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Published in: Abdominal Radiology 5/2019

01-05-2019 | Rectal Cancer | Hollow Organ GI

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

Authors: Seong-Jang Kim, Kyoungjune Pak, Keunyoung Kim

Published in: Abdominal Radiology | Issue 5/2019

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Abstract

Objective

The 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.

Methods

The 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.

Results

Across 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).

Conclusion

The 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.
Literature
1.
go back to reference Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018 CA Cancer J Clin 68(1):7–30CrossRef Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018 CA Cancer J Clin 68(1):7–30CrossRef
2.
3.
go back to reference Eberhard DA, Johnson BE, Amler LC, et al. (2005) 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. J Clin Oncol 23(25):5900–5909CrossRefPubMed Eberhard DA, Johnson BE, Amler LC, et al. (2005) 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. J Clin Oncol 23(25):5900–5909CrossRefPubMed
4.
go back to reference Jonker DJ, O’Callaghan CJ, Karapetis CS, et al. (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357(20):2040–2048CrossRefPubMed Jonker DJ, O’Callaghan CJ, Karapetis CS, et al. (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357(20):2040–2048CrossRefPubMed
5.
go back to reference Karapetis CS, Khambata-Ford S, Jonker DJ, et al. (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancers. N Engl J Med 359(17):1757–1765CrossRefPubMed Karapetis CS, Khambata-Ford S, Jonker DJ, et al. (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancers. N Engl J Med 359(17):1757–1765CrossRefPubMed
6.
go back to reference Lievre A, Bachet JB, Boige V, et al. (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 26(3):374–379CrossRefPubMed Lievre A, Bachet JB, Boige V, et al. (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 26(3):374–379CrossRefPubMed
7.
go back to reference Amado RG, Wolf M, Peeters M, et al. (2008) Wild-type KRAS is required for panitumumab efficiency in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634CrossRefPubMed Amado RG, Wolf M, Peeters M, et al. (2008) Wild-type KRAS is required for panitumumab efficiency in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634CrossRefPubMed
8.
go back to reference Conlin A, Smith G, Carey FA, Wolf CR, Steele RJ (2005) The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma. Gut 54(9):1283–1286CrossRefPubMedPubMedCentral Conlin A, Smith G, Carey FA, Wolf CR, Steele RJ (2005) The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma. Gut 54(9):1283–1286CrossRefPubMedPubMedCentral
9.
10.
go back to reference Czernin J, Allen-Auerbach M, Schelbert HR (2007) Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006. J Nucl Med 48(Suppl 1):78S–88SPubMed Czernin J, Allen-Auerbach M, Schelbert HR (2007) Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006. J Nucl Med 48(Suppl 1):78S–88SPubMed
11.
go back to reference Bar-Shalom R, Yefremov N, Guralnik L, et al. (2003) Clinical performance of PET/CT in evaluation of cancer: additional value for diagnostic imaging and patient management. J Nucl Med 44(8):1200–1209PubMed Bar-Shalom R, Yefremov N, Guralnik L, et al. (2003) Clinical performance of PET/CT in evaluation of cancer: additional value for diagnostic imaging and patient management. J Nucl Med 44(8):1200–1209PubMed
13.
go back to reference Yun J, Rago C, Cheong I, et al. (2009) Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 325(5947):1555-1559CrossRefPubMedPubMedCentral Yun J, Rago C, Cheong I, et al. (2009) Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 325(5947):1555-1559CrossRefPubMedPubMedCentral
14.
go back to reference Chen SW, Lin CY, Ho CM, et al. (2015) Genetic Alterations in Colorectal Cancer Have Different Patterns on 18F-FDG PET/CT. Clin Nucl Med 40(8):621–626CrossRefPubMed Chen SW, Lin CY, Ho CM, et al. (2015) Genetic Alterations in Colorectal Cancer Have Different Patterns on 18F-FDG PET/CT. Clin Nucl Med 40(8):621–626CrossRefPubMed
15.
go back to reference Oner AO, Budak ES, Yıldırım S, Aydın F, Sezer C (2017) The value of 18FDG PET/CT parameters, hematological parameters and tumor markers in predicting KRAS oncogene mutation in colorectal cancer. Hell J Nucl Med 20(2):160-165PubMed Oner AO, Budak ES, Yıldırım S, Aydın F, Sezer C (2017) The value of 18FDG PET/CT parameters, hematological parameters and tumor markers in predicting KRAS oncogene mutation in colorectal cancer. Hell J Nucl Med 20(2):160-165PubMed
16.
go back to reference Whiting PF, Rutjes AW, Westwood ME, et al. (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155(8):529–536CrossRefPubMed Whiting PF, Rutjes AW, Westwood ME, et al. (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155(8):529–536CrossRefPubMed
17.
go back to reference Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM (2003) The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 56(11):1129–1135CrossRefPubMed Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM (2003) The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 56(11):1129–1135CrossRefPubMed
19.
go back to reference Deeks JJ, Macaskill P, Irwig L (2005) The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 58(9):882–893CrossRefPubMed Deeks JJ, Macaskill P, Irwig L (2005) The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 58(9):882–893CrossRefPubMed
20.
go back to reference Hamza TH, van Houwelingen HC, Stijnen T (2008) The binomial distribution of meta-analysis was preferred to model within-study variability. J Clin Epidemiol 61(1):41–51CrossRefPubMed Hamza TH, van Houwelingen HC, Stijnen T (2008) The binomial distribution of meta-analysis was preferred to model within-study variability. J Clin Epidemiol 61(1):41–51CrossRefPubMed
21.
go back to reference Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH (2005) Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 58(10):982–990CrossRefPubMed Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH (2005) Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 58(10):982–990CrossRefPubMed
22.
go back to reference Rutter CM, Gatsonis CA (2001) A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Stat Med 20(19):2865–2884CrossRefPubMed Rutter CM, Gatsonis CA (2001) A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Stat Med 20(19):2865–2884CrossRefPubMed
23.
go back to reference Lijmer JG, Mol BW, Heisterkamp S, et al. (1999) Empirical evidence of design-related bias in studies of diagnostic tests. JAMA 282(11):1061–1066CrossRefPubMed Lijmer JG, Mol BW, Heisterkamp S, et al. (1999) Empirical evidence of design-related bias in studies of diagnostic tests. JAMA 282(11):1061–1066CrossRefPubMed
24.
go back to reference Stengel D, Bauwens K, Sehouli J, Ekkernkamp A, Porzsolt F (2003) A likelihood ratio approach to meta-analysis of diagnostic studies. J Med Screen 10(1):47–51CrossRefPubMed Stengel D, Bauwens K, Sehouli J, Ekkernkamp A, Porzsolt F (2003) A likelihood ratio approach to meta-analysis of diagnostic studies. J Med Screen 10(1):47–51CrossRefPubMed
25.
go back to reference Leeflang MM, Deeks JJ, Gatsonis C & Bossuyt PM; Cochrane Diagnostic Test Accuracy Working Group (2008) Systematic Reviews of diagnostic test accuracy. Ann Intern Med 149(12):889–897CrossRef Leeflang MM, Deeks JJ, Gatsonis C & Bossuyt PM; Cochrane Diagnostic Test Accuracy Working Group (2008) Systematic Reviews of diagnostic test accuracy. Ann Intern Med 149(12):889–897CrossRef
26.
go back to reference Chen SW, Chiang HC, Chen WT, et al. (2014) Correlation between PET/CT parameters and KRAS expression in colorectal cancer. Clin Nucl Med 39(8):685–689CrossRefPubMed Chen SW, Chiang HC, Chen WT, et al. (2014) Correlation between PET/CT parameters and KRAS expression in colorectal cancer. Clin Nucl Med 39(8):685–689CrossRefPubMed
28.
go back to reference Cho A, Jo K, Hwang SH, et al. (2017) Correlation between KRAS mutation and 18F-FDG uptake in stage IV colorectal cancer. Abdom Radiol (NY) 42(6):1621–1626CrossRef Cho A, Jo K, Hwang SH, et al. (2017) Correlation between KRAS mutation and 18F-FDG uptake in stage IV colorectal cancer. Abdom Radiol (NY) 42(6):1621–1626CrossRef
29.
go back to reference Kawada K, Nakamoto Y, Kawada M, et al. (2012) Relationship between 18F-Fluorodeoxyglucose accumulation and KRAS/BRAF mutations in colorectal cancer. Clin Cancer Res 18(6):1696–1703CrossRefPubMed Kawada K, Nakamoto Y, Kawada M, et al. (2012) Relationship between 18F-Fluorodeoxyglucose accumulation and KRAS/BRAF mutations in colorectal cancer. Clin Cancer Res 18(6):1696–1703CrossRefPubMed
30.
go back to reference Kawada K, Toda K, Nakamoto Y, et al. (2015) Relationship Between 18F-FDG PET/CT Scans and KRAS Mutations in Metastatic Colorectal Cancer. J Nucl Med 56(9):1322–1327CrossRefPubMed Kawada K, Toda K, Nakamoto Y, et al. (2015) Relationship Between 18F-FDG PET/CT Scans and KRAS Mutations in Metastatic Colorectal Cancer. J Nucl Med 56(9):1322–1327CrossRefPubMed
31.
go back to reference Krikelis D, Skoura E, Kotoula V, et al. (2014) Lack of association between KRAS mutations and 18F-FDG PET/CT in Caucasian metastatic colorectal cancer patients. Anticancer Res 34(5):2571–2579PubMed Krikelis D, Skoura E, Kotoula V, et al. (2014) Lack of association between KRAS mutations and 18F-FDG PET/CT in Caucasian metastatic colorectal cancer patients. Anticancer Res 34(5):2571–2579PubMed
32.
go back to reference Lee JH, Kang J, Baik SH, et al. (2016) Relationship Between 18F-Fluorodeoxyglucose Uptake and V-Ki-Ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog Mutation in Colorectal Cancer Patients: Variability Depending on C-Reactive Protein Level. Medicine (Baltimore) 95(1):e2236CrossRef Lee JH, Kang J, Baik SH, et al. (2016) Relationship Between 18F-Fluorodeoxyglucose Uptake and V-Ki-Ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog Mutation in Colorectal Cancer Patients: Variability Depending on C-Reactive Protein Level. Medicine (Baltimore) 95(1):e2236CrossRef
33.
go back to reference Lovinfosse P, Koopmansch B, Lambert F, et al. (2016) 18F-FDG PET/CT imaging in rectal cancer: relationship with the RAS mutational status. Br J Radiol 89(1063):20160212CrossRefPubMedPubMedCentral Lovinfosse P, Koopmansch B, Lambert F, et al. (2016) 18F-FDG PET/CT imaging in rectal cancer: relationship with the RAS mutational status. Br J Radiol 89(1063):20160212CrossRefPubMedPubMedCentral
35.
go back to reference Forrester K, Almoguera C, Han K, Grizzle WE, Perucho M (1987) Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. Nature 327(6120):298–303 Forrester K, Almoguera C, Han K, Grizzle WE, Perucho M (1987) Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. Nature 327(6120):298–303
36.
go back to reference Caicedo C, Garcia-Velloso MJ, Lozano MD, et al. (2014) 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 41(11):2058–2065CrossRefPubMed Caicedo C, Garcia-Velloso MJ, Lozano MD, et al. (2014) 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 41(11):2058–2065CrossRefPubMed
37.
go back to reference Jadvar H, Alavi A, Gambhir SS (2009) 18F-FDG uptake in lung, breast, and colon cancers: molecular biology correlates and disease characterization. J Nucl Med 50(11):1820–1827CrossRefPubMedPubMedCentral Jadvar H, Alavi A, Gambhir SS (2009) 18F-FDG uptake in lung, breast, and colon cancers: molecular biology correlates and disease characterization. J Nucl Med 50(11):1820–1827CrossRefPubMedPubMedCentral
38.
go back to reference Lee SM, Bae SK, Jung SJ, Kim CK (2015) 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 40(12):950–958CrossRefPubMed Lee SM, Bae SK, Jung SJ, Kim CK (2015) 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 40(12):950–958CrossRefPubMed
39.
go back to reference Takamochi K, Mogushi K, Kawaji H, et al. (2017) Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in lung adenocarcinoma. PLoS One 12(4):e0175622CrossRefPubMedPubMedCentral Takamochi K, Mogushi K, Kawaji H, et al. (2017) Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in lung adenocarcinoma. PLoS One 12(4):e0175622CrossRefPubMedPubMedCentral
40.
go back to reference Ikeno Y, Seo S, Iwaisako K, et al. (2018) Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by 18F-FDG-PET is associated with the KRAS mutation status and prognosis. J Transl Med 16(1):95CrossRefPubMedPubMedCentral Ikeno Y, Seo S, Iwaisako K, et al. (2018) Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by 18F-FDG-PET is associated with the KRAS mutation status and prognosis. J Transl Med 16(1):95CrossRefPubMedPubMedCentral
Metadata
Title
Diagnostic performance of F-18 FDG PET/CT for prediction of KRAS mutation in colorectal cancer patients: a systematic review and meta-analysis
Authors
Seong-Jang Kim
Kyoungjune Pak
Keunyoung Kim
Publication date
01-05-2019
Publisher
Springer US
Published in
Abdominal Radiology / Issue 5/2019
Print ISSN: 2366-004X
Electronic ISSN: 2366-0058
DOI
https://doi.org/10.1007/s00261-018-01891-3

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