A high number of co-occurring genomic alterations detected by NGS is associated with worse clinical outcomes in advanced EGFR-mutant lung adenocarcinoma: Data from LATAM population.

BACKGROUND: Co-occurring genomic alterations identified downstream main oncogenic drivers have become more evident since the introduction of next-generation sequencing (NGS) analyses at diagnosis and progression. Emerging evidence has stated that co-occurring genomic alterations at diagnosis might represent de novo and primary resistance mechanisms to tyrosine kinase inhibitors (TKIs) in advanced EGFR-mutant (EGFRm) non-small lung cancer (NSCLC). In this study, we assessed the prognostic role of co-occurring genomic alterations in advanced EGFRm NSCLC. METHODS: A cohort of 111 patients with advanced NSCLC harboring EGFR-sensitive mutations detected by PCR was analyzed in 5 Latin American oncological centers from January 2019 to December 2020. All eligible patients received upfront therapy with EGFR-TKI. Co-occurring genomic alterations were determined at diagnosis in every patient by the NGS (FoundationOneCDx) comprehensive platform, which evaluates 324 known cancer-related genes. RESULTS: EGFR exon19 deletion was the most frequent oncogenic driver mutation (60.4 %) detected by NGS. According to the NGS assay, 31 % and 68.3 % of patients had 1-2 and ≥ 3 co-occurring genomic alterations, respectively. The most frequent co-occurring genomic alterations were TP53 mutations (64.9 %) followed by CDKN2AB alterations (13.6 %), BRCA2 (13.6 %), and PTEN (12.7 %) mutations. Baseline central nervous system disease was present in 42.7 % of patients. First- or second-generation EGFR TKIs (gefitinib, afatinib, or erlotinib) were the most common treatment in 67.5 % of patients, while osimertinib was administered in 27.9 % of cases. The median PFS in all evaluated patients was 13.63 months (95 %CI: 11.79-15.52). Using ≥ 3 co-occurring alterations as the cut-off point, patients with ≥ 3 co-occurring genomic alterations showed a median PFS, of 12.7 months (95 %CI: 9.92-15.5) vs 21.3 months (95 %CI: 13.93-NR) in patients with 2 or less co-occurring genomic alterations [HR 3.06, (95 %CI: 1.55-5.48) p = 0.0001]. Also, patients with a TP53 mutation had a shorter PFS, 13.6 (95 %CI: 10.7-15.5) vs 19.2 months (95 %CI: 12.8-NR); in wild type TP53 [HR 2.01 (95 %CI: 1.18-3.74) p = 0.12]. In the multivariate analysis, the number (≥3) of concurrent genomic alterations and ECOG PS of 2 or more were related to a significant risk factor for progression [HR 2.79 (95 %CI: 1.49-5.23) p = 0.001 and HR 2.42 (95 %CI: 1.22-4.80) p = 0.011 respectively]. CONCLUSION: EGFR-mutant NSCLC is not a single oncogene-driven disease in the majority of cases, harboring a higher number of co-occurring genomic alterations. This study finds the number of co-occurring genomic alterations and the presence of TP53 mutations as negative prognostic biomarkers, which confers potentially earlier resistance mechanisms to target therapy.

Impact of Testicular Germ Cell Tumor Laterality on Recurrence-Free Survival in the Mexican Population.

BACKGROUND: To date, the prognostic value of laterality for testicular germ cell tumors remains unknown. Herein, we describe this prognostic factor in the Mexican population. METHODS: A retrospective single-center study that included 37 patients with primary testicular germ cell tumors was conducted. Primary outcome was recurrence-free survival (RFS) at 2 years. Secondary outcomes were RFS by histology, progression-free survival by laterality, and 2-year overall survival. RESULTS: Thirty-seven patients were included, of which five showed relapses. By laterality, the 2-year RFS rate was 100% for left tumors and 77.3% for right tumors, with a trend toward statistical significance (P = 0.058). By histology, the RFS rate was higher for seminomas than non-seminomas (89% vs. 83%, respectively) without this difference being statistically significant. Progression-free survival was higher for right tumors than left tumors (91% vs. 80%, respectively) but without reaching statistical significance. The overall survival rate for the entire cohort was 94.5%. CONCLUSIONS: Our study shows that patients with primary germ cell tumors of the right testicle have a higher risk of recurrence than those with primary germ cell tumors of the left testicle, with a trend toward statistical significance.

Síndrome hemofagocítico. Reporte de un caso y revisión de la literatura / Hemophagocytic syndrome. Case report and review of the literature

Resumen El síndrome hemofagocítico es una enfermedad caracterizada por fiebre, citopenias, esplenomegalia y otras alteraciones en laboratorios debido a una activación excesiva de los macrófagos, debido a mutaciones genéticas o secundario a infecciones, malignidad o enfermedades reumatológicas. Debido a la poca especificidad de los síntomas, el diagnóstico usualmente se realiza de manera tardía. Su manejo requiere el tratamiento de la causa subyacente, y de ser necesario, medicamentos que disminuyan la respuesta inflamatoria.

Abstract Hemophagocytic syndrome is a disease characterized by fever, cytopenia, splenomegaly and other alterations in laboratories due to excessive activation of macrophages, by genetic mutations or secondary to infections, malignancy or rheumatological diseases. Because of the low specificity of the symptoms, the diagnosis is usually late. Its management requires the treatment of the underlying cause and, if necessary, medications that decrease the inflammatory response.

Risk of Pneumonitis with the Use of Different Immune Checkpoint Inhibitors in a Mexican Population.

PURPOSE: The incidence of pneumonitis reported in previous trials in patients with advanced cancer and use of programmed cell death protein 1 (PD-1) immunotherapy inhibitors was 2.7-3.6%. However, none of these trials included Mexican populations. METHODS: This was a retrospective analysis involving 87 patients with advanced cancer who received PD-1 inhibitors as part of their therapy. The primary outcome was the incidence of pneumonitis after using PD-1 inhibitors. The secondary outcomes were major risk factors and radiological patterns of pneumonitis. RESULTS: We found 13 cases of pneumonitis, giving an overall incidence of 15%; three of the cases were high-grade (grade 3). A ground-glass pattern was the major form found by chest computed tomography scans. We did not find any significant risk factor for pneumonitis. CONCLUSION: The incidence of pneumonitis secondary to treatment with PD-1 inhibitors in our Mexican population was 15%, which is 5 times higher than that found in other studies. No risk factor was identified for this increased incidence of drug-induced pneumonitis following the use of PD-1 inhibitors.