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STATEMENT OF PROBLEM: Implementation of fabrication trueness analysis by using a recently introduced nonmetrology-grade freeware program may help clinicians and dental laboratory technicians in their routine practice. However, knowledge of the performance of this freeware program when compared with the International Organization for Standardization recommended metrology-grade analysis software program is limited. PURPOSE: The purpose of this in vitro study was to evaluate the effect of an analysis software program on measured deviations in the complete arch, implant-supported framework scans. MATERIAL AND METHODS: A total of 20 complete arch, implant-supported frameworks were fabricated from a master standard tessellation language (STL) file from either polyetheretherketone (PEEK) or titanium (Ti) (n=10). All frameworks were then digitized by using different scanners to generate test STLs. All STL files were imported into a nonmetrology-grade freeware program (Medit Link) and a metrology-grade software program (Geomagic Control X) to measure the overall and marginal deviations of frameworks from the master STL file by using the root mean square (RMS) method. Data were analyzed by using the two 1-sided paired t test procedure, in which 50 µm was considered as the minimal clinically meaningful difference (α=.05). RESULTS: When overall RMS values were considered, the nonmetrology-grade freeware program was not inferior to the metrology-grade software program (P<.05). When marginal RMS values were considered, the nonmetrology-grade freeware program was inferior to the metrology-grade software program only when PEEK frameworks were scanned with an E4 laboratory scanner (P>.05). CONCLUSIONS: The use of the tested nonmetrology-grade freeware program resulted in overall deviation measurements similar to those when a metrology-grade software program was used. The freeware program was inferior when marginal deviations were analyzed on E4 scans of a PEEK framework, which was the only scanner-material pair that led to a significant difference, among the 15 pairs tested.
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INTRODUCTION: Somatic KRAS mutations occur in 25% of patients with NSCLC. Treatment with MEK inhibitor monotherapy has not been successful in clinical trials to date. Compensatory activation of FGFR1 was identified as a mechanism of trametinib resistance in KRAS-mutant NSCLC, and combination therapy with trametinib and ponatinib was synergistic in in vitro and in vivo models. This study sought to evaluate this drug combination in patients with KRAS-mutant NSCLC. METHODS: A phase 1 dose escalation study of trametinib and ponatinib was conducted in patients with advanced NSCLC with KRAS mutations. A standard 3-plus-3 dose escalation was done. Patients were treated with the study therapy until intolerable toxicity or disease progression. RESULTS: A total of 12 patients with KRAS-mutant NSCLC were treated (seven at trametinib 2 mg and ponatinib 15 mg, five at trametinib 2 mg and ponatinib 30 mg). Common toxicities observed were rash, diarrhea, and fever. Serious adverse events potentially related to therapy were reported in five patients, including one death in the study and four cardiovascular events. Serious events were observed at both dose levels. Of note, 75% (9 of 12) were assessable for radiographic response and no confirmed partial responses were observed. The median time on study was 43 days. CONCLUSIONS: In this phase 1 study, in patients with KRAS-mutant advanced NSCLC, combined treatment with trametinib and ponatinib was associated with cardiovascular and bleeding toxicities. Exploring the combination of MEK and FGFR1 inhibition in future studies is potentially warranted but alternative agents should be considered to improve safety and tolerability.
