Rapid diagnosis of genetic mutations is important for targeted therapies such as EGFR tyrosine kinase inhibitors. KRAS mutation and ALK rearrangement are also important in determining treatment. The purpose of our study was to evaluate the diagnostic value of 18F-FDG PET to predict KRAS mutation and ALK rearrangement in order to determine the frequency of these genetic markers in our lung adenocarcinoma cases and contribute to forthcoming meta-analysis studies.
Methods
A total of 218 patients with lung adenocarcinoma (EGFR analyzed) who were seen at our clinic between 2012 and 2014 were included in the study. The results of the 18 F-FDG-PET scans for each patient were retrospectively recorded with the associated medical documents. ALK rearrangements were analyzed in 166 of the 218 patients, while 50 of the 218 patients were analyzed for KRAS mutational status. SPSS 15.0 for Windows was used for statistical analysis.
Results
FDG avidity was higher in cases with KRAS mutations and ALK rearrangements than those without, but the difference was not significant. ALK rearrangements were more common in younger, female, and nonsmoking patients with lung adenocarcinoma.
Conclusions
The small numbers of KRAS mutations and ALK rearrangements are the limitation of this study for evaluation of diagnostic imaging. The frequency of these genetic alterations was as reported in the literature. We believe that our work will contribute to future meta-analysis.
ChoiH, PaengJC, KimDW, et al. Metabolic and metastatic characteristics of ALK-rearranged lung adenocarcinoma on FDG PET/CT.Lung Cancer. 2013;79 (3):242–247.
JackmanDM, MillerVA, CioffrediLA, et al. Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials.Clin Cancer Res.2009;15 (16):5267–5273.
4.
MassarelliE, Varella-GarciaM, TangX, et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer.Clin Cancer Res.2007;13 (10): 2890–2896.
5.
PapadopoulouE, TsoulosN, TsirigotiA, et al. Determination of EGFR and KRAS mutational status in Greek non-small-cell lung cancer patients.Oncol Lett.2015;10 (4):2176–2184.
6.
CollissonEA, CampbellJD, BrooksAN, et al. Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma.Nature.2014;511 (7511):543–550.
7.
LohinaiZ, HodaMA, FabianK, et al. Distinct epidemiology and clinical consequence of classic versus rare EGFR mutations in lung adenocarcinoma.J Thorac Oncol.2015;10 (5): 738–746.
8.
JeongCJ, LeeHY, HanJ, et al. Role of imaging biomarkers in predicting anaplastic lymphoma kinase-positive lung adenocarcinoma.Clin Nucl Med.2015;40 (1):e34–39.
9.
KwakEL, BangYJ, CamidgeDR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer.N Engl J Med.2010;363 (18):1693–1703.
10.
OuSH, KwakEL, Siwak-TappC, et al. Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification.J Thorac Oncol.2011;6 (5):942–946.
11.
VanuytselLJ, VansteenkisteJF, StroobantsSG, et al. The impact of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) lymph node staging on the radiation treatment volumes in patients with non-small cell lung cancer.Radiother Oncol.2000;55 (3):317–324.
12.
ShiraishiK, NomoriH, OhbaY, et al. Repeat FDG-PET for predicting pathological tumor response and prognosis after neoadjuvant treatment in nonsmall cell lung cancer: comparison with computed tomography.Ann Thorac Cardiovasc Surg.2010;16 (6):394–400.
13.
EschmannSM, FriedelG, PaulsenF, et al. Impact of staging with 18F-FDG-PET on outcome of patients with stage III non-small cell lung cancer: PET identifies potential survivors.Eur J Nucl Med Mol Imaging.2007;34 (1):54–59.
14.
YunJ, RagoC, CheongI, et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells.Science.2009;325 (5947):1555–1559.
15.
WeihuaZ, TsanR, HuangWC, et al. Survival of cancer cells is maintained by EGFR independent of its kinase activity.Cancer Cell.2008;13 (5):385–393.
16.
JorissenRN, WalkerF, PouliotN, GarrettTP, WardCW, BurgessAW.Epidermal growth factor receptor: mechanisms of activation and signalling.Exp Cell Res.2003;284 (1):31–53.
NaII, ByunBH, KimKM, et al. 18F-FDG uptake and EGFR mutations in patients with non-small cell lung cancer: a single-institution retrospective analysis.Lung Cancer.2010;67 (1): 76–80.
19.
MakRH, DigumarthySR, MuzikanskyA, et al. 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.
20.
CaicedoC, Garcia-VellosoMJ, LozanoMD, 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;41 (11):2058–2065.
21.
LeeSM, BaeSK, JungSJ, KimCK.FDG uptake in non-small cell lung cancer is not an independent predictor of EGFR or KRAS mutation status: a retrospective analysis of 206 patients.Clin Nucl Med.2015;40 (12):950–958.
22.
TravisWD, GirouxDJ, ChanskyK, et al. The IASLC Lung Cancer Staging Project: Proposals for the inclusion of Carcinoid tumours in the forthcoming (seventh) edition of the TNM Classification for Lung cancer.J Thorac Oncol.2008;3:1213–1223.
ShepherdFA, DomergC, HainautP, et al. Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy.J Clin Oncol.2013;31 (17):2173–2181.
25.
SunJM, HwangDW, AhnJS, AhnMJ, ParkK.Prognostic and predictive value of KRAS mutations in advanced non-small cell lung cancer.PLoS ONE.2013;8 (5):e64816.
26.
MetroG, ChiariR, BennatiC, et al. Clinical outcome with platinum-based chemotherapy in patients with advanced nonsquamous EGFR wild-type non-small-cell lung cancer segregated according to KRAS mutation status.Clin Lung Cancer.2014;15 (1):86–92.
27.
BhattacharyaS, SocinskiMA, BurnsTF.KRAS mutant lung cancer: progress thus far on an elusive therapeutic target.Clin Transl Med.2015;4 (1):35.
28.
HirschFR, SudaK, WiensJ, BunnPAJr.New and emerging targeted treatments in advanced non-small-cell lung cancer.Lancet.2016;388 (10048):1012–1024.
29.
SudaK, TomizawaK, MitsudomiT.Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation.Cancer Metastasis Rev.2010;29 (1):49–60.
30.
RobertsPJ, StinchcombeTE.KRAS mutation: should we test for it, and does it matter?J Clin Oncol.2013;31 (8): 1112–1121.
31.
BergethonK, ShawAT, OuSH, et al. ROS1 rearrangements define a unique molecular class of lung cancers.J Clin Oncol.2012;30 (8):863–870.
32.
LozanoMD, LabianoT, EchevesteJ, et al. Assessment of EGFR and KRAS mutation status from FNAs and core-needle biopsies of non-small cell lung cancer.Cancer Cytopathol.2015;123 (4):230–236.
33.
IhleNT, ByersLA, KimES, et al. Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome.J Natl Cancer Inst.2012;104 (3): 228–239.
34.
YipSS, KimJ, CorollerTP, et al. Associations between somatic mutations and metabolic imaging phenotypes in non-small cell lung cancer.J Nucl Med.2017;58 (4):569–576.
35.
TakamochiK, MogushiK, KawajiH, et al. Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in lung adenocarcinoma.PLoS ONE.2017;12 (4):e0175622.
36.
SherwoodJ, DeardenS, RatcliffeM, WalkerJ.Mutation status concordance between primary lesions and metastatic sites of advanced non-small-cell lung cancer and the impact of mutation testing methodologies: a literature review.J Exp Clin Cancer Res.2015;34 (1):92.
37.
SchmidK, OehlN, WrbaF, PirkerR, PirkerC, FilipitsM.EGFR/ KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases.Clin Cancer Res.2009;15 (14):4554–4560.
38.
HanCB, MaJT, LiF, et al. EGFR and KRAS mutations and altered c-Met gene copy numbers in primary non-small cell lung cancer and associated stage N2 lymph node-metastasis.Cancer Lett.2012;314 (1):63–72.
39.
SodaM, ChoiYL, EnomotoM, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.Nature.2007;448 (7153):561–566.
40.
PaikJH, ChoiCM, KimH, et al. Clinicopathologic implication of ALK rearrangement in surgically resected lung cancer: a proposal of diagnostic algorithm for ALK-rearranged adenocarcinoma.Lung Cancer.2012;76 (3):403–409.
41.
KoivunenJP, MermelC, ZejnullahuK, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer.Clin Cancer Res.2008;14 (13):4275–4283.
42.
HuangCT, YenRF, ChengMF, et al. Correlation of F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value and EGFR mutations in advanced lung adenocarcinoma.Med Oncol.2010;27 (1):9–15.
43.
KoKH, HsuHH, HuangTW, 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;41 (10):1889–1897.
44.
Wehrenberg-KleeE, TurkerNS, HeidariP, et al. Differential receptor tyrosine kinase PET imaging for therapeutic guidance.J Nucl Med.2016;57 (9):1413–1419.
