Metastatic Non-Small Cell Lung Cancer (MSK, Nature Medicine 2022)

Overview

Prospective international cohort study of advanced NSCLC patients undergoing plasma ctDNA sequencing via the Resolution Bioscience ctDx Lung platform, evaluating ctDNA detection as a prognostic and therapy-matching biomarker PMID:36357680.

Composition

  • 1,127 adults with stage IV or recurrent NSCLC analyzed (1,357 initially enrolled) at Memorial Sloan Kettering (New York) and GenesisCare (Sydney, Australia); cancer types LUAD and LUSC; most (1,003; 89%) provided a single plasma sample PMID:36357680.

Assays / panels (linked)

  • ctDx Lung targeted plasma NGS; MSK patients additionally profiled with tissue MSK-IMPACT, and from June 2019 with plasma MSK-ACCESS; both MSK assays use matched WBC sequencing to remove clonal hematopoiesis and germline variants PMID:36357680.

Papers using this cohort

  • PMID:36357680 — Jee et al., Overall survival with ctDNA-guided therapy in advanced NSCLC.
  • PMID:39147831 — ctDNA-based prediction of cancer-associated VTE; international generalizability cohort (n = 463 advanced NSCLC) from MSK and GenesisCare sequenced with ctDx Lung.

Notable findings derived from this cohort

  • ctDNA detection rate was 722/1,127 (64%), and ctDNA detection was an independent poor prognostic marker (HR 2.05; 95% CI 1.74–2.42; P<0.001) even after correction for clinicopathologic factors and PET-based metabolic tumor volume PMID:36357680.
  • Among ctDNA-positive patients, 255 (23%) matched to targeted therapy by ctDNA sequencing had longer OS than ctDNA-positive patients not receiving targeted therapy (HR 0.63; 95% CI 0.52–0.76; P<0.001) PMID:36357680.
  • 25% of patients had alterations detected only in ctDNA (not in time-matched tissue), disproportionately subclonal resistance drivers such as RICTOR and PIK3CA, and associated with short survival PMID:36357680.
  • Operational metrics: only 2% of ctDx Lung / MSK-ACCESS samples failed vs 13% tissue sequencing failures; turnaround 11 days vs 33 days for MSK-IMPACT PMID:36357680.
  • Used as an international generalizability cohort (n = 463 advanced NSCLC) for a ctDNA-based VTE prediction model; the LB+ random survival forest achieved a c-index of 0.67 in this cohort, outperforming Khorana score (0.54). PMID:39147831

Sources

This page was processed by crosslinker on 2026-05-04.