Neurooncología

Challenges in Launching a Precision Pediatric Oncology Program in Argentina

Mon, 01 Jun 2026 00:00:00 GMT

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.

Prognostic significance of CDKN2A/B hemizygous deletion in IDH-mutant astrocytomas : a systematic review and meta-analysis

Tue, 17 Mar 2026 00:00:00 GMT

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.

Efficacy and safety of erdafitinib in pediatric patients with advanced solid tumors and FGFR alterations in the phase 2 RAGNAR trial

Sat, 01 Jun 2024 00:00:00 GMT

Efficacy and safety of erdafitinib in pediatric patients with advanced solid tumors and FGFR alterations in the phase 2 RAGNAR trial Olaf Witt, Sameer Farouk Sait; Diez, Blanca; Cardoso, Agustín; Reardon, David A.; Welsh, Liam; Shih, Kent C.; Baldini, Capucine; Massard, Christophe; Loriot, Yohann; Pant, Shubham; Sweiti, Hussein; Thomas, Shibu; Hammond, Constance; Najmi, Saltanat; Triantos, Spyros; Crow, Lauren; Geoerger, Birgit Background: Erdafitinib is an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved in the US for adult patients (pts) with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations, as determined by an FDA-approved companion diagnostic test, whose disease has progressed on or after ≥1 line of prior systemic therapy. Primary analysis of the RAGNAR study Broad Panel Cohort demonstrated tumor agnostic efficacy in pts with solid tumors harboring predefined FGFR mutations or fusions (Pant 2023). Here we report on Final Analysis of efficacy and safety results from the Pediatric Cohort of the RAGNAR study. Methods: Pediatric pts ≥6 years with advanced solid tumors and any FGFR mutation, fusion, or tandem duplication received oral erdafitinib. Starting doses were 8 mg, 5 mg, and 3 mg daily for ages > 15 years, 12 to < 15 years, and 6 to < 12 years, respectively, in 21-day cycles with possible individualized up-titration based on serum phosphate and adverse events (AEs). The primary endpoint was objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 or Response Assessment in Neuro-Oncology [RANO]) by independent review committee (IRC). Secondary endpoints included ORR by investigator, duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). Results: 11 pts (median age 13 years; range, 6-16; 64% female) received erdafitinib. Median follow-up was 9.7 months at data cutoff. Histologies included low-grade glioma (LGG-6 pts); high-grade glioma (HGG-3 pts); soft tissue sarcoma (1 pt), and temporal neurocytoma (TNEURO-1 pt). 7, 1, and 3 pts had FGFR1, FGFR2,and FGFR3 alterations, respectively. 6, 4, and 1 pts had FGFR fusions, mutations, and tandem duplication, respectively. Pts had a median of 1 prior line of systemic treatment; 6 (55%) had prior radiotherapy. At data cutoff, 1 of 3 pts (33%) with HGG and an FGFR1-TACC1 fusion achieved a partial response based on investigator assessment with a response duration of 19.8 months. Investigator-assessed objective responses were not observed in the other tumor types. DCR and CBR were 100% in pts with LGG and 67% in pts with HGG. Most common treatment-emergent adverse events (TEAEs) included hyperphosphatemia (64%), diarrhea (64%), pain in extremity (45%), alanine transaminase increased (36%), nausea (36%), and onycholysis (27%). No central serous retinopathy events occurred; related serious adverse events (SAEs) occurred in 4 (36%) pts, including 1 SAE of epiphysiolysis; there were no related TEAEs leading to death. Conclusions: In this small pediatric population comprising primarily refractory HGG and LGG with any FGFR alteration, erdafitinib demonstrated limited objective responses but promising disease control with acceptable safety.

Clinical efficacy of a next-generation sequencing (NGS) and immunohistochemistry (IHC) panel in patients with advanced cancer in Argentina.

Wed, 29 May 2024 00:00:00 GMT

Clinical efficacy of a next-generation sequencing (NGS) and immunohistochemistry (IHC) panel in patients with advanced cancer in Argentina. Cantarella, Florencia; Mendoza Bertelli, Andrea; Girotti, Romina; Marino, Ana Clara; Brest, Esteban; Dibarbora, Delfina; Mahmoud, Yamil; Veigas, Florencia; Enrico, Diego Hernan; Tsou, Florencia; Lacava, Juan A.; Piazzoni, Luciano; Riso, Aldo Alejandro; Martinengo, Gastón L.; Rodriguez, Andrés; Beguelin, Zenon; Cerrato, Sebastián; Jerez, Ignacio; Salanova, Rubén Background: The analysis of somatic genomic alterations, evaluation of DNA mismatch repair (MMR) proteins, and examination of PD-L1 expression in tumor biopsies are crucial for prognosis and informed therapeutic decisions. However, their clinical implementation in Argentina faces challenges due to economic costs and lack of evidence. To address this, we conducted a retrospective study to assess the impact of this molecular panel testing on treatment decisions and clinical management of cancer patients in Argentina. Additionally, we evaluated its ability to detect clinically relevant alterations and analyzed the frequency and cooccurrence of mutations in our cohort. Methods: Tumor tissue samples from 266 patients with primary tumors, representing 26 different anatomical sites (53% lung cancer), underwent molecular testing using the Optimus panel developed by Biomakers. The assay integrates somatic sequencing of 52 genes through NGS with IHC assessment ofMMRand PD-L1 proteins. A retrospective evaluation of the clinical effectiveness of the test was conducted on 133 patients. Genomic and clinical data were analyzed usingRwith the pairwise Fisher’s exact test applied for statistical analysis. Results: This panel facilitates molecular characterization, identifying clinically relevant genetic alterations in 65% of patients and detecting deficiency in MMR proteins in 3%. Findings align with global clinical trial availability for identified alterations in 97% of cases. KRAS is the most frequently mutated gene (38%), followed by EGFR (19%), PIK3CA (12%), BRAF (9%), CDK4, and CTNNB1 (5% each), correlating with lung cancer overrepresentation. Simultaneous alterations in EGFR, PIK3CA, CTNNB1, and KIT genes were observed. Pan-tumoral interaction analysis revealed mutual exclusivity between KRAS mutations and those in EGFR, BRAF, CDK4, and CTNNB1. CTNNB1 mutations co-occurred with EGFR mutations, akin to KIT and PDGFRA (p,0.05). The retrospective analysis indicated that the Optimus panel contributed to clinical management of patients in 56% of cases, with 85% detecting clinically relevant variants, aiding treatment definition in 74% of these cases. Conclusions: The Biomakers-developed Optimus panel empowers the molecular characterization of genomic and proteomic biomarkers across tumor types. Its significance in clinical practice lies in contribution to vital decision-making processes, particularly in treatment selection.