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Erschienen in: Nuclear Medicine and Molecular Imaging 3/2012

01.09.2012 | Original Article

Correlation Between 18F-Fluorodeoxyglucose Uptake and Epidermal Growth Factor Receptor Mutations in Advanced Lung Cancer

verfasst von: Yun-Jung Choi, Byoung Chul Cho, Yong Hyu Jeong, Hyo Jung Seo, Hyun Jeong Kim, Arthur Cho, Jae Hoon Lee, Mijin Yun, Tae Joo Jeon, Jong Doo Lee, Won Jun Kang

Erschienen in: Nuclear Medicine and Molecular Imaging | Ausgabe 3/2012

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Abstract

Purpose

Mutations in the epidermal growth factor receptor (EGFR) gene have been identified as potential targets for the treatment and prognostic factors for non-small cell lung cancer (NSCLC). We assessed the correlation between fluorodeoxyglucose (FDG) uptake and EGFR mutations, as well as their prognostic implications.

Methods

A total of 163 patients with pathologically confirmed NSCLC were enrolled (99 males and 64 females; median age, 60 years). All patients underwent FDG positron emission tomography before treatment, and genetic studies of EGFR mutations were performed. The maximum standardized uptake value (SUVmax) of the primary lung cancer was measured and normalized with regard to liver uptake. The SUVmax between the wild-type and EGFR mutant groups was compared. Survival was evaluated according to SUVmax and EGFR mutation status.

Results

EGFR mutations were found in 57 patients (60.8 %). The SUVmax tended to be higher in wild-type than mutant tumors, but was not significantly different (11.1 ± 5.7 vs. 9.8 ± 4.4, P = 0.103). The SUVmax was significantly lower in patients with an exon 19 mutation than in those with either an exon 21 mutation or wild type (P = 0.003 and 0.009, respectively). The EGFR mutation showed prolonged overall survival (OS) compared to wild-type tumors (P = 0.004). There was no significant difference in survival according to SUVmax. Both OS and progression-free survival of patients with a mutation in exon 19 were significant longer than in patients with wild-type tumors.

Conclusion

In patients with NSCLC, a mutation in exon 19 was associated with a lower SUVmax and is a reliable predictor for good survival.
Literatur
1.
Zurück zum Zitat Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. Cancer statistics, 2004. CA Cancer J Clin. 2004;54:8–29.PubMedCrossRef Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. Cancer statistics, 2004. CA Cancer J Clin. 2004;54:8–29.PubMedCrossRef
2.
Zurück zum Zitat Shin HR, Ahn YO, Bae JM, Shin MH, Lee DH, Lee CW, et al. Cancer incidence in Korea. Cancer Res Treat. 2002;34:405–8. Shin HR, Ahn YO, Bae JM, Shin MH, Lee DH, Lee CW, et al. Cancer incidence in Korea. Cancer Res Treat. 2002;34:405–8.
3.
Zurück zum Zitat Won YJ, Sung J, Jung KW, Kong HJ, Park S, Shin HR, et al. Nationwide cancer incidence in Korea, 2003–2005. Cancer Res Treat. 2009;41:122–31.PubMedCrossRef Won YJ, Sung J, Jung KW, Kong HJ, Park S, Shin HR, et al. Nationwide cancer incidence in Korea, 2003–2005. Cancer Res Treat. 2009;41:122–31.PubMedCrossRef
5.
Zurück zum Zitat Lee C, Kang KH, Koh Y, Chang J, Chung HS, Park SK, et al. Characteristics of lung cancer in Korea, 1997. Lung Cancer. 2000;30:15–22.PubMedCrossRef Lee C, Kang KH, Koh Y, Chang J, Chung HS, Park SK, et al. Characteristics of lung cancer in Korea, 1997. Lung Cancer. 2000;30:15–22.PubMedCrossRef
6.
Zurück zum Zitat Pao W, Miller VA. Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions. J Clin Oncol. 2005;23:2556–68.PubMedCrossRef Pao W, Miller VA. Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions. J Clin Oncol. 2005;23:2556–68.PubMedCrossRef
7.
Zurück zum Zitat Gettinger S. Targeted therapy in advanced non-small-cell lung cancer. Semin Respir Crit Care Med. 2008;29:291–301.PubMedCrossRef Gettinger S. Targeted therapy in advanced non-small-cell lung cancer. Semin Respir Crit Care Med. 2008;29:291–301.PubMedCrossRef
8.
Zurück zum Zitat Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.PubMedCrossRef Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.PubMedCrossRef
9.
Zurück zum Zitat Glynn C, Zakowski MF, Ginsberg MS. Are there imaging characteristics associated with epidermal growth factor receptor and KRAS mutations in patients with adenocarcinoma of the lung with bronchioloalveolar features? J Thorac Oncol. 2010;5:344–8.PubMedCrossRef Glynn C, Zakowski MF, Ginsberg MS. Are there imaging characteristics associated with epidermal growth factor receptor and KRAS mutations in patients with adenocarcinoma of the lung with bronchioloalveolar features? J Thorac Oncol. 2010;5:344–8.PubMedCrossRef
10.
Zurück zum Zitat Downey RJ, Akhurst T, Gonen M, Vincent A, Bains MS, Larson S, et al. Preoperative F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value predicts survival after lung cancer resection. J Clin Oncol. 2004;22:3255–60.PubMedCrossRef Downey RJ, Akhurst T, Gonen M, Vincent A, Bains MS, Larson S, et al. Preoperative F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value predicts survival after lung cancer resection. J Clin Oncol. 2004;22:3255–60.PubMedCrossRef
11.
Zurück zum Zitat Cho A, Lim I, Na I, Choe D, Park J, Kim B, et al. Evaluation of adrenal masses in lung cancer patients using F-18 FDG PET/CT. Nucl Med Mol Imaging. 2011;45:52–8.CrossRef Cho A, Lim I, Na I, Choe D, Park J, Kim B, et al. Evaluation of adrenal masses in lung cancer patients using F-18 FDG PET/CT. Nucl Med Mol Imaging. 2011;45:52–8.CrossRef
12.
Zurück zum Zitat Vesselle H, Schmidt RA, Pugsley JM, Li M, Kohlmyer SG, Vallieres E, et al. Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res. 2000;6:3837–44.PubMed Vesselle H, Schmidt RA, Pugsley JM, Li M, Kohlmyer SG, Vallieres E, et al. Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res. 2000;6:3837–44.PubMed
13.
Zurück zum Zitat Downey RJ, Akhurst T, Gonen M, Park B, Rusch V. Fluorine-18 fluorodeoxyglucose positron emission tomographic maximal standardized uptake value predicts survival independent of clinical but not pathologic TNM staging of resected non-small cell lung cancer. J Thorac Cardiovasc Surg. 2007;133:1419–27.PubMedCrossRef Downey RJ, Akhurst T, Gonen M, Park B, Rusch V. Fluorine-18 fluorodeoxyglucose positron emission tomographic maximal standardized uptake value predicts survival independent of clinical but not pathologic TNM staging of resected non-small cell lung cancer. J Thorac Cardiovasc Surg. 2007;133:1419–27.PubMedCrossRef
14.
Zurück zum Zitat Cerfolio RJ, Bryant AS, Ohja B, Bartolucci AA. The maximum standardized uptake values on positron emission tomography of a non-small cell lung cancer predict stage, recurrence, and survival. J Thorac Cardiovasc Surg. 2005;130:151–9.PubMedCrossRef Cerfolio RJ, Bryant AS, Ohja B, Bartolucci AA. The maximum standardized uptake values on positron emission tomography of a non-small cell lung cancer predict stage, recurrence, and survival. J Thorac Cardiovasc Surg. 2005;130:151–9.PubMedCrossRef
15.
Zurück zum Zitat Zhu A, Shim H. Current molecular imaging positron emitting radiotracers in oncology. Nucl Med Mol Imaging. 2011;45:1–14.CrossRef Zhu A, Shim H. Current molecular imaging positron emitting radiotracers in oncology. Nucl Med Mol Imaging. 2011;45:1–14.CrossRef
16.
Zurück zum Zitat Na II, Byun BH, Kim KM, Cheon GJ, du Choe H, 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;67:76–80.PubMedCrossRef Na II, Byun BH, Kim KM, Cheon GJ, du Choe H, 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;67:76–80.PubMedCrossRef
17.
Zurück zum Zitat 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;27:9–15.PubMedCrossRef 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;27:9–15.PubMedCrossRef
18.
Zurück zum Zitat Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest. 2009;136:260–71.PubMedCrossRef Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest. 2009;136:260–71.PubMedCrossRef
19.
Zurück zum Zitat Han SW, Kim TY, Hwang PG, Jeong S, Kim J, Choi IS, et al. Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol. 2005;23:2493–501.PubMedCrossRef Han SW, Kim TY, Hwang PG, Jeong S, Kim J, Choi IS, et al. Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol. 2005;23:2493–501.PubMedCrossRef
20.
Zurück zum Zitat Cho BC, Im CK, Park MS, Kim SK, Chang J, Park JP, et al. Phase II study of erlotinib in advanced non-small-cell lung cancer after failure of gefitinib. J Clin Oncol. 2007;25:2528–33.PubMedCrossRef Cho BC, Im CK, Park MS, Kim SK, Chang J, Park JP, et al. Phase II study of erlotinib in advanced non-small-cell lung cancer after failure of gefitinib. J Clin Oncol. 2007;25:2528–33.PubMedCrossRef
21.
Zurück zum Zitat Mak RH, Digumarthy SR, Muzikansky A, Engelman JA, Shepard JA, Choi NC, et al. Role of 18F-fluorodeoxyglucose positron emission tomography in predicting epidermal growth factor receptor mutations in non-small cell lung cancer. Oncologist. 2011;16:319–26.PubMedCrossRef Mak RH, Digumarthy SR, Muzikansky A, Engelman JA, Shepard JA, Choi NC, et al. Role of 18F-fluorodeoxyglucose positron emission tomography in predicting epidermal growth factor receptor mutations in non-small cell lung cancer. Oncologist. 2011;16:319–26.PubMedCrossRef
22.
Zurück zum Zitat Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006;366:2–16.PubMedCrossRef Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006;366:2–16.PubMedCrossRef
23.
Zurück zum Zitat Gazdar AF. Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene. 2009;28:S24–31.PubMedCrossRef Gazdar AF. Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene. 2009;28:S24–31.PubMedCrossRef
24.
Zurück zum Zitat Greulich H, Chen TH, Feng W, Janne PA, Alvarez JV, Zappaterra M, et al. Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants. PLoS Med. 2005;2:e313.PubMedCrossRef Greulich H, Chen TH, Feng W, Janne PA, Alvarez JV, Zappaterra M, et al. Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants. PLoS Med. 2005;2:e313.PubMedCrossRef
25.
Zurück zum Zitat Jackman DM, Yeap BY, Sequist LV, Lindeman N, Holmes AJ, Joshi VA, et al. Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res. 2006;12:3908–14.PubMedCrossRef Jackman DM, Yeap BY, Sequist LV, Lindeman N, Holmes AJ, Joshi VA, et al. Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res. 2006;12:3908–14.PubMedCrossRef
26.
Zurück zum Zitat Carey KD, Garton AJ, Romero MS, Kahler J, Thomson S, Ross S, et al. Kinetic analysis of epidermal growth factor receptor somatic mutant proteins shows increased sensitivity to the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib. Cancer Res. 2006;66:8163–71.PubMedCrossRef Carey KD, Garton AJ, Romero MS, Kahler J, Thomson S, Ross S, et al. Kinetic analysis of epidermal growth factor receptor somatic mutant proteins shows increased sensitivity to the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib. Cancer Res. 2006;66:8163–71.PubMedCrossRef
27.
Zurück zum Zitat Mulloy R, Ferrand A, Kim Y, Sordella R, Bell DW, Haber DA, et al. Epidermal growth factor receptor mutants from human lung cancers exhibit enhanced catalytic activity and increased sensitivity to gefitinib. Cancer Res. 2007;67:2325–30.PubMedCrossRef Mulloy R, Ferrand A, Kim Y, Sordella R, Bell DW, Haber DA, et al. Epidermal growth factor receptor mutants from human lung cancers exhibit enhanced catalytic activity and increased sensitivity to gefitinib. Cancer Res. 2007;67:2325–30.PubMedCrossRef
28.
Zurück zum Zitat Won YW, Han JY, Lee GK, Park SY, Lim KY, Yoon KA, et al. Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations. J Clin Pathol. 2011;64:947–52.PubMedCrossRef Won YW, Han JY, Lee GK, Park SY, Lim KY, Yoon KA, et al. Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations. J Clin Pathol. 2011;64:947–52.PubMedCrossRef
29.
Zurück zum Zitat Zasadny KR, Wahl RL. Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: variations with body weight and a method for correction. Radiology. 1993;189:847–50.PubMed Zasadny KR, Wahl RL. Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: variations with body weight and a method for correction. Radiology. 1993;189:847–50.PubMed
30.
Metadaten
Titel
Correlation Between 18F-Fluorodeoxyglucose Uptake and Epidermal Growth Factor Receptor Mutations in Advanced Lung Cancer
verfasst von
Yun-Jung Choi
Byoung Chul Cho
Yong Hyu Jeong
Hyo Jung Seo
Hyun Jeong Kim
Arthur Cho
Jae Hoon Lee
Mijin Yun
Tae Joo Jeon
Jong Doo Lee
Won Jun Kang
Publikationsdatum
01.09.2012
Verlag
Springer-Verlag
Erschienen in
Nuclear Medicine and Molecular Imaging / Ausgabe 3/2012
Print ISSN: 1869-3474
Elektronische ISSN: 1869-3482
DOI
https://doi.org/10.1007/s13139-012-0142-z

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