Value of [¹⁸F]FDG PET/CT for predicting epidermal growth factor receptor gene mutation status in patients with newly diagnosed non-small cell lung cancer: a retrospective single center study

Purpose of the study. The aim of this study was to evaluate the role of [¹⁸F]FDG PET/CT for predicting epidermal growth factor receptor (EGFR) gene mutation status in patients with newly diagnosed non-small cell lung cancer (NSCLC).

Patients and methods. This retrospective single center study included 63 patients with newly diagnosed NSCLC who underwent [¹⁸F]FDG PET/CT. Acquisition was performed in accordance with the EANM guideline using the Discovery IQ Gen 2 PET/CT system (GE HealthCare). All patients were divided into a mutant group (n = 30) and a wild-type group (n = 33) based on EGFR mutation status. Maximal diameter and volume of each primary tumor lesion were measured, [¹⁸F]FDG uptake was analyzed by measurement of SUVmax, SUVpeak, MTV and TLG. TLG was measured using two independent segmentation methods by the following tools: 3D-Isocontour with 41% of SUVmax threshold for PET image (TLG_41%) and Solid Lung Lesion Segmentation for deep-inspiration breath-hold CT image (TLG_CT). The anatomical volume derived from the second method was used to manually adjust the isocontour threshold for PET image ensuring that tumor MTV is equal to its anatomical volume. Additionally, TLR index was calculated as the ratio of lesion SUVpeak to liver SUVmean. 9 EGFR-mutant patients were excluded from MTV and TLG analysis due to the inability to use both tumor segmentation methods. Acquisition data of NEMA IEC Body Phantom Set NU2-2018 was applied for plotting the recovery coefficients curves that used for following partial volume effect (PVE) correction.

Results. Medians of lesions’ maximal diameters and volumes in the mutant and wild-type groups were, respectively: 3 [2.5; 4] and 3.6 [2.5; 4.4] cm, 7 [5.2; 14.7] and 12.1 [4.6; 24.4] ml. Medians of PET-metrics in the mutant and wild-type groups were, respectively: SUVmax without PVE correction (PVE) – 6.6 [3.6; 9.3] and 8.5 [6.4; 10], after correction (cPVE) – 5.7 [3.2; 7.6] and 6.8 [5.4; 8.1]; PVE SUVpeak – 5.7 [2.8; 7.6] and 6.6 [5.2; 8.8], cPVE SUVpeak – 5.2 [3; 6.8] and 6.7 [4.7; 7.7]; PVE MTV_41% – 5.4 [3.3; 10.4] and 9 [3.6; 16.2], cPVE MTV_41% – 5.2 [3.3; 10.1] and 6.2 [3.6; 11.7]; PVE TLG_41% – 21.5 [9.2; 37.8] and 36.9 [10.2; 78], cPVE TLG_41% – 28.9 [16; 46.4] and 24.9 [12.9; 66.4]; PVE TLG_CT – 27.8 [11.5; 52.1] and 54.7 [14.4; 123], cPVE TLG_CT – 31 [14.7; 51.7] and 35.8 [16.2; 82.6]; PVE TLR – 3 [2; 5.2] and 4 [3; 5.3], cPVE TLR – 3 [2.1; 4.5] and 3.6 [2.7; 5]. No significant differences in lesions’ maximal diameters, volumes, evaluated PVE and cPVE PET-metrics were found between the mutant and wild-type groups of patients (p > 0,05).

Conclusion. Our results suggest that [¹⁸F]FDG PET/CT has no significant value for predicting the EGFR gene mutation status in patients with newly diagnosed NSCLC.

1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229–263. https://doi.org/10.3322/caac.21834

2. Malignant neoplasms in Russia in 2023 (morbidity and mortality). Edited by Kaprin AD, Starinsky VV, Shakhzadova AO. Moscow: P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Radiology Research Centre of the Ministry of Health of the Russian Federation, 2024. 276 p. (In Russ.). Available at: https://oncology-association.ru/wp-content/uploads/2024/08/zis-2023-elektronnaya-versiya.pdf. Accessed: 21.04.2025.

3. Non-small cell lung cancer. NCCN clinical practice guidelines in oncology. National Comprehensive Cancer Network, 2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed: 21.04.2025.

4. Wee P, Wang Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers (Basel). 2017 May 17;9(5):52. https://doi.org/10.3390/cancers905005

5. Prabhakar CN. Epidermal growth factor receptor in non-small cell lung cancer. Transl Lung Cancer Res. 2015 Apr;4(2):110-118. https://doi.org/10.3978/j.issn.2218-6751.2015.01.01

6. Mikheev DV, Chernyakova AP, Mitiushkina NV, Tyurin VI, Nikitina AS, Asadulaeva KA, et al. The Spectrum of Uncommon EGFR Mutations in Non-Small Cell Lung Cancer. Problems in Oncology. 2024;70(6):1115–1121. (In Russ.). https://doi.org/10.37469/0507-3758-2024-70-6-1115-1121

7. Borisova EI, Gutorov SL. Rational drug therapy of non-small cell lung cancer. Journal of Modern Oncology. 2011;13(3):45–49. (In Russ.).

8. Lung cancer. Clinical recommendations. Moscow: Ministry of Health of the Russian Federation, 2021. (In Russ.). Available at: https://oncology-association.ru/wp-content/uploads/2022/07/zlokachestvennoe-novoobrazovanie-bronhov-i-legkogo.pdf. Accessed: 21.04.2025.

9. Huang CT, Yen RF, Cheng MF, Hsu YC, Wei PF, Tsai YJ, et al. Correlation of F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value and EGFR mutations in advanced lung adenocarcinoma. Med Oncol. 2010 Mar;27(1):9–15. https://doi.org/10.1007/s12032-008-9160-1

10. Ko KH, Hsu HH, Huang TW, Gao HW, Shen DHY, Chang WC, et al. Value of 18F-FDG uptake on PET/CT and CEA level to predict epidermal growth factor receptor mutations in pulmonary adenocarcinoma. Eur J Nucl Med Mol Imaging. 2014 Oct;41(10):1889–1897. https://doi.org/10.1007/s00259-014-2802-y

11. Kanmaz ZD, Aras G, Tuncay E, Bahadir A, Kocaturk C, Yasar ZA, et al. Contribution of 18Fluorodeoxyglucose positron emission tomography uptake and TTF-1 expression in the evaluation of the EGFR mutation in patients with lung adenocarcinoma. Cancer Biomark. 2016;16(3):489–498. https://doi.org/10.3233/CBM-160588

12. Na II, Byun BH, Kim KM, Cheon GJ, Choe DH, Koh JS, et al. 18F-FDG uptake and EGFR mutations in patients with non-small cell lung cancer: a single-institution retrospective analysis. Lung Cancer. 2010 Jan;67(1):76–80. https://doi.org/10.1016/j.lungcan.2009.03.010

13. Cho A, Hur J, Moon YW, Hong SR, Suh YJ, Kim YJ, et al. Correlation between EGFR gene mutation, cytologic tumor markers, 18F-FDG uptake in non-small cell lung cancer. BMC Cancer. 2016 Mar 16:16:224. https://doi.org/10.1186/s12885-016-2251-z

14. Lv Z, Fan J, Xu J, Wu F, Huang Q, Guo M, et al. Value of 18F-FDG PET/CT for predicting EGFR mutations and positive ALK expression in patients with non-small cell lung cancer: a retrospective Analysis of 849 Chinese patients. Eur J Nucl Med Mol Imaging. 2018 May;45(5):735–750. https://doi.org/10.1007/s00259-017-3885-z

15. Guan J, Xiao NJ, Chen M, Zhou WL, Zhang YW, Wang S, et al. 18F-FDG uptake for prediction EGFR mutation status in non-small cell lung cancer. Medicine (Baltimore). 2016 Jul;95(30):e4421. https://doi.org/10.1097/MD.0000000000004421

16. Wang J, Wen X, Yang G, Cui Y, Hao M, Qiao X, et al. The predictive value of 18F-FDG PET/CT in an EGFR-mutated lung adenocarcinoma population. Transl Cancer Res. 2022 Jul;11(7):2338–2347. https://doi.org/10.21037/tcr-22-1726

17. Hong IK, Lee JM, Hwang IK, Paik SS, Kim C, Lee SH. Diagnostic and predictive values of 18F-FDG PET/CT metabolic parameters in EGFR-mutated advanced lung adenocarcinoma. Cancer Manag Res. 2020 Jul 28;12:6453–6465. https://doi.org/10.2147/CMAR.S259055

18. Mak RH, Digumarthy SR, Muzikansky A, Engelman JA, Shepard JAO, Choi NC, Sequist LV. Role of 18F-fluorodeoxyglucose positron emission tomography in predicting epidermal growth factor receptor mutations in non-small cell lung cancer. Oncologist. 2011;16(3):319–326. https://doi.org/10.1634/theoncologist.2010-0300

19. Liu A, Han A, Zhu H, Ma L, Huang Y, Li M, et al. The role of metabolic tumor volume (MTV) measured by [18F]FDG PET/CT in predicting EGFR gene mutation status in non-small cell lung cancer. Oncotarget. 2017 May 16;8(20):33736–33744. https://doi.org/10.18632/oncotarget.16806

20. Du B, Wang S, Cui Y, Liu G, Li X, Li Y. Can 18F-FDG PET/CT predict EGFR status in patients with non-small cell lung cancer? A systematic review and meta-analysis. BMJ Open. 2021 Jun 8;11(6):e044313. https://doi.org/10.1136/bmjopen-2020-044313

21. Caicedo C, Garcia-Velloso MJ, Lozano MD, Labiano T, Diaz CV, Lopez-Picazo JM, et al. Role of [18F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2014 Nov;41(11):2058– 2065. https://doi.org/10.1007/s00259-014-2833-4

22. Igde MH, Ozturk A, Oruc O, Oztas S, Kavas M. The relationship of PET/CT SUVmax with EGFR mutation status and ALK rearrangement in lung adenocarcinoma. Hell J Nucl Med. 2022 May-Aug;25(2):188–195. https://doi.org/10.1967/s002449912486