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Direct dose correlation of MRI morphologic alterations of healthy liver tissue after robotic liver SBRT

Direkte Dosiskorrelation von MRT-morphologischen Veränderungen von gesundem Lebergewebe nach robotergestützter Leber-SBRT

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Abstract

Purpose

For assessing healthy liver reactions after robotic SBRT (stereotactic body radiotherapy), we investigated early morphologic alterations on MRI (magnetic resonance imaging) with respect to patient and treatment plan parameters.

Patients and methods

MRI data at 6–17 weeks post-treatment from 22 patients with 42 liver metastases were analyzed retrospectively. Median prescription dose was 40 Gy delivered in 3–5 fractions. T2- and T1-weighted MRI were registered to the treatment plan. Absolute doses were converted to EQD2 (Equivalent dose in 2Gy fractions) with α/β-ratios of 2 and 3 Gy for healthy, and 8 Gy for modelling pre-damaged liver tissue.

Results

Sharply defined, centroid-shaped morphologic alterations were observed outside the high-dose volume surrounding the GTV. On T2-w MRI, hyperintensity at EQD2 isodoses of 113.3 ± 66.1 Gy2, 97.5 ± 54.7 Gy3, and 66.5 ± 32.0 Gy8 significantly depended on PTV dimension (p = 0.02) and healthy liver EQD2 (p = 0.05). On T1-w non-contrast MRI, hypointensity at EQD2 isodoses of 113.3 ± 49.3 Gy2, 97.4 ± 41.0 Gy3, and 65.7 ± 24.2 Gy8 significantly depended on prior chemotherapy (p = 0.01) and total liver volume (p = 0.05). On T1-w gadolinium-contrast delayed MRI, hypointensity at EQD2 isodoses of 90.6 ± 42.5 Gy2, 79.3 ± 35.3 Gy3, and 56.6 ± 20.9 Gy8 significantly depended on total (p = 0.04) and healthy (p = 0.01) liver EQD2.

Conclusions

Early post-treatment changes in healthy liver tissue after robotic SBRT could spatially be correlated to respective isodoses. Median nominal doses of 10.1–11.3 Gy per fraction (EQD2 79–97 Gy3) induce characteristic morphologic alterations surrounding the lesions, potentially allowing for dosimetric in-vivo accuracy assessments. Comparison to other techniques and investigations of the short- and long-term clinical impact require further research.

Zusammenfassung

Zielsetzung

Zur Beurteilung gesunder Leberreaktionen nach robotergestützter SBRT untersuchten wir frühzeitige morphologische Veränderungen im MRT (Magnetresonanztomographie) hinsichtlich Patienten- und Behandlungsplanparameter.

Patienten und Methoden

MRT-Daten von 22 Patienten von 42 Lebermetastasen wurden 6–17 Wochen nach Behandlung retrospektiv analysiert. Die mediane Verschreibungsdosis betrug 40 Gy in 3–5 Fraktionen. T2- und T1-gewichtete MRT-Sequenzen wurden zum Bestrahlungsplan registriert. Absolute Dosen wurden in EQD2 mit α/β-Verhältnissen von 2 und 3 Gy für die Modellierung von gesundem und 8 Gy für die von vorgeschädigtem Lebergewebe umgerechnet.

Ergebnisse

Scharf definierte, zumeist zentroidförmige morphologische Veränderungen wurden außerhalb des Hochdosisvolumens um das ursprüngliche GTV herum beobachtet. Hyperintensitäten auf T2-gewichtetem MRT bei EQD2-Isodosen von 113,3 ± 66,1 Gy2, 97,5 ± 54,7 Gy3 und 66,5 ± 32,0 Gy8 hingen signifikant von PTV-Dimension (p = 0,02) und gesundem Leber-EQD2 (p = 0,05) ab. Hypointensitäten auf T1-gewichtetem non-Kontrast-MRT bei EQD2-Isodosen von 113,3 ± 49,3 Gy2, 97,4 ± 41,0 Gy3 und 65,7 ± 24,2 Gy8 waren signifikant von vorheriger Chemotherapie (p = 0,01) und dem Gesamtlebervolumen (p = 0,05) abhängig. Hypointensitäten auf T1-gewichtetem Gadolinium-Kontrast-MRT bei EQD2-Isodosen von 90,6 ± 42,5 Gy2, 79,3 ± 35,3 Gy3 und 56,6 ± 20,9 Gy8 hingen signifikant von Gesamtlebervolumen (p = 0,04) und Volumen der gesunden Leber-EQD2 (p = 0,01) ab.

Schlussfolgerung

Nach robotergestützter SBRT konnten frühe postradiogene Veränderungen des gesunden Lebergewebes räumlich zu den entsprechenden Isodosislinien korreliert werden. Mediane nominale Fraktionsdosen von 10,1–11,3 Gy (EQD2 79–97 Gy3) induzieren charakteristische morphologische Veränderungen um die bestrahlten Läsionen, die möglicherweise dosimetrische In-vivo-Genauigkeitsanalysen erlauben. Der Vergleich zu anderen Behandlungsmethoden und Untersuchungen zu klinischen Kurz- und Langzeitfolgen stehen noch aus.

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Acknowledgements

The Velocity software was provided within the framework of a research agreement between the University Medical Center Mannheim and Varian Medical Systems (USA). We especially thank Yvette Bellingan (Varian, USA) for the excellent assistance with the software. We would also kindly thank Dr. Thorsten Peter (Güstrow, Germany) for his significant support.

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Authors and Affiliations

  1. Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer Ufer 1–3, 68167, Mannheim, Germany

    Judit Boda-Heggemann MD, Anika Jahnke PhD & Frederik Wenz MD

  2. Department of Radiation Oncology, University Medical Center Schleswig-Holstein, Kiel, Germany

    Mark K. H. Chan PhD, Leila S. Ghaderi Ardekani MSc, Jürgen Dunst MD & Oliver Blanck PhD

  3. Department of Radiology and Nuclear Medicine, University Medical Center Schleswig-Holstein, Lübeck, Germany

    Peter Hunold MD

  4. Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein, Kiel, Germany

    Jost Philipp Schäfer MD

  5. Saphir Radiosurgery Center, Güstrow, Germany

    Stefan Huttenlocher MD, Stefan Wurster MD & Oliver Blanck PhD

  6. Department of Radiation Oncology, University Medicine Greifswald, Greifswald, Germany

    Stefan Wurster MD

  7. Department of Radiation Oncology, University Medical Center Schleswig-Holstein, Lübeck, Germany

    Dirk Rades MD

  8. Department of Radiation Oncology, University Medicine Rostock, Rostock, Germany

    Guido Hildebrandt MD

  9. UO di Radioterapia, Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy

    Frank Lohr MD

  10. Department of Radiation Oncology, University Hospital Copenhagen, Copenhagen, Denmark

    Jürgen Dunst MD

Authors
  1. Judit Boda-Heggemann MD
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  2. Anika Jahnke PhD
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  3. Mark K. H. Chan PhD
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  4. Leila S. Ghaderi Ardekani MSc
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  6. Jost Philipp Schäfer MD
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  7. Stefan Huttenlocher MD
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  8. Stefan Wurster MD
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  9. Dirk Rades MD
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  10. Guido Hildebrandt MD
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  11. Frank Lohr MD
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  12. Jürgen Dunst MD
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  13. Frederik Wenz MD
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  14. Oliver Blanck PhD
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Corresponding author

Correspondence to Judit Boda-Heggemann MD.

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Conflict of interest

J. Boda-Heggemann, A. Jahnke, M.K.H. Chan, L.S. Ghaderi Ardekani, P. Hunold, J.P. Schäfer, S. Huttenlocher, S. Wurster, D. Rades, G. Hildebrandt, F. Lohr, J. Dunst, F. Wenz, and O. Blanck declare that they have no competing interests.

Ethical standards

This retrospective study was approved by the local ethics committees of the medical faculty of the universities of Rostock (A2016-0008) for the clinical part and Kiel (D458/17) for the response assessment part.

Additional information

J. Boda-Heggemann and A. Jahnke contributed equally to this publication

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Boda-Heggemann, J., Jahnke, A., Chan, M.K.H. et al. Direct dose correlation of MRI morphologic alterations of healthy liver tissue after robotic liver SBRT. Strahlenther Onkol 194, 414–424 (2018). https://doi.org/10.1007/s00066-018-1271-9

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