Browsing by Author "Garrido, Marcelo"
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- ItemA nomogram for predicting serious complications in patients with solid tumors and apparently stable febrile neutropenia: prospective data on 781 consecutive episodes from the FINITE study(2014) Ghanem, Ismael; Rebollo, Maite Antonio; Garrido, Marcelo; Martínez, Jerónimo; Font, Carme; Ramchandani, Avinash; Biosca, Merce; Beato, Carmen; Martínez de Castro, Eva; Castanon, Eduardo; Virizuela Echaburu, Juan; Espinosa, Javier; Sevillano, Elena; Aragon Manrique, Isabel; Cardona, Merce; Mondejar, Rebeca; Baron, Francisco; Acevedo Claros, Francisco Nicolás; Jiménez-Fonseca, Paula; Carmona Bayonas, AlbertoBackground: An accurate estimate of the likelihood of serious complications in patients with otherwise apparently stable febrile neutropenia (FN) may assist in decision-making regarding individualized therapy. Our group has developed a prognostic score for predicting complications in patients with solid tumors and apparently stable episodes called CISNE (Clinical Index for Stable Febrile Neutropenia). The purpose of this study is to present a nomogram based on the previously mentioned index in a broader dataset of patients. Methods: FINITE is a prospective and multicenter study which aims to investigate prognostic factors and outcomes of FN episodes with clinical stability at first assessment, defined as events without acute organ dysfunction, vital signs abnormalities or major infections. We performed a nomogram based on the CISNE score which includes the following prognostic variables: ECOG PS≥2, chronic obstructive pulmonary disease, cardiovascular disease, mucositis NCI grade ≥2, monocytes <200/mm3 and stress-induced hyperglycemia. A calibration plot was used to analyze the accuracy of this multivariate nomogram. Results: From October 2012 to December 2013, 781 patients with apparently stable FN were recruited in 21 Spanish hospitals. The rate of infection-related complications and death was 15.6% (95% confidence interval [CI], 12.9-18.6%) and 1.7% (95% CI, 0.98%-3.01%). A nomogram was designed according to the CISNE score. The area under the ROC curve was 0.836 (95% CI, 0.808-0.861). The observed and predicted probabilities also matched closely. Conclusions: Our group has developed a user-friendly nomogram for predicting complications in patients with apparently stable FN. This nomogram may be particularly useful to prevent premature discharges of cancer patients starting inpatient management.
- ItemAssessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population(2024) Owen, Gareth Ivor; Córdova-Delgado, Miguel; Bustos, Bernabé I.; Cerpa Castro, Leslie; González Hevia, Pamela Andrea; Morales-Pison, Sebastián; García-Bloj, Benjamín; Garrido, Marcelo; Miquel, Juan Francisco; Quiñones, Luis A.Background: Pharmacogenomic knowledge as a biomarker for cancer care has transformed clinical practice, however, as current guidelines are primarily derived from Eurocentric populations, this limits their application in Latin America, particularly among Hispanic or Latino groups. Despite advancements, systemic chemotherapy still poses challenges in drug toxicity and suboptimal response. This study explores pharmacogenetic markers related to anticancer drugs in a Chilean cohort, filling a gap in Latin American research. Notably, the influence of native South American Mapuche-Huilliche ancestry. Methods: To explore pharmacogenetic markers related to anticancer drugs, we utilized an ethnically Admixed Chilean genome-wide association studies (GWAS) dataset of 1095 unrelated individuals. Pharmacogenomic markers were selected from PharmGKB, totaling 36 level 1 and 2 evidence single nucleotide polymorphisms (SNPs) and 571 level 3 SNPs. Comparative analyses involved assessing SNP frequencies across diverse populations from the 1000 Genomes Project. Haplotypes were estimated, and linkage disequilibrium was examined. Ancestry-based association analyses explored relationships between SNPs and Mapuche-Huilliche and European ancestries. Chi-square distribution with p ≤ 0.05 and Bonferroni’s multiple adjustment tests determined statistical differences between allele frequencies. Results: Our study reveals significant disparities in SNP frequency within the Chilean population. Notably, dihydropyrimidine dehydrogenase (DPYD) variants (rs75017182 and rs67376798), linked to an increased risk of severe fluoropyrimidine toxicity, exhibit an exceptionally low frequency (minor allele frequency (MAF) < 0.005). Nudix hydrolase 15 (NUDT15) rs116855232, associated with hematological mercaptopurine toxicity, is relatively common (MAF = 0.062), and is further linked to Mapuche-Huilliche ancestry. Thiopurine methyltransferase enzyme (TPMT), implicated in severe toxicity to mercaptopurines, SNPs rs1142345 and rs1800460 of TMPT gene demonstrate higher MAFs in Admixed Americans and the Chilean population (MAF range 0.031–0.057). Finally, the variant in the UDP-glucuronosyltransferase 1 gene (UGT1A1) rs4148323, correlated with irinotecan neutropenia, exhibits the highest MAF in East Asian (MAF = 0.136) and Chilean (MAF = 0.025) populations, distinguishing them from other investigated populations. Conclusions: This study provides the first comprehensive pharmacogenetic characterization of cancer therapy-related SNPs and highlights significant disparities in SNP frequencies within the Chilean population. Our findings underscore the necessity for inclusive research and personalized therapeutic strategies to ensure the equitable and effective application of precision medicine across diverse global communities.
- ItemBenefit of adjuvant 5-fluorouracil based chemotherapy for colon cancer: a retrospective cohort study(SOC MEDICA SANTIAGO, 2016) Mondaca, Sebastian; Villalon, Constanza; Luis Leal, Jose; Zuniga, Alvaro; Bellolio, Felipe; Padilla, Oslando; Palma, Silvia; Garrido, Marcelo; Nervi, BrunoBackground: Multiple clinical trials have demonstrated the benefits of adjuvant 5-fluorouracil-based chemotherapy for patients with resectable colon cancer (CC), especially in stage III. Aim: To describe the clinical characteristics of a cohort of CC patients treated at a single university hospital in Chile since 2002, and to investigate if chemotherapy had an effect on survival rates. Material and Methods: Review of a tumor registry of the hospital. Medical records of patients with CC treated between 2002 and 2012 were reviewed. Death certificates from the National Identification Service were used to determine mortality. Overall survival was described using the Kaplan-Meier method. A multivariate Cox proportional hazard regression model was also used. Results: A total of 370 patients were treated during the study period (202 in stage II and 168 in stage III). Adjuvant chemotherapy was administered to 22 and 70% of patients in stage II and III respectively. The median follow-up period was 4.6 years. The 5-year survival rate for stage II patients was 79% and there was no benefit observed with adjuvant chemotherapy. For stage III patients, the 5-year survival rate was 81% for patients who received adjuvant chemotherapy, compared to 56% for those who did not receive chemotherapy (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.15-0.56). The benefit of chemotherapy was found to persist after adjustment for other prognostic variables (HR: 0.47; 95% CI: 0.23-0.94). Conclusions: Patients with colon cancer in stage III who received adjuvant chemotherapy had a better overall survival.
- ItemBeyond tobacco: genomic disparities in lung cancer between smokers and never-smokers(Springer Nature, 2024) Garrido, Javiera; Bernal, Yanara; González, Evelin; Blanco, Alejandro; Sepúlveda-Hermosilla, Gonzalo; Freire, Matías; Oróstica, Karen; Rivas, Solange; Marcelain, Katherine; Owen, Gareth Ivor; Ibáñez Cáceres, Carolina; Corvalán Rodríguez, Alejandro; Garrido, Marcelo; Assar, Rodrigo; Lizana, Rodrigo; Cáceres-Molina, Javier; Ampuero, Diego; Ramos, Liliana; Pérez, Paola; Aren, Osvaldo; Chernilo, Sara; Fernández, Cristina; Spencer, María L.; Aguila, Jacqueline F.; Dossetto, Giuliano B.; Olea, Mónica A.; Rasse, Germán; Sánchez, Carolina; Amorim, Maria Galli de; Bartelli, Thais F.; Nunes, Diana N.; Dias-Neto, Emmanuel; Freitas, Helano C.; Armisén, RicardoTobacco use is one of the main risk factors for Lung Cancer (LC) development. However, about 10–20% of those diagnosed with the disease are never-smokers. For Non-Small Cell Lung Cancer (NSCLC) there are clear differences in both the clinical presentation and the tumor genomic profiles between smokers and never-smokers. For example, the Lung Adenocarcinoma (LUAD) histological subtype in never-smokers is predominately found in young women of European, North American, and Asian descent. While the clinical presentation and tumor genomic profiles of smokers have been widely examined, never-smokers are usually underrepresented, especially those of a Latin American (LA) background. In this work, we characterize, for the first time, the difference in the genomic profiles between smokers and never-smokers LC patients from Chile. Methods We conduct a comparison by smoking status in the frequencies of genomic alterations (GAs) including somatic mutations and structural variants (fusions) in a total of 10 clinically relevant genes, including the eight most common actionable genes for LC (EGFR, KRAS, ALK, MET, BRAF, RET, ERBB2, and ROS1) and two established driver genes for malignancies other than LC (PIK3CA and MAP2K1). Study participants were grouped as either smokers (current and former, n = 473) or never-smokers (n = 200) according to self-report tobacco use at enrollment. Results Our findings indicate a higher overall GA frequency for never-smokers compared to smokers (58 vs. 45.7, p-value < 0.01) with the genes EGFR, KRAS, and PIK3CA displaying the highest prevalence while ERBB2, RET, and ROS1 the lowest. Never-smokers present higher frequencies in seven out of the 10 genes; however, smokers harbor a more complex genomic profile. The clearest differences between groups are seen for EGFR (15.6 vs. 21.5, p-value: < 0.01), PIK3CA (6.8 vs 9.5) and ALK (3.2 vs 7.5) in favor of never-smokers, and KRAS (16.3 vs. 11.5) and MAP2K1 (6.6 vs. 3.5) in favor of smokers. Alterations in these genes are comprised almost exclusively by somatic mutations in EGFR and mainly by fusions in ALK, and only by mutations in PIK3CA, KRAS and MAP2K1. Conclusions We found clear differences in the genomic landscape by smoking status in LUAD patients from Chile, with potential implications for clinical management in these limited-resource settings.
- ItemClinical Presentation and Perioperative Management of Pheochromocytomas and Paragangliomas: A 4-Decade Experience(ENDOCRINE SOC, 2021) Uslar, Thomas; San Francisco, Ignacio F.; Olmos, Roberto; Macchiavelo, Stefano; Zuniga, Alvaro; Rojas, Pablo; Garrido, Marcelo; Huete, Alvaro; Mendez, Gonzalo P.; Cortinez, Ignacio; Zemelman, Jose Tomas; Cifuentes, Joaquin; Castro, Fernando; Olivari, Daniela; Dominguez, Jose Miguel; Arteaga, Eugenio; Fardella, Carlos E.; Valdes, Gloria; Tagle, Rodrigo; Baudrand, RenePurpose: Latin American reports on pheochromocytomas and paragangliomas (PPGLs) are scarce. Recent studies demonstrate changes in clinical presentation and management of these patients. Herein, we assessed the main characteristics of PPGL patients in our academic center over the past 4 decades.
- ItemComplete response to immunotherapy plus chemotherapy after an unusual clinical response to afatinib and stereotactic radiosurgery in a patient with metastatic EGFR-mutant non–small-cell lung cancer(2020) Pizarro, Gonzalo; Pinto, Mauricio P.; Muñoz-Medel, Matías; Cordova-Delgado, Miguel; Bravo, M. Loreto; Nervi, Bruno; Sánchez, César; Ibañez, Carolina; Peña, José; Walbaum, Benjamín; Madrid, Jorge; Briones, Juan; Koch, Erica; Valbuena, Jose; Gonzalez, Sergio; Gejman, Roger; Acevedo, Francisco; Mondaca, Sebastian; Garrido, Marcelo; Vines, Eugenio; Galindo, Hector
- ItemCryptogenic organizing pneumonitis during oxaliplatin chemotherapy for colorectal cancer - Case report(AMER COLL CHEST PHYSICIANS, 2007) Garrido, Marcelo; O'Brien, Andres; Gonzalez, Sergio; Clavero, Jose Mignel; Orellana, EricThe patient presented here is a 30-year-old woman who underwent anterior resection for the initial treatment of rectal cancer. A postoperative study showed a single liver metastasis. The patient received adjuvant pelvic radiotherapy with concomitant 5-fluorouracil (5-FU) treatment followed by liver metastasectomy 6 weeks after the completion of radiation therapy and chemotherapy. Adjuvant therapy with 5-FU, leucovorin, and oxaliplatin (FOLFOX 4 regimen) was continued. The initial five cycles were well tolerated with the occurrence of only paresthesia that did not interfere with function. After the sixth cycle of the treatment, progressive dyspnea and persistent cough developed in the patient, although her clinical history was negative for lung disease. A chest radiograph revealed diffuse bilateral interstitial infiltrates, and a chest CT scan showed bilateral alveolar infiltrates predominant in the right lung. Lung biopsy by video-assisted thoracoscopy was performed, and the histologic report showed cryptogenic organizing pneumonitis (COP). Prednisone therapy (1 mg/kg/d) resulted in a very good clinical response. In fact, the patient had complete remission of respiratory symptoms including cough and dyspnea after 4 days of treatment, and the chest CT scan showed complete resolution of lung infiltrates after 4 weeks. One month later, the patient continued adjuvant treatment with six cycles of 5-FU, leucovorin, and irinotecan (ie, the FOLFIRI regimen) without complications. Thus, oxiplatin was implicated as the likely cause of this drug-induced lung toxicity, which is a very rare complication associated with platins. Diffuse interstitial lung disease, particularly COP, has been described following the administration of the cytotoxic agents bleomycin and busulfan, but a connection to oxaliplatin has not been reported before this case.
- ItemDiagnosis of mild platelet function disorders. Reliability and usefulness of light transmission platelet aggregation and serotonin secretion assays(2009) Quiroga Gutiérrez, Sara Teresita; Goycolea, Manuela; Matus Ritter, Valeria; Zúñiga Contreras, Pamela; Martínez, Carlos; Garrido, Marcelo; Aranda Lauriani, Eduardo Javier; Leighton Puga, Federico; Panes Becerra, Olga Teresa; Pereira Garcés, Jaime Ignacio; Mezzano, Diego
- ItemDifferentially Expressed Genes and Signaling Pathways Potentially Involved in Primary Resistance to Chemo-Immunotherapy in Advanced-Stage Gastric Cancer Patients(MDPI, 2023) Pinto, Mauricio P.; Bravo, María Loreto; Córdova Delgado, Miguel; Hill, Charlotte N.; Muñoz Medel, Matías; Retamal, Ignacio N.; Fernández, M. Fernanda; Sánchez, Carolina; Sáez, Mauricio A.; Morales Pison, Sebastián; García Bloj, Benjamín; Garrido, Marcelo; Latapiat, Verónica; Martín, Alberto J.M.; Fernández Ramírez, Ricardo; Owen Gareth IvorRecently, the combination of chemotherapy plus nivolumab (chemo-immunotherapy) has become the standard of care for advanced-stage gastric cancer (GC) patients. However, despite its efficacy, up to 40% of patients do not respond to these treatments. Our study sought to identify variations in gene expression associated with primary resistance to chemo-immunotherapy. Diagnostic endoscopic biopsies were retrospectively obtained from advanced GC patients previously categorized as responders (R) or non-responders (NR). Thirty-four tumor biopsies (R: n = 16, NR: n = 18) were analyzed by 3? massive analysis of cDNA ends (3?MACE). We found >30 differentially expressed genes between R and NRs. Subsequent pathway enrichment analyses demonstrated that angiogenesis and the Wnt-?-catenin signaling pathway were enriched in NRs. Concomitantly, we performed next generation sequencing (NGS) analyses in a subset of four NR patients that confirmed alterations in genes that belonged to the Wnt/?-catenin and the phosphoinositide 3-kinase (PI3K) pathways. We speculate that angiogenesis, the Wnt, and the PI3K pathways might offer actionable targets. We also discuss therapeutic alternatives for chemo-immunotherapy-resistant advanced-stage GC patients.
- ItemFirst-line endocrine therapy for advanced breast cancer. A real-world study at a Latin American university health institution(TAYLOR & FRANCIS LTD, 2020) Walbaum, Benjamin; Acevedo, Francisco; Medina, Lidia; Bravo, M. Loreto; Merino, Tomas; Camus, Mauricio; Dominguez, Francisco; Mondaca, Sebastian; Galindo, Hector; Nervi, Bruno; Ibanez, Carolina; Madrid, Jorge; Pena, Jose; Koch, Erica; Garrido, Marcelo; Pinto, Mauricio P.; Sanchez, CesarObjective: Clinical guidelines recommend the use of endocrine therapy (ET) in advanced hormone receptor positive (HR+) human epidermal growth factor receptor type 2 negative (HER2-) breast cancer (BC) patients in the absence of visceral disease or ET resistance. Furthermore, studies indicate similar response and survival rates using ET or cytotoxic chemotherapy (CT). Methods: Herein, we assessed clinical characteristics, type of systemic therapy and survival rates of advanced HR + HER2-BC patients in our database. Results: A total of 172 advanced HR + HER2-BC patients were treated at our institution between 1997 and 2019. Sixty percent received first-line ET (4% received combined ET). Median age of this subset was 55 years (range: 30-86). Similarly, the median age of patients that received CT was 54 years (range: 21-83). Over time, 30% of patients received ET in the 2000-2005 period; this increased to 70% in the 2016-2019 period (p = .045). Overall survival (OS) was 97 months and 51 months for patients treated with ET or CT, respectively (p = .002). Conclusions: To the best of our knowledge this is the first study assessing the use of ET in Chilean advanced HR + HER2-BC patients. Several patients in our institution receive CT without indication. The increase in ET usage over time can be attributed to better and faster immunohistochemical detection methods for Estrogen Receptor (ER), changes in educational and government policies, and a wider variety of ET options. Finally, clinical trials have failed to demonstrate a substantial benefit of CT over ET in this setting.
- ItemOncological resection, myasthenia gravis and staging as prognostic factors in thymic tumours: a Chilean case series(2021) Salas, Patricio; Solovera, Maria Eliana; Bannura, Felipe; Muñoz-Medel, Matias; Cordova-Delgado, Miguel; Sanchez, Cesar; Ibañez, Carolina; Garrido, Marcelo; Koch, Erica; Acevedo, Francisco; Mondaca, Sebastian; Nervi, Bruno; Madrid, Jorge; Peña, Jose; Pinto, Mauricio P.; Valbuena, José; Galindo, HectorBackground: Thymic epithelial tumours are rare and highly heterogeneous. Reports from the United States suggest an overall incidence of 0.15 per 100,000/year. In contrast, the incidence of these tumours in Latin America is largely unknown and reports are scarce, somewhat limited to case reports. Methods: Herein, we report a series of 38 thymic tumours from a single institution, retrospectively incorporated into this study. Patient characteristics and outcomes including age, sex, stage, paraneoplastic syndromes, treatment regimens and the date of decease were obtained from medical records. Results: Most cases in our series were females and young age (<50 years old) and early stage by Masaoka-Koga or the Moran staging systems. Also, a 34% of patients had myasthenia gravis (MG). Next, we analysed overall survival rates in our series and found that the quality of surgery (R0, R1 or R2), MG status and staging (Masaoka-Koga, Moran or TNM) were prognostic factors. Finally, we compared our data to larger thymic tumour series. Conclusions: Overall, our study confirms complete surgical resection as the standard, most effective treatment for thymic epithelial tumours. Also, the Masaoka-Koga staging system remains as a reliable prognostic factor but also the Moran staging system should be considered for thymomas.
- ItemPathological complete response to neoadjuvant chemotherapy, but not the addition of carboplatin, is associated with improved survival in Chilean triple negative breast cancer patients: a report of real world data(2021) Walbaum, Benjamin; Acevedo, Francisco; Median, Lidia; Bravo, M. Loreto; Merino, Tomas; Camus, Mauricio; Dominguez, Francisco; Mondaca, Sebastián; Galindo, Héctor; Nervi, Bruno; Ibañez, Carolina; Madrid, Jorge; Muñiz, Sabrina; Peña, José; Koch, Érica; Garrido, Marcelo; Pinto, Mauricio P.; Sánchez, CésarBackground: Breast cancer (BC) is the leading cause of cancer death for Chilean women. About 11% of cases are triple-negative (TN) BC. These are characterised by poor prognosis, higher risk of early recurrence and visceral dissemination versus other BC subtypes. Current standard treatment for early-stage non-metastatic TNBC patients consists of neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy. Pathological complete response (pCR) to NACT is associated with an increase in survival rates. In general, NACT and adjuvant regimens involve similar cytotoxic drugs. Recent studies have postulated that the use of platinum compounds in TNBC would increase response rates. However, their effects on patient survival remain uncertain. Materials and methods: We retrieved and analysed medical records from a total of 156 Chilean stage I–III TNBC female patients that received NACT and compared survival rates using carboplatin (Cb)-containing versus non-Cb-containing regimens at two health cancer centres. Results: Median age was 51 years (range: 24–81); 13.5% (n = 21) received Cb-containing regimens, 80.1% (n = 125) received sequential anthracyclines plus taxanes; 29.5% (n = 46) of the total group achieved pCR, 28% for the standard treatment and 35% (n = 8) for the Cb-containing group (p = 0.59). We confirmed pCR was associated with prolonged overall survival, invasive and distant disease-free survival (Log-rank p = 0.0236). But the addition of Cb was not associated with differences in survival measures (Log-rank p = 0.5216). Conclusions: To the best of authors’ knowledge, this is the first report on real-world data in the Chilean population assessing the effect of Cb-containing NACT in TNBC. The authors’ results suggest no survival benefit by the addition of Cb to standard NACT. However, we confirm an increase in survival associated to pCR regardless of treatment.