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Predicting tumor responses and patient survival in chemoradiotherapy-treated patients with non-small-cell lung cancer using dynamic contrast-enhanced integrated magnetic resonance–positron-emission tomography

Vorhersage von Tumoransprechen und Patientenüberleben bei den mit Chemoradiotherapie behandelten Patienten mit nicht-kleinzelligem Lungenkrebs mittels dynamischer kontrastverstärkter integrierter Magnetresonanz-Positronenemissionstomographie

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Abstract

Purpose

We investigated whether radiologic parameters by dynamic contrast-enhanced (DCE) integrated magnetic resonance–positron-emission tomography (MR-PET) predicts tumor response to treatment and survival in non-metastatic non-small-cell lung cancer (NSCLC) patients receiving chemoradiotherapy (CRT).

Methods

Patients underwent DCE integrated MR-PET imaging 1 week before CRT. The following parameters were analyzed: primary tumor size, gross tumor volume, maximal standardized uptake value (SUVmax), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), volume transfer constant (Ktrans), reverse reflux rate constant (kep), extracellular extravascular volume fraction (ve), blood plasma volume fraction (vp), and initial area under the time-concentration curve defined over the first 60 s post-enhancement (iAUC60). CRT responses were defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).

Results

Thirty patients were included. Non-responders demonstrated higher baseline TLG (p = 0.012), and lower baseline Ktrans (p = 0.020) and iAUC60 (p = 0.016) compared to responders, indicating the usefulness of DCE integrated MR-PET to predict treatment responses. Receiver operating characteristic curve indicated that TLG has the best differentiation capability to predict responders. By setting the threshold of TLG to 277, the sensitivity, specificity, and accuracy were 66.7%, 83.3%, and 75.0%, respectively, with an area under the curve of 0.776. The median follow-up time was 19.6 (range 7.8–32.0) months. In univariate analyses, baseline TLG >277 (p = 0.005) and baseline Ktrans <254 (10−3 min−1; p = 0.015) correlated with poor survival after CRT. In multivariate analysis, baseline TLG >277 remained the significant factor in predicting progression (p = 0.012) and death (p = 0.031).

Conclusions

The radiologic parameters derived from DCE integrated MR-PET scans are useful for predicting treatment response in NSCLC patients treated with CRT; furthermore, these parameters are correlated with clinical and survival outcomes including tumor progression and death.

Zusammenfassung

Ziel

Wir untersuchten, ob radiologische Parameter durch die dynamische kontrastverstärkte (DCE) integrierte Magnetresonanz-Positronenemissionstomographie (MR-PET) das Ansprechen des Tumors auf die Behandlung und das klinische Überleben bei Patienten mit nichtmetastasiertem nicht-kleinzelligem Lungenkrebs (NSCLC), die eine primäre Chemoradiotherapie (CRT) erhalten haben, vorhersagen können.

Methoden

Die Patienten unterzogen sich 1 Woche vor CRT einer DCE-integrierten 3T-MR-PET-Bildgebung. Folgende Parameter wurden analysiert: Primärtumorgröße, Gesamttumorvolumen, maximaler standardisierter Aufnahmewert (SUVmax), Gesamtläsionsglykolyse (TLG), scheinbarer Diffusionskoeffizient (ADC), Volumentransfer konstant (Ktrans), Rückflussrate konstant (kep), extrazelluläre extravaskuläre Volumenfraktion (ve), Blutplasma-Volumenfraktion (vp), und Anfangsbereich unter der Zeit-Konzentrationskurve, die über die ersten 60s nach der Verbesserung definiert wurde (iAUC60). Die CRT-Antworten wurden anhand der überarbeitete Response-Bewertungskriterien bei soliden Tumoren(RECIST)-Richtlinie (Version 1.1) definiert.

Ergebnisse

Dreißig Patienten wurden aufgenommen. Non-Responder zeigten im Vergleich zu den Respondern eine höhere Baseline-TLG (p = 0,012), eine niedrigere Baseline Ktrans (p = 0,020) und iAUC60 (p = 0,016), was auf den Nutzen von DCE-integriertem MR-PET für die Vorhersage von Behandlungsreaktionen hinweist. Die „Receiver-operating-characteristic“-(ROC-)Kurve zeigte, dass TLG die beste Unterscheidungsfähigkeit zur Vorhersage von Respondern hat. Durch die Festlegung des Schwellenwerts des TLG auf 277 betrugen Sensitivität, Spezifität und Genauigkeit jeweils 66,7, 83,3 und 75,0%, mit einer Fläche unter der Kurve von 0,776. Das durchschnittliche Follow-up betrug 19,6 Monate (Spanne 7,8–32,0 Monate). In univariaten Analysen korrelierten Baseline TLG >277 (p = 0,005) und Baseline Ktrans <254 (10−3 min−1; p = 0,015) mit einer schlechten Überlebenschance nach CRT. In der multivariaten Analyse blieb die Baseline-TLG >277 der signifikante Faktor bei der Prognose von Progression (p = 0,012) und Tod (p = 0,031).

Schlussfolgerung

Die radiologischen Parameter, die von DCE-integrierten MR-PET-Scans abgeleitet werden, sind nützlich für die Vorhersage des Behandlungserfolgs bei NSCLC-Patienten, die mit CRT behandelt werden, und sind mit der klinischen Überlebensrate einschließlich Tumorprogression und Tod korreliert.

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Acknowledgements

We thank Prof. Jin-Yuan Shih, Prof. Chao-Chi Ho, Dr. Tzu-Hsiu Tsai, Dr. Chia-Lin Hsu, Dr. Ching-Yao Yang, Dr. Chung-Yu Chen, and Dr. Sheng-Kai Liang for their guidance in conducting this work. We are thankful to the doctors, nurses, healthcare providers, and other sources of health information who contributed to this study. We also thank the staff of the Core Labs, Department of Medical Research, National Taiwan University Hospital, for their technical support.

Funding

This work was supported by the National Taiwan University Hospital (grant number: NTUH106-N3662 and NTUH107-M4007) and the Ministry of Science and Technology (MST, Taiwan, Contract numbers: MST 100-2221-E-002-031-MY3, 104-2221-E-002-093-MY3, and 107-2314-B-002-225-MY2).

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Authors and Affiliations

  1. Department of Medical Imaging, National Taiwan University Hospital, National Taiwan University College of Medicine, No.7, Chung-Shan South Road, 100, Taipei, Taiwan

    Yu-Sen Huang M.D. Ph.D., Jo-Yu Chen M.D., Yee-Fan Lee M.D. & Yeun-Chung Chang M.D. Ph.D.

  2. Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan

    Yu-Sen Huang M.D. Ph.D. & Jenny Ling-Yu Chen M.D. Ph.D.

  3. Department of Medical Imaging, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan

    Yu-Sen Huang M.D. Ph.D.

  4. Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

    Jenny Ling-Yu Chen M.D. Ph.D. & Sung-Hsin Kuo M.D. Ph.D.

  5. Department of Nuclear Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

    Jei-Yie Huang M.D. & Ruoh-Fang Yen M.D. Ph.D.

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  1. Yu-Sen Huang M.D. Ph.D.
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  2. Jenny Ling-Yu Chen M.D. Ph.D.
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  3. Jo-Yu Chen M.D.
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  4. Yee-Fan Lee M.D.
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  6. Sung-Hsin Kuo M.D. Ph.D.
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  7. Ruoh-Fang Yen M.D. Ph.D.
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  8. Yeun-Chung Chang M.D. Ph.D.
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Corresponding author

Correspondence to Yeun-Chung Chang M.D. Ph.D..

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Conflict of interest

Y.-S. Huang, J.L.-Y. Chen, J.-Y. Chen, Y.-F. Lee, J.-Y. Huang, S.-H. Kuo, R.-F. Yen and, Y.-C. Chang declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the National Taiwan University Hospital Research Ethics Committee (Approval number: 201501073RINA) and is registered with ClinicalTrials.gov, number NCT NCT03053804.

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Huang, YS., Chen, J.LY., Chen, JY. et al. Predicting tumor responses and patient survival in chemoradiotherapy-treated patients with non-small-cell lung cancer using dynamic contrast-enhanced integrated magnetic resonance–positron-emission tomography. Strahlenther Onkol 195, 707–718 (2019). https://doi.org/10.1007/s00066-018-1418-8

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