RESUMO
KEY POINTS: Nasal packing type was not associated with postoperative cerebrospinal fluid leaks Nondissolvable packing conferred an increased risk for postoperative sinonasal infections Nasal packing type did not influence short- and long-term quality-of-life scores.
Assuntos
Procedimentos de Cirurgia Plástica , Humanos , Vazamento de Líquido Cefalorraquidiano/cirurgia , Estudos Retrospectivos , Base do Crânio/cirurgia , Endoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Qualidade de VidaRESUMO
In the version of this article originally published, the graph in Extended Data Fig. 2c was a duplication of Extended Data Fig. 2b. The correct version of Extended Data Fig. 2c is now available online.
RESUMO
Immune checkpoint inhibitors have been successful across several tumor types; however, their efficacy has been uncommon and unpredictable in glioblastomas (GBM), where <10% of patients show long-term responses. To understand the molecular determinants of immunotherapeutic response in GBM, we longitudinally profiled 66 patients, including 17 long-term responders, during standard therapy and after treatment with PD-1 inhibitors (nivolumab or pembrolizumab). Genomic and transcriptomic analysis revealed a significant enrichment of PTEN mutations associated with immunosuppressive expression signatures in non-responders, and an enrichment of MAPK pathway alterations (PTPN11, BRAF) in responders. Responsive tumors were also associated with branched patterns of evolution from the elimination of neoepitopes as well as with differences in T cell clonal diversity and tumor microenvironment profiles. Our study shows that clinical response to anti-PD-1 immunotherapy in GBM is associated with specific molecular alterations, immune expression signatures, and immune infiltration that reflect the tumor's clonal evolution during treatment.