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Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases

Local tumour control and survival

Ganzhirnbestrahlung mit Hippocampusschonung und Dosiseskalation bei multiplen Hirnmetastasen

Lokale Tumorkontrolle und Überleben

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Abstract

Purpose

Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique.

Methods and materials

Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D98 % to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2–13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2–4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI.

Results

Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. Dmean to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance.

Conclusion

HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration.

Zusammenfassung

Hintergrund

Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusätzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie präsentieren wir erste Ergebnisse hinsichtlich lokaler Tumorkontrolle, des intrakraniellen progressionsfreien Überlebens (PFS), des Gesamtüberlebens (OS), der Toxizität und der Sicherheit dieser neuen Bestrahlungstechnik.

Methoden und Material

Es wurden 20 Patienten zwischen 2011 und 2013 mit einer HS-GHB (30 Gy in 12 Fraktionen, D98 % am Hippocampus ≤ 9 Gy) und simultan integriertem Boost (51 Gy) auf multiple (2 bis 13) Metastasen behandelt. Eingesetzt wurde eine individuell geplante VMAT („volumetric modulated arc therapy“)-Technik mit 2 bis 4 Bögen. Die Größe der Metastasen wurde bidimensional entlang der 2 größten Durchmesser in kontrastmittelverstärkten, T1-gewichteten dreidimensionalen MRT-Aufnahmen evaluiert.

Ergebnisse

Die mediane Nachbeobachtungszeit betrug 40 Wochen. Die mediane Zeit zur Progression der geboosteten Metastasen wurde nicht erreicht, was mit einer lokalen Tumorkontrolle von 73 % einhergeht. Das mediane PFS betrug 40 Wochen (1-Jahres-PFS 45,3 %). Das mediane OS betrug 71,5 Wochen (1-Jahres-OS 60 %). Es traten keine Toxizitäten > Grad 2 (NCI CTCAE v4.03) auf. Die Dmean auf die Hippocampi betrug 6,585 Gy ± 0,847 (α/β = 2 Gy). Zwei Patienten entwickelten je eine neue Metastase im Bereich der Hippocampusschonung.

Schlussfolgerung

HS-GHB (simultane integrierte Protektion, SIP) mit SIB auf die Metastasen ist ein sicheres und tolerables Therapiekonzept mit einer vorteilhaften lokalen Tumorkontrolle bei Patienten mit multiplen Hirnmetastasen bei gleichzeitiger Möglichkeit, die behandlungsbedingten neurokognitiven Einschränkungen von Lernen und Gedächtnis zu verhindern.

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Acknowledgments

The present study was supported by the German Cancer Consortium (DKTK).

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University Medical Center Freiburg, Robert-Koch-Str. 3, 79106, Freiburg, Germany

    Oliver Oehlke MD, PhD, David Wucherpfennig,  Franziska Fels MD,  Lars Frings PhD,  Vesna Prokic PhD &  Anca-Ligia Grosu MD

  2. Department of Radiation Oncology, St. Josefs Hospital, Offenburg, Germany

    Franziska Fels MD

  3. Department of Geriatrics and Gerontology, University Hospital Freiburg, Freiburg, Germany

    Lars Frings PhD

  4. Department of Nuclear Medicine, University Medical Center Freiburg, Freiburg, Germany

    Lars Frings PhD

  5. Department of Neuroradiology, University Medical Center Freiburg, Freiburg, Germany

    Karl Egger MD

  6. Department of Neurosurgery, University Medical Center Freiburg, Freiburg, Germany

    Astrid Weyerbrock MD

  7. Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway

    Carsten Nieder MD

  8. Institute of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway

    Carsten Nieder MD

  9. German Cancer Consortium (DKTK), Freiburg, Germany

    Anca-Ligia Grosu MD

  10. German Cancer Research Center (DKFZ), Heidelberg, Germany

    Anca-Ligia Grosu MD

Authors
  1. Oliver Oehlke MD, PhD
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  2. David Wucherpfennig
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  3. Franziska Fels MD
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  9. Anca-Ligia Grosu MD
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Corresponding author

Correspondence to Anca-Ligia Grosu MD.

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Conflict of interest

O. Oehlke, D. Wucherpfennig, F. Fels, L. Frings, K. Egger, A. Weyerbrock, V. Prokic, C. Nieder and A.-L. Grosu 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.

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Oehlke, O., Wucherpfennig, D., Fels, F. et al. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Strahlenther Onkol 191, 461–469 (2015). https://doi.org/10.1007/s00066-014-0808-9

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  • DOI: https://doi.org/10.1007/s00066-014-0808-9

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