Multinational Retrospective Central Pathology Review of Neuroblastoma: Lessons Learned to Establish a Regional Pathology Referral Center in Resource-Limited Settings.

CONTEXT.­: Several countries of the Central America and Caribbean region have been sharing regional neuroblastoma (NB) treatment guidelines. However, there is no standardization in the diagnosis, subclassification, or tumor biology to aid in the risk stratification of these patients. OBJECTIVE.­: To examine the histology and assess the accuracy of the local pathology reports; to evaluate the usefulness of manual MYCN immunohistochemistry (IHC); and to use NB as a model to identify the needs to establish a central pathology review (CPR) program in this region. DESIGN.­: A retrospective CPR of specimens derived from patients with a diagnosis of NB and treated under the regional NB guidelines between 2012 and 2017 was conducted, allowing for a comparison between local diagnoses and the CPR diagnoses. Manual MYCN IHC was performed in the confirmed NB specimens and the results compared with known fluorescence in situ hybridization or automated IHC results, when available. RESULTS.­: The 156 specimens reviewed included 460 blocks and 183 original slides. Neuroblastoma was confirmed in 138 samples (88.5%), but low concordance rates for Shimada classification (n = 39; 25.0%), mitotic-karyorrhectic index (n = 4; 2.5%), and International Neuroblastoma Pathology Classification (n = 18; 11.5%) were noted. Manual MYCN IHC performed on 120 specimens showed conclusive results in 89.2% (28 positive, 23.4%; 79 negative, 65.8%) and questionable results in 10.8% (n = 13). CONCLUSIONS.­: This retrospective CPR highlights the need for a CPR program to serve this region, to ensure correct diagnosis and subclassification of NB, and to provide manual MYCN IHC-with reflexing to fluorescence in situ hybridization, if questionable. This approach can further regional collaboration, enhance test utilization, and ultimately improve patients' outcomes.

Cost-effectiveness analysis of EGFR mutation testing in patients with non-small cell lung cancer (NSCLC) with gefitinib or carboplatin-paclitaxel.

OBJECTIVE: Assess the cost-effectiveness of an EGFR-mutation testing strategy for advanced NSCLC in first-line therapy with either gefitinib or carboplatin-paclitaxel in Mexican institutions. METHODS: Cost-effectiveness analysis using a discrete event simulation (DES) model to simulate two therapeutic strategies in patients with advanced NSCLC. Strategy one included patients tested for EGFR-mutation and therapy given accordingly. Strategy two included chemotherapy for all patients without testing. All results are presented in 2014 US dollars. The analysis was made with data from the Mexican frequency of EGFR-mutation. A univariate sensitivity analysis was conducted on EGFR prevalence. Progression-free survival (PFS) transition probabilities were estimated on data from the IPASS and simulated with a Weibull distribution, run with parallel trials to calculate a probabilistic sensitivity analysis. RESULTS: PFS of patients in the testing strategy was 6.76 months (95 % CI 6.10-7.44) vs 5.85 months (95 % CI 5.43-6.29) in the non-testing group. The one-way sensitivity analysis showed that PFS has a direct relationship with EGFR-mutation prevalence, while the ICER and testing cost have an inverse relationship with EGFR-mutation prevalence. The probabilistic sensitivity analysis showed that all iterations had incremental costs and incremental PFS for strategy 1 in comparison with strategy 2. CONCLUSION: There is a direct relationship between the ICER and the cost of EGFR testing, with an inverse relationship with the prevalence of EGFR-mutation. When prevalence is >10 % ICER remains constant. This study could impact Mexican and Latin American health policies regarding mutation detection testing and treatment for advanced NSCLC.

Dapagliflozin as an adjunct therapy to insulin in the treatment of patients with type 1 diabetes mellitus.

We have evaluated the efficacy of dapagliflozin in patients with type 1 diabetes mellitus (DM1) without adequate control. We expected that adding dapagliflozin to this population on top of their base treatment would lower their HbA1c levels. We conducted a pragmatic, open, 24-week study of treatment with 10 mg of oral dapagliflozin in patients with DM1 and chronic hyperglycemia. We evaluated glycemic control, lipid profile, weight, and insulin dose. Safety was assessed by adverse event reporting. Fasting glucose levels decreased from 176.42 ± 45.33 mg/dL to 139.67 ± 44.42 mg/dL (p = 0.05); although no significant valued was reached, postprandial glucose showed a decreased tendency from 230.25 ± 52.06 mg/dL to 193.83 ± 45.43 mg/dL (p = 0.08). The hemoglobin A1C (HbA1C) level decreased from 9.18 ± 1.02 (77 ± 11.1 mmol/mol) to 8.05 ± 1.09 % (64 ± 11.9 mmol/mol) (p = 0.0156); total cholesterol decreased from 299 ± 12 to 199 ± 7 mg/dL (p = 0.02); triglycerides decreased from 184 ± 15 to 160 ± 11 mg/dL (p = 0.0002), HDL-C decreased from 40 ± 17 to 42 ± 9 mg/dL (p = 0.54); and LDL-C decreased from 187 ± 19 to 170 ± 21 mg/dL (p = 0.049). No adverse events were reported. The beneficial effects of SGLT2 inhibitors on metabolic control and their safety after a 24-week open study demonstrate their potential indication as an adjunctive treatment with insulin in patients with DM1; however, long-term clinical trials should be considered.