1/ 🚨Excited to share our 🆕 publication in Annals of Oncology:

The clinical landscape of cell-free DNA alterations in 1,671 patients with advanced biliary tract cancer

doi.org/10.1016/j.anno…

🧵👇

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⭐️Highlights⭐️

🔎cfDNA data from 1,671 patients with advanced BTC
🎯Targetable genomic alterations (GA) detected in cfDNA in 44% of patients
🌎84% with any GA
🤝cfDNA-tissue concordance: ⬆️ IDH1 muts & BRAF V600E ⬇️ FGFR2 fusions
📉High cfDNA VAF a/w poor prognosis

Details👇

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🎯Targeted therapies have transformed management of advanced BTC.

📸⬇️highlights National Comprehensive Cancer Network (NCCN) guideline-recommended treatments for molecularly-defined BTCs.

🩸🧬cfDNA analysis is an attractive approach for tumor genomic profiling that overcomes limitations of 💉🧬 tissue biopsy.

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🔬We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology by analyzing NGS data of 2,068 cfDNA samples from 1,671 patients with advanced BTC from Guardant Health.

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⭐️84% of BTC patients had at least one genomic alteration (GA) detected in cfDNA

🌟44% had a targetable (Level 1-3B) GA in cfDNA based on OncoKB™ classification

💫12% had a Level 1 GA in cfDNA ➡️ FDA-recognized biomarker predictive of response to an FDA-approved drug in BTC

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📊Prevalence of specific alterations in cfDNA from patients with BTC that predict response to an FDA-approved therapy in BTC.

✅IDH1 muts 9.1%
✅FGFR2 fusions 1.4%
✅BRAF V600E 1.3%
✅NTRK fusions 0.1%
✅RET fusions 0.1%

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📊Prevalence of alts that predict response to other FDA-approved therapies:

✅PIK3CA muts 6.8%
✅ERBB2 amps 4.9%
✅BRCA1/2 muts 1.8%
✅KRAS G12C 1.0%

🔑Manuscript includes supp table with frequency of all alts present in cfDNA from this BTC cohort. Impt for drug discovery!

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To establish how well 🩸🧬 cfDNA recapitulates 💉🧬 tumor tissue, we compared the prevalence of mutations between the BTC cfDNA samples (N=1,671) with metastatic BTC tumor NGS data from AACR Project GENIE (N=349).

Correlation was impressively high ⬆️ (R2=0.96)‼️