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Concordance of epidermal growth factor receptor mutation detection in bodily fluids other than blood with tissue biopsy: A retrospective analysis

In Cancer Research, Statistics, and Treatment
By: Chougule A [Corresponding Author].
Contributor(s): Pange P | Kale S | Jagtap V | Nambiar K | Nikam A | Tiwrekar P | Trivedi V | Behel V | Kapoor A | Menon N | Patil V | Noronha V | Prabhash K | Banavali SD.
Material type: materialTypeLabelArticlePublisher: 2020Description: .Subject(s): Circulating tumor DNA | Epidermal growth factor receptor | Malignant body fluids | T790M mutation In: Cancer Research, Statistics, and Treatment Vol. 3, no. 3, p. 475-480.Summary: ABSTRACT Background: The concept of liquid biopsy as a surrogate for tumor tissue is not only restricted to blood-derived samples but also includes other malignant bodily fluids such as cerebrospinal fluid, pleural fluid, pericardial fluid, and ascites. The application of liquid biopsy in patients with metastatic lung cancer, with disease progression on epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment, is unexplored in India. Objective: We aimed to determine the presence of EGFR gene mutations in various bodily fluids of patients with EGFR-mutant progressive metastatic lung adenocarcinoma. Materials and Methods: In this retrospective study conducted at the Tata Memorial Hospital in Mumbai, India, data from 11 patients with advanced EGFR-mutant lung adenocarcinoma were analyzed. Between December 2017 and June 2018, the cell-free DNA (cfDNA) obtained from the malignant bodily fluids and plasma of 11 patients were tested for the presence of EGFR-sensitizing mutations using real-time reverse transcription-polymerase chain reaction. The status of EGFR-sensitizing mutations in plasma and other bodily fluids was compared with that of the baseline tissue biopsy. In addition, the status of the acquired T790M resistance mutation in exon 20 at disease progression was determined using plasma and other bodily fluids. Results: Of the 11 patients, at disease progression, EGFR sensitizing mutations (exon 19 deletion and exon 21 L858R insertion) could be detected in the plasma of 7 (63%) and in other bodily fluids of all the 11 (100%) patients. Thus, the concordance for EGFR-sensitizing mutation detection in the plasma and other bodily fluids with the baseline formalin-fixed paraffin-embedded tissue was 63% and 100%, respectively. In addition, the acquired T790M resistance mutation was detected in the plasma of 3 (27.3%) patients and other bodily fluids of 9 (81.8%) patients. Conclusion: The rate of detection of the T790M mutation is higher in the free DNA obtained from malignancy-involved bodily fluid supernatant as compared to the plasma cfDNA. Our results suggest that cfDNA obtained from bodily fluids other than plasma can be used for the detection of EGFR mutations and that the mutation status may be a useful predictor of the response to TKIs.
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Address for Corresponding Author: anu.c1112@gmail.com

ABSTRACT
Background: The concept of liquid biopsy as a surrogate for tumor tissue is not only restricted to blood-derived samples but also includes other malignant bodily fluids such as cerebrospinal fluid, pleural fluid, pericardial fluid, and ascites. The application of liquid biopsy in patients with metastatic lung cancer, with disease progression on epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment, is unexplored in India.
Objective: We aimed to determine the presence of EGFR gene mutations in various bodily fluids of patients with EGFR-mutant progressive metastatic lung adenocarcinoma.
Materials and Methods: In this retrospective study conducted at the Tata Memorial Hospital in Mumbai, India, data from 11 patients with advanced EGFR-mutant lung adenocarcinoma were analyzed. Between December 2017 and June 2018, the cell-free DNA (cfDNA) obtained from the malignant bodily fluids and plasma of 11 patients were tested for the presence of EGFR-sensitizing mutations using real-time reverse transcription-polymerase chain reaction. The status of EGFR-sensitizing mutations in plasma and other bodily fluids was compared with that of the baseline tissue biopsy. In addition, the status of the acquired T790M resistance mutation in exon 20 at disease progression was determined using plasma and other bodily fluids.
Results: Of the 11 patients, at disease progression, EGFR sensitizing mutations (exon 19 deletion and exon 21 L858R insertion) could be detected in the plasma of 7 (63%) and in other bodily fluids of all the 11 (100%) patients. Thus, the concordance for EGFR-sensitizing mutation detection in the plasma and other bodily fluids with the baseline formalin-fixed paraffin-embedded tissue was 63% and 100%, respectively. In
addition, the acquired T790M resistance mutation was detected in the plasma of 3 (27.3%) patients and other bodily fluids of 9 (81.8%) patients.
Conclusion: The rate of detection of the T790M mutation is higher in the free DNA obtained from malignancy-involved bodily fluid supernatant as compared to the plasma cfDNA. Our results suggest that cfDNA obtained from bodily fluids other than plasma can be used for the detection of EGFR mutations and that the mutation status may be a useful predictor of the response to TKIs.

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