Diagnostic performance of F-18 FDG PET/CT for prediction of KRAS mutation in colorectal cancer patients: a systematic review and meta-analysis

ObjectiveThe purpose of the current study was to investigate the diagnostic performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the prediction of v-Ki-ras-2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in colorectal cancer (CRC) patients through a systematic review and meta-analysis.MethodsThe PubMed and EMBASE database, from the earliest available date of indexing through April 30, 2018, were searched for studies evaluating the diagnostic performance of F-18 FDG PET/CT for prediction of KRAS mutation in CRC patients.ResultsAcross 9 studies (804 patients), the pooled sensitivity for F-18 FDG PET/CT was 0.66 (95% CI 0.60–0.73) without heterogeneity (I2 = 34.1, p = 0.14) and a pooled specificity of 0.67 (95% CI 0.62–0.72) without heterogeneity (I2 = 1.63, p = 0.42). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 2.0 (95% CI 1.7–2.4) and negative likelihood ratio (LR−) of 0.5 (95% CI 0.41–0.61). The pooled diagnostic odds ratio (DOR) was 4 (95% CI 3–6). Hierarchical summary receiver operating characteristic (ROC) curve indicates that the areas under the curve were 0.69 (95% CI 0.65–0.73).ConclusionThe current meta-analysis showed the low sensitivity and specificity of F-18 FDG PET/CT for prediction of KRAS mutation in CRC patients. The DOR was very low and the likelihood ratio scatter-gram indicated that F-18 FDG PET/CT might not be useful for prediction of KRAS mutation and not for its exclusion. Therefore, cautious application and interpretation should be paid to the F-18 FDG PET/CT for prediction of KRAS mutation in CRC patients.

[1]  Rebecca L. Siegel Mph,et al.  Cancer statistics, 2018 , 2018 .

[2]  Kenji Suzuki,et al.  Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in lung adenocarcinoma , 2017, PloS one.

[3]  William E. Grizzle,et al.  Detection of high incidence of K-ras oncogenes during human colon tumorigenesis , 1987, Nature.

[4]  G. Qiao,et al.  KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib , 2008 .

[5]  Lin Qiu,et al.  Relationship between KRAS mutations and dual time point 18F-FDG PET/CT imaging in colorectal liver metastases , 2018, Abdominal Radiology.

[6]  S. Chiang,et al.  Correlation Between PET/CT Parameters and KRAS Expression in Colorectal Cancer , 2014, Clinical nuclear medicine.

[7]  K. Iwaisako,et al.  Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by 18F-FDG-PET is associated with the KRAS mutation status and prognosis , 2018, Journal of Translational Medicine.

[8]  Kaori Togashi,et al.  Relationship between 18F-Fluorodeoxyglucose Accumulation and KRAS/BRAF Mutations in Colorectal Cancer , 2012, Clinical Cancer Research.

[9]  Dongsheng Tu,et al.  K-ras mutations and benefit from cetuximab in advanced colorectal cancer. , 2008, The New England journal of medicine.

[10]  Susan Mallett,et al.  Circulating MicroRNAs as a Novel Class of Diagnostic Biomarkers in Gastrointestinal Tumors Detection: A Meta-Analysis Based on 42 Articles , 2014, PloS one.

[11]  P. Bossuyt,et al.  The diagnostic odds ratio: a single indicator of test performance. , 2003, Journal of clinical epidemiology.

[12]  Sang Hyun Hwang,et al.  Correlation between KRAS mutation and 18F-FDG uptake in stage IV colorectal cancer , 2016, Abdominal Radiology.

[13]  A. Lièvre,et al.  KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  S G Thompson,et al.  Systematic Review: Why sources of heterogeneity in meta-analysis should be investigated , 1994, BMJ.

[15]  A. Alavi,et al.  18F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization* , 2009, Journal of Nuclear Medicine.

[16]  C M Rutter,et al.  A hierarchical regression approach to meta‐analysis of diagnostic test accuracy evaluations , 2001, Statistics in medicine.

[17]  M. Hatt,et al.  (18)F-FDG PET/CT imaging in rectal cancer: relationship with the RAS mutational status. , 2016, The British journal of radiology.

[18]  G Smith,et al.  The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma , 2005, Gut.

[19]  Jan-Gowth Chang,et al.  Genetic Alterations in Colorectal Cancer Have Different Patterns on 18F-FDG PET/CT , 2015, Clinical nuclear medicine.

[20]  Jonathan J Deeks,et al.  The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. , 2005, Journal of clinical epidemiology.

[21]  K. Kinzler,et al.  Glucose Deprivation Contributes to the Development of KRAS Pathway Mutations in Tumor Cells , 2009, Science.

[22]  H. Date,et al.  Relationship Between 18F-FDG PET/CT Scans and KRAS Mutations in Metastatic Colorectal Cancer , 2015, The Journal of Nuclear Medicine.

[23]  C. Meltzer,et al.  PET/CT: form and function. , 2007, Radiology.

[24]  Theo Stijnen,et al.  The binomial distribution of meta-analysis was preferred to model within-study variability. , 2008, Journal of clinical epidemiology.

[25]  Tae Joo Jeon,et al.  Relationship Between 18F-Fluorodeoxyglucose Uptake and V-Ki-Ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog Mutation in Colorectal Cancer Patients , 2016, Medicine.

[26]  A. Jemal,et al.  Cancer statistics, 2018 , 2018, CA: a cancer journal for clinicians.

[27]  M. Ostland,et al.  Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  Funda Aydın,et al.  The value of 18FDG PET/CT parameters, hematological parameters and tumor markers in predicting KRAS oncogene mutation in colorectal cancer. , 2017, Hellenic journal of nuclear medicine.

[29]  Heinrich R Schelbert,et al.  Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006. , 2007, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[30]  Wei-Chih Shen,et al.  Metabolic Imaging Phenotype Using Radiomics of [18F]FDG PET/CT Associated with Genetic Alterations of Colorectal Cancer , 2018, Molecular Imaging and Biology.

[31]  F.A.M. Bordonaba,et al.  Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer , 2009 .

[32]  Daniel J. Freeman,et al.  Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  M. Lozano,et al.  Role of [18F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer , 2014, European Journal of Nuclear Medicine and Molecular Imaging.

[34]  Patrick Bossuyt,et al.  Systematic Reviews of Diagnostic Test Accuracy , 2008, Annals of Internal Medicine.

[35]  P. Bossuyt,et al.  Empirical evidence of design-related bias in studies of diagnostic tests. , 1999, JAMA.

[36]  Johannes B Reitsma,et al.  Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. , 2005, Journal of clinical epidemiology.

[37]  Dongsheng Tu,et al.  Cetuximab for the treatment of colorectal cancer. , 2007, The New England journal of medicine.

[38]  A. Kuten,et al.  Clinical performance of PET/CT in evaluation of cancer: additional value for diagnostic imaging and patient management. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[39]  M. Lonneux FDG-PET and PET/CT in Colorectal Cancer. , 2008, PET clinics.

[40]  S. Jung,et al.  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 , 2015, Clinical nuclear medicine.

[41]  G. Fountzilas,et al.  Lack of association between KRAS mutations and 18F-FDG PET/CT in Caucasian metastatic colorectal cancer patients. , 2014, Anticancer research.

[42]  J. Sehouli,et al.  Original Paper: A likelihood ratio approach to meta-analysis of diagnostic studies , 2003 .