Efficacy of next-generation genomic sequencing (NGS) applied to cerebrospinal fluid (CSF) in the identification of actionable mutations in Mexican patients.

person Iván Romarico González Espinoza Hospital Ángeles Puebla, Puebla, Mexico info_outline Iván Romarico González Espinoza, Sergio Sánchez-Sosa, Abraham Castro-Ponce, Gabriela Sandoval-Amaro, Gabriela Juárez-Salazar, Ana Isabel Nieva, Galo Ismael Íñiguez López, Eric Acosta Ponce de León, Jorge Esteban Aranda, Julio Cesar Garibay Diaz, Mariana Chiquillo-Domínguez

Authors person Iván Romarico González Espinoza Hospital Ángeles Puebla, Puebla, Mexico info_outline Iván Romarico González Espinoza, Sergio Sánchez-Sosa, Abraham Castro-Ponce, Gabriela Sandoval-Amaro, Gabriela Juárez-Salazar, Ana Isabel Nieva, Galo Ismael Íñiguez López, Eric Acosta Ponce de León, Jorge Esteban Aranda, Julio Cesar Garibay Diaz, Mariana Chiquillo-Domínguez Organizations Hospital Ángeles Puebla, Puebla, Mexico, Hospital Ángeles Puebla, Puebla, PU, Mexico Abstract Disclosures Research Funding No funding sources reported Background: Among the benefits offered by NGS from liquid biopsy are the molecular classification of neoplasms as well as the identification of therapeutic targets, without the need to obtain a biopsy of the tumor when it is not feasible. Since 2016, the World Health Organization has included these biomarkers as part of its classification for better management. Additionally, in the case of metastatic tumors, it allows the identification of therapeutic targets as well as resistance mutations and even driver mutations to better understand their biology. In this study, we evaluated the efficacy of CSF NGS in the identification of actionable mutations in patients with CNS neoplasms, and its potential impact on the personalization of cancer treatments for patients in our center. Methods: A retrospective analysis of nine cases was performed in which CSF was used to identify NGS-actionable mutations, collecting, and descriptively analyzing clinical and molecular data from these patients. Results: Mean age was 51.89 years; 55.56% were men and 44.44% women; 66.67% had family history of cancer, of which 83.33% were first-degree relatives; 88.89% had neurological symptoms prior to the study; 33.33% were primary CNS tumors; 55.56% were secondary tumors metastatic to the CNS; 11.11% were indicated due to suspected CNS metastasis. At least 1 genomic alteration was found in 89% of the cases; the most frequently altered gene in primary tumors was TP53 (66.67%). In secondary tumors, the most frequently altered genes were AR and EGFR with 40% incidence each; Approved therapies were found in 55.56% of the cases, therapies approved in other neoplasms in 44.44%, and phase 2 or 3 clinical trials were available in 88.89%. Specific alterations found in are listed in the table. Survival rate at 6-month follow-up was 55.56%. Conclusions: In our patients, the study of CSF through NGS effectively identified actionable mutations with approved treatment in the analyzed neoplasms, other neoplasms, or clinical trials available for enrollment in most cases. In one case, it was possible to rule out the presence of metastasis in CNS, avoiding unnecessary toxicity. To our knowledge, this is the first study in our country that reports the findings of this technique in medical practice, however, more research is needed in bigger populations to optimize and validate the implementation of this study as part of the approach to patients with CNS tumors. Cases and alterations. Neoplasm Alteration Glioblastoma TP53 (R273C) Glioblastoma PIK3CA (E545A) MTOR (S2215F) Glioblastoma TP53(R282W) Lung Adenocarcinoma EGFR (Ex19del) EGFR (Amp) ERBB2 (Amp) MET (Amp) TP53 (P152L) ERBB3 (Amp) Lung Adenocarcinoma EGFR (L861Q) EGFR (Amp) Lung Adenocarcinoma AR (Amp) Melanoma BRAF (V600E) KRAS (A59T) AR (Amp) RAF1 (S259F) Squamous Cervical Cancer PIK3CA (Amp) Clear Cell Renal Carcinoma No Alterations