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Tumor mutational load predicts survival after immunotherapy across multiple cancer types.
Samstein, Robert M; Lee, Chung-Han; Shoushtari, Alexander N; Hellmann, Matthew D; Shen, Ronglai; Janjigian, Yelena Y; Barron, David A; Zehir, Ahmet; Jordan, Emmet J; Omuro, Antonio; Kaley, Thomas J; Kendall, Sviatoslav M; Motzer, Robert J; Hakimi, A Ari; Voss, Martin H; Russo, Paul; Rosenberg, Jonathan; Iyer, Gopa; Bochner, Bernard H; Bajorin, Dean F; Al-Ahmadie, Hikmat A; Chaft, Jamie E; Rudin, Charles M; Riely, Gregory J; Baxi, Shrujal; Ho, Alan L; Wong, Richard J; Pfister, David G; Wolchok, Jedd D; Barker, Christopher A; Gutin, Philip H; Brennan, Cameron W; Tabar, Viviane; Mellinghoff, Ingo K; DeAngelis, Lisa M; Ariyan, Charlotte E; Lee, Nancy; Tap, William D; Gounder, Mrinal M; D'Angelo, Sandra P; Saltz, Leonard; Stadler, Zsofia K; Scher, Howard I; Baselga, Jose; Razavi, Pedram; Klebanoff, Christopher A; Yaeger, Rona; Segal, Neil H; Ku, Geoffrey Y; DeMatteo, Ronald P.
Afiliação
  • Samstein RM; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Lee CH; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Shoushtari AN; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Hellmann MD; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Shen R; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Janjigian YY; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Barron DA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Zehir A; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Jordan EJ; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Omuro A; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Kaley TJ; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Kendall SM; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Motzer RJ; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Hakimi AA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Voss MH; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Russo P; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Rosenberg J; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Iyer G; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Bochner BH; Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Bajorin DF; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Al-Ahmadie HA; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Chaft JE; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Rudin CM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Riely GJ; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Baxi S; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Ho AL; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Wong RJ; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Pfister DG; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Wolchok JD; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Barker CA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Gutin PH; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Brennan CW; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Tabar V; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Mellinghoff IK; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • DeAngelis LM; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Ariyan CE; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Lee N; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Tap WD; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Gounder MM; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • D'Angelo SP; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Saltz L; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Stadler ZK; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Scher HI; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Baselga J; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Razavi P; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Klebanoff CA; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Yaeger R; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Segal NH; Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
  • Ku GY; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • DeMatteo RP; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nat Genet ; 51(2): 202-206, 2019 02.
Article em En | MEDLINE | ID: mdl-30643254
ABSTRACT
Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI. To examine this association more broadly, we analyzed the clinical and genomic data of 1,662 advanced cancer patients treated with ICI, and 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT). Among all patients, higher somatic TMB (highest 20% in each histology) was associated with better overall survival. For most cancer histologies, an association between higher TMB and improved survival was observed. The TMB cutpoints associated with improved survival varied markedly between cancer types. These data indicate that TMB is associated with improved survival in patients receiving ICI across a wide variety of cancer types, but that there may not be one universal definition of high TMB.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mutação / Neoplasias Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Genet Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mutação / Neoplasias Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Genet Ano de publicação: 2019 Tipo de documento: Article