / Practice guideline / Observational study / Prognostic study / Risk factors / Screening study / Systematic review Limits: Humans / Male / Female / Adult / Aged / Adolescent / Child Country/Region as subject: Europa / South America / Chile / Mexico Language: Spanish / English Journal: An. pediatr. (2003. Ed. impr.) / Aten. prim. (Barc., Ed. impr.) / Cir. pediátr / Clin. transl. oncol. (Print) / Int. microbiol / Nutr. hosp / Radiología (Madr., Ed. impr.) / Rev. Soc. Andal. Traumatol. Ortop. (Ed. impr.) / Rev. esp. anestesiol. reanim / Rev. esp. cir. ortop. traumatol. (Ed. impr.) Year: 2023 / 2022 / 2021 / 2024 Document type: Article Institution/Affiliation country: Universidad Andrés Bello/Chile / Hospital Clínico San Carlos/España / Centro de Investigaciones Biológicas Margarita Salas/Spain / Centro de Salud Delicias Norte/España / Clínica Alemana de Santiago/Chile / Consejo Asesor de la Federación de Asociaciones Científico-Médicas Españolas (FACME)/España / Consorcio Hospital General Universitario de Valencia/Spain / Fundación Dr. Alfredo Gantz Mann/Chile / Hospital Clínico San Carlos/España / Hospital Clínico Universitario Lozano Blesa/España

Full text: Available Collection: National databases / Spain Health context: SDG3 - Target 3C: Increase health financing and the recruitment, development, training and retention of the health workforce / Sustainable Health Agenda for the Americas / SDG3 - Health and Well-Being / SDG3 - Target 3.3 End transmission of communicable diseases / SDG3 - Target 3.4 Reduce premature mortality due to noncommunicable diseases / SDG3 -Target 3.5 Prevention and treatment of consumption of psychoactive substances Health problem: Authority and Accountability for Healthcare Workers / Goal 10: Communicable diseases / Goal 3 Human resources for health / Target 3.3: End transmission of communicable diseases / Antimicrobial Resistance / Leishmaniasis / Congenital and Chromosomal Anomalies / Alcohol Database: IBECS Main subject: Skin / Hip / Osteoarthritis / Pediatrics / Physical Examination / Professional Competence / Prostheses and Implants / Quality of Life / Reoperation / Speech Type of study: Diagnostic study / Evaluation study / Practice guideline / Observational study / Prognostic study / Risk factors / Screening study / Systematic review Limits: Humans / Male / Female / Adult / Aged / Adolescent / Child Country/Region as subject: Europa / South America / Chile / Mexico Language: Spanish / English Journal: An. pediatr. (2003. Ed. impr.) / Aten. prim. (Barc., Ed. impr.) / Cir. pediátr / Clin. transl. oncol. (Print) / Int. microbiol / Nutr. hosp / Radiología (Madr., Ed. impr.) / Rev. Soc. Andal. Traumatol. Ortop. (Ed. impr.) / Rev. esp. anestesiol. reanim / Rev. esp. cir. ortop. traumatol. (Ed. impr.) Year: 2023 / 2022 / 2021 / 2024 Document type: Article Institution/Affiliation country: Universidad Andrés Bello/Chile / Hospital Clínico San Carlos/España / Centro de Investigaciones Biológicas Margarita Salas/Spain / Centro de Salud Delicias Norte/España / Clínica Alemana de Santiago/Chile / Consejo Asesor de la Federación de Asociaciones Científico-Médicas Españolas (FACME)/España / Consorcio Hospital General Universitario de Valencia/Spain / Fundación Dr. Alfredo Gantz Mann/Chile / Hospital Clínico San Carlos/España / Hospital Clínico Universitario Lozano Blesa/España
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