P N Ding1, T M Becker2, V J Bray3, W Chua3, Y F Ma4, D Lynch5, J Po5, A W S Luk4, N Caixeiro2, P de Souza6, T L Roberts2. 1. Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia; Western Sydney University, Campbelltown, NSW, Australia; University of New South Wales, NSW, Australia; Medical Oncology Department, Liverpool Hospital, Liverpool, NSW, Australia. Electronic address: pei.ding@health.nsw.gov.au. 2. Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia; Western Sydney University, Campbelltown, NSW, Australia; University of New South Wales, NSW, Australia. 3. Medical Oncology Department, Liverpool Hospital, Liverpool, NSW, Australia. 4. Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia; University of New South Wales, NSW, Australia. 5. Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia; Western Sydney University, Campbelltown, NSW, Australia. 6. Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia; Western Sydney University, Campbelltown, NSW, Australia; University of New South Wales, NSW, Australia; Medical Oncology Department, Liverpool Hospital, Liverpool, NSW, Australia.
Abstract
OBJECTIVE: To determine the predictive and prognostic roles of three blood-based biomarkers: circulating tumour DNA (ctDNA), circulating tumour cells (CTC) and carcinoembryonic antigen (CEA), in patients with advanced epidermal growth factor receptor-mutated (EGFR+) lung cancer. MATERIALS AND METHODS: We recruited 28 patients with 103 serial blood samples. We performed mutational analyses for EGFR mutations using droplet digital PCR (ddPCR) on ctDNA. We evaluated the accuracy of EGFR mutation detection in ctDNA compared with tissue biopsy. We also quantified CTCs, ctDNA and CEA in serially collected blood samples, and evaluated the baseline and changes in these blood-based biomarkers with clinical outcomes. RESULTS: EGFR mutation detection in plasma was highly concordant as compared with tissue biopsy. Detectable baseline ctDNA was associated with higher disease burden (p < 0.01). Early disappearance of ctDNA at 4 weeks was associated with radiological response at 12 weeks of treatment (p = 0.01) and improved progression free survival (PFS) (HR 5.47, 95%CI 1.32-22.72, p = 0.02) and overall survival (OS) (HR 5.46, 95%CI 1.28-23.22, p = 0.02). A decrease in CTC count at 4 weeks was associated with improved PFS (HR 3.81, 95%CI 1.13-12.79, p = 0.03) but not OS. 85% of patients with radiological progression had a ctDNA rise compared with 22% of patients with stable disease (p=0.01). ctDNA rise was seen on average 170 days prior to radiological progression. There is a significant association between the rise of CEA level with radiological progression (p=0.001). CONCLUSION: Early change in ctDNA, CTC and CEA levels may be long-term predictors of treatment benefit and failure prior to availability of radiological response data.
OBJECTIVE: To determine the predictive and prognostic roles of three blood-based biomarkers: circulating tumour DNA (ctDNA), circulating tumour cells (CTC) and carcinoembryonic antigen (CEA), in patients with advanced epidermal growth factor receptor-mutated (EGFR+) lung cancer. MATERIALS AND METHODS: We recruited 28 patients with 103 serial blood samples. We performed mutational analyses for EGFR mutations using droplet digital PCR (ddPCR) on ctDNA. We evaluated the accuracy of EGFR mutation detection in ctDNA compared with tissue biopsy. We also quantified CTCs, ctDNA and CEA in serially collected blood samples, and evaluated the baseline and changes in these blood-based biomarkers with clinical outcomes. RESULTS:EGFR mutation detection in plasma was highly concordant as compared with tissue biopsy. Detectable baseline ctDNA was associated with higher disease burden (p < 0.01). Early disappearance of ctDNA at 4 weeks was associated with radiological response at 12 weeks of treatment (p = 0.01) and improved progression free survival (PFS) (HR 5.47, 95%CI 1.32-22.72, p = 0.02) and overall survival (OS) (HR 5.46, 95%CI 1.28-23.22, p = 0.02). A decrease in CTC count at 4 weeks was associated with improved PFS (HR 3.81, 95%CI 1.13-12.79, p = 0.03) but not OS. 85% of patients with radiological progression had a ctDNA rise compared with 22% of patients with stable disease (p=0.01). ctDNA rise was seen on average 170 days prior to radiological progression. There is a significant association between the rise of CEA level with radiological progression (p=0.001). CONCLUSION: Early change in ctDNA, CTC and CEA levels may be long-term predictors of treatment benefit and failure prior to availability of radiological response data.
Authors: Joseph W Po; Yafeng Ma; Bavanthi Balakrishnar; Daniel Brungs; Farhad Azimi; Adam Cooper; Erin Saricilar; Vinay Murthy; Paul de Souza; Therese M Becker Journal: Methods Mol Biol Date: 2021
Authors: Raquel Carrasco; Mercedes Ingelmo-Torres; Ascensión Gómez; Fiorella L Roldán; Natalia Segura; María José Ribal; Antonio Alcaraz; Laura Izquierdo; Lourdes Mengual Journal: World J Urol Date: 2022-06-17 Impact factor: 3.661
Authors: Pei N Ding; Therese Becker; Victoria Bray; Wei Chua; Yafeng Ma; Bo Xu; David Lynch; Paul de Souza; Tara Roberts Journal: Thorac Cancer Date: 2019-08-15 Impact factor: 3.500
Authors: Pei N Ding; Tara L Roberts; Wei Chua; Therese M Becker; Nicole Caixeiro; Paul de Souza; Bo Gao; Chee K Lee; Malinda Itchins; Helen Westman; Stephen Clarke; Prunella Blinman; Steven Kao; Tom John; Jose L Leal; Victoria J Bray Journal: Transl Lung Cancer Res Date: 2021-04
Authors: G M Walls; L McConnell; J McAleese; P Murray; T B Lynch; K Savage; G G Hanna; D Gonzalez de Castro Journal: Radiat Oncol Date: 2020-05-29 Impact factor: 3.481
Authors: Frederik van Delft; Hendrik Koffijberg; Valesca Retèl; Michel van den Heuvel; Maarten IJzerman Journal: Cancers (Basel) Date: 2020-04-30 Impact factor: 6.639