18F-fluorothymidine (FLT)-PET and diffusion-weighted MRI for early response evaluation in patients with small cell lung cancer: a pilot study

European Journal of Hybrid Imaging - Tập 4 Số 1 - 2020
Tine Nøhr Christensen1, Seppo W. Langer2, Katrine Engholm Villumsen1, Helle Hjorth Johannesen1, Johan Löfgren1, Sune H. Keller1, Adam E. Hansen1, Andreas Kjær3, Barbara Fischer4
1Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark
2Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
3Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark
4PET Centre, School of Biomedical Engineering and Imaging Science, Kings College London, London, UK

Tóm tắt

Abstract Background Small cell lung cancer (SCLC) is an aggressive cancer often presenting in an advanced stage and prognosis is poor. Early response evaluation may have impact on the treatment strategy. Aim We evaluated 18F-fluorothymidine-(FLT)-PET/diffusion-weighted-(DW)-MRI early after treatment start to describe biological changes during therapy, the potential of early response evaluation, and the added value of FLT-PET/DW-MRI. Methods Patients with SCLC referred for standard chemotherapy were eligible. FLT-PET/DW-MRI of the chest and brain was acquired within 14 days after treatment start. FLT-PET/DW-MRI was compared with pretreatment FDG-PET/CT. Standardized uptake value (SUV), apparent diffusion coefficient (ADC), and functional tumor volumes were measured. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian; spatial distribution of aggressive areas; and voxel-by-voxel analyses were evaluated to compare the biological information derived from the three functional imaging modalities. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian were also analyzed for ability to predict final treatment response. Results Twelve patients with SCLC completed FLT-PET/MRI 1–9 days after treatment start. In nine patients, pretreatment FDG-PET/CT was available for comparison. A total of 16 T-sites and 12 N-sites were identified. No brain metastases were detected. FDG-SUVpeak was 2.0–22.7 in T-sites and 5.5–17.3 in N-sites. FLT-SUVpeak was 0.6–11.5 in T-sites and 1.2–2.4 in N-sites. ADCmedian was 0.76–1.74 × 10− 3 mm2/s in T-sites and 0.88–2.09 × 10−3 mm2/s in N-sites. FLT-SUVpeak correlated with FDG-SUVpeak, and voxel-by-voxel correlation was positive, though the hottest regions were dissimilarly distributed in FLT-PET compared to FDG-PET. FLT-SUVpeak was not correlated with ADCmedian, and voxel-by-voxel analyses and spatial distribution of aggressive areas varied with no systematic relation. LT-SUVpeak was significantly lower in responding lesions than non-responding lesions (mean FLT-SUVpeak in T-sites: 1.5 vs. 5.7; p = 0.007, mean FLT-SUVpeak in N-sites: 1.6 vs. 2.2; p = 0.013). Conclusions FLT-PET and DW-MRI performed early after treatment start may add biological information in patients with SCLC. Proliferation early after treatment start measured by FLT-PET is a promising predictor for final treatment response that warrants further investigation. Trial registration Clinicaltrials.gov, NCT02995902. Registered 11 December 2014 - Retrospectively registered.

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Tài liệu tham khảo

Aktan M, Koc M, Kanyilmaz G, Yavuz BB (2017) Prognostic value of pre-treatment (18)F-FDG-PET uptake in small-cell lung cancer. Ann Nucl Med 31(6):462–468

Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W et al (2015) FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging 42(2):328–354

Brockenbrough JS, Souquet T, Morihara JK, Stern JE, Hawes SE, Rasey JS et al (2011) Tumor 3′-deoxy-3′-(18)F-fluorothymidine ((18)F-FLT) uptake by PET correlates with thymidine kinase 1 expression: static and kinetic analysis of (18)F-FLT PET studies in lung tumors. J Nucl Med 52(8):1181–1188

Chang H, Lee SJ, Lim J, Lee JS, Kim YJ, Lee WW (2019) Prognostic significance of metabolic parameters measured by (18)F-FDG PET/CT in limited-stage small-cell lung carcinoma. J Cancer Res Clin Oncol 145(5):1361-1367

Crandall JP, Tahari AK, Juergens RA, Brahmer JR, Rudin CM, Esposito G et al (2017) A comparison of FLT to FDG PET/CT in the early assessment of chemotherapy response in stages IB-IIIA resectable NSCLC. EJNMMI Res 7(1):8

Cysouw MCF, Kramer GM, Frings V, De Langen AJ, Wondergem MJ, Kenny LM et al (2017) Baseline and longitudinal variability of normal tissue uptake values of [(18)F]-fluorothymidine-PET images. Nucl Med Biol 51:18–24

Dayen C, Debieuvre D, Molinier O, Raffy O, Paganin F, Virally J et al (2017) New insights into stage and prognosis in small cell lung cancer: an analysis of 968 cases. J Thorac Dis 9(12):5101–5111

Dittmann H, Dohmen BM, Paulsen F, Eichhorn K, Eschmann SM, Horger M et al (2003) [18F] FLT PET for diagnosis and staging of thoracic tumours. Eur J Nucl Med Mol Imaging 30(10):1407–1412

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247

Everitt S, Ball D, Hicks RJ, Callahan J, Plumridge N, Trinh J et al (2017) Prospective study of serial imaging comparing fluorodeoxyglucose positron emission tomography (PET) and fluorothymidine PET during radical chemoradiation for non-small cell lung cancer: reduction of detectable proliferation associated with worse survival. Int J Radiat Oncol Biol Phys 99(4):947–955

Everitt SJ, Ball DL, Hicks RJ, Callahan J, Plumridge N, Collins M et al (2014) Differential (18)F-FDG and (18)F-FLT uptake on serial PET/CT imaging before and during definitive chemoradiation for non-small cell lung cancer. J Nucl Med 55(7):1069–1074

Fischer BM, Mortensen J, Langer SW, Loft A, Berthelsen AK, Daugaard G et al (2006) PET/CT imaging in response evaluation of patients with small cell lung cancer. Lung Cancer 54(1):41–49

Fu L, Zhu Y, Jing W, Guo D, Kong L, Yu J (2018) Incorporation of circulating tumor cells and whole-body metabolic tumor volume of (18)F-FDG PET/CT improves prediction of outcome in IIIB stage small-cell lung cancer. Chin J Cancer Res 30(6):596–604

Fujii M, Hotta K, Takigawa N, Hisamoto A, Ichihara E, Tabata M et al (2012) Influence of the timing of tumor regression after the initiation of chemoradiotherapy on prognosis in patients with limited-disease small-cell lung cancer achieving objective response. Lung Cancer 78(1):107–111

Gerbaudo VH, Killoran JH, Kim CK, Hornick JL, Nowak JA, Enzinger PC et al (2018) Pilot study of serial FLT and FDG-PET/CT imaging to monitor response to neoadjuvant chemoradiotherapy of esophageal adenocarcinoma: correlation with histopathologic response. Ann Nucl Med 32(3):165–174

Halvorsen TO, Herje M, Levin N, Bremnes RM, Brustugun OT, Flotten O et al (2016) Tumour size reduction after the first chemotherapy-course and outcomes of chemoradiotherapy in limited disease small-cell lung cancer. Lung Cancer 102:9–14

Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ et al (2018) First-line Atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med 379(23):2220-2229

Hoshikawa H, Kishino T, Mori T, Nishiyama Y, Yamamoto Y, Mori N (2013) The value of 18F-FLT PET for detecting second primary cancers and distant metastases in head and neck cancer patients. Clin Nucl Med 38(8):e318–e323

Jensen MM, Erichsen KD, Bjorkling F, Madsen J, Jensen PB, Hojgaard L et al (2010) Early detection of response to experimental chemotherapeutic Top216 with [18F] FLT and [18F] FDG PET in human ovary cancer xenografts in mice. PLoS One 5(9):e12965

Jensen MM, Kjaer A (2015) Monitoring of anti-cancer treatment with (18)F-FDG and (18)F-FLT PET: a comprehensive review of pre-clinical studies. Am J Nucl Med Mol Imaging 5(5):431–456

Kahraman D, Holstein A, Scheffler M, Zander T, Nogova L, Lammertsma AA et al (2012) Tumor lesion glycolysis and tumor lesion proliferation for response prediction and prognostic differentiation in patients with advanced non-small cell lung cancer treated with erlotinib. Clin Nucl Med 37(11):1058–1064

Kahraman D, Scheffler M, Zander T, Nogova L, Lammertsma AA, Boellaard R et al (2011) Quantitative analysis of response to treatment with erlotinib in advanced non-small cell lung cancer using 18F-FDG and 3′-deoxy-3′-18F-fluorothymidine PET. J Nucl Med 52(12):1871–1877

Keller SH, Holm S, Hansen AE, Sattler B, Andersen F, Klausen TL et al (2013) Image artifacts from MR-based attenuation correction in clinical, whole-body PET/MRI. MAGMA. 26(1):173–181

Kim H, Yoo IR, Boo SH, Park HL, OJH KSH (2018) Prognostic value of pre- and post-treatment FDG PET/CT parameters in small cell lung Cancer patients. Nucl Med Mol Imaging 52(1):31–38

Kishino T, Hoshikawa H, Nishiyama Y, Yamamoto Y, Mori N (2012) Usefulness of 3′-deoxy-3′-18F-fluorothymidine PET for predicting early response to chemoradiotherapy in head and neck cancer. J Nucl Med 53(10):1521–1527

Langer NH, Christensen TN, Langer SW, Kjaer A, Fischer BM (2014) PET/CT in therapy evaluation of patients with lung cancer. Expert Rev Anticancer Ther 14(5):595–620

Lattuca-Truc M, Timsit JF, Levra MG, Ruckly S, Villa J, Dumas I et al (2019) Trends in response rate and survival in small-cell lung cancer patients between 1997 and 2017. Lung Cancer 131:122–127

Lee J, Kim JO, Jung CK, Kim YS, Yoo Ie R, Choi WH et al (2014) Metabolic activity on [18f]-fluorodeoxyglucose-positron emission tomography/computed tomography and glucose transporter-1 expression might predict clinical outcomes in patients with limited disease small-cell lung cancer who receive concurrent chemoradiation. Clin Lung Cancer 15(2):e13–e21

Lee J, Lee J, Choi J, Kim JW, Cho J, Lee CG (2015) Early treatment volume reduction rate as a prognostic factor in patients treated with chemoradiotherapy for limited stage small cell lung cancer. Radiat Oncol J 33(2):117–125

Leimgruber A, Moller A, Everitt SJ, Chabrot M, Ball DL, Solomon B et al (2014) Effect of platinum-based chemoradiotherapy on cellular proliferation in bone marrow and spleen, estimated by (18)F-FLT PET/CT in patients with locally advanced non-small cell lung cancer. J Nucl Med 55(7):1075–1080

Luis G, JMTP P-A, Besse B, Moreno V, Lopez R, Sala MA et al (2019) Efficacy and safety profile of lurbinectedin in second-line SCLC patients: results from a phase II single-agent trial. J Clin Oncol 37:suppl; abstr 8506

Mileshkin L, Hicks RJ, Hughes BG, Mitchell PL, Charu V, Gitlitz BJ et al (2011) Changes in 18F-fluorodeoxyglucose and 18F-fluorodeoxythymidine positron emission tomography imaging in patients with non-small cell lung cancer treated with erlotinib. Clin Cancer Res 17(10):3304–3315

Minamimoto R, Fayad L, Advani R, Vose J, Macapinlac H, Meza J et al (2016) Diffuse large B-cell lymphoma: prospective multicenter comparison of early interim FLT PET/CT versus FDG PET/CT with IHP, EORTC, Deauville, and PERCIST criteria for early therapeutic monitoring. Radiology. 280(1):220–229

Mirili C, Guney IB, Paydas S, Seydaoglu G, Kapukaya TK, Ogul A et al (2019) Prognostic significance of neutrophil/lymphocyte ratio (NLR) and correlation with PET-CT metabolic parameters in small cell lung cancer (SCLC). Int J Clin Oncol 24(2):168–178

Mudd SR, Holich KD, Voorbach MJ, Cole TB, Reuter DR, Tapang P et al (2012) Pharmacodynamic evaluation of irinotecan therapy by FDG and FLT PET/CT imaging in a colorectal cancer xenograft model. Mol Imaging Biol 14(5):617–624

Nakajo M, Nakajo M, Jinguji M, Tani A, Kajiya Y, Tanabe H et al (2013) Diagnosis of metastases from postoperative differentiated thyroid cancer: comparison between FDG and FLT PET/CT studies. Radiology. 267(3):891–901

Nestle U, De Ruysscher D, Ricardi U, Geets X, Belderbos J, Pottgen C et al (2018) ESTRO ACROP guidelines for target volume definition in the treatment of locally advanced non-small cell lung cancer. Radiother Oncol 127(1):1–5

Nguyen NC, Yee MK, Tuchayi AM, Kirkwood JM, Tawbi H, Mountz JM (2018) Targeted therapy and immunotherapy response assessment with F-18 Fluorothymidine positron-emission tomography/magnetic resonance imaging in melanoma brain metastasis: a pilot study. Front Oncol 8:18

Nikaki A, Angelidis G, Efthimiadou R, Tsougos I, Valotassiou V, Fountas K et al (2017) (18)F-fluorothymidine PET imaging in gliomas: an update. Ann Nucl Med 31(7):495–505

Olin A, Ladefoged CN, Langer NH, Keller SH, Lofgren J, Hansen AE et al (2018) Reproducibility of MR-based attenuation maps in PET/MRI and the impact on PET quantification in lung cancer. J Nucl Med 59(6):999–1004

Pardo OE, Latigo J, Jeffery RE, Nye E, Poulsom R, Spencer-Dene B et al (2009) The fibroblast growth factor receptor inhibitor PD173074 blocks small cell lung cancer growth in vitro and in vivo. Cancer Res 69(22):8645–8651

Park SB, Choi JY, Moon SH, Yoo J, Kim H, Ahn YC et al (2014) Prognostic value of volumetric metabolic parameters measured by [18F]fluorodeoxyglucose-positron emission tomography/computed tomography in patients with small cell lung cancer. Cancer Imaging 14:2

Rasmussen JH, Fischer BM, Aznar MC, Hansen AE, Vogelius IR, Lofgren J et al (2015) Reproducibility of (18)F-FDG PET uptake measurements in head and neck squamous cell carcinoma on both PET/CT and PET/MR. Br J Radiol 88(1048):20140655

Ready N, Farago AF, de Braud F, Atmaca A, Hellmann MD, Schneider JG et al (2018) Third-line Nivolumab Monotherapy in recurrent small cell lung cancer: CheckMate 032. J Thorac Oncol 14(2):237-244

Ruben JD, Ball DL (2012) The efficacy of PET staging for small-cell lung cancer: a systematic review and cost analysis in the Australian setting. J Thorac Oncol 7(6):1015–1020

Samarin A, Burger C, Wollenweber SD, Crook DW, Burger IA, Schmid DT et al (2012) PET/MR imaging of bone lesions—implications for PET quantification from imperfect attenuation correction. Eur J Nucl Med Mol Imaging 39(7):1154–1160

Shen G, Jia Z, Deng H (2016) Apparent diffusion coefficient values of diffusion-weighted imaging for distinguishing focal pulmonary lesions and characterizing the subtype of lung cancer: a meta-analysis. Eur Radiol 26(2):556–566

Sohn HJ, Yang YJ, Ryu JS, Oh SJ, Im KC, Moon DH et al (2008) [18F] Fluorothymidine positron emission tomography before and 7 days after gefitinib treatment predicts response in patients with advanced adenocarcinoma of the lung. Clin Cancer Res 14(22):7423–7429

Thureau S, Chaumet-Riffaud P, Modzelewski R, Fernandez P, Tessonnier L, Vervueren L et al (2013) Interobserver agreement of qualitative analysis and tumor delineation of 18F-fluoromisonidazole and 3′-deoxy-3′-18F-fluorothymidine PET images in lung cancer. J Nucl Med 54(9):1543–1550

Trigonis I, Koh PK, Taylor B, Tamal M, Ryder D, Earl M et al (2014) Early reduction in tumour [18F] fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone. Eur J Nucl Med Mol Imaging 41(4):682–693

Tsuchida T, Morikawa M, Demura Y, Umeda Y, Okazawa H, Kimura H (2013) Imaging the early response to chemotherapy in advanced lung cancer with diffusion-weighted magnetic resonance imaging compared to fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography. J Magn Reson Imaging 38(1):80–88

Usuda K, Funasaki A, Sekimura A, Motono N, Matoba M, Doai M et al (2018) FDG-PET/CT and diffusion-weighted imaging for resected lung cancer: correlation of maximum standardized uptake value and apparent diffusion coefficient value with prognostic factors. Med Oncol 35(5):66

van Loon J, van Baardwijk A, Boersma L, Ollers M, Lambin P, De Ruysscher D (2011) Therapeutic implications of molecular imaging with PET in the combined modality treatment of lung cancer. Cancer Treat Rev 37(5):331–343

Vercellino L, Ouvrier MJ, Barre E, Cassinat B, de Beco V, Dosquet C et al (2017) Assessing bone marrow activity in patients with myelofibrosis: results of a pilot study of (18)F-FLT PET. J Nucl Med 58(10):1603–1608

Weiss E, Ford JC, Olsen KM, Karki K, Saraiya S, Groves R et al (2016) Apparent diffusion coefficient (ADC) change on repeated diffusion-weighted magnetic resonance imaging during radiochemotherapy for non-small cell lung cancer: a pilot study. Lung Cancer 96:113–119

Yabuuchi H, Hatakenaka M, Takayama K, Matsuo Y, Sunami S, Kamitani T et al (2011) Non-small cell lung cancer: detection of early response to chemotherapy by using contrast-enhanced dynamic and diffusion-weighted MR imaging. Radiology. 261(2):598–604

Yamamoto Y, Kameyama R, Murota M, Bandoh S, Ishii T, Nishiyama Y (2009) Early assessment of therapeutic response using FDG PET in small cell lung cancer. Mol Imaging Biol 11(6):467–472

Yap CS, Czernin J, Fishbein MC, Cameron RB, Schiepers C, Phelps ME et al (2006) Evaluation of thoracic tumors with 18F-fluorothymidine and 18F-fluorodeoxyglucose-positron emission tomography. Chest. 129(2):393–401

Yu J, Li W, Zhang Z, Yu T, Li D (2014) Prediction of early response to chemotherapy in lung cancer by using diffusion-weighted MR imaging. TheScientificWorldJournal. 2014:135841

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European Journal of Hybrid Imaging

Tập 4 Số 1

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