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Silvestrini C, Perelli L, Alcaraz A, Espinola N, Argento F. Budget impact of low-dose computed tomography screening for lung cancer in Argentina. Expert Rev Pharmacoecon Outcomes Res 2025:1-8. [PMID: 39875190 DOI: 10.1080/14737167.2025.2460523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 01/21/2025] [Accepted: 01/24/2025] [Indexed: 01/30/2025]
Abstract
BACKGROUND Lung cancer (LC) is a leading cause of cancer mortality in Argentina. Low-dose computed tomography (LDCT) had demonstrated higher efficacy than chest radiography as a screening method for early detection and reducing LC mortality. This study estimates the Budget Impact of implementing annual LDCT screening for individuals aged 55-74 with at least 30 pack-years of smoking in Argentina. RESEARCH DESIGN AND METHODS A budgetary impact model for a dynamic cohort was developed from the Argentine health system's perspective, accounting for LC incidents, prevalents and death probability, distinguishing by disease stage and survival years. Model parameters were sourced from literature and official databases, with costs expressed in 2023 USD. RESULTS In Argentina, 726,420 individuals were eligible for annual LC screening. The average annual budget was USD 196,611,452 in the current scenario and USD 207,439,560 in the projected scenario, leading to a 5.20% incremental cost due to more false positives in LDCT and screening costs. The budget impact per member per month was USD 0.019, slightly above the estimated threshold of USD 0.015. CONCLUSIONS The introduction of LDCT for LC screening increased the health system budget in Argentina but improved early disease detection.
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Affiliation(s)
- Constanza Silvestrini
- Department of Health Technology Assessment and Health Economics, Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina
| | - Lucas Perelli
- Department of Health Technology Assessment and Health Economics, Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina
| | - Andrea Alcaraz
- Department of Health Technology Assessment and Health Economics, Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina
| | - Natalia Espinola
- Department of Health Technology Assessment and Health Economics, Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina
| | - Fernando Argento
- Department of Health Technology Assessment and Health Economics, Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina
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Du NY, Li Y, Zheng H, Liu YK, Liu LS, Xie J, Kang S. Incorporating genotype information in a precise prediction model for platinum sensitivity in epithelial ovarian cancer. Front Oncol 2025; 14:1461772. [PMID: 39839768 PMCID: PMC11746020 DOI: 10.3389/fonc.2024.1461772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 12/13/2024] [Indexed: 01/23/2025] Open
Abstract
Objective Develop a predicting model that can help stratify patients with epithelial ovarian cancer (EOC) before platinum-based chemotherapy. Methods 148 patients with pathologically confirmed EOC and with a minimum 5-year follow-up were retrospectively enrolled. Patients were classified into platinum-sensitive and platinum-resistant groups according to treatment responses. The correlation between clinical factors and drug sensitivity was evaluated using statistical tests. Approximately 700,000 single-nucleotide polymorphism (SNP) sites were assessed for association with drug sensitivity via the Genome-wide Association Study (GWAS). LASSO regression and manual selection were employed to reduce the number of variables. A predicting model based on optimized variables was constructed. The predictive ability of the model was assessed using the Kaplan-Meier curve. Results No statistically significant association was found between clinical factors and drug sensitivity. Sixteen SNPs were preserved after the optimization. A predicting model for drug sensitivity was constructed based on those sixteen SNPs. Coefficients of the synergistic effect for each SNP were determined, and an algorithm of the Drug Sensitivity Index (DSI) was built. The DSI score can successfully distinguish the drug-sensitive or drug-resistant patients with sensitivity, specificity, positive predictive value, and accuracy of 94.7%, 83.3%, 90.8%, and 90.5%, respectively. In both the training set and validating samples, the Kaplan-Meier curve showed that the median PFS and mean OS were significantly differentiated between the predicted sensitive and resistant patients (p-value<0.001). Conclusions A mathematical model incorporating genotype information could help predict the drug sensitivity of platinum-based chemotherapy before the treatment in EOC patients. A personal chemotherapy could be achieved based on the model.
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Affiliation(s)
- Nai-Yi Du
- Department of Gynecology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Yan Li
- Department of Molecular Biology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Hui Zheng
- Department of Translation Medicine, Shijiazhuang Ninghong Biotechnology Co., Ltd., Shijiazhuang, Hebei, China
| | - Ya-Kun Liu
- Department of Gynecology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Lu-Sha Liu
- Department of Gynecology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Jianbang Xie
- Department of Translation Medicine, Shijiazhuang Ninghong Biotechnology Co., Ltd., Shijiazhuang, Hebei, China
| | - Shan Kang
- Department of Gynecology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
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Añorve Bailon D, Picó-Guzmán J, Cifuentes S, Trejo R, Rodríguez Cid J, Juarez-Vignon Whaley JJ, Heredia Zepeda AA, Gerson R, Camacho-Limas CP, Martínez-Herrera JF, Molina DB, Camarín Sánchez E, Shveid Gerson D. Estimation of the Clinical, Economic, and Social Burden of Stage IV Non-Small Cell Lung Cancer in Mexico. PHARMACOECONOMICS - OPEN 2024; 8:869-885. [PMID: 39107537 PMCID: PMC11499576 DOI: 10.1007/s41669-024-00514-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/18/2024] [Indexed: 10/25/2024]
Abstract
INTRODUCTION Lung cancer continues to be the leading cause of death among cancer patients worldwide. This study aimed to estimate the clinical, economic, and social burdens of stage IV non-small cell lung cancer (NSCLC) in private and public healthcare centers in Mexico, utilizing real-world evidence. METHODS The study population included patients >18 years of age diagnosed with stage IV NSCLC who received cancer treatment at the Centro Médico Nacional Siglo XXI (IMSS), the Centro Médico Nacional "20 de Noviembre" (ISSSTE), the Mexican Institute of Respiratory Diseases (INER), and the Medical Center ABC (American British Cowdray) from 1 January 2019 to 31 December 2020. The analysis included evaluation of epidemiological data, treatment regimens, and clinical outcomes, and emphasized pharmacological and non-pharmacological treatments, including detailed follow-up investigations, as part of comprehensive clinical management. Additionally, the study assessed the social burden through variables such as working-age absenteeism and presenteeism and caregiver productivity loss, as well as economic burden, considering both clinical and social components, with costs adjusted to 2022 Mexican pesos (MXN) values. RESULTS A total of 188 patients with metastatic NSCLC were studied. The main type of NSCLC tumor found in the sample was adenocarcinoma (81%). Treatment regimens included pharmacological treatments (78%), non-pharmacological treatments (25%), and palliative care (24%). Complications were present in 73% of the cohort, while 60% presented adverse events. Clinical management costs of up to MXN1,001,579 per patient in the public sector and MXN2,140,604 in the private sector were reported. It was estimated that working-age patients lose 84-335 days yearly due to absenteeism and presenteeism, while caregivers report a productivity loss equivalent to 13-30 days due to the management of NSCLC patients. These indirect costs of NSCLC contribute to the social burden. A working-age patient with stage IV disease is associated with an average indirect cost of MXN49,731-178,287 in public institutions, while in private institutions, the cost elevates to MXN438,103. CONCLUSIONS This study highlights the substantial clinical, economic, and social burdens of stage IV NSCLC in Mexico, revealing significant disparities between public and private healthcare sectors. It underscores the urgent need for standardized practices and equitable care across all systems.
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Affiliation(s)
| | | | - Sergio Cifuentes
- ISSSTE, Centro Médico Nacional "20 de Noviembre", Ciudad de México, CDMX, México
| | - Rogelio Trejo
- IMSS, Centro Médico Nacional Siglo XXI, Ciudad de México, México
| | - Jeronimo Rodríguez Cid
- Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, México
| | | | | | | | | | - José Fabián Martínez-Herrera
- Centro Médico ABC, Ciudad de México, México
- Universidad Científica del Sur, Cancer Research Networking, Lima, Peru
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Arrieta O, Arroyo-Hernández M, Soberanis-Piña PD, Viola L, Del Re M, Russo A, de Miguel-Perez D, Cardona AF, Rolfo C. Facing an un-met need in lung cancer screening: The never smokers. Crit Rev Oncol Hematol 2024; 202:104436. [PMID: 38977146 DOI: 10.1016/j.critrevonc.2024.104436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 06/24/2024] [Accepted: 06/29/2024] [Indexed: 07/10/2024] Open
Abstract
Lung cancer (LC) is the leading cause of cancer-related deaths worldwide and the second most common cancer in both men and women. In addition to smoking, other risk factors, such as environmental tobacco smoke, air pollution, biomass combustion, radon gas, occupational exposure, lung disease, family history of cancer, geographic variability, and genetic factors, play an essential role in developing LC. Current screening guidelines and eligibility criteria have limited efficacy in identifying LC cases (50 %), as most screening programs primarily target subjects with a smoking history as the leading risk factor. Implementing LC screening programs in people who have never smoked (PNS) can significantly impact cancer-specific survival and early disease detection. However, the available evidence regarding the feasibility and effectiveness of such programs is limited. Therefore, further research on LC screening in PNS is warranted to determine the necessary techniques for accurately identifying individuals who should be included in screening programs.
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Affiliation(s)
- Oscar Arrieta
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
| | | | | | - Lucia Viola
- Thoracic Oncology Unit, Fundación Neumológica Colombiana, Bogotá, Colombia
| | - Marzia Del Re
- Center for Thoracic Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY, USA
| | - Alessandro Russo
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Diego de Miguel-Perez
- Center for Thoracic Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY, USA
| | - Andrés F Cardona
- Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center 1/ Foundation for Clinical and Applied Cancer Research (FICMAC)/ Molecular Oncology and Biology Systems Research Group (Fox‑G), Universidad El Bosque, Bogotá, Colombia
| | - Christian Rolfo
- Center for Thoracic Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY, USA.
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Ahmad S, Bano N, Khanna K, Gupta D, Raza K. Reporting multitargeted potency of Tiaprofenic acid against lung cancer: Molecular fingerprinting, MD simulation, and MTT-based cell viability assay studies. Int J Biol Macromol 2024; 276:133872. [PMID: 39019378 DOI: 10.1016/j.ijbiomac.2024.133872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/08/2024] [Accepted: 07/12/2024] [Indexed: 07/19/2024]
Abstract
Lung Cancer (LC) is among the most death-causing cancers, has caused the most destruction and is a gender-neutral cancer, and WHO has kept this cancer on its priority list to find the cure. We have used high-throughput virtual screening, standard precision docking, and extra precise docking for extensive screening of Drug Bank compounds, and the uniqueness of this study is that it considers multiple protein targets of prognosis and metastasis of LC. The docking and MM\GBSA calculation scores for the Tiaprofenic acid (DB01600) against all ten proteins range from -8.422 to -5.727 kcal/mol and - 47.43 to -25.72 kcal/mol, respectively. Also, molecular fingerprinting helped us to understand the interaction pattern of Tiaprofenic acid among all the proteins. Further, we extended our analysis to the molecular dynamic simulation in a neutralised SPC water medium for 100 ns. We analysed the root mean square deviation, fluctuations, and simulative interactions among the protein, ligand, water molecules, and protein-ligand complexes. Most complexes have shown a deviation of <2 Å as cumulative understanding. Also, the fluctuations were lesser, and only a few residues showed the fluctuation with a huge web of interaction between the protein and ligand, providing an edge that supports that the protein and ligand complexes were stable. In the MTT-based Cell Viability Assay, Tiaprofenic Acid exhibited concentration-dependent anti-cancer efficacy against A549 lung cancer cells, significantly reducing viability at 100 μg/mL. These findings highlight its potential as a therapeutic candidate, urging further exploration into the underlying molecular mechanisms for lung cancer treatment.
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Affiliation(s)
- Shaban Ahmad
- Computational Intelligence and Bioinformatics Lab, Department of Computer Science, Jamia Millia Islamia, New Delhi 110025, India.
| | - Nagmi Bano
- Computational Intelligence and Bioinformatics Lab, Department of Computer Science, Jamia Millia Islamia, New Delhi 110025, India; Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India.
| | - Kushagra Khanna
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia.
| | - Dinesh Gupta
- Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India.
| | - Khalid Raza
- Computational Intelligence and Bioinformatics Lab, Department of Computer Science, Jamia Millia Islamia, New Delhi 110025, India.
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Sun YY, Li S, Liu C, Pan Y, Xiao Y. Identification of a methyltransferase-related long noncoding RNA signature as a novel prognosis biomarker for lung adenocarcinoma. Aging (Albany NY) 2024; 16:8747-8771. [PMID: 38771129 PMCID: PMC11164517 DOI: 10.18632/aging.205837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 03/18/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND Lung adenocarcinoma (LUAD) accounts for a high proportion of tumor deaths globally, while methyltransferase-related lncRNAs in LUAD were poorly studied. METHODS In our study, we focused on two distinct cohorts, TCGA-LUAD and GSE3021, to establish a signature of methyltransferase-related long non-coding RNAs (MeRlncRNAs) in LUAD. We employed univariate Cox and LASSO regression analyses as our main analytical tools. The GSE30219 cohort served as the validation cohort for our findings. Furthermore, to explore the differential pathway enrichments between groups stratified by risk, we utilized Gene Set Enrichment Analysis (GSEA). Additionally, single-sample GSEA (ssGSEA) was conducted to assess the immune infiltration landscape within each sample. Reverse transcription quantitative PCR (RT-qPCR) was also performed to verify the expression of prognostic lncRNAs in both clinically normal and LUAD samples. RESULTS In LUAD, we identified a set of 32 MeRlncRNAs. We further narrowed our focus to six prognostic lncRNAs to develop gene signatures. The TCGA-LUAD cohort and GSE30219 were utilized to validate the risk score model derived from these signatures. Our analysis showed that the risk score served as an independent prognostic factor, linked to immune-related pathways. Additionally, the analysis of immune infiltration revealed that the immune landscape in high-risk groups was suppressed, which could contribute to poorer prognoses. We also constructed a regulatory network comprising 6 prognostic lncRNAs, 19 miRNAs, and 21 mRNAs. Confirmatory RT-qPCR results aligned with public database findings, verifying the expression of these prognostic lncRNAs in the samples. CONCLUSION The prognostic gene signature of LUAD associated with MeRlncRNAs that we provided, may offer us a comprehensive picture of the prognosis prediction for LUAD patients.
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Affiliation(s)
- Yang Yong Sun
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Shuang Li
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Chang Liu
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Yaqiang Pan
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Ying Xiao
- Department of Emergency, Nanjing Jiangning Hospital, Jiangsu, China
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Salerno PRVDO, Palma Dallan LA, Rodrigues Pereira GT, Pego Fernandes PM, Mingarini Terra R, Rajagopalan S, Al-Kindi SG, de Oliveira Salerno JV. Trends in tracheal, bronchial and lung cancer attributed to smoking in South America: Global Burden of Disease analysis 1990-2019. Rev Panam Salud Publica 2024; 48:e30. [PMID: 38576842 PMCID: PMC10993800 DOI: 10.26633/rpsp.2024.30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 02/05/2024] [Indexed: 04/06/2024] Open
Abstract
Objective To investigate the burden of tracheal, bronchus, and lung (TBL) cancer due to tobacco exposure in the last 30 years in 12 South American countries. Methods We used the Global Burden of Disease (GBD) 2019 exposure-response function to analyze the total tobacco, smoking, and secondhand smoke exposure-related TBL cancer deaths and disability-adjusted life years (DALYs), for 12 South American countries, between 1990 and 2019. Metrics were described as absolute numbers or rates per 100 000 individuals. The relative change in burden was assessed by comparing the 1990-1994 to 2015-2019 periods. Results In 2019, the all-ages number of TBL cancer deaths and DALYs associated with tobacco exposure in South America was 29 348 and 658 204 in males and 14 106 and 318 277 in females, respectively. Age-adjusted death and DALYs rates for the region in 2019 were 182.8 and 4035 in males and 50.8 and 1162 in females, respectively. In males, 10/12 countries observed relative declines in TBL death rates attributed to tobacco exposure while only 4 countries reduced their mortality in females. Conclusion While significant efforts on tobacco control are under place in South America, substantial burden of TBL cancer persists in the region with significant sex-specific disparities. Increased country-specific primary data on TBL cancer and tobacco exposure is needed to optimize healthcare strategies and improve comprehension of regional trends.
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Affiliation(s)
- Pedro Rafael Vieira de Oliveira Salerno
- University Hospitals Cleveland Medical CenterClevelandUnited States of AmericaUniversity Hospitals Cleveland Medical Center, Cleveland, United States of America
| | - Luis Augusto Palma Dallan
- University Hospitals Cleveland Medical CenterClevelandUnited States of AmericaUniversity Hospitals Cleveland Medical Center, Cleveland, United States of America
| | - Gabriel Tensol Rodrigues Pereira
- University Hospitals Cleveland Medical CenterClevelandUnited States of AmericaUniversity Hospitals Cleveland Medical Center, Cleveland, United States of America
| | | | | | - Sanjay Rajagopalan
- University Hospitals Cleveland Medical CenterClevelandUnited States of AmericaUniversity Hospitals Cleveland Medical Center, Cleveland, United States of America
| | - Sadeer G Al-Kindi
- Houston Methodist HospitalHoustonUnited States of AmericaHouston Methodist Hospital, Houston, United States of America
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Knapp T, Nygaard J, Cassinat J, Galvez F, Gopalan PK. Lung Cancer Clinical Trials in Latin America in the Era of Cooperative Groups: A 20-Year Analysis. JCO Glob Oncol 2024; 10:e2300379. [PMID: 38574300 PMCID: PMC11003508 DOI: 10.1200/go.23.00379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 12/13/2023] [Accepted: 01/30/2024] [Indexed: 04/06/2024] Open
Abstract
PURPOSE The aim of this study is to characterize lung cancer treatment clinical trials in Latin America before (January 2001-December 2011) and after (January 2012-December 2021) the organization of major Latin American oncology cooperative groups. MATERIALS AND METHODS Interventional clinical trials were identified in ClinicalTrials.gov using the search terms "lung cancer," country filters for 20 Latin American countries, and study start dates January 1, 2001-December 31, 2011, and January 1, 2012-December 31, 2021. Clinical trials were categorized as either originating in Latin America (LA) or outside Latin America (non-LA) with participation of Latin American countries. Descriptive statistics, two-sided Z-scores, and chi-square analyses with 95% CIs were calculated. RESULTS Overall, 273 clinical trials involving Latin American countries between 2001 and 2021 were identified. Comparing 2001-2011 with 2012-2021, there was an increase in total clinical trials (100 v 173; P < .001). Only 9% (26 of 273) of all trials were LA trials. There was a marked decrease in the proportion of LA trials (14% v 7%, P = .058) and estimated enrollment to LA trials (3,245 v 1,190 patients; P < .001). Recruiting of patients with EGFR (29% v 7%; P < .01) and KRAS (18% v 2%; P < .01) driver mutations also decreased. Trial participation was highest in Brazil, Mexico, Argentina, Chile, and Peru and increased over time: Brazil (61 v 108; 77% increase), Mexico (40 v 88; 120% increase), Argentina (50 v 78; 56% increase), Chile (25 v 57; 128% increase), and Peru (14 v 37; 164% increase). CONCLUSION There was a significant increase in clinical trial participation by Latin American countries, from 2001-2011 to 2012-2021. However, there were few clinical trials which originated in Latin America or focused on patients with driver mutations.
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Affiliation(s)
- Thomas Knapp
- University of Central Florida College of Medicine, Orlando, FL
| | - Joseph Nygaard
- University of Central Florida College of Medicine, Orlando, FL
| | - Joshua Cassinat
- University of Central Florida College of Medicine, Orlando, FL
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Wang S, Cheng H, Huang Y, Li M, Gao D, Chen H, Su R, Guo K. HSP90a promotes the resistance to oxaliplatin in HCC through regulating IDH1-induced cell competition. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2024; 1871:119680. [PMID: 38280407 DOI: 10.1016/j.bbamcr.2024.119680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 01/06/2024] [Accepted: 01/18/2024] [Indexed: 01/29/2024]
Abstract
Though burgeoning research manifests that cell competition, an essential selection and quality control mechanism for maintaining tissue or organ growth and homeostasis in multicellular organisms, is closely related to tumorigenesis and development, the mechanism of cell competition associated with tumor drug resistance remains elusive. In the study, we uncovered that oxaliplatin-resistant hepatocellular carcinoma (HCC) cells exhibit a pronounced competitive advantage against their sensitive counterparts, which is related to lipid takeover of resistant cells from sensitive cells. Of note, such lipid takeover is dependent on the existence of isocitrate dehydrogenase 1 (IDH1) in resistant HCC cells. Mechanistically, IDH1 activity is regulated by heat shock protein 90 alpha (HSP90α) through binding with each other, which orchestrates the expressions of lipid metabolic enzymes and lipid accumulation in resistant HCC cells. Our results suggest that HCC cell competition-driven chemoresistance can be regulated by HSP90α/IDH1-mediated lipid metabolism, which may serve as a promising target for overcoming drug resistance in HCC.
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Affiliation(s)
- Sikai Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China
| | - Hongxia Cheng
- Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200434, China
| | - Yilan Huang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China
| | - Miaomiao Li
- Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Dongmei Gao
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China
| | - Huaping Chen
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University Nanning, Guangxi 530021, China
| | - Ruxiong Su
- Puning People's Hospital, Southern Medical University, Guangdong 515300, China
| | - Kun Guo
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China; Cancer Research Center, Institute of Biomedical Science, Fudan University, Shanghai 200032, China.
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Parra-Medina R, Castañeda-González JP, Montoya L, Paula Gómez-Gómez M, Clavijo Cabezas D, Plazas Vargas M. Prevalence of oncogenic driver mutations in Hispanics/Latin patients with lung cancer. A systematic review and meta-analysis. Lung Cancer 2023; 185:107378. [PMID: 37729688 DOI: 10.1016/j.lungcan.2023.107378] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/12/2023] [Accepted: 09/13/2023] [Indexed: 09/22/2023]
Abstract
INTRODUCTION The frequency of actionable mutations varies between races, and Hispanic/Latino (H/L) people are a population with different proportions of ancestry. Our purpose was to establish prevalence of actionable mutations in the H/L population with NSCLC. METHODS EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to April 2023 that evaluated the prevalence of ALK, BRAF, EGFR, HER-2, KRAS, MET, NTRK, RET, ROS1 in H/L patients. Meta-analyses were done to determine prevalence using a random effects model. RESULTS Fifty-five articles were included. EGFR and KRAS were the most prevalent genes with high heterogeneity across the countries. The overall mutation frequency for EGFR was 22%. The most frequent mutations in the EGFR gene were del19 (10%) and L858R (7%). The mean of KRAS mutation was a 14% prevalence. KRASG12C was the most frequent mutation with a 7% prevalence in an entire population. The overall frequency of ALK rearrangement was 5%. The mean frequency of ROS-1 rearrangement was 2%, and the frequencies of HER-2, MET, BRAF, RET, NTRK molecular alterations were 4%, 3%, 2%, 2%, and 1% respectively. Almost half of the cases were male, and 65.8% had a history of tobacco exposure. The most common clinical stage was IV. CONCLUSIONS The prevalence of driver mutations such as EGFR and KRAS in LA populations differs from what is reported in Asians and Europeans. In the present article, countries with a high proportion of Amerindian ancestry show a greater prevalence of EGFR in contrast to countries with a high proportion of Caucasians. Lack of information on some countries or studies with a small sample size affects the real prevalence data for the region.
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Affiliation(s)
- Rafael Parra-Medina
- Research Institute, Fundación Universitaria de Ciencias de la Salud - FUCS, Bogotá, Colombia; Department of Pathology, Fundación Universitaria de Ciencias de la Salud - FUCS, Bogotá, Colombia; Department of Pathology, Instituto Nacional de Cancerología, Bogotá, Colombia.
| | - Juan Pablo Castañeda-González
- Research Institute, Fundación Universitaria de Ciencias de la Salud - FUCS, Bogotá, Colombia; Department of Pathology, Fundación Universitaria de Ciencias de la Salud - FUCS, Bogotá, Colombia
| | - Luisa Montoya
- Department of Clinical Epidemiology and Biostatistics, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - María Paula Gómez-Gómez
- Department of Pathology, Fundación Universitaria de Ciencias de la Salud - FUCS, Bogotá, Colombia
| | - Daniel Clavijo Cabezas
- Department of Pathology, Fundación Universitaria de Ciencias de la Salud - FUCS, Bogotá, Colombia
| | - Merideidy Plazas Vargas
- Department of Epidemiology, Fundación Universitaria de Ciencias de la Salud - FUCS, Bogotá, Colombia
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Lam DCL, Liam CK, Andarini S, Park S, Tan DSW, Singh N, Jang SH, Vardhanabhuti V, Ramos AB, Nakayama T, Nhung NV, Ashizawa K, Chang YC, Tscheikuna J, Van CC, Chan WY, Lai YH, Yang PC. Lung Cancer Screening in Asia: An Expert Consensus Report. J Thorac Oncol 2023; 18:1303-1322. [PMID: 37390982 DOI: 10.1016/j.jtho.2023.06.014] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 05/23/2023] [Accepted: 06/10/2023] [Indexed: 07/02/2023]
Abstract
INTRODUCTION The incidence and mortality of lung cancer are highest in Asia compared with Europe and USA, with the incidence and mortality rates being 34.4 and 28.1 per 100,000 respectively in East Asia. Diagnosing lung cancer at early stages makes the disease amenable to curative treatment and reduces mortality. In some areas in Asia, limited availability of robust diagnostic tools and treatment modalities, along with variations in specific health care investment and policies, make it necessary to have a more specific approach for screening, early detection, diagnosis, and treatment of patients with lung cancer in Asia compared with the West. METHOD A group of 19 advisors across different specialties from 11 Asian countries, met on a virtual Steering Committee meeting, to discuss and recommend the most affordable and accessible lung cancer screening modalities and their implementation, for the Asian population. RESULTS Significant risk factors identified for lung cancer in smokers in Asia include age 50 to 75 years and smoking history of more than or equal to 20 pack-years. Family history is the most common risk factor for nonsmokers. Low-dose computed tomography screening is recommended once a year for patients with screening-detected abnormality and persistent exposure to risk factors. However, for high-risk heavy smokers and nonsmokers with risk factors, reassessment scans are recommended at an initial interval of 6 to 12 months with subsequent lengthening of reassessment intervals, and it should be stopped in patients more than 80 years of age or are unable or unwilling to undergo curative treatment. CONCLUSIONS Asian countries face several challenges in implementing low-dose computed tomography screening, such as economic limitations, lack of efforts for early detection, and lack of specific government programs. Various strategies are suggested to overcome these challenges in Asia.
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Affiliation(s)
- David Chi-Leung Lam
- Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Chong-Kin Liam
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Sita Andarini
- Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia - Persahabatan Hospital, Jakarta, Indonesia
| | - Samina Park
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Daniel S W Tan
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore; Division of Medical Oncology, National Cancer Centre Singapore, Duke-NUS Medical School, Singapore
| | - Navneet Singh
- Lung Cancer Clinic, Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Seung Hun Jang
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Varut Vardhanabhuti
- Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, People's Republic of China
| | - Antonio B Ramos
- Department of Thoracic Surgery and Anesthesia, Lung Center of the Philippines, Quezon City, Philippines
| | - Tomio Nakayama
- Division of Screening Assessment and Management, National Cancer Center Institute for Cancer Control, Japan
| | - Nguyen Viet Nhung
- Vietnam National Lung Hospital, University of Medicine and Pharmacy, VNU Hanoi, Vietnam
| | - Kazuto Ashizawa
- Department of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Yeun-Chung Chang
- Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jamsak Tscheikuna
- Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | | | - Wai Yee Chan
- Imaging Department, Gleneagles Hospital Kuala Lumpur, Jalan Ampang, 50450 Kuala Lumpur; Department of Biomedical Imaging, University of Malaya, Kuala Lumpur, Malaysia
| | - Yeur-Hur Lai
- School of Nursing, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Nursing, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Pan-Chyr Yang
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan & National Taiwan University Hospital, Taipei, Taiwan.
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Leiter A, Veluswamy RR, Wisnivesky JP. The global burden of lung cancer: current status and future trends. Nat Rev Clin Oncol 2023; 20:624-639. [PMID: 37479810 DOI: 10.1038/s41571-023-00798-3] [Citation(s) in RCA: 446] [Impact Index Per Article: 223.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/20/2023] [Indexed: 07/23/2023]
Abstract
Lung cancer is the leading cause of cancer-related death worldwide. However, lung cancer incidence and mortality rates differ substantially across the world, reflecting varying patterns of tobacco smoking, exposure to environmental risk factors and genetics. Tobacco smoking is the leading risk factor for lung cancer. Lung cancer incidence largely reflects trends in smoking patterns, which generally vary by sex and economic development. For this reason, tobacco control campaigns are a central part of global strategies designed to reduce lung cancer mortality. Environmental and occupational lung cancer risk factors, such as unprocessed biomass fuels, asbestos, arsenic and radon, can also contribute to lung cancer incidence in certain parts of the world. Over the past decade, large-cohort clinical studies have established that low-dose CT screening reduces lung cancer mortality, largely owing to increased diagnosis and treatment at earlier disease stages. These data have led to recommendations that individuals with a high risk of lung cancer undergo screening in several economically developed countries and increased implementation of screening worldwide. In this Review, we provide an overview of the global epidemiology of lung cancer. Lung cancer risk factors and global risk reduction efforts are also discussed. Finally, we summarize lung cancer screening policies and their implementation worldwide.
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Affiliation(s)
- Amanda Leiter
- Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Rajwanth R Veluswamy
- Division of Hematology and Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Juan P Wisnivesky
- Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Mosegui GBG, Vianna CMDM, Antoñanzas Villar F, Rodrigues MPDS. Perda de Produtividade Atribuída a Neoplasias na América do Sul. REVISTA BRASILEIRA DE CANCEROLOGIA 2023. [DOI: 10.32635/2176-9745.rbc.2023v69n1.3289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023] Open
Abstract
Introdução: A carga da doença tem sido empregada em estimativas do impacto das neoplasias, mas a perda de produtividade em razão dessas enfermidades ainda não foi tão explorada. Objetivo: Estimar os anos de vida produtiva perdidos (AVPP) e a perda de produtividade por conta da mortalidade prematura relacionada ao câncer em países da América do Sul em 2019. Método: Dados de mortalidade disponíveis no Global Burden of Disease (GBD) Study 2019 foram usados para estimar a carga de doença atribuível a neoplasias. A perda de produtividade em termos monetários foi calculada usando um proxy da abordagem do capital humano (ACH). Os cálculos foram realizados por sexo, nas faixas etárias de trabalho. Resultados: O total de óbitos foi de 192.240 e o de AVPP, 2.463.155. A perda total de produtividade permanente foi de US$ 4,4 bilhões e US$ 9,4 bilhões em purchasing power parity (PPP) – 0,13% do produto interno bruto (PIB) da região. O custo total por morte foi de US$ 23.617. Houve diferenças significativas entre os países, mas a variação dos cenários mostra robustez das estimativas. Conclusão: O câncer impõe um ônus econômico significativo à América do Sul tanto em termos de saúde quanto de produtividade. Sua caracterização pode subsidiar os governos na alocação de recursos destinados ao planejamento de políticas e execução de intervenções de saúde.
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Boyeras I, Roberti J, Seijo M, Suárez V, Morero JL, Patané AK, Kaen D, Lamot S, Castro M, Re R, García A, Vujacich P, Videla A, Recondo G, Fernández-Pazos A, Lyons G, Paladini H, Benítez S, Martín C, Defranchi S, Paganini L, Quadrelli S, Rossini S, Garcia Elorrio E, Sobrino E. Argentine consensus recommendations for lung cancer screening programmes: a RAND/UCLA-modified Delphi study. BMJ Open 2023; 13:e068271. [PMID: 36737082 PMCID: PMC9900059 DOI: 10.1136/bmjopen-2022-068271] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 01/16/2023] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Lung cancer (LC) screening improves LC survival; the best screening method in terms of improving survival is low-dose CT (LDCT), outpacing chest X-ray and sputum cytology. METHODS A consensus of experts in Argentina was carried out to review the literature and generate recommendations for LC screening programmes. A mixed-method study was used with three phases: (1) review of the literature; (2) modified Delphi consensus panel; and (3) development of the recommendations. The Evidence to Decision (EtD) framework was used to generate 13 evaluation criteria. Nineteen experts participated in four voting rounds. Consensus among participants was defined using the RAND/UCLA method. RESULTS A total of 16 recommendations scored ≥7 points with no disagreement on any criteria. Screening for LC should be performed with LDCT annually in the population at high-risk, aged between 55 and 74 years, regardless of sex, without comorbidities with a risk of death higher than the risk of death from LC, smoking ≥30 pack-years or former smokers who quit smoking within 15 years. Screening will be considered positive when finding a solid nodule ≥6 mm in diameter (or ≥113 mm3) on baseline LDCT and 4 mm in diameter if a new nodule is identified on annual screening. A smoking cessation programme should be offered, and cardiovascular risk assessment should be performed. Institutions should have a multidisciplinary committee, have protocols for the management of symptomatic patients not included in the programme and distribute educational material. CONCLUSION The recommendations provide a basis for minimum requirements from which local institutions can develop their own protocols adapted to their needs and resources.
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Affiliation(s)
- Iris Boyeras
- Angel Roffo Oncology Institute, Universtiy of Buenos Aires, Buenos Aires, Argentina
| | - Javier Roberti
- Department of Healthcare Quality and Patient Safety, Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina
- Centre for Research in Epidemiology and Public Health (CIESP), CONICET, Buenos Aires, Buenos Aires, Argentina
| | - Mariana Seijo
- Department of Healthcare Quality and Patient Safety, Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina
| | - Verónica Suárez
- Pneumonology Service, Clínica Bazterrica, Buenos Aires, Argentina
| | | | | | - Diego Kaen
- Hospital de Clínicas Virgen María de Fátima, National University of La Rioja, La Rioja, Argentina
| | | | - Mónica Castro
- Angel Roffo Oncology Institute, Universtiy of Buenos Aires, Buenos Aires, Argentina
| | - Ricardo Re
- Center for Medical Education and Clinical Research Norberto Quirno (CEMIC), Buenos Aires, Argentina
| | - Artemio García
- Prof. Posadas National Hospital, El Palomar, Buenos Aires, Argentina
- British Hospital of Buenos Aires, Buenos Aires, Federal District, Argentina
| | - Patricia Vujacich
- Hospital de Clínicas José de San Martín, University of Buenos Aires, Buenos Aires, Argentina
| | | | - Gonzalo Recondo
- Center for Medical Education and Clinical Research Norberto Quirno (CEMIC), Buenos Aires, Argentina
| | | | - Gustavo Lyons
- British Hospital of Buenos Aires, Buenos Aires, Federal District, Argentina
| | - Hugo Paladini
- Medical Images Service MIT Group, Santa Fe, Argentina
| | - Sergio Benítez
- Hospital Zonal Juan Ramón Carrillo, San Carlos de Bariloche, Río Negro, Argentina
| | - Claudio Martín
- Alexander Fleming Institute, Buenos Aires, Argentina
- Municipal Hospital María Ferrer, Buenos Aires, Argentina
| | - Sebastián Defranchi
- Favaloro Foundation University Hospital, Buenos Aires, Federal District, Argentina
| | | | - Silvia Quadrelli
- British Hospital of Buenos Aires, Buenos Aires, Federal District, Argentina
- Sanatorio Güemes, Buenos Aires, Federal District, Argentina
| | | | - Ezequiel Garcia Elorrio
- Department of Healthcare Quality and Patient Safety, Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina
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Ballén DF, Carvajal-Fierro CA, Beltrán R, Alarcón ML, Vallejo-Yepes C, Brugés-Maya R. Survival Outcomes of Metastatic Non-small Cell Lung Cancer Patients With Limited Access to Immunotherapy and Targeted Therapy in a Cancer Center of a Low- and Middle-Income Country. Cancer Control 2023; 30:10732748231189785. [PMID: 37537995 PMCID: PMC10403982 DOI: 10.1177/10732748231189785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023] Open
Abstract
OBJECTIVE To describe the survival outcomes of metastatic non-small cell lung cancer patients with limited access to immunotherapy and targeted therapy in a cancer reference center in Colombia. METHODS A retrospective analysis of metastatic non-small cell lung cancer patients treated between 2013 and 2018 was performed, majority diagnosed with adenocarcinoma. It was carried out in a public cancer reference center that provides care to patients of low and middle socioeconomic status. Overall survival and progression-free survival were evaluated by Kaplan-Meier analysis and log-rank test. A Cox regression model was performed for univariate and multivariate analysis. RESULTS 209 patients were included with majority of adenocarcinoma (79.5%). First-line treatment was cytotoxic chemotherapy (50.2%), EGFR-targeted therapy (14.8%), chemoimmunotherapy (1.9%), and ALK-targeted therapy (1.4%). 31.6% received best supportive care. Median time of follow-up was 13 months, median overall survival was 11.2 months (95% CI, 7.9-14.4), 13 months for adenocarcinoma (95% CI, 8.1-17.9), and 2.5 months for squamous cell carcinoma (95% CI, 0.6-4.4) (P < .001). Median progression-free survival was 9.3 months (95% CI, 7.9-10.7) without differences according to the type of first-line therapy. Median time-to-treatment was 55 days and only 54% of patients with a tested actionable mutation in EGFR received an EGFR-targeted therapy as the first-line treatment. Multivariate analysis showed that squamous cell carcinoma histology and receiving best supportive care were independent factors for worse overall survival ((HR:1.8, 95% CI, 1.076-3.082, P=.026) and (HR:14.6, 95% CI, 8.921-24.049, P < .001), respectively). Meanwhile, squamous cell carcinoma histology was an independent factor for worse progression-free survival (HR:3.4, 95% CI, 1.540-7.464, P=.002). CONCLUSIONS Despite advances in precision medicine, during the study period, cytotoxic chemotherapy was the most used treatment in our patients. Furthermore, about a third of them received best supportive care. The use of targeted therapies has been restricted by access to molecular diagnosis and remained low until 2018. Access to immunotherapy should be prioritized.
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Affiliation(s)
- Diego-Felipe Ballén
- Clinical Oncologist, Instituto Nacional de Cancerología, Bogotá, Colombia. Clinical Professor, Department of Internal Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Carlos Andrés Carvajal-Fierro
- Thoracic Surgeon, Instituto Nacional de Cancerología, Bogotá, Colombia. Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo (CTIC), Bogotá, Colombia
| | - Rafael Beltrán
- Thoracic Surgeon, Instituto Nacional de Cancerología, Bogotá, Colombia
| | | | | | - Ricardo Brugés-Maya
- Clinical Oncologist, Instituto Nacional de Cancerología, Bogotá, Colombia. Clinical Professor, Department of Internal Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia
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Pan YQ, Xiao Y, Li Z, Tao L, Chen G, Zhu JF, Lv L, Liu JC, Qi JQ, Shao A. Comprehensive analysis of the significance of METTL7A gene in the prognosis of lung adenocarcinoma. Front Oncol 2022; 12:1071100. [PMID: 36620541 PMCID: PMC9817104 DOI: 10.3389/fonc.2022.1071100] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 11/18/2022] [Indexed: 12/25/2022] Open
Abstract
Background The most common subtype of lung cancer, called lung adenocarcinoma (LUAD), is also the largest cause of cancer death in the world. The aim of this study was to determine the importance of the METTL7A gene in the prognosis of patients with LUAD. Methods This particular study used a total of four different LUAD datasets, namely TCGA-LUAD, GSE32863, GSE31210 and GSE13213. Using RT-qPCR, we were able to determine METTL7A expression levels in clinical samples. Univariate and multivariate Cox regression analyses were used to identify factors with independent effects on prognosis in patients with LUAD, and nomograms were designed to predict survival in these patients. Using gene set variation analysis (GSVA), we investigated differences in enriched pathways between METTL7A high and low expression groups. Microenvironmental cell population counter (MCP-counter) and single-sample gene set enrichment analysis (ssGSEA) methods were used to study immune infiltration in LUAD samples. Using the ESTIMATE technique, we were able to determine the immune score, stromal score, and estimated score for each LUAD patient. A competing endogenous RNA network, also known as ceRNA, was established with the help of the Cytoscape program. Results We detected that METTL7A was down-regulated in pan-cancer, including LUAD. The survival study indicates that METTL7A was a protective factor in the prognosis of LUAD. The univariate and multivariate Cox regression analyses revealed that METTL7A was a robust independent prognostic indicator in survival prediction. Through the use of GSVA, several immune-related pathways were shown to be enriched in both the high-expression and low-expression groups of METTL7A. Analysis of the tumor microenvironment revealed that the immune microenvironment of the group with low expression was suppressed, which may be connected to the poor prognosis. To explore the ceRNA regulatory mechanism of METTL7A, we finally constructed a regulatory network containing 1 mRNA, 2 miRNAs, and 5 long non-coding RNAs (lncRNAs). Conclusion In conclusion, we presented METTL7A as a potential and promising prognostic indicator of LUAD. This biomarker has the potential to offer us with a comprehensive perspective of the prediction of prognosis and treatment for LUAD patients.
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Affiliation(s)
- Ya-Qiang Pan
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Ying Xiao
- Department of Radiation Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhenhua Li
- Department of Thoracic Surgery, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Long Tao
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Ge Chen
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Jing-Feng Zhu
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Lu Lv
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Jian-Chao Liu
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Jun-Qing Qi
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - AiZhong Shao
- Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China,*Correspondence: AiZhong Shao,
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Galvez‐Nino M, Ruiz R, Roque K, Coanqui O, Valdivieso N, Olivera M, Ganti AK, Mas L. Real-world outcomes of anti-EGFR therapy in advanced non-small cell lung cancer EGFR mutated in Peru. Thorac Cancer 2022; 14:61-67. [PMID: 36369763 PMCID: PMC9807447 DOI: 10.1111/1759-7714.14714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 10/17/2022] [Accepted: 10/18/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Despite the advances in the management of advanced non-small cell lung cancer (NSCLC), the access to genetic profiling and target therapies remains a challenge in Latin America, even in countries with a higher rate of targetable mutations. The aim of this study is to evaluate the clinical outcomes of anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) treatment in a Peruvian real-world setting. METHODS This is a retrospective study of recurrent or advanced NSCLC EGFR mutated patients diagnosed and treated with anti-EGFR TKI at Instituto Nacional de Enfermedades Neoplásicas (INEN) between January 1, 2015 to December 31, 2020. The outcomes were objective response rate (ORR), progression free survival (PFS), and overall survival (OS). RESULTS We identify 613 stage IV or recurrent NSCLC patients who were tested for EGFR mutations and found a pathogenic mutation in 39.5% of patients. Only 51.2% of them received anti-EGFR TKI as institutional treatment. ORR was 58%, after median follow-up of 32 months, the estimated median PFS was 13.9 months (11.1-16.7 months), and the estimated median OS was 21.7 months (18.5-24.9 months). No differences were found in PFS according to line of treatment or brain metastases at diagnosis (p = 0.46 and p = 0.07, respectively), respect to OS there were no differences line of treatment (p = 0.12), significant difference were found in presence of brain metastases (p = 0.006). CONCLUSION Our study demonstrates that erlotinib for advanced NSCLC harboring EGFR-activating mutations is effective even in patients usually excluded from clinical trial, like those previously exposed to one or more lines of chemotherapy or with brain metastases.
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Affiliation(s)
- Marco Galvez‐Nino
- Department of Medical OncologyInstituto Nacional de Enfermedades NeoplásicasLimaPeru,Escuela Profesional de Medicina HumanaUniversidad Privada San Juan BautistaLimaPeru
| | - Rossana Ruiz
- Department of Medical OncologyInstituto Nacional de Enfermedades NeoplásicasLimaPeru,Universidad Científica del SurLimaPeru
| | - Katia Roque
- Department of Medical OncologyInstituto Nacional de Enfermedades NeoplásicasLimaPeru,Escuela Profesional de Medicina HumanaUniversidad Privada San Juan BautistaLimaPeru
| | - Ofelia Coanqui
- Department of Medical OncologyInstituto Nacional de Enfermedades NeoplásicasLimaPeru,Escuela Profesional de Medicina HumanaUniversidad Privada San Juan BautistaLimaPeru
| | - Natalia Valdivieso
- Department of Medical OncologyInstituto Nacional de Enfermedades NeoplásicasLimaPeru
| | - Mivael Olivera
- Department of Medical OncologyInstituto Nacional de Enfermedades NeoplásicasLimaPeru
| | - Apar Kishor Ganti
- VA Nebraska Western Iowa Health Care System, University of Nebraska Medical CenterOmahaNebraskaUSA
| | - Luis Mas
- Department of Medical OncologyInstituto Nacional de Enfermedades NeoplásicasLimaPeru,Universidad Peruana Cayetano HerediaLimaPeru
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Muacevic A, Adler JR, Garcia-Rivello H, Jansen AM, Parra Medina R, Stefani SD. BRAF Testing in Melanoma and Colorectal Cancer in Latin America: Challenges and Opportunities. Cureus 2022; 14:e31972. [PMID: 36589179 PMCID: PMC9795961 DOI: 10.7759/cureus.31972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/27/2022] [Indexed: 11/29/2022] Open
Abstract
The incidence of colorectal cancer in Argentina and Brazil has reached levels comparable to those in higher-income countries. Similarly, the incidence of melanoma in Latin America has increased during the past decades. BRAFmutation is seen frequently in melanomas and colorectal cancer. Discovering the expression of this specific biomarker in both cancers has unleashed the potential for targeted molecular therapies.In patients with BRAF-mutated melanoma, adopting a combined targeted treatment approach has shown a dramatic increase in overall survival. However, several barriers impede the development of early BRAF testing in Latin America, jeopardizing the potential for personalized therapies and care. To address this, the Americas Health Foundation convened a virtual meeting of Latin American oncologists to address the barriers to BRAF testing in melanoma and colorectal cancer. During a three-day conference, expert oncologists used literature reviews and personal experience to detail the barriers to early BRAF testing in their region. They proposed actionable steps to overcome the barriers identified, which included deficiencies in knowledge, treatment options, equitable distribution, timely results, and local data on BRAF mutations. Oncologists proposed several actions to overcome barriers, including raising public and healthcare awareness about the importance of BRAF testing, expanding treatment options in clinics across the region, developing centers in underserved areas, and increasing affordable treatment options for patients who test positive for BRAF mutations.
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Giraldo-Osorio A, Ruano-Ravina A, Rey-Brandariz J, Arias-Ortiz N, Candal-Pedreira C, Pérez-Ríos M. [Lung cancer mortality trends in Colombia, 1985-2018Tendências na mortalidade por câncer de pulmão na Colômbia de 1985 a 2018]. Rev Panam Salud Publica 2022; 46:e127. [PMID: 36177300 PMCID: PMC9512683 DOI: 10.26633/rpsp.2022.127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 05/02/2022] [Indexed: 12/03/2022] Open
Abstract
Objetivo. Determinar la evolución de la mortalidad por cáncer de pulmón en Colombia en el período 1985-2018 en la población de 35 años y más e identificar cambios en la tendencia. Métodos. Análisis de series temporales de mortalidad. Se calcularon las tasas específicas y estandarizadas por sexo y grupos de edad. Mediante la regresión joinpoint se estimó el porcentaje de cambio anual de las tasas y se identificaron puntos de cambio. Resultados. En el período 1985-2018 se registraron 105 553 muertes por cáncer de pulmón en la población de 35 años y más. Las tasas estandarizadas muestran una tendencia decreciente en el período 1985-2005, excepto en mayores de 64 años. Conclusiones. La tendencia de las tasas de mortalidad por cáncer de pulmón es decreciente en Colombia. Es necesario potenciar medidas de prevención primaria y secundaria sobre el consumo de tabaco y vigilar otros factores de riesgo como el radón residencial o la ocupación.
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Affiliation(s)
- Alexandra Giraldo-Osorio
- Grupo de Investigación Promoción de la Salud y Prevención de la Enfermedad (GIPSPE) Departamento de Salud Pública, Universidad de Caldas Colombia Grupo de Investigación Promoción de la Salud y Prevención de la Enfermedad (GIPSPE), Departamento de Salud Pública, Universidad de Caldas, Colombia
| | - Alberto Ruano-Ravina
- Área de Medicina Preventiva y Salud Pública Universidad de Santiago de Compostela España Área de Medicina Preventiva y Salud Pública, Universidad de Santiago de Compostela, España
| | - Julia Rey-Brandariz
- Área de Medicina Preventiva y Salud Pública Universidad de Santiago de Compostela España Área de Medicina Preventiva y Salud Pública, Universidad de Santiago de Compostela, España
| | - Nelson Arias-Ortiz
- Registro Poblacional de Cáncer de Manizales Instituto de Investigaciones en Salud Universidad de Caldas Colombia Registro Poblacional de Cáncer de Manizales, Instituto de Investigaciones en Salud, Universidad de Caldas, Colombia
| | - Cristina Candal-Pedreira
- Área de Medicina Preventiva y Salud Pública Universidad de Santiago de Compostela España Área de Medicina Preventiva y Salud Pública, Universidad de Santiago de Compostela, España
| | - Mónica Pérez-Ríos
- Área de Medicina Preventiva y Salud Pública Universidad de Santiago de Compostela España Área de Medicina Preventiva y Salud Pública, Universidad de Santiago de Compostela, España
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Tamí-Maury I, Garcia H, Onigbogi M, Ismael J, Manrique J, Vazquez V, Rojas C, Suchil L. Smoking cessation knowledge and perceptions of cancer care providers at six Latin American cancer institutions. Rev Panam Salud Publica 2022; 46:e121. [PMID: 36177301 PMCID: PMC9512687 DOI: 10.26633/rpsp.2022.121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 06/20/2022] [Indexed: 11/24/2022] Open
Abstract
Objective To assess the characteristics, self-reported tobacco use, knowledge, and perceptions about smoking cessation among cancer care providers (CCPs), as well as perceived barriers to inform interventions that can potentially improve quitting rates and the prognosis of cancer patients in Latin America. Methods A cross-sectional study was conducted among 996 CCPs in six cancer institutions located in Argentina, Brazil, Colombia, Mexico, and Peru. An online survey consisting of 28 close-ended questions adapted from the 2012 International Association for the Study of Lung Cancer survey and the Global Adult Tobacco Survey was administered. Results The majority of CCPs, ranging from 86.1% in Mexico to 95.9% in Brazil, agreed or strongly agreed that smoking cessation should be integrated into cancer treatment. However, inadequate training on smoking cessation was reported by 66.9%, 69.4%, 70.4%, 72.9%, 85.8%, and 86.4% in Mexico, Colombia (Floridablanca), Argentina, Peru, Brazil, and Colombia (Medellín), respectively, and this difference was statistically significant (p < 0.001). Moreover, current cigarette smoking prevalence among CCPs was 2.5% in Brazil, 4.6% in Peru, 6.3% in Colombia (Floridablanca), 10.4% in Colombia (Medellín), 11.5% in Mexico, and 15.1% in Argentina, showing a statistically significant difference (p < 0.001). Conclusions Efforts in Latin America should be geared toward assisting CCPs with their quitting efforts and training in smoking cessation practices aimed at achieving a better prognosis and improving cancer patients' quality of life.
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Affiliation(s)
- Irene Tamí-Maury
- The University of Texas Health Science Center at HoustonHoustonTexasUnited States of AmericaThe University of Texas Health Science Center at Houston, Houston, Texas, United States of America
| | - Hector Garcia
- Cancer Institute Las Americas AunaMedellínColombiaCancer Institute Las Americas Auna, Medellín, Colombia
| | - Modupe Onigbogi
- The University of Texas Health Science Center at HoustonHoustonTexasUnited States of AmericaThe University of Texas Health Science Center at Houston, Houston, Texas, United States of America
| | - Julia Ismael
- National Cancer InstituteBuenos AiresArgentinaNational Cancer Institute, Buenos Aires, Argentina
| | - Javier Manrique
- National Institute of Neoplastic DiseasesLimaPeruNational Institute of Neoplastic Diseases, Lima, Peru
| | | | - Carlos Rojas
- FOSCAL Cancer CenterBucaramangaColombiaFOSCAL Cancer Center, Bucaramanga, Colombia
| | - Laura Suchil
- National Cancer InstituteMexico CityMexicoNational Cancer Institute, Mexico City, Mexico
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21
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Martin CM, Puello‐Guerrero A, Mas‐Lopez LA, Campos‐Gómez S, Orlando‐Orlandi FJ, Tejado Gallegos LF, Huggenberger R. Real-world KINDLE-Latin America subset data on treatment patterns and clinical outcomes in patients with stage III non-small-cell lung cancer. Cancer Med 2022; 12:1247-1259. [PMID: 35789068 PMCID: PMC9883579 DOI: 10.1002/cam4.4990] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 04/13/2022] [Accepted: 04/25/2022] [Indexed: 02/02/2023] Open
Abstract
INTRODUCTION Stage III non-small-cell lung cancer (NSCLC) management is challenging given the heterogeneous nature of the disease. The LATAM subset of the real-world, global KINDLE study reported the treatment patterns and clinical outcomes for LATAM from the pre-immuno-oncology era. METHODS The study was conducted in seven countries (Argentina, Chile, Colombia, Dominican Republic, Mexico, Peru and Uruguay) in stage III NSCLC (American Joint Committee on Cancer, 7th edition) diagnosed between January 2013 and December 2017. Retrospective data from patients' medical records (index date to the end of follow-up) were collected. Summary statistics, Kaplan-Meier survival estimates and a two-sided 95% confidence interval (CI) were provided. Cox proportional hazard model was used for univariate and multi-variate analyses. RESULTS A total of 231 patients was enrolled, the median age was 65.0 years (range 21.0-89.0), 60.6% were males, 76.6% had smoking history, 64.0% had adenocarcinoma and 28.7% underwent curative resection. Multiple treatment regimens (>25) were used; chemotherapy alone was the most common (24.8%). The overall median progression-free survival (mPFS) and median overall survival (mOS) were 14.8 months (95% CI, 12.1-18.6) and 48.6 months (95% CI, 34.7 to not calculable). Significantly better mPFS and mOS were observed for stage IIIA with curative surgery and resectable tumours and stage IIIB with an Eastern Cooperative Oncology Group score of 0/1, female gender, resectable tumours, adenocarcinoma and curative surgery (p < 0.05). CONCLUSION Results show diversity in treatment practices and the corresponding clinical outcomes in stage III NSCLC. There is a need to streamline treatment selection and sequencing to decrease relapse rates after initial therapy.
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Affiliation(s)
| | - Adrián Puello‐Guerrero
- Universidad Autónoma de Santo Domingo (UASD), Instituto Nacional del Cáncer (INCART)Santo DomingoDominican Republic
| | | | - Saul Campos‐Gómez
- Centro Oncológico EstatalInstituto de Seguridad Social del Estado de México y MunicipiosTolucaMexico
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22
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Arrieta O, Zatarain-Barrón ZL, Cardona AF, Corrales L, Martin C, Cuello M. Uniting Latin America Through Research: How Regional Research Can Strengthen Local Policies, Networking, and Outcomes for Patients With Lung Cancer. Am Soc Clin Oncol Educ Book 2022; 42:1-7. [PMID: 35503985 DOI: 10.1200/edbk_349951] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Lung cancer represents a considerable global health threat, leading the list in terms of cancer-related deaths worldwide. An important proportion of lung cancer cases occur within Latin America, and current projections show that over the next decade, the number of deaths due to lung cancer will double in the region, underscoring the need to implement evidence-based interventions to improve outcomes. Several challenges have limited the progress in lung cancer research in Latin America for many years, though recently the surge of multidisciplinary, transnational, and transcultural research groups have overcome many of these limitations. The increase in region-specific knowledge has improved cancer care in the area, providing clinicians with a specific demographic and molecular profile for Hispanic patients with lung cancer; as a result, the implementation of precision oncology has benefited from a profound knowledge of the patient profile. Nonetheless, there are still challenges to improve research in Latin America, including stabilizing funding sources to continue independent research, supporting mentoring programs and an early immersion in clinical research for early career fellows, and overcoming barriers for publishing.
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Affiliation(s)
- Oscar Arrieta
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
| | | | - Andrés F Cardona
- Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center (CTIC), Bogotá, Colombia
| | - Luis Corrales
- Clinical Oncology Department, Centro de Investigaciones y Manejo del Cancer, San Jose, Costa Rica
| | - Claudio Martin
- Thoracic Oncology Unit, Instituto Fleming, Buenos Aires, Argentina
| | - Mauricio Cuello
- Medical Oncology Department, Hospital de Clinica, Universidad de la Republica, Montevideo, Uruguay
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23
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Abstract
We estimated cancer mortality statistics for the current year in seven major Latin American countries, with a focus on colorectal cancer. We retrieved official death certification data and population figures from the World Health Organization and the Pan American Health Organization databases. We analysed mortality from all neoplasms combined and for selected cancer sites. We estimated numbers of deaths and age-standardized mortality rates for the year 2021 using a logarithmic Poisson count data joinpoint model. Total cancer mortality is predicted to decline in all countries considered for both sexes, with the exception of Argentinian women. The lowest total mortality rates were predicted in Mexico (65.4/100 000 men and 62.3 in women), the highest ones were in Cuba (133.3/100 000 men and 91.0 in women). Stomach cancer rates have been decreasing since 1970 in all countries; colorectal cancer started to decline over recent calendar periods. Rates for this cancer were unfavourable in the youngest age group. Lung cancer trends declined in males and remained comparatively low in all countries except Cuba. In Cuba, lung cancer rates in women overtook those for breast. Mortality from cancers of the breast, (cervix) uterus, ovary, prostate and bladder, as well as leukemia mostly showed favourable trends. A marked variability in rates across Latin American countries persists, and rates were relatively high for stomach, uterus, prostate and lung cancers, as compared to Europe and North America, suggesting the need to improve preventive strategies. Colorectal cancer mortality was relatively low in Latin America, except in Argentina, and short-term predictions remain moderately favourable.
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24
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Rivas S, Armisén R. El cáncer de pulmón de células no pequeñas en la era de la medicina de precisión. REVISTA MÉDICA CLÍNICA LAS CONDES 2022. [DOI: 10.1016/j.rmclc.2022.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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25
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Fuchs-Tarlovsky V, Castillo Pineda JC, Rodríguez Veintimilla D, Calvo Higuera I, Grijalva Guerrero P, Gómez García A, Frias-Toral E, Santana Porbén S. Cancer-Related Malnutrition: Epidemiological Results from the Latin American Study of Malnutrition in the Oncology Practice. Nutr Cancer 2021; 74:2479-2488. [PMID: 34930068 DOI: 10.1080/01635581.2021.2014902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Malnutrition can affect the patient diagnosed with, and treated for, cancer. However, until a dedicated study is completed, estimates of malnutrition rates will be disparate and unrepresentative of cancer patients' nutritional reality. Objective: To estimate the prevalence of malnutrition among patients being cared for cancer in Latin American (LATAM) hospitals by means of a multicenter, multinational study. Methods: The Latin American Study of Malnutrition in Oncology (LASOMO) was completed with 1,842 patients (Women: 56.2%; Age ≥ 60 years: 43.2%; Chemotherapy: 55.1%; Radiotherapy: 17.8%; Surgery: 27.1%) assisted at 52 health centers from 10 LATAM countries. Malnutrition prevalence was estimated from the (B + C) scores assigned to the patient with the Subjective Global Assessment by Detsky et al. (1987). Malnutrition prevalence was distributed regarding the demographic features of the patient, the primary tumor location, and the current cytoreducing treatment. Results: Malnutrition affected 59.1% of the surveyed patients. Malnutrition prevalence was higher among male patients and those with tumors of the digestive tract and the hemolymphopoietic system. Malnutrition was also associated with the current cytoreducing modality, with chemotherapy returning the highest prevalence. Conclusions: Malnutrition can be present in more than half of the patients being cared for cancer in LATAM health centers. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.2014902.
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Affiliation(s)
- Vanessa Fuchs-Tarlovsky
- Servicio de Nutrición Clínica, Hospital General de México "Dr. Eduardo Liceaga", Ciudad México, México
| | | | - Dolores Rodríguez Veintimilla
- Sociedad de Lucha contra el Cáncer, Guayaquil, Guayas, Ecuador.,Federación Latinoamericana de Terapia Nutricional, Nutrición Clínica y Metabolismo
| | | | | | - Anel Gómez García
- Centro de Investigación Biomédica, Michoacán, Instituto Mexicano del Seguro Social, Ciudad México, México
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26
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Martin C, Cuello M, Barajas O, Recondo G, Aruachan S, Perroud H, Sena S, Bonilla C, Orlandi F, Berutti S, Garcia Cocco V, Gomez A, Korbenfeld E, Zapata M, Cundom J, Orellana E, Goncalves S, Reinhold F. Real-world evaluation of molecular testing and treatment patterns for EGFR mutations in non-small cell lung cancer in Latin America. Mol Clin Oncol 2021; 16:6. [PMID: 34881026 PMCID: PMC8647188 DOI: 10.3892/mco.2021.2439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 09/08/2021] [Indexed: 12/24/2022] Open
Abstract
Lung cancer is a leading cause of cancer-related deaths in Latin America, with non-small cell lung cancer (NSCLC) being the most prevalent. The current study aimed to report real-world data on epidermal growth factor receptor (EGFR) mutational testing and treatment regimens at diagnosis and progression in patients with metastatic NSCLC across four Latin American countries (Argentina, Chile, Colombia and Uruguay). A retrospective, multicenter, observational study was conducted in patients with NSCLC using medical records from participating countries. The study population was categorized into two cohorts: Cohort 1 comprised of newly diagnosed, treatment-naïve patients with stage IV NSCLC; and cohort 2 comprised of stage IV NSCLC EGFR mutation (EGFRm)-positive patients who had progressed after first- or second-generation EGFR-tyrosine kinase inhibitor (TKI) treatment. Measures included demographic variables, health characteristics, treatment regimen, molecular testing rate and turnaround time at diagnosis and at progression for cohorts 1 and 2, respectively. Descriptive statistics were used to summarize all study measures. Of the 462 patients enrolled, 431 were newly diagnosed or treatment naïve with metastatic NSCLC. In cohort 1, the majority of patients with private health insurance (57.31%) underwent molecular diagnosis while only 41.3% of patients within the public sector had access to testing. The average molecular testing rate in cohort 1 varied across countries, with Argentina having the highest testing rate (79%) and Uruguay the lowest (27.63%). EGFRm was observed in 22% of patients. Cohort 2 comprised 31 patients who had progressed after first- or second-generation EGFR-TKI treatment and of these, only 22 (70.97%) underwent testing after progression. Access to molecular testing is still a challenge impacting the choice of first-line treatment in Latin American patients with NSCLC. These findings underline the unmet needs of ensuring early diagnosis, molecular profiling and use of correct treatment to alleviate NSCLC burden in the region.
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Affiliation(s)
- Claudio Martin
- Department of Clinical Oncology, Institute Alexander Fleming, Buenos Aires C1426ANZ, Argentina
| | - Mauricio Cuello
- Department of Oncology, Hospital of Clinics, Montevideo 11600, Uruguay
| | - Olga Barajas
- Department of Medical Oncology, Arturo Lopez Perez Foundation, Santiago 7500000, Chile
| | - Gonzalo Recondo
- Department of Thoracic Oncology, Medical education and Clinical Research Centre, University Institute (CEMIC), Buenos Aires C1431FWO, Argentina
| | - Sandra Aruachan
- Department of Clinical Oncology, High Technology Medical Institute Oncomedica, Monteria 23001, Colombia
| | - Herman Perroud
- Department of Clinical Oncology, Women's Health Centre, Rosario 2000, Argentina
| | - Susana Sena
- Department of Clinical Oncology; German Hospital, Buenos Aires PC C1118AAT, Argentina
| | - Carlos Bonilla
- Clinical Oncology Unit, National Cancer Institute of Colombia, Bogotá 110411, Colombia
| | - Francisco Orlandi
- Department of Clinical Oncology, Orlandi Oncology, Providencia 7500713, Chile
| | - Susana Berutti
- Department of Clinical Oncology, Italian Hospital of La Plata, La Plata B1900AXI, Argentina
| | | | - Alvaro Gomez
- Department of Medical Oncology, Hemato-oncologos SA, Cali 760042, Colombia
| | - Ernesto Korbenfeld
- Department of Medical Oncology, British Hospital of Buenos Aires, Buenos Aires C1280AEB, Argentina
| | - Maycos Zapata
- Department of Medical Oncology, Cancer Institute Las Americas, Antioquia 050025, Colombia
| | - Juan Cundom
- Department of Medical Oncology, Lanari Institute, University of Buenos Aires, Buenos Aires C1427ARN, Argentina
| | - Eric Orellana
- Department of Clinical Oncology, Clinic Santa Maria, Santiago 7500000, Chile
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27
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Angel MO, Pupareli C, Soule T, Tsou F, Leiva M, Losco F, Esteso F, O Connor JM, Luca R, Petracci F, Girotti R, Mahmoud YD, Martín C, Chacón M. Implementation of a molecular tumour board in LATAM: the impact on treatment decisions for patients evaluated at Instituto Alexander Fleming, Argentina. Ecancermedicalscience 2021; 15:1312. [PMID: 35047063 PMCID: PMC8723751 DOI: 10.3332/ecancer.2021.1312] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND The role of the molecular tumour board (MTB) is to recommend personalised therapy for patients with cancer beyond standard-of-care treatment. A comprehensive molecular analysis of the tumour in a molecular pathology laboratory is important for all targeted therapies approaches. Here we report the 1-year experience of the Instituto Alexander Fleming Molecular Tumour Board. PATIENTS AND METHODS The MTB of the Instituto Alexander Fleming was launched in December 2019 in a monthly meeting. In each interactive monthly session, five cases were presented and discussed by the members. These cases were referred by the treating oncologists. The MTB recommendations were sent to each physician individually, and to the rest of the meeting participants. This was discussed with the patients/families by the treating oncologist. The final decision to choose therapy was left to the treating physicians. Of the 32 patients presented at MTB, 28 (87.5%) had potentially actionable alterations and only 4 (12.5%) had no actionable mutation. Six (19%) patients received a local regulatory agency approved drug recommendation, nine (28%) patients received an off-label approval treatment recommendation and three (9%) patients did not receive the treatment due to access and reimbursement of the drug. CONCLUSION In most of the cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. Molecular-guided extended personalised patient care is effective for a small but clinically significant proportion of patients in challenging clinical situations. We believe that the implementation of a MTB is feasible in the Latin America (LATAM) region.
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Affiliation(s)
- Martín Osvaldo Angel
- Genitourinary Oncology Unit, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
- https://orcid.org/0000-0002-1463-8887
| | - Carmen Pupareli
- Thoracic Oncology Unit, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
| | - Tomas Soule
- Sarcoma and Melanoma Oncology Unit, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
| | - Florencia Tsou
- Thoracic Oncology Unit, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
- https://orcid.org/0000-0002-0322-0434
| | - Mariano Leiva
- Head and Neck Oncology Unit, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
| | - Federico Losco
- Genitourinary Oncology Unit, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
- https://orcid.org/0000-0001-5084-3012
| | - Federico Esteso
- Gastrointestinal Oncology Unit, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
- https://orcid.org/0000-0003-1977-9846
| | - Juan Manuel O Connor
- Gastrointestinal Oncology Unit, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
- https://orcid.org/0000-0002-6975-5466
| | - Romina Luca
- Gastrointestinal Oncology Unit, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
| | - Fernando Petracci
- Breast Cancer Unit, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
- https://orcid.org/0000-0002-7701-3331
| | - Romina Girotti
- Laboratorio de Inmuno-Oncología Traslacional, Instituto de Biología y Medicina Experimental (IBYME), Vuelta de Obligado 2490, Ciudad Autonoma de Buenos Aires, C1428ADN, Argentina
| | - Yamil Damián Mahmoud
- Laboratorio de Inmuno-Oncología Traslacional, Instituto de Biología y Medicina Experimental (IBYME), Vuelta de Obligado 2490, Ciudad Autonoma de Buenos Aires, C1428ADN, Argentina
- https://orcid.org/0000-0001-7254-5892
| | - Claudio Martín
- Thoracic Oncology Unit, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
- https://orcid.org/0000-0003-4135-7332
| | - Matías Chacón
- Clinical Oncology, Instituto Alexander Fleming, Cramer 1180, Ciudad Autonoma de Buenos Aires, C1426ANZ, Argentina
- https://orcid.org/0000-0001-6872-4185
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28
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Sotelo MJ, Luis García J, Torres-Mattos C, Milián H, Carracedo C, González-Ruiz MÁ, Mielgo-Rubio X, Trujillo-Reyes JC, Couñago F. Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer. World J Clin Oncol 2021; 12:912-925. [PMID: 34733613 PMCID: PMC8546659 DOI: 10.5306/wjco.v12.i10.912] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 07/29/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Patients with early-stage non-small-cell lung cancer (NSCLC) are candidates for curative surgery; however, despite multiple advances in lung cancer management, recurrence rates remain high. Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival (OS), but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients. The high efficacy of tyrosine kinase inhibitors (TKIs) against epidermal growth factor receptor-mutated (EGFR) in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease. Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment, in patients with resected EGFR-mutated NSCLC, and shown that they significantly prolong disease-free survival (DFS), but this benefit does not translate to OS. Recently, an interim analysis of the ADAURA trial demonstrated that, surprisingly, osimertinib improved DFS. This led to the study being stopped early, leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup. These targeted agents are also being evaluated in locally-advanced disease, with promising results, although prospective studies with larger sample sizes are needed to confirm these results. In this article, we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.
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Affiliation(s)
- Miguel J Sotelo
- Department of Medical Oncology, Hospital María Auxiliadora; Department of Medical Oncology, Centro Oncológico Aliada; Oncological Research Unit, Clínica San Gabriel, Lima 15801, Peru
| | - José Luis García
- Department of Thoracic Surgery, Hospital Universitario La Princesa; Department of Thoracic Surgery, MD Anderson Cancer Center; Department of Thoracic Surgery, Hospital HM, Madrid 28006, Spain
| | - Cesar Torres-Mattos
- Department of Medical Oncology, Hospital Nacional Guillermo Almenara; Oncological Research Unit, Clínica San Gabriel, Lima 15033, Peru
| | - Héctor Milián
- Department of Thoracic Surgery, Hospital Universitario La Princesa, Madrid 28006, Spain
| | - Carlos Carracedo
- Department of Medical Oncology, Centro Oncológico Aliada, Lima 15036, Peru
| | | | - Xabier Mielgo-Rubio
- Department of Oncology, Hospital Universitario Fundación Alcorcón, Alcorcón 28922, Madrid, Spain
| | | | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid; Hospital La Luz; Universidad Europea de Madrid, Madrid 28223, Spain
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Wu L, Wen Z, Song Y, Wang L. A novel autophagy-related lncRNA survival model for lung adenocarcinoma. J Cell Mol Med 2021; 25:5681-5690. [PMID: 33987935 PMCID: PMC8184679 DOI: 10.1111/jcmm.16582] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 04/09/2021] [Accepted: 04/19/2021] [Indexed: 12/12/2022] Open
Abstract
Long non‐coding RNA (lncRNA) is an important regulatory factor in the development of lung adenocarcinoma, which is related to the control of autophagy. LncRNA can also be used as a biomarker of prognosis in patients with lung adenocarcinoma. Therefore, it is important to determine the prognostic value of autophagy‐related lncRNA in lung adenocarcinoma. In this study, autophagy‐related mRNAs‐lncRNAs were screened from lung adenocarcinoma and a co‐expression network of autophagy‐related mRNAs‐lncRNAs was constructed by using The Cancer Genome Atlas (TCGA). The univariate and multivariate Cox proportional hazard analyses were used to evaluate the prognostic value of the autophagy‐related lncRNAs and finally obtained a survival model composed of 11 autophagy‐related lncRNAs. Through Kaplan‐Meier analysis, univariate and multivariate Cox regression analysis and time‐dependent receiver operating characteristic (ROC) curve analysis, it was further verified that the survival model was a new independent prognostic factor for patients with lung adenocarcinoma. In addition, based on the survival model, gene set enrichment analysis (GSEA) was used to illustrate the function of genes in low‐risk and high‐risk groups. These 11 lncRNAs were GAS6‐AS1, AC106047.1, AC010980.2, AL034397.3, NKILA, AL606489.1, HLA‐DQB1‐AS1, LINC01116, LINC01806, FAM83A‐AS1 and AC090559.1. The hazard ratio (HR) of the risk score was 1.256 (1.196‐1.320) (P < .001) in univariate Cox regression analysis and 1.215 (1.149‐1.286) (P < .001) in multivariate Cox regression analysis. And the AUC value of the risk score was 0.809. The 11 autophagy‐related lncRNA survival models had important predictive value for the prognosis of lung adenocarcinoma and may become clinical autophagy‐related therapeutic targets.
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Affiliation(s)
- Liwei Wu
- Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Zilu Wen
- Department of Scientific Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yanzheng Song
- Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.,TB Center, Shanghai Emerging & Re-emerging Infectious Diseases Institute, Shanghai, China
| | - Lin Wang
- Department of Thoracic Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
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30
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Lara Gongora AB, Werutsky G, Jardim DL, Nogueira-Rodrigues A, Barrios CH, Mathias C, Maluf F, Riechelmann R, Fraga M, Gomes H, William WN, Yamada CAF, de Castro Jr G, Rosa DD, de Melo AC, Sala R, Bustamante E, Bretel D, Arrieta O, Cardona AF, Bastos DA. Impact of the COVID-19 Pandemic on Oncology Clinical Research in Latin America (LACOG 0420). JCO Glob Oncol 2021; 7:649-658. [PMID: 33956499 PMCID: PMC8162498 DOI: 10.1200/go.20.00663] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 03/01/2021] [Accepted: 04/06/2021] [Indexed: 01/08/2023] Open
Abstract
PURPOSE COVID-19 has affected cancer care worldwide. Clinical trials are an important alternative for the treatment of oncologic patients, especially in Latin America, where trials can be the only opportunity for some of them to access novel and, sometimes, standard treatments. METHODS This was a cross-sectional study, in which a 22-question survey regarding the impact of the COVID-19 pandemic on oncology clinical trials was sent to 350 representatives of research programs in selected Latin American institutions, members of the Latin American Cooperative Oncology Group. RESULTS There were 90 research centers participating in the survey, with 70 of them from Brazil. The majority were partly private or fully private (n = 77; 85.6%) and had confirmed COVID-19 cases at the institution (n = 57; 63.3%). Accruals were suspended at least for some studies in 80% (n = 72) of the responses, mostly because of sponsors' decision. Clinical trials' routine was affected by medical visits cancelation, reduction of patients' attendance, reduction of other specialties' availability, and/or alterations on follow-up processes. Formal COVID-19 mitigation policies were adopted in 96.7% of the centers, including remote monitoring and remote site initiation visits, telemedicine visits, reduction of research team workdays or home office, special consent procedures, shipment of oral drugs directly to patients' home, and increase in outpatient diagnostic studies. Importantly, some of these changes were suggested to be part of future oncology clinical trials' routine, particularly the ones regarding remote methods, such as telemedicine. CONCLUSION To our knowledge, this was the first survey to evaluate the impact of COVID-19 on Latin American oncology clinical trials. The results are consistent with surveys from other world regions. These findings may endorse improvements in clinical trials' processes and management in the postpandemic period.
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Affiliation(s)
- Aline B. Lara Gongora
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Hospital Sírio-Libanês, São Paulo, Brazil
| | - Gustavo Werutsky
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
| | - Denis L. Jardim
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Hospital Sírio-Libanês, São Paulo, Brazil
| | - Angelica Nogueira-Rodrigues
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Brazilian Group of Gynecologic Oncology (EVA), Belo Horizonte, Brazil
- Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Carlos H. Barrios
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
| | - Clarissa Mathias
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Núcleo de Oncologia da Bahia (NOB)/Oncoclínicas, Salvador, Brazil
- Sociedade Brasileira de Oncologia Clínica (SBOC), São Paulo, Brazil
| | - Fernando Maluf
- Hospital Sírio-Libanês, São Paulo, Brazil
- Beneficência Portuguesa de São Paulo, São Paulo, Brazil
- Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Rachel Riechelmann
- A.C. Camargo Cancer Center, São Paulo, Brazil
- Brazilian Gastrointestinal Tumors Group (GTG), Porto Alegre, Brazil
| | - Maurício Fraga
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Universidade Federal de Santa Maria (UFSM), Santa Maria, Brazil
| | - Henry Gomes
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima, Peru
| | - William N. William
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Beneficência Portuguesa de São Paulo, São Paulo, Brazil
- Brazilian Group of Thoracic Oncology (GBOT), Porto Alegre, Brazil
| | - Camilla A. F. Yamada
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Beneficência Portuguesa de São Paulo, São Paulo, Brazil
| | - Gilberto de Castro Jr
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Hospital Sírio-Libanês, São Paulo, Brazil
- Brazilian Group of Thoracic Oncology (GBOT), Porto Alegre, Brazil
- Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, Brazil
| | - Daniela D. Rosa
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Brazilian Group of Breast Cancer Studies (GBECAM), Porto Alegre, Brazil
- Hospital Moinhos de Vento, Porto Alegre, Brazil
| | - Andreia C. de Melo
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Brazilian Group of Gynecologic Oncology (EVA), Belo Horizonte, Brazil
- Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil
| | - Raul Sala
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Grupo Argentino de Investigación Clínica en Oncología, Rosario, Argentina
| | - Eva Bustamante
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Chilean Cooperative Group for Oncologic Research (GOCCHI), Santiago, Chile
| | - Denisse Bretel
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Grupo de Estudios Clínicos Oncológicos Peruano (GECOPERU), Lima, Peru
| | - Oscar Arrieta
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Instituto Nacional de Cancerología, Ciudad del México, México City, México
| | - Andrés F. Cardona
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia
| | - Diogo A. Bastos
- Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil
- Hospital Sírio-Libanês, São Paulo, Brazil
- Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, Brazil
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Carrot-Zhang J, Soca-Chafre G, Patterson N, Thorner AR, Nag A, Watson J, Genovese G, Rodriguez J, Gelbard MK, Corrales-Rodriguez L, Mitsuishi Y, Ha G, Campbell JD, Oxnard GR, Arrieta O, Cardona AF, Gusev A, Meyerson M. Genetic Ancestry Contributes to Somatic Mutations in Lung Cancers from Admixed Latin American Populations. Cancer Discov 2021; 11:591-598. [PMID: 33268447 PMCID: PMC7933062 DOI: 10.1158/2159-8290.cd-20-1165] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 10/26/2020] [Accepted: 11/19/2020] [Indexed: 12/24/2022]
Abstract
Inherited lung cancer risk, particularly in nonsmokers, is poorly understood. Genomic and ancestry analysis of 1,153 lung cancers from Latin America revealed striking associations between Native American ancestry and their somatic landscape, including tumor mutational burden, and specific driver mutations in EGFR, KRAS, and STK11. A local Native American ancestry risk score was more strongly correlated with EGFR mutation frequency compared with global ancestry correlation, suggesting that germline genetics (rather than environmental exposure) underlie these disparities. SIGNIFICANCE: The frequency of somatic EGFR and KRAS mutations in lung cancer varies by ethnicity, but we do not understand why. Our study suggests that the variation in EGFR and KRAS mutation frequency is associated with genetic ancestry and suggests further studies to identify germline alleles that underpin this association.See related commentary by Gomez et al., p. 534.This article is highlighted in the In This Issue feature, p. 521.
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Affiliation(s)
- Jian Carrot-Zhang
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
- Departments of Genetics and Medicine, Harvard Medical School, Boston, Massachusetts
| | - Giovanny Soca-Chafre
- Personalized Medicine Laboratory, Instituto Nacional de Cancerologia, México City, México
| | - Nick Patterson
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
- Departments of Genetics and Medicine, Harvard Medical School, Boston, Massachusetts
| | - Aaron R Thorner
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Anwesha Nag
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Jacqueline Watson
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
| | - Giulio Genovese
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
- Departments of Genetics and Medicine, Harvard Medical School, Boston, Massachusetts
| | - July Rodriguez
- Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia
| | - Maya K Gelbard
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Luis Corrales-Rodriguez
- Medical Oncology, Hospital San Juan de Dios, San José, Costa Rica
- Centro de Investigación y Manejo del Cáncer - CIMCA, San José, Costa Rica
| | - Yoichiro Mitsuishi
- Division of Respiratory Medicine, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan
| | - Gavin Ha
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Joshua D Campbell
- Division of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
| | - Geoffrey R Oxnard
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Oscar Arrieta
- Personalized Medicine Laboratory, Instituto Nacional de Cancerologia, México City, México.
- Thoracic Oncology Unit, Instituto Nacional de Cancerología, México City, México
| | - Andres F Cardona
- Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia.
- Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia
| | - Alexander Gusev
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
- Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts
| | - Matthew Meyerson
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
- Departments of Genetics and Medicine, Harvard Medical School, Boston, Massachusetts
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Alvarez-Gomez RM, De la Fuente-Hernandez MA, Herrera-Montalvo L, Hidalgo-Miranda A. Challenges of diagnostic genomics in Latin America. Curr Opin Genet Dev 2021; 66:101-109. [PMID: 33517184 DOI: 10.1016/j.gde.2020.12.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 12/11/2020] [Accepted: 12/16/2020] [Indexed: 12/24/2022]
Abstract
Cancer genome sequencing methods have now become essential for diagnostic purposes, for devising treatment strategies, and for monitoring disease regression and progression. However, access to these benefits has not permeated homogeneously throughout the world; certain regions, such as Latin America, have been slower at adopting these technologies in terms of their routine use, development and patient access. There are also differences among Latin American subregions with respect to their prioritized types of neoplasia and the drugs that are available and approved in them. An overview of the current situation, including the status of genomics for cancer diagnostics and efforts by type of cancer is presented. In addition, we discuss the perspective of initiatives, alliances, and educational/research programs that pledge to make cancer genomics diagnosis a reality for Latin American individuals' health.
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Affiliation(s)
- Rosa Maria Alvarez-Gomez
- National Institute of Genomic Medicine, Periferico Sur 4809, Arenal Tepepan, Tlalpan, 14610, Mexico City, Mexico; National Cancer Institute, San Fernando 22, Seccion XVI, Tlalpan, Mexico City, Mexico
| | - Marcela Angelica De la Fuente-Hernandez
- National Institute of Genomic Medicine, Periferico Sur 4809, Arenal Tepepan, Tlalpan, 14610, Mexico City, Mexico; Doctoral Program in Biological Sciences, National Autonomous University of Mexico, C.U., Coyoacan, 04510, Mexico City, Mexico
| | - Luis Herrera-Montalvo
- National Institute of Genomic Medicine, Periferico Sur 4809, Arenal Tepepan, Tlalpan, 14610, Mexico City, Mexico
| | - Alfredo Hidalgo-Miranda
- National Institute of Genomic Medicine, Periferico Sur 4809, Arenal Tepepan, Tlalpan, 14610, Mexico City, Mexico.
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Hu Y, Zhang J, Hu H, Xu S, Xu L, Chen E. Gefitinib encapsulation based on nano-liposomes for enhancing the curative effect of lung cancer. Cell Cycle 2020; 19:3581-3594. [PMID: 33300430 DOI: 10.1080/15384101.2020.1852756] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Gefitinib (GEB) is one of the drugs used for patients with epidermal growth factor receptor (EGFR)-positive mutations in non-small cell lung cancer (NSCLC). However, application of GEB is limited by its low water solubility, stability, and utilization rate, especially the side effects while GEB is given by oral. In this study, nanoliposome was used as a carrier to prepare nanoliposome compound drug (GL) by embedding GEB in the nanoliposome perfectly combined with green nontoxic solvent and thin-film dispersion method. The nanoliposome structure was expected to improve the water solubility and biocompatibility of GEB, thus improving the effect of cancer treatment. The surface electronegative nanoliposomes can effectively avoid protein adsorption and prolong the circulation time in vivo. Meanwhile, the ratio of lecithin to cholesterol (LE/CH) was explored to maximize the encapsulation efficiency of nanoliposome. Subsequent test results showed that GL exhibited better stability, smaller particle size and higher encapsulation efficiency. In addition, in vitro drug release curve also further confirmed that GL had a promising drug sustained-release effect. In particular, a series of in vitro tests such as cell activity, apoptosis, colony formation, scratch, invasion, and cell cycle assays were performed. The results indicated that GL significantly enhanced the pro-apoptotic effect on A549 cells. Most cell cycles of A549 cells were blocked in the G0/G1 phase influenced by GL, thus inhibiting the proliferation of cancer cells. In vivo anti-tumor studies showed that compared with pure GEB, GL had a significant inhibiting effect on NSCLC. In conclusion, the GL which was synthesized by a simple method in this study significantly improved the treatment effect of cancer cells, which proved that the nanoliposome carrier had an excellent application prospect in the treatment of lung cancer.
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Affiliation(s)
- Yanjie Hu
- Department of Pulmology and Critical Care Medicine, Regional medical center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China
| | - Jisong Zhang
- Department of Pulmology and Critical Care Medicine, Regional medical center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China
| | - Huihui Hu
- Department of Pulmology and Critical Care Medicine, Regional medical center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China
| | - Shan Xu
- Department of Pulmology and Critical Care Medicine, Regional medical center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China
| | - Li Xu
- Department of Pulmology and Critical Care Medicine, Regional medical center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China
| | - Enguo Chen
- Department of Pulmology and Critical Care Medicine, Regional medical center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China
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34
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The challenges of implementing low-dose computed tomography for lung cancer screening in low- and middle-income countries. NATURE CANCER 2020; 1:1140-1152. [PMID: 35121933 DOI: 10.1038/s43018-020-00142-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 10/09/2020] [Indexed: 12/12/2022]
Abstract
Lung cancer accounts for an alarming human and economic burden in low- and middle-income countries (LMICs). Recent landmark trials from high-income countries (HICs) by demonstrating that low-dose computed tomography (LDCT) screening effectively reduces lung cancer mortality have engendered enthusiasm for this approach. Here we examine the effectiveness and affordability of LDCT screening from the viewpoint of LMICs. We consider resource-restricted perspectives and discuss implementation challenges and strategies to enhance the feasibility and cost-effectiveness of LDCT screening in LMICs.
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35
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Buja A, Rivera M, De Polo A, Brino ED, Marchetti M, Scioni M, Pasello G, Bortolami A, Rebba V, Schiavon M, Calabrese F, Mandoliti G, Baldo V, Conte P. Estimated direct costs of non-small cell lung cancer by stage at diagnosis and disease management phase: A whole-disease model. Thorac Cancer 2020; 12:13-20. [PMID: 33219738 PMCID: PMC7779199 DOI: 10.1111/1759-7714.13616] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/24/2020] [Accepted: 07/25/2020] [Indexed: 01/10/2023] Open
Abstract
Background Non‐small cell lung cancer (NSCLC) is the first cause of cancer‐related death among men and the second among women worldwide. It also poses an economic threat to the sustainability of healthcare services. This study estimated the direct costs of care for patients with NSCLC by stage at diagnosis, and management phase of pathway recommended in local and international guidelines. Methods Based on the most up‐to‐date guidelines, we developed a very detailed “whole‐disease” model listing the probabilities of all potentially necessary diagnostic and therapeutic actions involved in the management of each stage of NSCLC. We assigned a cost to each procedure, and obtained an estimate of the total and average per‐patient costs of each stage of the disease and phase of its management. Results The mean expected cost of a patient with NSCLC is 21,328 € (95% C.I. −20 897−22 322). This cost is 16 291 € in stage I, 19530 € in stage II, 21938 € in stage III, 22175 € in stage IV, and 28 711 € for a Pancoast tumor. In the early stages of the disease, the main cost is incurred by surgery, whereas in the more advanced stages radiotherapy, medical therapy, treatment for progressions, and supportive care become variously more important. Conclusions An estimation of the direct costs of care for NSCLC is fundamental in order to predict the burden of new oncological therapies and treatments on healthcare services, and thus orient the decisions of policy‐makers regarding the allocation of resources. Key points Significant findings of the study The high costs of surgery make the early stages of the disease no less expensive than the advanced stages. What this study adds An estimation of the direct costs of care is fundamental in order to orient the decisions of policy‐makers regarding the allocation of resources.
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Affiliation(s)
- Alessandra Buja
- Department of Cardiologic, Vascular, and Thoracic Sciences and Public Health, University of Padua, Padua, Italy
| | - Michele Rivera
- Department of Cardiologic, Vascular, and Thoracic Sciences and Public Health, University of Padua, Padua, Italy
| | - Anna De Polo
- Department of Cardiologic, Vascular, and Thoracic Sciences and Public Health, University of Padua, Padua, Italy
| | | | | | - Manuela Scioni
- Statistics Department, University of Padua, Padua, Italy
| | - Giulia Pasello
- Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
| | | | - Vincenzo Rebba
- "Marco Fanno" Department of Economics and Management, University of Padua, Padua, Italy
| | - Marco Schiavon
- Department of Cardiologic, Vascular, and Thoracic Sciences and Public Health, University of Padua, Padua, Italy
| | - Fiorella Calabrese
- Department of Cardiologic, Vascular, and Thoracic Sciences and Public Health, University of Padua, Padua, Italy
| | - Giovanni Mandoliti
- U.O.C. Radioterapia oncologica, Ospedale Santa Maria della Misericordia, AULSS 5 "Polesana", Rovigo, Italy
| | - Vincenzo Baldo
- Department of Cardiologic, Vascular, and Thoracic Sciences and Public Health, University of Padua, Padua, Italy
| | - PierFranco Conte
- Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.,Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
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Li JP, Li R, Liu X, Huo C, Liu TT, Yao J, Qu YQ. A Seven Immune-Related lncRNAs Model to Increase the Predicted Value of Lung Adenocarcinoma. Front Oncol 2020; 10:560779. [PMID: 33163400 PMCID: PMC7591457 DOI: 10.3389/fonc.2020.560779] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Accepted: 08/13/2020] [Indexed: 12/27/2022] Open
Abstract
Background Recent research has shown that immune-related lncRNA plays a crucial part in the tumor immune microenvironment. This study tried to identify immune-related lncRNAs and construct a robust prediction model to increase the predicted value of lung adenocarcinoma (LUAD). Methods RNA expression data of LUAD were download from the Cancer Genome Atlas (TCGA) database. Immune genes were acquired from the Molecular Signatures Database (MSigDB). The immune gene related lncRNAs were acquired by the “limma R” package and Cytoscape3.7.1. Cox regression analysis was applied to construct this forecast model. The prognostic model was validated by the testing cohort which was acquired by the bootstrap method. Results A total of 551 lncRNA expression profiles including 497 LUAD tissues and 54 non-LUAD tissues were obtained. A total of 331 immune genes were acquired. The result of the Cox regression analysis showed that seven lncRNAs (AC022784-1, NKILA, AC026355-1, AC068338-3, LINC01843, SYNPR-AS1, and AC123595-1) can be performed to construct the prediction model to forecast the prognosis of LUAD. Kaplan–Meier curves indicated that our prediction model can distribute LUAD patients into two different risk groups (high and low) with significant statistical significance (P = 1.484e-07). Cox analysis and independent analysis illustrated that the seven-lncRNAs prediction model was an isolated factor by comparing it with other clinical variables. We validated the accuracy of our model in the testing dataset. Furthermore, the prognostic model also showed higher predictive efficiency than three other published prognostic models. The two different survival groups represented diverse immune features according to principal components analysis. GSEA analysis (gene set enrichment analysis) indicated that seven-lncRNAs signatures may be involved in the progression of tumorigenesis. Conclusions We have established a seven immune-related lncRNAs prediction model. This prognostic model had significant clinical significance that increased the predicted value and guided the personalized treatment for LUAD patients.
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Affiliation(s)
- Jian-Ping Li
- Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Rui Li
- Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xiao Liu
- Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Chen Huo
- Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Ting-Ting Liu
- Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jie Yao
- Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yi-Qing Qu
- Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China
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37
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Heredia D, Barrón F, Cardona AF, Campos S, Rodriguez-Cid J, Martinez-Barrera L, Alatorre J, Salinas MÁ, Lara-Mejia L, Flores-Estrada D, Arrieta O. Brigatinib in ALK-positive non-small cell lung cancer: real-world data in the Latin American population (Bri-world extend CLICaP). Future Oncol 2020; 17:169-181. [PMID: 32986959 DOI: 10.2217/fon-2020-0747] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background: Brigatinib has demonstrated its efficacy as first-line therapy and in further lines for ALK-positive non-small cell lung cancer (NSCLC) patients; however, real-world data in Latin America are scarce. Methods: From January 2018 to March 2020, 46 patients with advanced ALK-positive NSCLC received brigatinib as second or further line of therapy in Mexico and Colombia. The primary end point was progression-free survival (PFS); secondary end point was time to treatment discontinuation (TTD). Results: At a median follow-up of 9.3 months, the median PFS was 15.2 months (95% CI: 11.6-18.8), and TTD was 18.46 months (95% CI: 9.54-27.38). The estimated overall survival at 12 months was 80%. Safety profile was consistent with previously published data. Conclusion: Brigatinib is an effective treatment for previously treated ALK-positive NSCLC patients in a real-world setting.
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Affiliation(s)
- David Heredia
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, México 14080
| | - Feliciano Barrón
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, México 14080
| | - Andrés F Cardona
- Clinical & Translational Oncology Group, Clínica del Country, Bogotá, Colombia.,Molecular Oncology & Biology Systems Group (G-FOX), Universidad El Bosque, Bogotá, Colombia
| | - Saul Campos
- Centro Oncológico Estatal ISSEMyM, Toluca Estado de México, México 50180
| | | | | | - Jorge Alatorre
- National Institute of Respiratory Diseases, México City, México 14080
| | - Miguel Ángel Salinas
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, México 14080
| | - Luis Lara-Mejia
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, México 14080
| | - Diana Flores-Estrada
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, México 14080
| | - Oscar Arrieta
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, México 14080
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38
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Deng Y, Zhao P, Zhou L, Xiang D, Hu J, Liu Y, Ruan J, Ye X, Zheng Y, Yao J, Zhai Z, Wang S, Yang S, Wu Y, Li N, Xu P, Zhang D, Kang H, Lyu J, Dai Z. Epidemiological trends of tracheal, bronchus, and lung cancer at the global, regional, and national levels: a population-based study. J Hematol Oncol 2020; 13:98. [PMID: 32690044 PMCID: PMC7370495 DOI: 10.1186/s13045-020-00915-0] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 06/09/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Investigations of disease incidence, mortality, and disability-adjusted life years (DALYs) are valuable for facilitating preventive measures and health resource planning. We examined the tracheal, bronchus, and lung (TBL) cancer burdens worldwide according to sex, age, and social development index (SDI) at the global, regional, and national levels. METHODS We assessed the TBL cancer burden using data from the Global Burden of Disease (GBD) database, including 21 regions, 195 countries, and territories in the diagnostic period 1990-2017. The data of TBL cancer-related mortality and DALYs attributable to all known risk factors were also analyzed. Age-standardized rates (ASRs) and their estimated annual percentage changes (EAPCs) were calculated. RESULTS Incident cases, deaths, and DALYs of TBL cancer increased worldwide (100.44%, 82.30%, and 61.27%, respectively). The age-standardized incidence rate (ASIR) was stable (EAPC = 0.02, 95% confidence interval [CI] - 0.03 to 0.08), but the age-standardized death (EAPC = - 0.34, 95%CI - 0.38 to - 0.3) and DALY rate decreased generally (EAPC = - 0.74, 95%CI - 0.8 to - 0.68). However, the change trend of ASIR and ASDR among sexes was on the contrary. China and the USA always had the highest incidence, mortality, and DALYs of TBL cancer. Significant positive correlations between ASRs and SDI were observed, especially among females. High (36.86%), high-middle (28.78%), and middle SDI quintiles (24.91%) carried the majority burden of TBL cancer. Tobacco remained the top cause of TBL cancer death and DALYs, followed by air pollution, the leading cause in the low-middle and low-SDI quintiles. Metabolic risk-related TBL cancer mortality and DALYs among females increased but was stable among males. The main ages of TBL cancer onset and death were > 50 years, and the DALYs concentrated in 50 - 69 years. CONCLUSIONS To significantly reduce the growing burden of TBL cancer, treatment resources need to be skewed according to factors such as risks and geography, especially for high-risk groups and high-burden areas. Asia had the greatest TBL cancer burden, followed by high-income North America. Tobacco remains the leading cause of death and DALYs, followed by air pollution. Effective prevention measures against tobacco and air pollution should be strengthened.
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Affiliation(s)
- Yujiao Deng
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Peng Zhao
- Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Linghui Zhou
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Dong Xiang
- Celilo Cancer Center, Oregon Health Science Center affiliated Mid-Columbia Medical Center, The Dalles, OR USA
| | - Jingjing Hu
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA USA
| | - Yu Liu
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jian Ruan
- Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xianghua Ye
- Department of Radiotherapy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yi Zheng
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jia Yao
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Zhen Zhai
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Shuqian Wang
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Si Yang
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Ying Wu
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Na Li
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Peng Xu
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Dai Zhang
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Huafeng Kang
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jun Lyu
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, 510632 China
| | - Zhijun Dai
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Du L, Ma N, Dai X, Yu W, Huang X, Xu S, Liu F, He Q, Liu Y, Wang Q, Liu X, Zheng H, Qu B. Precise prediction of the radiation pneumonitis in lung cancer: an explorative preliminary mathematical model using genotype information. J Cancer 2020; 11:2329-2338. [PMID: 32127959 PMCID: PMC7052914 DOI: 10.7150/jca.37708] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 01/06/2020] [Indexed: 12/25/2022] Open
Abstract
Purpose: Radiation pneumonitis (RP) is the most significant dose-limiting toxicity and is one major obstacle for lung cancer radiotherapy. Grade ≥2 RP usually needs clinical interventions and serve RP could be life threatening. Clinically, tissue response could be strikingly different even two similar patients after identical radiotherapy. Previous methods for the RP prediction can hardly distinguish substantial variations among individuals. Reliable predictive factors or methods emphasizing the individual differences are strongly desired by clinical radiation oncologists. The purpose of this study is to develop an approach for the personalized RP risk prediction. Experimental Design: One hundred eighteen lung cancer patients who received radiotherapy were enrolled. Seven hundred thousand single-nucleotide polymorphism (SNP) sites were assessed via Generalized Linear Models via Lasso and Elastic-Net Regularization (GLMNET) to determine their synergistic effects on the RP risk prediction. Non-genetic factors including patient's phenotypes and clinical interventional parameters were separately assessed by statistic test. Based on the results of the aforementioned analysis, a multiple linear regression model named Radiation Pneumonitis Index (RPI) was built, for the assessment of Grade ≥2RP risk. Results: Only previous surgery and fractional dose were discovered statistical significantly associated with grade ≥2RP. Thirty-nine effective SNPs for predicting the Grade ≥2RP risk were discovered and their coefficients of the synergistic effect were determined. The RPI score can successfully distinguish the RP≥2 population with 92.0% sensitivity and 100% specificity. Conclusions: Individual radiation sensitivity can be determined with genotype information and personalized radiotherapy could be achieved based on mathematical model result.
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Affiliation(s)
- Lehui Du
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, 100853, P.R. China
| | - Na Ma
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, 100853, P.R. China
| | - Xiangkun Dai
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, 100853, P.R. China
| | - Wei Yu
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, 100853, P.R. China
| | - Xiang Huang
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, 100853, P.R. China
| | - Shouping Xu
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, 100853, P.R. China
| | - Fang Liu
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, 100853, P.R. China
| | - Qiduo He
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, 100853, P.R. China
| | - Yanli Liu
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, 100853, P.R. China
| | - Qian Wang
- Tianjia Genomes Tech CO., LTD., Hefei, 238014, P. R. China
| | - Xiangtao Liu
- Tianjia Genomes Tech CO., LTD., Hefei, 238014, P. R. China
| | - Hui Zheng
- Tianjia Genomes Tech CO., LTD., Hefei, 238014, P. R. China
| | - Baolin Qu
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, 100853, P.R. China
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Corrales L, Rosell R, Cardona AF, Martín C, Zatarain-Barrón ZL, Arrieta O. Lung cancer in never smokers: The role of different risk factors other than tobacco smoking. Crit Rev Oncol Hematol 2020; 148:102895. [PMID: 32062313 DOI: 10.1016/j.critrevonc.2020.102895] [Citation(s) in RCA: 114] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 01/21/2020] [Accepted: 01/29/2020] [Indexed: 12/16/2022] Open
Abstract
Lung cancer (LC), the leading cause of cancer-related deaths worldwide, is a complex and highly heterogeneous disease. Additional to its biological complexity, LC patients are often confronted with a high degree of stigma, mostly from the association of the disease with tobacco. Nonetheless, a proportion of LC patients are never-smokers, a population which we are beginning to comprehensively explore. Several risk factors have been linked to LC in never-smokers. Studies have consistently shown that radon exposure and domestic fuel smoke increase LC risk. Additionally, infections such as Mycobacterium tuberculosis, and Human Papilloma Virus are also risk factors. Other less conclusive associations include inflammatory diseases such as asthma and sarcoidosis. Moreover, we are now aware that molecular characteristics of LC vary widely according to smoking history, with important therapeutic implications. This review comprehensively assesses the current knowledge in terms of risk factors and disease characteristics in the never-smoker lung cancer population.
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Affiliation(s)
- Luis Corrales
- Centro de Investigación y Manejo del Cáncer (CIMCA), San José, Costa Rica; Hospital San Juan de Dios, San José, Costa Rica
| | - Rafael Rosell
- Catalan Institute of Oncology, Germans Trias i Pujol Research Institute and Hospital Campus Can Ruti Barcelona, Spain
| | - Andrés F Cardona
- Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia; Clinical and Traslational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá, Colombia
| | - Claudio Martín
- Medical Oncology Department, Thoracic Oncology Section, Instituto Fleming, Buenos Aires, Argentina
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Carioli G, Bertuccio P, Malvezzi M, Rodriguez T, Levi F, Boffetta P, La Vecchia C, Negri E. Cancer mortality predictions for 2019 in Latin America. Int J Cancer 2019; 147:619-632. [PMID: 31637709 DOI: 10.1002/ijc.32749] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 10/03/2019] [Accepted: 10/09/2019] [Indexed: 12/11/2022]
Abstract
We estimated mortality figures for 2019 in seven Latin American countries, with focus on breast cancer. We retrieved cancer death certification and population data from the WHO and PAHO databases. We obtained mortality statistics for Argentina, Brazil, Chile, Colombia, Cuba, Mexico and Venezuela for 1970-2015. We predicted current death numbers and age-standardised (world population) mortality rates using joinpoint regression models. Total cancer mortality is predicted to decline in all countries and both sexes, except Argentinian women. Cuba had the highest all cancer rates for 2019, 136.9/100,000 men and 90.4 women, while Mexico showed the lowest ones, 63.8/100,000 men and 61.9 women. Stomach cancer showed favourable trends over the whole period, while colorectal cancer only recently. Lung cancer rates declined in men, while in women they decreased slightly over the most recent years, only. In Cuban women, lung cancer rates overtook breast cancer ones. Breast cancer showed overall favourable trends, but rates are rising in young women. Prostate and uterine cancer had favourable trends. Pancreas, ovary, bladder and leukaemias showed slightly decreasing trends. Between 1990 and 2019, mortality from all neoplasms is predicted to fall by about 18% in Argentina, 26% in Chile, 14% in Colombia, 17% in Mexico and 13% in Venezuela, corresponding to almost 0.5 million avoided cancer deaths. No decline was observed in Brazil and Cuba. Of concern, the persisting high rates of (cervix) uterus cancer, the high lung cancer rates in Cuba, the possible increases in breast cancer in young women, and the lack of overall declines in Brazil, Cuba and Venezuelan men.
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Affiliation(s)
- Greta Carioli
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Paola Bertuccio
- Department of Biomedical and Clinical Sciences, L. Sacco, Università degli Studi di Milano, Milan, Italy
| | - Matteo Malvezzi
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Teresa Rodriguez
- Navarra General Hospital, Navarra Health Service, Pamplona, Navarra, Spain
| | - Fabio Levi
- Institute of Social and Preventive Medicine (IUMSP), University of Lausanne, Lausanne, Switzerland
| | - Paolo Boffetta
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Eva Negri
- Department of Biomedical and Clinical Sciences, L. Sacco, Università degli Studi di Milano, Milan, Italy
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Arai RJ, Guindalini RSC, Llera AS, O'Connor JM, Muller B, Lema M, Freitas HC, Soria T, Delgado L, Landaverde D, Montenegro P, Riechelmann RP. Personalizing Precision Oncology Clinical Trials in Latin America: An Expert Panel on Challenges and Opportunities. Oncologist 2019; 24:e709-e719. [PMID: 30910864 DOI: 10.1634/theoncologist.2018-0318] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Accepted: 01/30/2019] [Indexed: 12/12/2022] Open
Abstract
The participation of patients in precision oncology trials needs to fulfill molecular-based selection criteria. This strongly limits accrual, and as a consequence, screening successes have decreased, costs have increased, and fewer subjects are enrolled. To achieve narrowed targets, studies have been forced to be multicenter and multinational to reach a larger pool of candidates. However, this globalization faces many challenges, as, for example, in the case of precision oncology trials. These trials have a complex structure that is dependent upon a high-tech infrastructure and knowledge in a dynamic environment. Given the movement of precision clinical cancer research to regions other than Europe and the U.S., it is important to evaluate the feasibility of performing such trials in lower-middle- and low-income countries. Here we critically discuss the advantages of conducting precision oncology clinical trials in Latin America and make suggestions on how to overcome the main challenges involved. IMPLICATIONS FOR PRACTICE: Precision clinical trials in oncology are studies that require candidates to have tumors with specific molecular alterations, which are considered the target for the trial experimental therapy. Because many molecular alterations are rare, fewer patients are enrolled. This has led to trials being forced to be multicenter and multinational, including trials in Latin America. This article discusses the challenges and opportunities to conduct precision oncology trials in Latin America, aiming to help sponsors and investigators to solve complex issues that ultimately lead to more of such trials being run in the region, potentially benefiting more Latin American patients with cancer.
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Affiliation(s)
- Roberto Jun Arai
- Núcleo de Pesquisa, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Rodrigo Santa Cruz Guindalini
- Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- CLION, CAM Group, Salvador, Brazil
| | - Andrea Sabina Llera
- Genocan Laboratory, Fundación Instituto Leloir - CONICET, Buenos Aires, Argentina
| | | | | | | | | | | | - Lucía Delgado
- Department of Oncology, Hospital de Clínicas, Universidad de la República Oriental del Uruguay, Montevideo, Uruguay
| | - Denis Landaverde
- Hospital Mexico and Universidad de Costa Rica, San José, Costa Rica
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Arrieta O, Barrón F, Maldonado F, Cabrera L, Corona-Cruz JF, Blake M, Ramírez-Tirado LA, Zatarain-Barrón ZL, Cardona AF, García O, Arén O, De la Garza J. Radical consolidative treatment provides a clinical benefit and long-term survival in patients with synchronous oligometastatic non-small cell lung cancer: A phase II study. Lung Cancer 2019; 130:67-75. [PMID: 30885354 DOI: 10.1016/j.lungcan.2019.02.006] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Revised: 01/30/2019] [Accepted: 02/06/2019] [Indexed: 12/22/2022]
Abstract
OBJECTIVES Evidence is rapidly accumulating for the use of radical consolidative treatment (RCT) for patients with oligometastatic non-small cell lung cancer (NSCLC). Nonetheless, published studies have several limitations, including a selection of patients whose favorable characteristics might dictate therapeutic success, as well as scarce prospective data regarding overall survival (OS). The objective of this study was to determine whether RCT increases OS in patients with oligometastatic NSCLC. MATERIALS AND METHODS In this prospective, single-arm phase II study, we sought to evaluate the efficacy of RCT in patients with oligometastatic NSCLC in terms of OS. Patients with pathologically confirmed stage IV NSCLC who presented ≤5 synchronous, any-site metastases (including central nervous system [CNS] metastases), as assessed by PET-CT, were included. All patients received four initial cycles of systemic treatment. Following, those with stable disease/partial response received RCT to the primary site and metastases. The response to RCT was evaluated with PET-CT. The primary end-point was OS. Secondary end-points included progression-free survival (PFS) and best response by PET-CT. The study is registered in clinicaltrials.gov (NCT02805530). RESULTS Thirty-seven patients were included in the analysis. The mean age was 55.8 years (range: 33-75 years). At diagnosis, 43.2% of patients presented with CNS metastases. Following RCT, 19 (51.4%) patients achieved a complete-response (CR) by PET-CT, while 18 (48.6%) had a non-complete response (NON-CR). The median OS was nonreached (NR) and was positively affected by CR on PET-CT (NR vs. 27.4 [95% CI: 16.4-38.3]; p = 0.011). The median PFS was 23.5 months (95% CI: 13.6-33.3) and was positively affected by CR on PET-CT (NR vs. 14.3 [95% CI: 11.7-16.9]; p < 0.001; HR: 0.19 [0.07-0.52]; p=0.001). CONCLUSION Patients with oligometastatic NSCLC who undergo RCT have a high response rate and favorable OS. Patients with a CR by PET-CT have significantly longer OS, rendering this an important potential prognostic marker.
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Affiliation(s)
- Oscar Arrieta
- Thoracic Oncology Unit, National Cancer Institute (INCan), San Fernando #22, Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico.
| | - Feliciano Barrón
- Thoracic Oncology Unit, National Cancer Institute (INCan), San Fernando #22, Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico
| | - Federico Maldonado
- Thoracic Oncology Unit, National Cancer Institute (INCan), San Fernando #22, Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico
| | - Luis Cabrera
- Thoracic Oncology Unit, National Cancer Institute (INCan), San Fernando #22, Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico; Médica Sur Oncology Center, Mexico
| | - José Francisco Corona-Cruz
- Thoracic Oncology Unit, National Cancer Institute (INCan), San Fernando #22, Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico
| | - Monika Blake
- Thoracic Oncology Unit, National Cancer Institute (INCan), San Fernando #22, Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico
| | - Laura Alejandra Ramírez-Tirado
- Thoracic Oncology Unit, National Cancer Institute (INCan), San Fernando #22, Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico
| | - Zyanya Lucia Zatarain-Barrón
- Thoracic Oncology Unit, National Cancer Institute (INCan), San Fernando #22, Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico
| | - Andrés F Cardona
- Clinical and Traslational Oncology Group, Clínica del Country, Bogotá, Colombia; Foundation for Clinical and Applied Cancer Research- FICMAC, Bogotá, Colombia; Clinical Research and Biology Systems Department, Universidad El Bosque, Bogotá, Colombia
| | - Osvaldo García
- Thoracic Oncology Unit, National Cancer Institute (INCan), San Fernando #22, Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico
| | - Osvaldo Arén
- Centro de Investigación Clínica Bradford Hill, Santiago, Chile
| | - Jaime De la Garza
- Thoracic Oncology Unit, National Cancer Institute (INCan), San Fernando #22, Sección XVI, Tlalpan, CP 14080, Mexico City, Mexico
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Gejman R, González S, Muñoz-Medel M, Nervi B, Sánchez C, Ibáñez C, Peña J, Madrid J, Briones J, Pérez P, Garrido M, Galindo H. Prevalence of EGFR Mutations and Clinico-Pathological Characteristics of Chilean Lung Cancer Patients. Asian Pac J Cancer Prev 2019; 20:1-4. [PMID: 30677862 PMCID: PMC6485557 DOI: 10.31557/apjcp.2019.20.1.1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background: Lung cancer (LC) is the second leading cause of cancer death in Chile, causing >3,000 deaths every year. Epidemiological LC data in Chile is scarce and scattered. Here, we aimed to quantify the prevalence of Epidermal Growth Factor Receptor (EGFR) gene mutations in a Chilean cancer center. These data may identify individuals that could benefit from targeted therapies such as Tyrosine Kinase Inhibitors (TKIs). Methods: A total of 1,405 Biopsies from 1,381 LC patients were retrospectively analyzed retrieving clinical data from EGFR mutants including age, gender, histological type, smoking habits and type of EGFR mutation. We also analyzed overall survival (OS) rates. Results: From all patients 21.7% had clinically relevant EGFR mutations, and a median age at diagnosis of 65 years. Most were female (64%), classified as adenocarcinomas (94.5%), and non-smokers/light smokers (93.1%). The most prevalent mutation was exon-19 deletions (50.6%) followed by Leucine-to Arginine 858; OS was 15 months. Clinical follow-up information was available for 83 patients. The use of TKIs in these patients significantly improved OS. Conclusion: The prevalence of EGFR mutations in the studied population was 21.7%, comparable to other countries in Latin America. The most frequent EGFR mutation was exon-19 deletion, OS in this group was 15 months, and TKIs significantly improved OS.
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Affiliation(s)
- Roger Gejman
- Department of Pathology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.
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Arrieta O, Cardona A, Bramuglia G, Cruz-Rico G, Corrales L, Martín C, Imaz-Olguín V, Castillo O, Cuello M, Rojas-Bilbao É, Casas G, Fernández C, Arén Frontera O, Denninghoff V, Recondo G, Avilés-Salas A, Mas-Lopez LA, Oblitas G, Rojas L, Piottante A, Jiménez-García E, Sánchez-Sosa S, Sáenz-Frias J, Lupera H, Ramírez-Tirado L, Vargas C, Carranza H, Astudillo H, Wills L, Pichelbaur E, Raez L. Molecular Epidemiology of ALK Rearrangements in Advanced Lung Adenocarcinoma in Latin America. Oncology 2018; 96:207-216. [DOI: 10.1159/000493733] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 09/12/2018] [Indexed: 11/19/2022]
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