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3’-Deoxy-3’-[18F]-fluorothymidine PET/CT in early determination of prognosis in patients with esophageal squamous cell cancer

Comparison with [18F]-FDG PET/CT

3’-Deoxy-3’-[18F]-Fluorothymidin-PET/CT für die Vorhersage der biologischen Tumorantwort und der Prognose des Ösophagusplattenepithelkarzinoms

Vergleich mit der [18F]-FDG-PET/CT

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Abstract

Purpose

The purpose of this work was to investigate the prognostic value of response analysis using early 3’-deoxy-3’-[18F]-fluorothymidine (18F-FLT) PET/CT in esophageal squamous cancer patients and make a comparison with [18F]-fluorodeoxyglucose (18F-FDG) PET/CT.

Patients and materials

For 34 patients with esophageal squamous cell cancer, both 18F-FLT PET/CT and 18F-FDG PET/CT scans were performed at baseline (pre), 4 weeks after the start of radiotherapy or chemoradiotherapy (interim), and 2 weeks after therapy completion (final). SUVmax1, SUVmax2, and SUVmax3 represent SUVmax (SUV: standard uptake values) measured on the pre, interim, and final scans, respectively. GTVFLT-PET and GTVFDG-PET (GTV: gross tumor volume) were measured on the pre and interim scans. ΔSUV/ΔGTV represents the fractional changes of SUVmax/GTV between two different time points. PET parameters were evaluated for correlations with outcome.

Results

Regarding 18F-FLT PET/CT, according to receiver operating characteristic (ROC) curve analysis, parameters for predicting 2-year progression-free survival (PFS) and locoregional control (LRC) showed the highest area under curve (AUC) on interim 18F-FLT PET/CT scans (ΔSUV12, AUC of 0.812 for PFS, 0.775 for LRC, with a cutoff of 60 %; P = 0.008), compared with the parameters on pre and final scans. Patients with a ΔSUV12 greater than 60 %, who were defined as interim PET-negative group, were associated with better 2-year PFS and LRC than the interim PET-positive group (PFS: 70.6 % vs. 35.2 %, P = 0.025; LRC: 84.2 % vs 52.9, P = 0.046). In terms of 18F-FDG PET/CT, ΔSUV13 on the final 18F-FDG PET/CT scan demonstrated better prediction (AUC of 0.812 for PFS, 0.807 for LRC, with a cutoff of 75 %; P = 0.016) than the parameters on pre and interim scans. An SUVmax decrease ≥ 75 % on the final 18F-FDG PET/CT scan was associated with better clinical outcome (PFS: 73.3 % vs. 36.8 %, P = 0.022; LRC: 86.7 % vs 52.6, P = 0.029). These correlations were most prominent in the subgroup of patients treated with chemoradiotherapy.

Conclusion

Early interim 18F-FLT PET/CT is a significant predictor of 2-year PFS and LRC, which is correlated better with early responses and late outcomes than interim 18F-FDG PET/CT in esophageal squamous cancer patients.

Zusammenfassung

Ziel

Das Ziel der Arbeit war es, die Vorhersage der biologischen Tumorantwortmit einer frühen [18F]-Fluorothymidin(FLT)-PET/CT bei mit Radiochemotherapie behandelten Patienten mit einem Plattenepithelkarzinom des Ösophagus zu untersuchen und die Ergebnisse mit der [18F]-Fluorodeoxyglukose(FDG)-PET/CT zu vergleichen.

Patienten und Methodik

Bei 34 Patienten mit einem Plattenepithelkarzinom des Ösophagus, wurden beide [18F]-FLT-PET/CT- und [18F]-FDG-PET/CT-Untersuchungen jeweils zu Beginn, 4 Wochen nach Beginn der Strahlen- oder Radiochemotherapie und 2 Wochen nach Therapieabschluss durchgeführt. SUVmax1, SUVmax2 und SUVmax3 (SUV: „standard uptake values“) entsprechen der gemessenen SUVmax vor-, zwischen- und nach der Strahlen- oder Radiochemotherapie. Das makroskopische Tumorvolumen (GTV: „gross tumor volume“) GTVFLT-PET und GTVFDG-PET wurde anhand der PET/CT-Ergebnisse vor und während der Strahlentherapie vollzogen. ΔSUV/ΔGTV entspricht der Änderungsrate von SUVmax/GTV zwischen den beiden unterschiedlichen Zeitpunkten. Es wurde die Korrelation der PET/CT-Parameter mit dem Outcome analysiert.

Ergebnisse

Die Analyse der ROC-(Receiver-Operating-Characteristic-Kurve- zeigte, dass im Vergleich zu den Untersuchungen vor- und nach Strahlentherapie während der [18F]-FLT-PET/CT die höchste Fläche unter der Kurve („area under the curve“, AUC) für die Parameter zur Vorhersage des progressionsfreien 2-Jahres-Überlebens (PFS) und der lokalen Kontrolle (LRC) festgestellt wurden (ΔSUV12, AUC von 0,812 für PFS und 0,775 für LRC, bei einem Grenzwert von 60 %; P = 0,008) . Patienten mit einem ΔSUV12 größer als 60 %, die als PET-negative Patienten definiert wurden, hatten eine höhere LKC und ein besseres 2-Jahres-PFS als PET-positive Patienten (LRC: 84,2 % vs. 52,9; P = 0,046; PFS: 70,6 % vs. 35,2 %; P = 0,025). Die Analyse der [18F]-FDG-PET/CT ergab, dass ΔSUV13 bei der PET/CT nach Strahlentherapie eine bessere Vorhersage der Prognose ermöglicht, als die PET/CT vor- und während der Strahlentherapie (AUC 0,812 für PFS; 0,807 für LRC, bei einem Grenzwert von 75 %; P = 0,016). Eine Reduktion der SUVmax von mehr als 75 % warmit einem besseren klinischen Outcome der Patienten assoziiert (PFS: 73,3 % vs. 36,8 %; P = 0,022; LRC: 86,7 % vs. 52,6; P = 0,029). Für die Subgruppe der Patienten, die mit einer Chemoradiotherapie behandelt wurden, waren diese Korrelationen deutlicher.

Schlussfolgerungen

Die frühe [18F]-FLT-PET/CT während der Strahlentherapie ist ein signifikanter Prädiktor für das 2-Jahres-PFS und die LRC und korreliert bei Plattenepithelkarzinomen des Ösophagus im Vergleich zur [18F]-FDG-PET/CT besser mit einem frühem Ansprechen und einem späten Outcome.

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Compliance with ethical guidelines

Acknowledgements

This study was supported by grant No. 81101067 from National Nature Science Foundation of China.

Conflict of interest

H. Chen, Y. Li, H. Wu, L. Sun, Q. Lin, L. Zhao and H. An state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

Consent was obtained from all patients identifiable from images or other information within the manuscript. In the case of underage patients, consent was obtained from a parent or legal guardian.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Xiamen Cancer Center, the First Affiliated Hospital of Xiamen University, Xiamen, China

    Haojun Chen M.D., Hua Wu M.D., Ph.D., Long Sun M.D., Ph.D. & Long Zhao M.D.

  2. Department of Radiation Oncology, Xiamen Cancer Center, the First Affiliated Hospital of Xiamen University, Xiamen, China

    Yimin Li M.D. & Qin Lin M.D., Ph.D.

  3. Department of Medical Oncology, Xiamen Cancer Center, the First Affiliated Hospital of Xiamen University, Xiamen, China

    Hanxiang An M.D., Ph.D.

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  1. Haojun Chen M.D.
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  2. Yimin Li M.D.
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  3. Hua Wu M.D., Ph.D.
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  4. Long Sun M.D., Ph.D.
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Corresponding authors

Correspondence to Hua Wu M.D., Ph.D. or Hanxiang An M.D., Ph.D..

Additional information

Haojun Chen and Yimin Li contributed equally to this work.

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Chen, H., Li, Y., Wu, H. et al. 3’-Deoxy-3’-[18F]-fluorothymidine PET/CT in early determination of prognosis in patients with esophageal squamous cell cancer. Strahlenther Onkol 191, 141–152 (2015). https://doi.org/10.1007/s00066-014-0744-8

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