Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019
Dynamic monitoring of HER2 amplification in circulating DNA of patients with metastatic colorectal cancer treated with cetuximab.
СтатьяНазвание и аннотация: Перевод в очереди
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Liu R, Zhao X, Guo W, Huang M, Qiu L, Zhang W, Zhang Z, Li W, Zhu X, Chen Z
Аннотация
PURPOSE: Cetuximab (CTX) has been used to treat metastatic colorectal cancer (mCRC) with wild-type (wt) RAS and BRAF genes. Meanwhile HER2 amplification reportedly denoted CTX-resistant mCRC tumors. We investigated whether monitoring of HER2 amplification in circulating DNA allowed early detection of mCRC progression and CTX resistance.
METHODS: We analyzed HER2 amplification in circulating DNA at 8-week intervals using ddPCR from 36 patients with RASwt/BRAFwt mCRC, who progressed after CTX treatments between July 2015 and January 2018.
RESULTS: Of the 36 patients, 5 (13.9%) exhibited dynamic fluctuations of HER2 amplification in plasma in the course of CTX treatment, of whom 2 were positive for HER2 amplification in matched tumor specimens at baseline (per FISH). All 5 primary sites were left side: 3 rectums and 2 descending colon. HER2 ratio fluctuations in circulating DNA not only reflected changes in tumor volume, but their obvious increases presaged CT-documented progress by an average lead time of 2 months. Interestingly, progression-free survival did not significantly differ between these 5 patients and those without HER2 amplification (HR 1.06, 95% CI 0.40-2.77, P = 0.909).
CONCLUSION: Plasma HER2 amplification detected by ddPCR changed over time and predicted resistance to CTX, by an average lead time of 2 months. Further study is needed to validate our findings.
METHODS: We analyzed HER2 amplification in circulating DNA at 8-week intervals using ddPCR from 36 patients with RASwt/BRAFwt mCRC, who progressed after CTX treatments between July 2015 and January 2018.
RESULTS: Of the 36 patients, 5 (13.9%) exhibited dynamic fluctuations of HER2 amplification in plasma in the course of CTX treatment, of whom 2 were positive for HER2 amplification in matched tumor specimens at baseline (per FISH). All 5 primary sites were left side: 3 rectums and 2 descending colon. HER2 ratio fluctuations in circulating DNA not only reflected changes in tumor volume, but their obvious increases presaged CT-documented progress by an average lead time of 2 months. Interestingly, progression-free survival did not significantly differ between these 5 patients and those without HER2 amplification (HR 1.06, 95% CI 0.40-2.77, P = 0.909).
CONCLUSION: Plasma HER2 amplification detected by ddPCR changed over time and predicted resistance to CTX, by an average lead time of 2 months. Further study is needed to validate our findings.