Top

Published in:

01-10-2017 | Original Paper

Correlation of early PET findings with tumor response to molecular targeted agents in patients with advanced driver-mutated non-small cell lung cancer

Authors: Tomonobu Koizumi, Toshirou Fukushima, Daisuke Gomi, Takashi Kobayashi, Nodoka Sekiguchi, Keiko Mamiya, Kazunari Tateishi, Akane Katou, Kazuhiro Oguchi

Published in: Medical Oncology | Issue 10/2017

Abstract

Recent advances in positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) have facilitated not only the diagnosis and staging of lung cancer, but also the prediction of treatment outcome. The present study was designed to assess the usefulness of early FDG-PET examination for predicting subsequent tumor size reduction in response to molecular targeted agents in metastatic non-small cell lung cancer (NSCLC) with sensitive gene anomalies. I. In 29 targeted lesions of 10 NSCLC patients, changes in FDG uptake before and on day 7 after the initiation of molecular targeted therapy (gefitinib, n = 7; crizotinib, n = 3) were compared with subsequent radiographic tumor size reduction by RECIST. FDG uptake was evaluated as the maximum standardized uptake value (SUVmax) of each targeted lesion. SUVmax decreased in all lesions after therapy (mean SUVmax 8.3 ± 3.4 before to 3.7 ± 1.8 after therapy, p < 0.05). The % decrease in SUVmax of each lesion was significantly correlated with the % tumor size reduction (r = 0.44). In addition, the reduction rate of SUVmax in metastatic bone lesions after initiation of molecular targeted therapy was significantly lower than that in targeted organs (27.1 ± 27.5 vs. 51.2 ± 21.3%, respectively, p < 0.05). Early reduction in FDG-PET uptake after initiation of molecular targeted agents was able to predict subsequent tumor reduction in patients harboring EGFR-mutated or ALK-positive NSCLC. In addition, nontargeted bone metastasis may have different glucose metabolism after TKI treatment compared with other involved organs.

Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015;4:36–54.PubMedPubMedCentral

Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. M. Maemondo, A. Inoue, K. Kobayashi, S. Sugawara, S. Oizumi, H. Isobe, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380–8.CrossRef

Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M, West Japan Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11:121–8.CrossRef

Ku GY, Haaland BA, de Lima Lopes G Jr. Gefitinib vs. chemotherapy as first-line therapy in advanced non-small cell lung cancer: meta-analysis of phase III trials. Lung Cancer. 2011;74:469–73.CrossRefPubMed

Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F, PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371:2167–77.CrossRef

Fukuhara T, Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Saijo Y, Hagiwara K, Morita S, Nukiwa T. Factors associated with a poor response to gefitinib in the NEJ002 study: smoking and the L858R mutation. Lung Cancer. 2015;88:181–6.CrossRefPubMed

Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693–703.CrossRefPubMedPubMedCentral

Taniguchi K, Okami J, Kodama K, Higashiyama M, Kato K. Intratumor heterogeneity of epidermal growth factor receptor mutations in lung cancer and its correlation to the response to gefitinib. Cancer Sci. 2008;99:929–35.CrossRefPubMed

Park S, Holmes-Tisch AJ, Cho EY, Shim YM, Kim J, Kim HS, Lee J, Park YH, Ahn JS, Park K, Jänne PA, Ahn MJ. Discordance of molecular biomarkers associated with epidermal growth factor receptor pathway between primary tumors and lymph node metastasis in non-small cell lung cancer. J Thorac Oncol. 2009;4:809–15.CrossRefPubMed

10.

Gow CH, Chang YL, Hsu YC, Tsai MF, Wu CT, Yu CJ, Yang CH, Lee YC, Yang PC, Shih JY. Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. Ann Oncol. 2009;20:696–702.CrossRefPubMed

11.

Ushiki A, Koizumi T, Kobayashi N, Kanda S, Yasuo M, Yamamoto H, Kubo K, Aoyagi D, Nakayama J. Genetic heterogeneity of EGFR mutation in pleomorphic carcinoma of the lung: response to gefitinib and clinical outcome. Jpn J Clin Oncol. 2009;39:267–70.CrossRefPubMed

12.

Hicks RJ. Role of 18F-FDG PET in assessment of response in non-small cell lung cancer. J Nucl Med. 2009;50(Suppl 1):31S–42S.CrossRefPubMed

13.

Paesmans M, Berghmans T, Dusart M, Garcia C, Hossein-Foucher C, Lafitte JJ, Mascaux C, Meert AP, Roelandts M, Scherpereel A, Terrones Munoz V, Sculier JP. European Lung Cancer Working Party, and on behalf of the IASLC Lung Cancer Staging Project. Primary tumor standardized uptake value measured on fluorodeoxyglucose positron emission tomography is of prognostic value for survival in non-small cell lung cancer: update of a systematic review and meta-analysis by the European Lung Cancer Working Party for the International Association for the Study of Lung Cancer Staging Project. J Thorac Oncol. 2010;5:612–9.CrossRefPubMed

14.

Uehara H, Tsutani Y, Okumura S, Nakayama H, Adachi S, Yoshimura M, Miyata Y, Okada M. Prognostic role of positron emission tomography and high-resolution computed tomography in clinical stage IA lung adenocarcinoma. Ann Thorac Surg. 2013;96:1958–65.CrossRefPubMed

15.

Shang J, Ling X, Zhang L, Tang Y, Xiao Z, Cheng Y, Guo B, Gong J, Huang L, Xu H. Comparison of RECIST, EORTC criteria and PERCIST for evaluation of early response to chemotherapy in patients with non-small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2016;43:1945–53.CrossRefPubMed

16.

Na II, Byun BH, Kang HJ, Cheon GJ, Koh JS, Kim CH, Choe DH, Ryoo BY, Lee JC, Lim SM, Yang SH. 18F-fluoro-2-deoxy-glucose uptake predicts clinical outcome in patients with gefitinib-treated non-small cell lung cancer. Clin Cancer Res. 2008;14:2036–41.CrossRefPubMed

17.

Takahashi R, Hirata H, Tachibana I, Shimosegawa E, Inoue A, Nagatomo I, Takeda Y, Kida H, Goya S, Kijima T, Yoshida M, Kumagai T, Kumanogoh A, Okumura M, Hatazawa J, Kawase I. Early [18F]fluorodeoxyglucose positron emission tomography at two days of gefitinib treatment predicts clinical outcome in patients with adenocarcinoma of the lung. Clin Cancer Res. 2012;18:220–8.CrossRefPubMed

18.

Sunaga N, Oriuchi N, Kaira K, Yanagitani N, Tomizawa Y, Hisada T, Ishizuka T, Endo K, Mori M. Usefulness of FDG-PET for early prediction of the response to gefitinib in non-small cell lung cancer. Lung Cancer. 2008;59:203–10.CrossRefPubMed

19.

Su H, Bodenstein C, Dumont RA, Seimbille Y, Dubinett S, Phelps ME, Herschman H, Czernin J, Weber W. Monitoring tumor glucose utilization by positron emission tomography for the prediction of treatment response to epidermal growth factor receptor kinase inhibitors. Clin Cancer Res. 2006;12:5659–67.CrossRefPubMed

20.

Zander T, Scheffler M, Nogova L, Kobe C, Engel-Riedel W, Hellmich M, Papachristou I, Toepelt K, Draube A, Heukamp L, Buettner R, Ko YD, Ullrich RT, Smit E, Boellaard R, Lammertsma AA, Hallek M, Jacobs AH, Schlesinger A, Schulte K, Querings S, Stoelben E, Neumaier B, Thomas RK, Dietlein M, Wolf J. Early prediction of nonprogression in advanced non-small-cell lung cancer treated with erlotinib by using [(18)F]fluorodeoxyglucose and [(18)F]fluorothymidine positron emission tomography. J Clin Oncol. 2011;29:1701–8.CrossRefPubMed

21.

Zhao F, Ding G, Huang W, Li M, Fu Z, Yang G, Kong L, Zhang Y, Yu J. FDG-PET Predicts pain response and local control in palliative radiotherapy with or without systemic treatment in patients with bone metastasis from non-small-cell Lung cancer. Clin Lung Cancer. 2015;16:e111–9.CrossRefPubMed

Title: Correlation of early PET findings with tumor response to molecular targeted agents in patients with advanced driver-mutated non-small cell lung cancer
Authors: Tomonobu Koizumi
Toshirou Fukushima
Daisuke Gomi
Takashi Kobayashi
Nodoka Sekiguchi
Keiko Mamiya
Kazunari Tateishi
Akane Katou
Kazuhiro Oguchi
Publication date: 01-10-2017
Publisher: Springer US
Published in: Medical Oncology / Issue 10/2017
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-017-1032-0

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Correlation of early PET findings with tumor response to molecular targeted agents in patients with advanced driver-mutated non-small cell lung cancer

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 10/2017

Molecular modeling and structure-based drug discovery approach reveals protein kinases as off-targets for novel anticancer drug RH1

Clinical benefit of antiangiogenic therapy in advanced and metastatic chondrosarcoma

Retraction Note to: Metabolic syndrome factors and risk of postoperative depression in high-grade glioma patients in a 1.5-year prospective study

Fluorescence in situ hybridization as prognostic predictor of tumor recurrence during treatment with Bacillus Calmette–Guérin therapy for intermediate- and high-risk non-muscle-invasive bladder cancer

EGFR and KRAS mutations do not enrich for the activation of IL-6, JAK1 or phosphorylated STAT3 in resected lung adenocarcinoma

Low dose versus standard dose of corticosteroids in the management of adverse events of special interest from abiraterone acetate: data from a literature-based meta-analysis

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page