Brief Report: Droplet Digital Polymerase Chain Reaction Versus Plasma Next-Generation Sequencing in Detecting Clearance of Plasma EGFR Mutations and Carcinoembryonic Antigen Levels as a Surrogate Measure
Introduction: To compare the performance of droplet digital polymerase chain reaction (ddPCR) and plasma next-generation sequencing (NGS) in detecting clearance of plasma EGFR (pEGFR) mutations. Methods: Patients with treatment-naive advanced EGFR-mutated lung cancer treated with first-line tyrosine...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S266636432300142X |
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| author | Stephanie P.L. Saw, MRCP Gek San Tan, MSc Wei Chong Tan, MRCP Aaron C. Tan, PhD Gillianne G.Y. Lai, MRCP Darren W.T. Lim, MRCP Ravindran Kanesvaran, MRCP Wan Ling Tan, MRCP Sze Huey Tan, PhD Kiat Hon Lim, FRCPA Anders J. Skanderup, PhD Daniel S.W. Tan, PhD |
| author_facet | Stephanie P.L. Saw, MRCP Gek San Tan, MSc Wei Chong Tan, MRCP Aaron C. Tan, PhD Gillianne G.Y. Lai, MRCP Darren W.T. Lim, MRCP Ravindran Kanesvaran, MRCP Wan Ling Tan, MRCP Sze Huey Tan, PhD Kiat Hon Lim, FRCPA Anders J. Skanderup, PhD Daniel S.W. Tan, PhD |
| author_sort | Stephanie P.L. Saw, MRCP |
| collection | DOAJ |
| description | Introduction: To compare the performance of droplet digital polymerase chain reaction (ddPCR) and plasma next-generation sequencing (NGS) in detecting clearance of plasma EGFR (pEGFR) mutations. Methods: Patients with treatment-naive advanced EGFR-mutated lung cancer treated with first-line tyrosine kinase inhibitors (TKIs) were included. pEGFR were measured at baseline and first response assessment using ddPCR and NGS. Clearance of pEGFR was defined as undetectable levels after a positive baseline result. Results were correlated with time-to-treatment failure (TTF). In exploratory analysis, corresponding change in carcinoembryonic antigen (CEA) levels was evaluated. Results: Between January 1, 2020, and December 31, 2021, 27 patients were recruited. Ex19del comprised 74% (20 of 27) and L858R 26% (seven of 27). Osimertinib was used in 59% (16 of 27), dacomitinib 4% (one of 27), and gefitinib/erlotinib 37% (10 of 27). Sensitivity of ddPCR and NGS in detecting pEGFR mutation at baseline was 70% (19 of 27) and 78% (21 of 27), respectively (p = 0.16). All patients with detectable pEGFR by ddPCR were detected by NGS.At a median of 8 (range 3–24) weeks post-TKI initiation, clearance of pEGFR was achieved in 68% (13 of 19) and 71% (15 of 21) using ddPCR and NGS, respectively. Concordance between ddPCR and NGS was 79% (kappa = 0.513, p = 0.013). Clearance of pEGFR was associated with longer median TTF (not reached versus 6 months, p = 0.03) and median decrease in CEA levels by 70% from baseline.In another cohort of 124 patients, decrease in CEA levels by greater than 70% within 90 days of TKI initiation was associated with doubling of both TTF and overall survival. Conclusions: Plasma NGS trended toward higher sensitivity than ddPCR in detecting pEGFR, although both had similar concordance in detecting pEGFR clearance. Our results support using NGS at diagnosis and interchangeability of NGS and ddPCR for monitoring, whereas CEA could be explored as a surrogate for pEGFR clearance. |
| first_indexed | 2024-03-08T21:24:24Z |
| format | Article |
| id | doaj.art-95ba3defcb024f6c832156416fd09357 |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-03-08T21:24:24Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
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| series | JTO Clinical and Research Reports |
| spelling | doaj.art-95ba3defcb024f6c832156416fd093572023-12-21T07:37:25ZengElsevierJTO Clinical and Research Reports2666-36432023-12-01412100599Brief Report: Droplet Digital Polymerase Chain Reaction Versus Plasma Next-Generation Sequencing in Detecting Clearance of Plasma EGFR Mutations and Carcinoembryonic Antigen Levels as a Surrogate MeasureStephanie P.L. Saw, MRCP0Gek San Tan, MSc1Wei Chong Tan, MRCP2Aaron C. Tan, PhD3Gillianne G.Y. Lai, MRCP4Darren W.T. Lim, MRCP5Ravindran Kanesvaran, MRCP6Wan Ling Tan, MRCP7Sze Huey Tan, PhD8Kiat Hon Lim, FRCPA9Anders J. Skanderup, PhD10Daniel S.W. Tan, PhD11Division of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore; Corresponding author. Address for correspondence: Stephanie P. L. Saw, MRCP, Division of Medical Oncology, National Cancer Centre Singapore, Singhealth Duke-NUS Oncology Academic Clinical Programme, 30 Hospital Boulevard, Singapore 168583.Division of Pathology, Singapore General Hospital, SingaporeDivision of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, SingaporeDivision of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, SingaporeDivision of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, SingaporeDivision of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, SingaporeDivision of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, SingaporeDivision of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, SingaporeDivision of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore; Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, SingaporeDivision of Pathology, Singapore General Hospital, SingaporeGenome Institute of Singapore, SingaporeDivision of Medical Oncology, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, National University of Singapore, SingaporeIntroduction: To compare the performance of droplet digital polymerase chain reaction (ddPCR) and plasma next-generation sequencing (NGS) in detecting clearance of plasma EGFR (pEGFR) mutations. Methods: Patients with treatment-naive advanced EGFR-mutated lung cancer treated with first-line tyrosine kinase inhibitors (TKIs) were included. pEGFR were measured at baseline and first response assessment using ddPCR and NGS. Clearance of pEGFR was defined as undetectable levels after a positive baseline result. Results were correlated with time-to-treatment failure (TTF). In exploratory analysis, corresponding change in carcinoembryonic antigen (CEA) levels was evaluated. Results: Between January 1, 2020, and December 31, 2021, 27 patients were recruited. Ex19del comprised 74% (20 of 27) and L858R 26% (seven of 27). Osimertinib was used in 59% (16 of 27), dacomitinib 4% (one of 27), and gefitinib/erlotinib 37% (10 of 27). Sensitivity of ddPCR and NGS in detecting pEGFR mutation at baseline was 70% (19 of 27) and 78% (21 of 27), respectively (p = 0.16). All patients with detectable pEGFR by ddPCR were detected by NGS.At a median of 8 (range 3–24) weeks post-TKI initiation, clearance of pEGFR was achieved in 68% (13 of 19) and 71% (15 of 21) using ddPCR and NGS, respectively. Concordance between ddPCR and NGS was 79% (kappa = 0.513, p = 0.013). Clearance of pEGFR was associated with longer median TTF (not reached versus 6 months, p = 0.03) and median decrease in CEA levels by 70% from baseline.In another cohort of 124 patients, decrease in CEA levels by greater than 70% within 90 days of TKI initiation was associated with doubling of both TTF and overall survival. Conclusions: Plasma NGS trended toward higher sensitivity than ddPCR in detecting pEGFR, although both had similar concordance in detecting pEGFR clearance. Our results support using NGS at diagnosis and interchangeability of NGS and ddPCR for monitoring, whereas CEA could be explored as a surrogate for pEGFR clearance.http://www.sciencedirect.com/science/article/pii/S266636432300142XEGFR-mutated NSCLCddPCRNGSCEA |
| spellingShingle | Stephanie P.L. Saw, MRCP Gek San Tan, MSc Wei Chong Tan, MRCP Aaron C. Tan, PhD Gillianne G.Y. Lai, MRCP Darren W.T. Lim, MRCP Ravindran Kanesvaran, MRCP Wan Ling Tan, MRCP Sze Huey Tan, PhD Kiat Hon Lim, FRCPA Anders J. Skanderup, PhD Daniel S.W. Tan, PhD Brief Report: Droplet Digital Polymerase Chain Reaction Versus Plasma Next-Generation Sequencing in Detecting Clearance of Plasma EGFR Mutations and Carcinoembryonic Antigen Levels as a Surrogate Measure JTO Clinical and Research Reports EGFR-mutated NSCLC ddPCR NGS CEA |
| title | Brief Report: Droplet Digital Polymerase Chain Reaction Versus Plasma Next-Generation Sequencing in Detecting Clearance of Plasma EGFR Mutations and Carcinoembryonic Antigen Levels as a Surrogate Measure |
| title_full | Brief Report: Droplet Digital Polymerase Chain Reaction Versus Plasma Next-Generation Sequencing in Detecting Clearance of Plasma EGFR Mutations and Carcinoembryonic Antigen Levels as a Surrogate Measure |
| title_fullStr | Brief Report: Droplet Digital Polymerase Chain Reaction Versus Plasma Next-Generation Sequencing in Detecting Clearance of Plasma EGFR Mutations and Carcinoembryonic Antigen Levels as a Surrogate Measure |
| title_full_unstemmed | Brief Report: Droplet Digital Polymerase Chain Reaction Versus Plasma Next-Generation Sequencing in Detecting Clearance of Plasma EGFR Mutations and Carcinoembryonic Antigen Levels as a Surrogate Measure |
| title_short | Brief Report: Droplet Digital Polymerase Chain Reaction Versus Plasma Next-Generation Sequencing in Detecting Clearance of Plasma EGFR Mutations and Carcinoembryonic Antigen Levels as a Surrogate Measure |
| title_sort | brief report droplet digital polymerase chain reaction versus plasma next generation sequencing in detecting clearance of plasma egfr mutations and carcinoembryonic antigen levels as a surrogate measure |
| topic | EGFR-mutated NSCLC ddPCR NGS CEA |
| url | http://www.sciencedirect.com/science/article/pii/S266636432300142X |
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