Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer
© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society..
BACKGROUND: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay.
METHODS: This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single-nucleotide variants in plasma samples.
RESULTS: The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001).
CONCLUSIONS: ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Cancer - (2024) vom: 29. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tan, Aaron C [VerfasserIn] |
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| Links: |
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| Themen: |
Circulating tumor DNA |
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| Anmerkungen: |
Date Revised 29.02.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1002/cncr.35263 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer |
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| 520 | |a © 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. | ||
| 520 | |a BACKGROUND: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay | ||
| 520 | |a METHODS: This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single-nucleotide variants in plasma samples | ||
| 520 | |a RESULTS: The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001) | ||
| 520 | |a CONCLUSIONS: ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Lai, Gillianne G Y |e verfasserin |4 aut | |
| 700 | 1 | |a Saw, Stephanie P L |e verfasserin |4 aut | |
| 700 | 1 | |a Chua, Kevin L M |e verfasserin |4 aut | |
| 700 | 1 | |a Takano, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Ong, Boon-Hean |e verfasserin |4 aut | |
| 700 | 1 | |a Koh, Tina P T |e verfasserin |4 aut | |
| 700 | 1 | |a Jain, Amit |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Wan Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Quan Sing |e verfasserin |4 aut | |
| 700 | 1 | |a Kanesvaran, Ravindran |e verfasserin |4 aut | |
| 700 | 1 | |a Rajasekaran, Tanujaa |e verfasserin |4 aut | |
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| 700 | 1 | |a Renner, Derrick |e verfasserin |4 aut | |
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| 700 | 1 | |a Malhotra, Meenakshi |e verfasserin |4 aut | |
| 700 | 1 | |a Sethi, Himanshu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Minetta C |e verfasserin |4 aut | |
| 700 | 1 | |a Aleshin, Alexey |e verfasserin |4 aut | |
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| 700 | 1 | |a Tan, Eng-Huat |e verfasserin |4 aut | |
| 700 | 1 | |a Skanderup, Anders J |e verfasserin |4 aut | |
| 700 | 1 | |a Ang, Mei-Kim |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Daniel S W |e verfasserin |4 aut | |
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