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EJNMMI Research
Published in: EJNMMI Research 1/2019

Open Access 01-12-2019 | Esophageal Cancer | Original research

Efficacy of 4′-[methyl-11C] thiothymidine PET/CT before and after neoadjuvant therapy for predicting therapeutic responses in patients with esophageal cancer: a pilot study

Authors: Masatoshi Hotta, Ryogo Minamimoto, Kazuhiko Yamada, Kyoko Nohara, Daisuke Soma, Kazuhiko Nakajima, Jun Toyohara, Kei Takase

Published in: EJNMMI Research | Issue 1/2019

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Abstract

Background

4′-[Methyl-11C] thiothymidine (4DST) has been introduced as a new cell proliferation imaging PET tracer that incorporates into DNA directly. The aim of this prospective study was to evaluate the efficacy of 4DST PET/CT for predicting responses to neoadjuvant therapy in patients with esophageal cancer comparing with FDG PET/CT.

Methods

Twenty-six patients who had pre- and post-therapeutic 4DST and FDG PET/CT and underwent esophagectomy following neoadjuvant therapy were used for the analysis. Based on pathological findings, patients were divided into two groups: non-responders and responders. The maximum standardized uptake value (SUVmax), metabolic tumor volume, total lesion glycolysis, and total lesion proliferation of the primary lesion were measured for FDG and 4DST PET.

Results

The pathological diagnosis revealed 16 responders and 10 non-responders. Non-responders showed significantly higher 4DST post-therapeutic SUVmax (postSUVmax) than responders, whereas FDG postSUVmax showed no statistically significant difference (non-responders vs. responders: 4DST, 6.7 vs. 3.3, p = 0.001; FDG, 6.1 vs. 4.5, p = 0.11). Responders showed a greater reduction in percentage changes of 4DST and FDG SUVmax (ΔSUVmax) from baseline to post-therapeutic PET (non-responders vs. responders: 4DST, − 2.9% vs. − 56.7%, p < 0.001; FDG, − 36.3% vs. − 72.6%, p < 0.001). In ROC analysis, ΔSUVmax and postSUVmax with 4DST provided great diagnostic performance for predicting responses (area under the curve: 4DST ΔSUVmax = 0.92, 4DST postSUVmax = 0.88).

Conclusions

4DST PET/CT has a great potential for predicting pathologic response to neoadjuvant therapy in patients with esophageal cancer; it may be slightly superior to that with FDG PET/CT.
Literature
1.
Gebski V, Burmeister B, Smithers BM, et al. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007;8:226–34.CrossRef
2.
Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.CrossRef
3.
4.
Brucher BL, Becker K, Lordick F, et al. The clinical impact of histopathologic response assessment by residual tumor cell quantification in esophageal squamous cell carcinomas. Cancer. 2006;106:2119–27.CrossRef
5.
Tong DK, Law S, Kwong DL, et al. Histological regression of squamous esophageal carcinoma assessed by percentage of residual viable cells after neoadjuvant chemoradiation is an important prognostic factor. Ann Surg Oncol. 2010;17:2184–92.CrossRef
6.
Kwee RM. Prediction of tumor response to neoadjuvant therapy in patients with esophageal cancer with use of 18F FDG PET: a systematic review. Radiology. 2010;254:707–17.CrossRef
7.
Klaeser B, Nitzsche E, Schuller JC, et al. Limited predictive value of FDG-PET for response assessment in the preoperative treatment of esophageal cancer: results of a prospective multi-center trial (SAKK 75/02). Onkologie. 2009;32:724–30.CrossRef
8.
van Heijl M, Omloo JM, van Berge Henegouwen MI, et al. Fluorodeoxyglucose positron emission tomography for evaluating early response during neoadjuvant chemoradiotherapy in patients with potentially curable esophageal cancer. Ann Surg. 2011;253:56–63.CrossRef
9.
Toyohara J, Kumata K, Fukushi K, et al. Evaluation of 4′-[methyl-14C] thiothymidine for in vivo DNA synthesis imaging. J Nucl Med. 2006;47:1717–22.PubMed
10.
Toyohara J, Okada M, Toramatsu C, et al. Feasibility studies of 4′-[methyl-(11)C] thiothymidine as a tumor proliferation imaging agent in mice. Nucl Med Biol. 2008;35:67–74.CrossRef
11.
Plotnik DA, Wu S, Linn GR, et al. In vitro analysis of transport and metabolism of 4′-thiothymidine in human tumor cells. Nucl Med Biol. 2015;42:470–4.CrossRef
12.
Been LB, Suurmeijer AJ, Cobben DC, et al. [18F]FLT-PET in oncology: current status and opportunities. Eur J Nucl Med Mol Imaging. 2004;31:1659–72.CrossRef
13.
Minamimoto R, Toyohara J, Seike A, et al. 4′-[Methyl-11C]-thiothymidine PET/CT for proliferation imaging in non-small cell lung cancer. J Nucl Med. 2012;53:199–206.CrossRef
14.
Minamimoto R, Toyohara J, Ito H, et al. A pilot study of 4′-[methyl-11C]-thiothymidine PET/CT for detection of regional lymph node metastasis in non-small cell lung cancer. EJNMMI Res. 2014;4:10.CrossRef
15.
Minamimoto R, Nakaigawa N, Nagashima Y, et al. Comparison of 11C-4DST and 18F-FDG PET/CT imaging for advanced renal cell carcinoma: preliminary study. Abdom Radiol (NY). 2016;41:521–30.CrossRef
16.
Hoshikawa H, Mori T, Maeda Y, et al. Influence of volumetric 4′-[methyl-(11)C]-thiothymidine PET/CT parameters for prediction of the clinical outcome of head and neck cancer patients. Ann Nucl Med. 2017;31:63–70.CrossRef
17.
Toyohara J, Nariai T, Sakata M, et al. Whole-body distribution and brain tumor imaging with (11)C-4DST: a pilot study. J Nucl Med. 2011;52:1322–8.CrossRef
18.
Werner-Wasik M, Nelson AD, Choi W, et al. What is the best way to contour lung tumors on PET scans? Multiobserver validation of a gradient-based method using a NSCLC digital PET phantom. Int J Radiat Oncol Biol Phys. 2012;82:1164–71.CrossRef
19.
Wahl RL, Jacene H, Kasamon Y, et al. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):122s–50s.CrossRef
20.
Japan Esophageal Society. Japanese classification of esophageal cancer, 11th edition: part I. Esophagus. 2017;14:1–36.CrossRef
21.
Odawara S, Kitajima K, Katsuura T, et al. Tumor response to neoadjuvant chemotherapy in patients with esophageal cancer assessed with CT and FDG-PET/CT - RECIST 1.1 vs. PERCIST 1.0. Eur J Radiol. 2018;101:65–71.CrossRef
22.
Tani Y, Nakajima M, Kikuchi M, et al. (1)(8)F-Fluorodeoxyglucose positron emission tomography for evaluating the response to neoadjuvant chemotherapy in advanced esophageal cancer. Anticancer Res. 2016;36:367–73.PubMed
23.
Sasaki K, Uchikado Y, Okumura H, et al. Role of (18)F-FDG-PET/CT in esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy. Anticancer Res. 2017;37:859–64.CrossRef
24.
Hamai Y, Hihara J, Emi M, et al. Ability of fluorine-18 fluorodeoxyglucose positron emission tomography to predict outcomes of neoadjuvant chemoradiotherapy followed by surgical treatment for esophageal squamous cell carcinoma. Ann Thorac Surg. 2016;102:1132–9.CrossRef
25.
Cong L, Wang S, Gao T, et al. The predictive value of 18F-FDG PET for pathological response of primary tumor in patients with esophageal cancer during or after neoadjuvant chemoradiotherapy: a meta-analysis. Jpn J Clin Oncol. 2016;46:1118–26.PubMed
26.
Wieder HA, Brucher BL, Zimmermann F, et al. Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. J Clin Oncol. 2004;22:900–8.CrossRef
27.
Roedl JB, Colen RR, Holalkere NS, et al. Adenocarcinomas of the esophagus: response to chemoradiotherapy is associated with decrease of metabolic tumor volume as measured on PET-CT. Comparison to histopathologic and clinical response evaluation. Radiother Oncol. 2008;89:278–86.CrossRef
28.
Toyohara J, Elsinga PH, Ishiwata K, et al. Evaluation of 4′-[methyl-11C] thiothymidine in a rodent tumor and inflammation model. J Nucl Med. 2012;53:488–94.CrossRef
29.
Toyohara J, Sakata M, Oda K, et al. Longitudinal observation of [11C]4DST uptake in turpentine-induced inflammatory tissue. Nucl Med Biol. 2013;40:240–4.CrossRef
30.
van Rossum PS, Fried DV, Zhang L, et al. The value of (18)F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma. Eur J Nucl Med Mol Imaging. 2017;44:71–80.CrossRef
31.
32.
Omloo JM, van Heijl M, Hoekstra OS, et al. FDG-PET parameters as prognostic factor in esophageal cancer patients: a review. Ann Surg Oncol. 2011;18:3338–52.CrossRef
33.
Van de Wiele C, Kruse V, Smeets P, et al. Predictive and prognostic value of metabolic tumour volume and total lesion glycolysis in solid tumours. Eur J Nucl Med Mol Imaging. 2013;40:290–301.CrossRef
34.
Touboul E, Huguet F, Talbot JN. Use of PET for staging, treatment evaluation, and follow-up in esophageal cancers. Cancer Radiother. 2008;12:633–9.CrossRef
35.
Levine EA, Farmer MR, Clark P, et al. Predictive value of 18-fluoro-deoxy-glucose-positron emission tomography (18F-FDG-PET) in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer. Ann Surg. 2006;243:472–8.CrossRef
36.
Lemarignier C, Di Fiore F, Marre C, et al. Pretreatment metabolic tumour volume is predictive of disease-free survival and overall survival in patients with oesophageal squamous cell carcinoma. Eur J Nucl Med Mol Imaging. 2014;41:2008–16.CrossRef
37.
Vesselle H, Schmidt RA, Pugsley JM, et al. Lung cancer proliferation correlates with [F-18] fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res. 2000;6:3837–44.PubMed
38.
Gerbaudo VH, Killoran JH, Kim CK, et al. 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. 2018;32:165–74.CrossRef
Metadata
Title
Efficacy of 4′-[methyl-11C] thiothymidine PET/CT before and after neoadjuvant therapy for predicting therapeutic responses in patients with esophageal cancer: a pilot study
Authors
Masatoshi Hotta
Ryogo Minamimoto
Kazuhiko Yamada
Kyoko Nohara
Daisuke Soma
Kazuhiko Nakajima
Jun Toyohara
Kei Takase
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2019
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-019-0478-9

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