Browsing by Author "Mondaca, Sebastian"
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- 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.
- ItemClinical utility of next-generation sequencing-based ctDNA testing for common and novel ALK fusions(2021) Mondaca, Sebastian; Lebow, Emily S.; Namakydoust, Azadeh; Razavi, Pedram; Reis-Filho, Jorge S.; Shen, Ronglai; Offin, Michael; Tu, Hai-Yan; Murciano-Goroff, Yonina; Xu, Chongrui; Makhnin, Alex; Martinez, Andres; Pavlakis, Nick; Clarke, Stephen; Itchins, Malinda; Lee, Adrian; Rimner, Andreas; Gomez, Daniel; Rocco, Gaetano; Chaft, Jamie E.; Riely, Gregory J.; Rudin, Charles M.; Jones, David R.; Li, Mark; Shaffer, Tristan; Hosseini, Seyed Ali; Bertucci, Caterina; Lim, Lee P.; Drilon, Alexander; Berger, Michael F.; Benayed, Ryma; Arcila, Maria E.; Isbell, James M.; Li, Bob T.Objectives: Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) can detect ALK fusions, though data on clinical utility of this technology in the real world is limited. Materials and Methods: Patients with lung cancer without known oncogenic drivers or who had acquired resistance to therapy (n = 736) underwent prospective plasma ctDNA NGS. A subset of this cohort (n = 497) also had tissue NGS. We evaluated ALK fusion detection, turnaround time (TAT), plasma and tissue concordance, matching to therapy, and treatment response. Results: ctDNA identified an ALK fusion in 21 patients (3%) with a variety of breakpoints and fusion partners, including EML4, CLTC, and PON1, a novel ALK fusion partner. TAT for ctDNA NGS was shorter than tissue NGS (10 vs. 20 days; p < 0.001). Among ALK fusions identified by ctDNA, 93% (13/14, 95% CI 66%- 99%) were concordant with tissue evaluation. Among ALK fusions detected by tissue NGS, 54% (13/24, 95% CI 33%-74%) were concordant with plasma ctDNA. ctDNA matched patients to ALK-directed therapy with subsequent clinical response, including four patients matched on the basis of ctDNA results alone due to inadequate or delayed tissue testing. Serial ctDNA analysis detected MET amplification (n = 2) and ALK G1202R mutation (n = 2) as mechanisms of acquired resistance to ALK-directed therapy. Conclusion: Our findings support a complementary role for ctDNA in detection of ALK fusions and other alterations at diagnosis and therapeutic resistance settings.
- 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
- ItemDifferential expression of programmed cell death ligand 1 (PD-L1) and inflammatory cells in basal cell carcinoma subtypes(2022) Gompertz-Mattar, Matias; Perales, Juan; Sahu, Aditi; Mondaca, Sebastian; Gonzalez, Sergio; Uribe, Pablo; Navarrete-Dechent, CristianFew studies have evaluated programmed cell death ligand (PD-L1) expression and lymphocytic infiltrates in Basal Cell Carcinoma (BCC). The objectives of this study are to assess PD-L1 expression and markers of local immune response in nodular, superficial, and morpheaform BCC, and compare it to normal, sun-exposed skin from the periphery of intradermal nevi. This was a retrospective study that included three histological subtypes of BCCs, and sun-exposed skin from the periphery of dermal nevi as quality controls. Tissue microarrays (TMA) were constructed with subsequent staining of H&E and immunohistochemistry (IHC) for CD4, CD8, FOXP3 and PD-L1. Non-automated quantification of the infiltrate in the intratumoral and stromal compartments on TMAs was performed. A total of 115 BCC (39 nodular, 39 morpheaform, and 37 superficial) and 41 sun-exposed skin samples were included (mean age 65.4 years; 52.6% females). BCC showed higher expression of PD-L1 (5.4 vs 0.7%, p < 0.001), CD8 (29.8 vs 19.7%, p = 0.002), and FOXP3 (0.3 vs 0.06%, p = 0.022) compared to sun-exposed skin. There was a higher PD-L1 expression in nodular BCC compared with other subtypes. Low-risk BCC subtypes (superficial and nodular) exhibited more PD-L1 expression in intratumoral and stromal immune infiltrates as compared to high-risk BCC subtypes. As a limitation, no immune cells function was evaluated in this study, only the presence/absence of T-lymphocyte sub-populations was recorded. Substantial differences in both PD-L1 expression and lymphocytic infiltrates were found amongst the histological subtypes of BCC and sun-exposed skin. Highest PD-L1 expression was found in nodular BCCs which suggests a potentially targetable strategy in the treatment of this most common BCC subtype.
- 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.
- ItemKinetic of humoral response induced by SARS-CoV-2 infection in convalescent plasma receptors and donors(WILEY, 2021) Barrera, Aldo; Martinez Valdebenito, Constanza; Rojas Orellana, Luis; Vizcaya Altamirano, Cecilia; Elena Ceballos, Maria; Pereira, Jaime; Chang, Mayling; Mondaca, Sebastian; Sarmiento, Mauricio; Ross, Patricio; Henriquez, Carolina; Nervi, Bruno; Ferres, Marcela; Balcells, Elvira; Le Corre, Nicole
- 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.
- ItemQuantitative Ocular Surface Changes in Patients Undergoing Immune Checkpoint Inhibitor Therapy(2024) Chen, Kevin; Bruron, Maria Carolina Ibanez; Mondaca, Sebastian; Pizarro, Gonzalo; Liberman, Paulina; Berkenstock, Meghan K.PurposeTo describe the clinical course and evaluate treatment of ocular surface changes in patients receiving immune checkpoint inhibitor (ICI) therapy.MethodsMultiple markers of ocular surface dryness were evaluated in 16 patients on ICI therapy. The Wilcoxon rank-sum test was used to determine the significant change in the initial and final ocular surface indices.ResultsFifty percent of the eyes demonstrated worsening Schirmer I scores; 29% showed an increase in lissamine green staining. During follow-up, 43% of patients experienced a decline in OSDI scores. Treatments included preservative-free artificial tears (88%), cyclosporine (25%), topical corticosteroids (31%), warm compresses (25%); punctal plugs (13%). Median follow-up time was 3.4 months (range:0-79 ); median ICI treatment duration was 7 months (range:1-40). Four patients died during the observation period.ConclusionA significant proportion of patients experience changes in ocular surface markers while treated with ICIs. Medical intervention can lead to stabilization of ocular surface disease.