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Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition.
Nabet, Barzin Y; Esfahani, Mohammad S; Moding, Everett J; Hamilton, Emily G; Chabon, Jacob J; Rizvi, Hira; Steen, Chloe B; Chaudhuri, Aadel A; Liu, Chih Long; Hui, Angela B; Almanza, Diego; Stehr, Henning; Gojenola, Linda; Bonilla, Rene F; Jin, Michael C; Jeon, Young-Jun; Tseng, Diane; Liu, Cailian; Merghoub, Taha; Neal, Joel W; Wakelee, Heather A; Padda, Sukhmani K; Ramchandran, Kavitha J; Das, Millie; Plodkowski, Andrew J; Yoo, Christopher; Chen, Emily L; Ko, Ryan B; Newman, Aaron M; Hellmann, Matthew D; Alizadeh, Ash A; Diehn, Maximilian.
Affiliation
  • Nabet BY; Department of Radiation Oncology, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Esfahani MS; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Moding EJ; Department of Radiation Oncology, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Hamilton EG; Department of Radiation Oncology, Stanford University, Stanford, CA, USA; Program in Cancer Biology, Stanford University, Stanford, CA, USA.
  • Chabon JJ; Department of Radiation Oncology, Stanford University, Stanford, CA, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
  • Rizvi H; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Steen CB; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Chaudhuri AA; Department of Radiation Oncology, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
  • Liu CL; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Hui AB; Department of Radiation Oncology, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Almanza D; Department of Radiation Oncology, Stanford University, Stanford, CA, USA; Program in Cancer Biology, Stanford University, Stanford, CA, USA.
  • Stehr H; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Gojenola L; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Bonilla RF; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
  • Jin MC; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Jeon YJ; Department of Radiation Oncology, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of Korea.
  • Tseng D; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Liu C; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Merghoub T; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell School of Medicine, New York, NY, USA; Parker Institute for Cancer Immunotherapy at MSK
  • Neal JW; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Wakelee HA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Padda SK; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Ramchandran KJ; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  • Das M; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA, USA.
  • Plodkowski AJ; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Yoo C; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
  • Chen EL; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
  • Ko RB; Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
  • Newman AM; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
  • Hellmann MD; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell School of Medicine, New York, NY, USA; Parker Institute for Cancer Immunotherapy at MSK, Memorial
  • Alizadeh AA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA. Electronic address: a
  • Diehn M; Department of Radiation Oncology, Stanford University, Stanford, CA, USA; Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA. Electronic address: diehn@stanford.edu.
Cell ; 183(2): 363-376.e13, 2020 10 15.
Article in En | MEDLINE | ID: mdl-33007267
ABSTRACT
Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers, Pharmacological / Circulating Tumor DNA / Immune Checkpoint Inhibitors Type of study: Diagnostic_studies / Prognostic_studies Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Cell Year: 2020 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers, Pharmacological / Circulating Tumor DNA / Immune Checkpoint Inhibitors Type of study: Diagnostic_studies / Prognostic_studies Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Cell Year: 2020 Type: Article Affiliation country: United States