Epidermal Growth Factor Receptor Mutation Testing from Pleural Effusions of Patients with Advanced Lung Adenocarcinoma in Serbia - European Medical Journal

Epidermal Growth Factor Receptor Mutation Testing from Pleural Effusions of Patients with Advanced Lung Adenocarcinoma in Serbia

3 Mins
Oncology
Authors:
*Milena Cavic, Miodrag Vukovic, Ana Damjanovic, Aleksandra Stefanovic, Marijana Pavlovic, Ivana Boljević, Katarina Zivic, Miljana Tanic, Radmila Janković
Disclosure:

Cavic has received a grant from the Science Fund of the Republic of Serbia, LungCARD – MSCA-RISE project (Horizon 2020, European Commission, Grant agreement No. 734790); served as President for the Serbian Society for Cancer Research; is Diagnostics Working Group Co-chair for the Screening and Early Detection Committee of the International Association for the Study of Lung Cancer; National Societies Committee member for the European Association for Cancer Research; and FEBS Advanced Courses Committee Member for the Biochemical Society of Serbia. Tanic has received a grant from the Science Fund of the Republic of Serbia. Janković has received a grant from the LungCARD – MSCA-RISE project (Horizon 2020, European Commission, Grant agreement No. 734790); and has received funds from AstraZeneca, Roche, Merck, and Tadeka. All authors have received a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant agreement No. 451-03-68/2022-14/ 200043).

Citation:
EMJ. ;10[1]:34-35. DOI/10.33590/emjoncol/10026480. https://doi.org/10.33590/emjoncol/10026480.
Keywords:
Epidermal growth factor receptor (EGFR), liquid biopsy, lung adenocarcinoma, pleural effusion.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

BACKGROUND AND AIMS

High incidence of lung cancer in Serbia is derived from high smoking rates, the lack of a nationwide screening programme, and the presence of environmental risk factors.1 By histology, adenocarcinoma accounts for approximately 50% of all lung cancer cases, with approximately 60% of new diagnoses already in advanced disease stages, where targeted therapies and immunotherapy are indicated. In Serbia, epidermal growth factor receptor (EGFR) mutation testing is still performed on liquid biopsy of patients with lung cancer only by quantitative PCR.2,3 The aim of this study was to evaluate the efficacy of this approach in pleural effusions of patients with non-small cell lung cancer (NSCLC) at diagnosis and after progression on EGFR tyrosine kinase inhibitors (EGFR-TKI) in Serbia.

MATERIALS AND METHODS

Mutation testing was performed on blood and pleural effusions of patients with advanced lung adenocarcinoma (Stage IIIB or IV; Eastern Cooperative Oncology Group [ECOG] Performance Status 0, 1, or 2) using the Cobas® EGFR Mutation Test (Roche, Basel, Switzerland), which detects 42 mutations in exons 18, 19, 20, and 21 of the EGFR gene with sensitivity of 5%.

RESULTS

In the period from 2016–2021, 124 patients were tested at baseline (53% males; 47% females; age range 37–83 years; median 61), and 104 after progression on first line EGFR-TKIs (41% males; 59% females; age range: 34–81 years; median age: 60). At diagnosis, nine mutated samples were detected (7.3%) with a turnaround time of 2 working days, and a 99.2% testing success rate. At progression, an accordance rate of only 67% with the initial driver mutation was observed from blood. The T790M mutation was detected in 34 patients (49% of the mutated samples; 33% of the total), which rendered them eligible for third generation EGFR-TKIs. In the same period, only six samples (4.8%) of pleural effusions were sent to our laboratory along with blood, all from patients at progression. The testing was performed with a turnaround time of 2 working days, a 100% testing success rate, and an accordance rate of 100% with the initial driver mutation. In 50% of concurrently sent samples, the T790M mutation was detected in the pleural effusion, while the corresponding blood sample showed only the presence of the driver mutation (Figure 1).

Figure 1: A Presentation of a clinical case from the Laboratory for Molecular Genetics, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.
ctDNA: circulating tumour DNA; NSCLC: non-small cell lung cancer; TKI: tyrosine kinase inhibitors.

A 49-year-old male patient with advanced NSCLC on first generation TKIs was referred to the Laboratory for Molecular Genetics at the Institute for Oncology and Radiology of Serbia, Belgrade, Serbia to detect the presence of the resistant mutation T790M in the EGFR gene at progression. The presence of the resistant mutation was first tested in blood, but only the driver mutation ex19del was detected. One month later, three additional patient samples were sent for molecular testing with following results: lung biopsy from liquid nitrogen (ex19del), circulating tumour DNA from blood (ex19del), and circulating tumour DNA from pleural effusion (ex19del+T790M). The resistant mutation T790M was detected only in the pleural effusion. The patient was characterised as a candidate for third generation TKIs according to that result.

CONCLUSION

EGFR mutation testing from pleural effusion has proven valuable as an alternative liquid biopsy sample to blood, for detecting the T790M acquired resistance mutation in patients with advanced NSCLC who progressed on first-line EGFR-TKIs in Serbia. Pleural effusion samples should be considered as a valuable source of genetic material and might be proposed by future guidelines for concurrent EGFR mutation testing alongside blood whenever available.4,5

References
Cavic M et al. Lung cancer in Serbia. J Thorac Oncol. 2022;17(7):867-72. Cavic M et al. EGFR mutation testing from liquid biopsy of non-small cell lung cancer at the Institute for Oncology and Radiology of Serbia. J BUON. 2020;25(6):2635-48. Cavic M et al. Exploring the real-world effect of the SARS-CoV-2 pandemic on the molecular diagnostics for cancer patients and high-risk individuals. Expert Rev Mol Diagn. 2021;21(1):101-7. Heitzer E et al. Recommendations for a practical implementation of circulating tumor DNA mutation testing in metastatic non-small-cell lung cancer. ESMO Open. 2022;7(2):100399. Zhang P al. Detection of EGFR gene mutation status from pleural effusions and other body fluid specimens in patients with lung adenocarcinoma. Thorac Cancer. 2019;10(12):2218.

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