Browsing by Author "Ibáñez Cáceres, Carolina"
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- ItemA randomized, open-label, phase 3 trial of pembrolizumab plus epacadostat versus sunitinib or pazopanib as first-line treatment for metastatic renal cell carcinoma (KEYNOTE-679/ECHO-302)(2024) Lara, Primo N.; Villanueva, Luis; Ibáñez Cáceres, Carolina; Erman, Mustafa; Lee, Jae L.; Heinrich, Daniel; Lipatov, Oleg N.; Gedye, Craig; Gokmen, Erhan; Acevedo, Alejandro; Semenov, Andrey; Park, Se H.; Gafanov, Rustem A.; Kose, Fatih; Jones, Mark; Du, Xiaoqi; Munteanu, Mihaela; Perini, Rodolfo; Choueiri, Toni K.; Motzer, Robert J.Background: Immunotherapy-based combinations have emerged as standard therapies for patients with metastatic renal cell carcinoma (mRCC). Pembrolizumab, a PD-1 inhibitor, combined with epacadostat, an indoleamine 2,3-deoxygenase 1 selective inhibitor, demonstrated promising antitumor activity in a phase 1 study in advanced solid tumors, including mRCC. Methods: KEYNOTE-679/ECHO-302 was a randomized, open-label, parallel-group, multicenter, phase 3 study (NCT03260894) that compared pembrolizumab plus epacadostat with sunitinib or pazopanib as first-line treatment for mRCC. Eligible patients had histologically confirmed locally advanced or metastatic clear cell RCC and had not received systemic therapy. Patients were randomly assigned 1:1 to pembrolizumab 200 mg IV every 3 weeks plus epacadostat 100 mg orally twice daily versus sunitinib 50 mg orally once daily (4 weeks on treatment followed by 2 weeks off treatment) or pazopanib 800 mg orally once daily. Original dual primary end points were progression-free survival and overall survival. Enrollment was stopped when a phase 3 study in melanoma of pembrolizumab plus epacadostat compared with pembrolizumab monotherapy did not meet its primary end point. This protocol was amended, and primary end point was changed to investigator-assessed objective response rate (ORR) per RECIST 1.1. Results: One-hundred-twenty-nine patients were randomly assigned to receive pembrolizumab plus epacadostat (n = 64) or sunitinib/pazopanib (n = 65). Median (range) follow-up, defined as time from randomization to data cutoff, was 10.3 months (2.2–14.3) and 10.3 months (2.7–13.8) in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. ORRs were similar between pembrolizumab plus epacadostat (31.3% [95% CI 20.2–44.1] and sunitinib/pazopanib (29.2% [18.6–41.8]). Grade 3–5 treatment-related adverse events occurred in 34.4% and 42.9% of patients in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. One patient in the sunitinib/pazopanib arm died of septic shock (not treatment-related). Circulating kynurenine levels decreased in the pembrolizumab plus epacadostat arm, but not to levels observed in healthy subjects. Conclusions: ORRs were similar between pembrolizumab plus epacadostat and sunitinib/pazopanib as first-line treatment in patients with mRCC. Safety and tolerability appeared similar between treatment arms; no new safety concerns were identified. Antitumor responses observed in patients with RCC receiving pembrolizumab plus epacadostat may be driven primarily by pembrolizumab.
- 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.
- ItemExamen de detección de virus papiloma humano en el tamizaje de cáncer cervicouterino en un Servicio de Salud de Santiago, Chile(2015) Terrazas, Solana; Ibáñez Cáceres, Carolina; Lagos, Marcela; Poggi, Helena; Brañes, Jorge; Barriga Cosmelli, María Isabel; Cartagena, Jaime; Núñez, Felipe; González, Francisca; Cook, María Paz; Van De Wyngard, Vanesa; Ferreccio Readi, Catterina; Terrazas, Solana; Ibáñez Cáceres, Carolina; Lagos, Marcela; Poggi, Helena; Brañes, Jorge; Barriga, María I.; Cartagena, Jaime; Núñez, Felipe; González, Francisca; Cook, María Paz; Van De Wyngard, Vanesa; Ferreccio Readi, Catterina
- ItemHigh linoleic acid levels in red blood cells predict a poor response to neoadjuvant chemotherapy in human epidermal growth factor receptor type 2-positive breast cancer patients(2024) Rodrigo Valenzuela; Walbaum García, Benjamín Vicente; Farías Castro, Camila ; Acevedo Claros, Francisco Nicolás; Vargas Añazco, Catalina Andrea; Bennett Lason, José Tomás; Bravo, M. Loreto; Pinto, Mauricio P.; Medina Araya, Lidia Marjorie; Merino Lara, Tomás Rodrigo; Ibáñez Cáceres, Carolina; Parada Daza, Alejandra Cristina; Sánchez Rojel, César GiovanniObjective Polyunsaturated fatty acids are categorized as ω-3 or ⍵-6. Previous studies demonstrate that breast cancers display a high expression of fatty acid synthase and high fatty acid levels. Our study sought to determine if changes in plasma or red blood cell membrane fatty acid levels were associated with the response to preoperative (neoadjuvant) chemotherapy in non-metastatic breast cancer patients.MethodsOur prospective study assessed fatty acid levels in plasma and red blood cell membrane. Response to neoadjuvant chemotherapy was evaluated by the presence or absence of pathologic complete response and/or residual cancer burden.ResultsA total of 28 patients were included. First, patients who achieved pathologic complete response had significantly higher neutrophil-to-lymphocyte ratio versus no pathologic complete response (P = 0.003). Second, total red blood cell membrane polyunsaturated fatty acids were higher in the absence of pathologic complete response (P = 0.0028). Third, total red blood cell membrane ⍵-6 polyunsaturated fatty acids were also higher in no pathologic complete response (P < 0.01). Among ⍵-6 polyunsaturated fatty acids, red blood cell membrane linoleic acid was higher in the absence of pathologic complete response (P < 0.01). Notably, plasma polyunsaturated fatty acid, ⍵-6, and linoleic acid levels did not have significant differences. A multivariate analysis confirmed red blood cell membrane linoleic acid was associated with no pathologic complete response; this was further confirmed by receiver operating characteristic analysis (specificity = 92.3%, sensitivity = 76.9%, and area under the curve = 0.855).ConclusionsPending further validation, red blood cell membrane linoleic acid might serve as a predictor biomarker of poorer response to neoadjuvant chemotherapy in non-metastatic human epidermal growth factor receptor type 2–positive breast cancer. Measuring fatty acids in red blood cell membrane could offer a convenient, minimally invasive strategy to identifying patients more likely to respond or those with chemoresistance.
- ItemHPV vaginal self-sampling among women non-adherent to Papanicolaou screening in Chile(2013) Léniz Martelli, Javiera; Barriga Cosmelli, María Isabel; Lagos Lucero, Marcela; Ibáñez Cáceres, Carolina; Puschel Illanes, Klaus; Catterina Ferreccio
- ItemImpact of Adjuvant FOLFOX on Quality of Life and Peripheral Neuropathy Incidence in Patients With Gastric Cancer: A Prospective Cohort Study(Elsevier Inc., 2023) Mondaca Contreras, Sebastián Patricio; Pinto, Mauricio P.; Briones Carvajal, Juan Rodrigo; Caire, Nicole; Peña Prado, José Tomas; Koch Hein, Erica Cristina; Muñiz Muñoz, Maria Sabrina; Herrera, María Elisa; Sanchez Rojel, Cesar Giovanni; Galindo Aranibar, Héctor Gonzalo; Pizarro Brito, Gonzalo Ignacio; Acevedo Claros, Francisco Nicolas; Ibáñez Cáceres, Carolina; Balmaceda Araque, Carlos Felipe; Norero, Enrique; Duran, Doris; Garrido Salvo, Marcelo Adán; Nervi Nattero, BrunoObjectives: Perioperative and adjuvant chemotherapy have demonstrated clinical benefits in localized gastric cancer. Nevertheless, the reports on their effects on patient's health-related quality of life (HRQoL) are scarce. Here, we prospectively assessed quality of life and the incidence of chemotherapy-induced peripheral neuropathy (CIPN) in a cohort of patients treated with adjuvant FOLFOX. Methods: Localized stomach or gastroesophageal junction adenocarcinoma patients who underwent curative resection were recruited at a single center. All patients received adjuvant FOLFOX6, and HRQoL and CIPN were assessed using the European organization for research and treatment of cancer quality life (EORTC) C30 and the EORTC CIPN20 questionnaires, respectively. Clinically significant deterioration of HRQoL was also assessed as a coprimary outcome in a longitudinal analysis. Results: We recruited a total of 63 patients. Median age was 62.5 years, and 75% had stomach tumors. Twenty-four weeks after the start of treatment, the probability of being free from HRQoL deterioration and CIPN was 29% (95% confidence interval [CI] 18%-42%) and 6% (95% CI 2%-17%), respectively. Five-year disease-free survival was 45% (95% CI 24%-64%) and 5-year overall survival was 63% (95% CI 48%-76%). Conclusions: Adjuvant FOLFOX is associated with a high rate of long-term survival in localized gastric cancer; nevertheless, it has detrimental effects on patients’ quality of life.
- ItemLeptin promotes a more aggressive behavior of ovarian cancer cells : a potential explanation for a worse prognosis in obese ovarian cancer patients(2015) Cuello F., Mauricio; Kato Cardemil, Sumie Rode; Abarzúa Catalán, L.; Delpiano, A.; García, K.; Sanhueza, C.; Ibáñez Cáceres, Carolina; Brañes Yunusic, Jorge Antonio; Castellón E.; Owen, Gareth Ivor; Trigo, C.
- ItemLeptin stimulates migration and invasion and maintains cancer stem-like properties in ovarian cancer cells : an explanation for poor outcomes in obese women(2015) Kato Cardemil, Sumie Rode; Abarzúa Catalán, Lorena; Trigo, César; Delpiano, Ana; Sanhueza, Cristobal; García, Karen; Ibáñez Cáceres, Carolina; Hormazábal, Katherine; Díaz Bórquez, Daniela Aida; Brañes Yunusic, Jorge Antonio; Castellón, Enrique; Bravo, Erasmo; Owen, Gareth Ivor; Cuello F., Mauricio
- ItemMulti-Objective Optimization for Personalized Prediction of Venous Thromboembolism in Ovarian Cancer Patients(2020) Fresard, M. E.; Erices Vidal, Rafaela Miguelina; Bravo Castillo, Maria Loreto; Cuello F., Mauricio; Owen, Gareth Ivor; Ibáñez Cáceres, Carolina; Rodríguez Fernández, María
- ItemPalbociclib in advanced stage hormone receptor-positive breast cancer: real- world data from a Chilean multicentre registry(2023) Walbaum García, Benjamín Vicente; Reyes, José Miguel ; Rodríguez, Pablo ; Muñiz Muñoz, María Sabrina; Medina Araya, Lidia Marjorie; Ibáñez Cáceres, Carolina; Merino Lara, Tomás Rodrigo; Pinto, Mauricio ; Bravo, María Loreto ; Acevedo Claros, Francisco Nicolás; Bennett Laso, José Tomás; Sánchez Rojel, César GiovanniBackground The addition of cyclin-dependent kinases inhibitors (CDKi) to endocrine therapy (ET) as the first- or second line treatment improves progression-free and overall survival (OS) in hormone receptor-positive, HER2 negative (HR+/HER2-) advanced stage breast cancer (ABC). Our study compared survival rates and prognostic factors in Chilean patients that used palbociclib as first or subsequent (≥second) lines of treatment in a real-world setting.Methods Our retrospective population-cohort study included HR+/HER2- ABC patients. We calculated 5-year OS and performed a multivariate analysis to determine prognostic factors.Results A total of 106 patients were included. Median age was 49 years (19–86), 28.3% (30) had de novo stage IV disease; 63% received palbociclib with ET as first line, 54% of them with aromatase inhibitor over fulvestrant. Median OS for the entire cohort was 99 months and 5-year OS was 69%. Patients that received first line palbociclib had a 5-year OS of 89% versus 43% for ET monotherapy or ≥second line palbociclib (p = 0.0062). Multivariate analysis showed that the year at diagnosis and CDKi timing (first line versus ≥second line) were significantly associated with OS.Conclusion Our real-world data show that first-line CDKi + ET provides a statistically significant benefit in OS versus ≥second line in HR+/HER2- ABC patients.
- ItemScreening trial of human papillomavirus for early detection of cervical cancer in Santiago, Chile(2013) Ferreccio Readi, Catterina; Barriga Cosmelli, María Isabel; Lagos Lucero, Marcela; Ibáñez Cáceres, Carolina; Poggi, Helena; González, F.; Terrazas Martins, Solana; Katki, H.; Núñez, F.; Cartagena, J.; Van De Wyngard, V.; Vinales, D.; Brañes, Jorge
- ItemSuboptimal use of ovarian function suppression in very young women with early breast cancer: a real-world data study(2024) Heredia Castro, Ana Manuela; Walbaum García, Benjamín Vicente; Vidal, María ; Itriago Giménez, Laura Morella; Camus Appuhn, Mauricio Gonzalo; Domínguez Covarrubias, Francisco José; Manzor, Manuel ; Martínez, Raúl ; Murature, Geraldine ; Muñiz Muñoz, María Sabrina; Navarro, Marisel ; Guerra, Constanza ; Merino Lara, Tomás Rodrigo; Medina Araya, Lidia Marjorie; Ibáñez Cáceres, Carolina; Ramírez Parada, Karol Lilia; Acevedo Claros, Francisco Nicolás; Sánchez Rojel, César GiovanniPurpose The incidence of breast cancer in young women (BCYW) has increased in recent decades. Malignant disease in this subset is characterized by its aggressiveness and poor prognosis. Ovarian function suppression (OFS) in these patients improves survival especially in hormone receptor-positive (HR +) cases. The Regan Composite Risk (RCR) is a prognostic tool to identify high-risk HR + BC candidates for OFS. Our study sought to characterize a Chilean cohort of early HR + BCYW assessing the use of OFS and its related prognosis and the utility of RCR in our patients.MethodsThis was a retrospective population cohort study that included ≤ 35-year-old early HR + /human epidermal growth factor receptor 2 -negative (HER2-) BC patients treated between 2001 and 2021. Analysis included clinical-pathological characteristics, treatment strategies, and survival. Also, we evaluated the association between RCR and survival.ResultsA total of 143 patients were included into our study, representing 2.9% of all early BC cases in our registry. Median age was 31 years old (range: 19–35). Most patients (93%) received endocrine therapy (ET). Of these, 18% received OFS. No survival differences were observed among treatment strategies. Median RCR score for patients treated with CT plus ET was significantly higher vs. ET alone (2.95 vs. 1.91; p = 0.0001). Conversely, patients treated with tamoxifen alone had significantly lower RCR scores vs. OFS (2.72 vs. 3.14; p = 0.04). Higher RCR scores were associated with poorer overall survival.ConclusionLess than 20% of very young women with early HR + /HER2-BC in our cohort received OFS, in most cases, this involved surgical oophorectomy. RCR score was higher in patients that underwent CT and OFS and was associated with survival, regardless of treatment. We confirm the RCR score as a valuable prognostic tool to identify high-risk BC patients who could benefit from OFS.
- ItemUpper-Limb Disability and the Severity of Lymphedema Reduce the Quality of Life of Patients with Breast Cancer-Related Lymphedema(2023) Ramírez Parada, Karol Lilia; González Santos, Angela ; Riady Aleuy, Layla ; Pinto, Mauricio P.; Ibáñez Cáceres, Carolina; Merino Lara, Tomás Rodrigo; Acevedo Claros, Francisco Nicolás; Walbaum García, Benjamín Vicente; Fernández Verdejo, Rodrigo ; Sánchez Rojel, César GiovanniBreast cancer-related lymphedema (BCRL) is characterized by arm swelling, pain, and discomfort, reducing the quality of life (QoL) of affected individuals. BRCL is caused via the blockage or disruption of the lymphatic vessels following cancer treatments, leading to an accumulation of fluid in the affected arm. While current BCRL rehabilitation treatments seek to reduce arm swelling, our study aimed to examine the impact of both the magnitude of lymphedema (ΔVolume) and arm disability on three dimensions of QoL: social, physical, and psychological. Using the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) and the Upper Limb Lymphedema 27 questionnaire (ULL) in a group of 30 patients, we found that the magnitude of lymphedema (ΔVolume) was associated with the social dimension of QoL (r = 0.37, p = 0.041), but not with other dimensions. On the other hand, arm disability was associated with all evaluated dimensions of QoL (social, physical, and psychological: p < 0.001, p = 0.019, and p = 0.050 (borderline), respectively). These findings suggest that BCRL rehabilitation strategies should not only aim to reduce the magnitude of lymphedema but should also seek to improve or preserve arm functionality to enhance the QoL of BCRL patients.