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Intensity-modulated proton therapy, volumetric-modulated arc therapy, and 3D conformal radiotherapy in anaplastic astrocytoma and glioblastoma

A dosimetric comparison

Intensitätsmodulierte Protonentherapie, volumenmodulierte Arc-Therapie und dreidimensionale konformale Radiotherapie beim anaplastischen Astrozytom und Glioblastom

Ein dosimetrischer Vergleich

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Abstract

Purpose

The prognosis for high-grade glioma (HGG) patients is poor; thus, treatment-related side effects need to be minimized to conserve quality of life and functionality. Advanced techniques such as proton radiation therapy (PRT) and volumetric-modulated arc therapy (VMAT) may potentially further reduce the frequency and severity of radiogenic impairment.

Materials and methods

We retrospectively assessed 12 HGG patients who had undergone postoperative intensity-modulated proton therapy (IMPT). VMAT and 3D conformal radiotherapy (3D-CRT) plans were generated and optimized for comparison after contouring crucial neuronal structures important for neurogenesis and neurocognitive function. Integral dose (ID), homogeneity index (HI), and inhomogeneity coefficient (IC) were calculated from dose statistics. Toxicity data were evaluated.

Results

Target volume coverage was comparable for all three modalities. Compared to 3D-CRT and VMAT, PRT showed statistically significant reductions (p < 0.05) in mean dose to whole brain (−20.2 %, −22.7 %); supratentorial (−14.2 %, −20,8 %) and infratentorial (−91.0 %, −77.0 %) regions; brainstem (−67.6 %, −28.1 %); pituitary gland (−52.9 %, −52.5 %); contralateral hippocampus (−98.9 %, −98.7 %); and contralateral subventricular zone (−62.7 %, −66.7 %, respectively). Fatigue (91.7 %), radiation dermatitis (75.0 %), focal alopecia (100.0 %), nausea (41.7 %), cephalgia (58.3 %), and transient cerebral edema (16.7 %) were the most common acute toxicities.

Conclusion

Essential dose reduction while maintaining equal target volume coverage was observed using PRT, particularly in contralaterally located critical neuronal structures, areas of neurogenesis, and structures of neurocognitive functions. These findings were supported by preliminary clinical results confirming the safety and feasibility of PRT in HGG.

Zusammenfassung

Zielsetzung

Die Prognose bei „High-grade“-Gliomen (HGG) ist infaust. Gerade bei diesen Patienten sollten therapieassoziierte Nebenwirkungen minimiert werden, um die Lebensqualität und Funktionalität zu erhalten. Moderne Radiotherapietechniken, wie die Protonenradiotherapie (PRT) und die volumenmodulierte Arc-Therapie (VMAT), haben das Potential, die Dosisbelastung von Risikoorganen weiter zu reduzieren.

Material und Methoden

12 HGG-Patienten, die eine postoperative intensitätsmodulierten Protonentherapie (IMPT) erhalten hatten, wurden retrospketiv bewertet. Zum Vergleich wurden VMAT- und 3D-konformale Radiotherapiepläne (3D-CRT) generiert, in denen die Dosisverteilung in wichtigen Arealen der Neurogenese und neurokognitiven Funktion bestimmt wurden. Anhand von Dosisstatistiken wurden die Integraldosis (ID), der Homogenitätsindex (HI) und der Inhomogenitätskoeffizient (IC) berechnet und die therapieassoziierte Toxizität bestimmt.

Ergebnisse

Für alle drei Techniken war die Zielvolumenabdeckung vergleichbar gut. PRT reduzierte die Dmean im Vergleich zur 3D-CRT und VMAT im Ganzhirn (−20,2 %; −22,7 %), im supratentoriellen (−14,2 %; −20,8 %) und infratentoriellen Hirn (−91 %; −77,0 %), im Hirnstamm (−67,6 %; −28, %), in der Hypophyse (−52,9 %; −52,5 %), im kontralateralen Hippokampus (−98,9 %; −98,7 %) und in der kontralateralen subventrikulären Zone (−62,7 %; −66,7 %) signifikant (p < 0,05). Die häufigsten akuten Nebenwirkungen waren Fatigue (91,7 %), radiogene Dermatitis (75,0 %), fokale Alopezie (100,0 %), Nausea (41,7 %), Cephalgien (58,3 %) und vorübergehende zerebrale Ödeme (16,7 %).

Schlussfolgerung

Durch die PRT konnte bei Aufrechterhaltung der Zielvolumenabdeckung eine signifikante Dosisreduktion insbesondere in kontralateralen kritischen neuronalen Strukturen sowie in essentiellen Arealen für die neurokognitiven Funktionen und Neurogenese beobachtet werden. Die vorläufigen klinischen Ergebnisse bestätigen die sichere Durchführbarkeit und Praktikabilität der PRT bei HGG.

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Acknowledgements

We thank Eric Tonndorf-Martini and Thomas Mielke for excellent technical assistance. We acknowledge financial support of the Dietmar-Hopp-Stiftung.

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Authors and Affiliations

  1. Heidelberg Institute of Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    S. Adeberg,  S. B. Harrabi, N. Bougatf, D. Bernhardt,  J. Rieber,  S. A. Koerber,  M. Syed,  T. Sprave,  A. Mohr,  T. Haberer,  K. Herfarth,  J. Debus &  S. Rieken

  2. Heidelberg Ion-Beam Therapy Center (HIT), Im Neuenheimer Feld 450, 69120, Heidelberg, Germany

    S. Adeberg,  S. B. Harrabi, N. Bougatf,  J. Rieber,  S. A. Koerber,  T. Haberer,  K. Herfarth,  J. Debus &  S. Rieken

  3. Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    S. Adeberg,  S. B. Harrabi, N. Bougatf, D. Bernhardt,  J. Rieber,  S. A. Koerber,  M. Syed,  T. Sprave,  A. Mohr,  A. Abdollahi,  K. Herfarth,  J. Debus &  S. Rieken

  4. Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    S. Adeberg &  J. Debus

  5. Department of Radiation Oncology, Technische Universität München, Ismaninger Straße 22, 81675, München, Germany

    S. E. Combs

  6. Institut für Innovative Radiotherapie (iRT), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Ingostädter Landtraße 1, Neuherberg, Germany

    S. E. Combs

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  1. S. Adeberg
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  2. S. B. Harrabi
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  3. N. Bougatf
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  12. S. E. Combs
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  14. J. Debus
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  15. S. Rieken
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Corresponding author

Correspondence to S. Adeberg.

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Conflict of interest

S. Adeberg, S.B. Harrabi, N. Bougatf, D. Bernhardt, J. Rieber, S. A. Koerber, M. Syed, T. Sprave, A. Mohr, A. Abdollahi, T. Haberer, S. E. Combs, K. Herfarth, J. Debus, and S. Rieken state that there are no conflicts of interest.

Ethical standards

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).

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Adeberg, S., Harrabi, S.B., Bougatf, N. et al. Intensity-modulated proton therapy, volumetric-modulated arc therapy, and 3D conformal radiotherapy in anaplastic astrocytoma and glioblastoma. Strahlenther Onkol 192, 770–779 (2016). https://doi.org/10.1007/s00066-016-1007-7

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