https://repositorio.fleni.org.ar/xmlui/handle/123456789/38 2026-09-01T12:02:19Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1572 Challenges in Launching a Precision Pediatric Oncology Program in Argentina Paladino, María Mercedes; Pinto, Nicolás; Verón, David; Morosini, Fabiana; García Rivello, Hernán; Alves da Quinta, Daniela; Ganiewich, Daiana; Varela, Mariana; Diez, Blanca; de Dávila, María Teresa; Villarroel, Milena; de Sá Rodrigues, Karla Emília; Villanueva, Gabriela; Solorzano, Daniel; Casanovas, Alejandra; Rotondaro, Cecilia; Arrossi, Silvina; Chantada, Guillermo L.; Llera, Andrea S. Background/objectives: Advances in pediatric cancer care have underscored the importance of tumor sequencing for diagnosis and treatment selection. However, access to genomic diagnostics in Latin America remains limited. The COPPA Project, an initiative based in Argentina, was conceived to assess the feasibility of delivering clinically useful genomic sequencing for childhood cancers at no cost while maximizing the clinical value of genomic data through multidisciplinary molecular tumor boards (MTBs). Design/methods: Project planning involved securing funding, establishing a sequencing facility, selecting and optimizing an NGS panel, training technical staff in sequencing and interpretation, addressing sample transportation logistics, recruiting oncologists from multiple institutions, and promoting the establishment and participation in a virtual MTB. Tumors underwent sequencing using the Illumina Cancer Childhood Panel. Results were reported and discussed with the treating physicians and during MTB meetings. A survey was administered to MTB participants to assess perceived barriers and facilitators related to the project. Results: A total of 38 tumors were analyzed, 24 of which were sequenced in-house. Genomic findings were considered to have clinical utility in 67% of cases. Barriers such as a low demand for studies and oncologists' lack of time for MTBs were identified. Survey responses highlighted the educational value of the MTBs, with all respondents reporting increased knowledge of precision medicine and greater motivation to adopt genomic testing in clinical practice. Conclusion: This study identifies key barriers and facilitators encountered in a middle-income setting. These findings may inform future efforts to implement precision medicine approaches for pediatric cancer in the region. 2026-06-01T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1568 Prognostic significance of CDKN2A/B hemizygous deletion in IDH-mutant astrocytomas : a systematic review and meta-analysis Nakasu, Satoshi; Deguchi, Shoichi; Mezmezian, Mónica Beatriz; Mitsuya, Koichi; Notsu, Akifumi; Nakasu, Yoko The prognostic significance of CDKN2A/B hemizygous deletion (HemD) in IDH-mutant astrocytomas (A-IDHm) remains unclear. We conducted a systematic review and WHO grade-specific meta-analysis of primary tumors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Effect sizes included hazard ratios (HRs) and restricted mean survival time (RMST) for overall survival. The pooled frequency of HemD in grade 2 A-IDHm was 13.8% (95% confidence interval [CI]: 8.5–21.7%; 12 studies; I2 = 23.6%), lower than that in grade 3 tumors (25.2% [CI: 20.5–30.5%; 12 studies; I2 = 0%]) and grade 4 tumors with CDKN2A/B non-homozygous deletion (29.5% [CI: 23.3–36.6%]; 11 studies; I2 = 0%). Stratification by WHO grade revealed a significant association in grade 2 tumors (pooled HR [pHR]: 1.98 [CI: 1.03–3.80]; four studies; 369 patients; P = 0.04; I2 = 0%), but no significant association in grade 3 (pHR: 1.78 [CI: 0.99–3.20]; five studies, 239 patients; P = 0.054; I2 = 0%) or grade 4 tumors (pHR: 1.39 [CI: 0.85–2.26]; five studies; 192 patients; P = 0.18; I2 = 0%). The RMST difference reached statistical significance only in WHO grade 2 tumors, suggesting a potential prognostic effect of HemD in low-grade A-IDHm. 2026-03-17T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/995 Análisis del valor diagnóstico de la metilomica en tumores cerebrales primarios de una única institución Yorio, Florencia; Cerrato, Sebastián; Calabrese, Bernadette; Palomar, Nicolás; Cardoso, Agustín; Arakaki, Naomi; Martinetto, Horacio; Diez, Blanca; Muggeri, Alejandro Introducción: Existen importantes discrepancias en el diagnóstico histopatológico de los aproximadamente 100 tipos de tumores cerebrales primarios. En los últimos años se han incorporado técnicas como la biología molecular y más recientemente el análisis del perfil de metilación de ADN (metilómica) que permitiría alcanzar un diagnóstico más preciso. Objetivos: Determinar el valor diagnóstico de la metilómica en tumores primarios del sistema nervioso central. Materiales y métodos: se realizó un análisis retrospectivo comparando el diagnóstico convencional aportado por informes de anatomía patológica con el diagnóstico proporcionado por un clasificador online basado en perfiles de metilación de ADN (según este clasificador un score de coincidencia ≥0.9 sugiere diagnóstico de certeza del tipo/subtipo tumoral). Se evaluaron 119 pacientes con tumores cerebrales primarios tratados en nuestra institución, desde Marzo 2019 a Febrero 2023. Se incluyeron pacientes de todas las edades. Resultados: Noventa y uno de 119 pacientes (76%) tuvieron un score > 0,9 por análisis metilómico. En 86/119 pacientes (72%) hubo coincidencia entre el diagnostico histopatológico y el análisis por perfil de metilación. En 5/119 pacientes (4%) hubo discrepancia entre la clasificación por perfil de metilación y el análisis histopatológico. En pacientes sin diagnóstico histopatológico preciso, 10/22 tuvieron score >0,9 por metilómica. Es decir, en un 47% de los casos con dificultades para arribar a un diagnóstico histopatológico, la metilación de ADN permitió realizar un diagnóstico preciso. En los casos de Meduloblastoma, la coincidencia patología-metilómica fue del 100% aunque se observó un 28% de error diagnóstico cuando se utilizó sólo la IHQ para determinar el subtipo molecular. Conclusiones: Un adecuado seguimiento y tratamiento oncológico requiere de un correcto diagnóstico inicial. El perfil de metilación de ADN en tumores primarios del sistema nervioso central provee una nueva herramienta que aporta información relevante para obtener un diagnóstico aun en los casos en que el análisis histopatológico no es concluyente. 2023-12-15T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/767 Characteristics of children ≤36 months of age with DIPG: A report from the international DIPG registry Bartlett, Allison L.; Lane, Adam; Chaney, Brooklyn; Yanez Escorza, Nancy; Black, Katie; Cochrane, Anne; Minturn, Jane; Bartels, Ute; Warren, Kathy; Hansford, Jordan; Ziegler, David; Diez, Blanca; Goldman, Stewart; Packer, Roger; Kieran, Mark; DeWire-Schottmiller, Mariko; Erker, Craig; Monje-Deisseroth, Michelle; Wagner, Lars; Koschmann, Carl Background: Children ≤36 months with diffuse intrinsic pontine glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes. Methods: Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed. Results: Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3-, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (P = .018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation. Conclusions: Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis. 2022-12-01T00:00:00Z