TY - JOUR
T1 - 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
AU - Tan, Aaron C.
AU - Lai, Gillianne G.Y.
AU - Saw, Stephanie P.L.
AU - Chua, Kevin L.M.
AU - Takano, Angela
AU - Ong, Boon Hean
AU - Koh, Tina P.T.
AU - Jain, Amit
AU - Tan, Wan Ling
AU - Ng, Quan Sing
AU - Kanesvaran, Ravindran
AU - Rajasekaran, Tanujaa
AU - Kalashnikova, Ekaterina
AU - Renner, Derrick
AU - Sudhaman, Sumedha
AU - Malhotra, Meenakshi
AU - Sethi, Himanshu
AU - Liu, Minetta C.
AU - Aleshin, Alexey
AU - Lim, Wan Teck
AU - Tan, Eng Huat
AU - Skanderup, Anders J.
AU - Ang, Mei Kim
AU - Tan, Daniel S.W.
N1 - Publisher Copyright:
© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - circulating tumor DNA
KW - early-stage lung cancer
KW - liquid biopsy
KW - non–small cell lung cancer
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U2 - 10.1002/cncr.35263
DO - 10.1002/cncr.35263
M3 - Article
C2 - 38422026
AN - SCOPUS:85186190241
SN - 0008-543X
JO - Cancer
JF - Cancer
ER -