RESUMO
Background: MET exon 14 alterations are actionable oncogenic drivers. Durable responses to MET inhibitors are observed in patients with advanced MET exon 14-altered lung cancers in prospective trials. In contrast, the activity of immunotherapy, PD-L1 expression and tumor mutational burden (TMB) of these tumors and are not well characterized. Patients and methods: Patients with MET exon 14-altered lung cancers of any stage treated at two academic institutions were identified. A review of clinicopathologic and molecular features, and an analysis of response to single-agent or combination immune checkpoint inhibition were conducted. PD-L1 immunohistochemistry was carried out and TMB was calculated by estimation from targeted next-generation sequencing panels. Results: We identified 147 patients with MET exon 14-altered lung cancers. PD-L1 expression of 0%, 1%-49%, and ≥50% were 37%, 22%, and 41%, respectively, in 111 evaluable tumor samples. The median TMB of MET exon 14-altered lung cancers was lower than that of unselected non-small-cell lung cancers (NSCLCs) in both independently evaluated cohorts: 3.8 versus 5.7 mutations/megabase (P < 0.001, n = 78 versus 1769, cohort A), and 7.3 versus 11.8 mutations/megabase (P < 0.001, n = 62 versus 1100, cohort B). There was no association between PD-L1 expression and TMB (Spearman's rho=0.18, P = 0.069). In response-evaluable patients (n = 24), the objective response rate was 17% (95% CI 6% to 36%) and the median progression-free survival was 1.9 months (95% CI 1.7-2.7). Responses were not enriched in tumors with PD-L1 expression ≥50% nor high TMB. Conclusion: A substantial proportion of MET exon 14-altered lung cancers express PD-L1, but the median TMB is lower compared with unselected NSCLCs. Occasional responses to PD-1 blockade can be achieved, but overall clinical efficacy is modest.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Éxons/genética , Neoplasias Pulmonares/patologia , Mutação , Proteínas Proto-Oncogênicas c-met/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Estudos de Coortes , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
OJECTIVES: The purpose of this study was to evaluate the outcomes of endoscopically harvested saphenous vein (EHSV) for lower extremity bypass (LEB) surgery. METHODS: Data from 91 consecutive patients who underwent LEB using EHSV between February 2003 and November 2012 were analyzed. Outcomes of interest were wound infection, patency, re-intervention and limb loss. RESULTS: Fifty-eight (64%) and 33 (36%) patients underwent femoropopliteal (FP) and femorotibial (FT) bypass using EHSV. Three (3%) patients had superficial and 1 (1%) deep wound infection. Primary and primary assisted patency at 5 years was 68% and 71% in the FP group and 56% and 65% in the FT group. Six (6%) patients underwent major amputation. No predicting factors for wound infection or graft patency were found. CONCLUSIONS: EHSV carries a low incidence of perioperative wound complication and has a reasonable mid-to-long-term patency regardless of the length of vein harvested.
