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Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases

Plan comparison and early clinical evaluation

Ausgleichsfilterfreie Radiochirurgie bei der Behandlung von Hirnmetastasen

Ein Planvergleich und erste klinische Ergebnisse

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Abstract

Background

Radiosurgical treatment of brain metastases is well established in daily clinical routine. Utilization of flattening-filter-free beams (FFF) may allow for more rapid delivery of treatment doses and improve clinical comfort. Hence, we compared plan quality and efficiency of radiosurgery in FFF mode to FF techniques.

Materials and methods

Between November 2014 and June 2015, 21 consecutive patients with 25 brain metastases were treated with stereotactic radiosurgery (SRS) in FFF mode. Brain metastases received dose-fractionation schedules of 1 × 20 Gy or 1 × 18 Gy, delivered to the conformally enclosing 80 % isodose. Three patients with critically localized or large (>3 cm) brain metastases were treated with 6 × 5 Gy. Plan quality and efficiency were evaluated by analyzing conformity, dose gradients, dose to healthy brain tissue, treatment delivery time, and number of monitor units. FFF plans were compared to those using the FF method, and early clinical outcome and toxicity were assessed.

Results

FFF mode resulted in significant reductions in beam-on time (p < 0.001) and mean brain dose (p = 0.001) relative to FF-mode comparison plans. Furthermore, significant improvements in dose gradients and sharper dose falloffs were found for SRS in FFF mode (−1.1 %, −29.6 %; p ≤ 0.003), but conformity was slightly superior in SRS in FF mode (−1.3 %; p = 0.001). With a median follow-up time of 5.1 months, 6‑month overall survival was 63.3 %. Local control was observed in 24 of 25 brain metastases (96 %).

Conclusion

SRS in FFF mode is time efficient and provides similar plan quality with the opportunity of slightly reduced dose exposure to healthy brain tissue when compared to SRS in FF mode. Clinical outcomes appear promising and show only modest treatment-related toxicity.

Zusammenfassung

Hintergrund

Die radiochirurgische Behandlung (SRS) von Hirnmetastasen wird vielfach in der klinischen Routine durchgeführt. Die zusätzliche Anwendung von ausgleichsfilterfreien Bestrahlungstechniken (FFF) kann die Bestrahlungszeit verkürzen und den Patientenkomfort erhöhen. Daher führten wir einen Plan- und Effizienzvergleich zwischen der Radiochirurgie in FFF-Technik und FF-Technik durch.

Material und Methode

Zwischen November 2014 und Juni 2015 wurden 21 Patienten mit 25 Hirnmetastasen mit SRS in FFF-Technik behandelt. Die Hirnmetastasen wurden mit 1 × 20 Gy oder 1 × 18 Gy auf die konformal umschließende 80 %-Isodose bestrahlt. Drei Patienten mit kritisch lokalisierten oder großen Metastasen (>3 cm) erhielten eine Bestrahlung mit 6 × 5 Gy. Konformität, Dosisgradienten, Behandlungszeiten, Normalgewebsdosis (Gehirn) sowie Anzahl an Monitoreinheiten wurden zur Evaluation der Planqualität herangezogen. Des Weiteren wurden Überleben und Toxizität analysiert.

Ergebnisse

Sowohl die Bestrahlungszeit sank signifikant um 57,9 % (p ≤ 0,001) für die SRS in FFF-Technik im Vergleich zur FF-Technik. als auch die durchschnittliche Bestrahlungsdosis des Gehirns (p = 0,001). Des Weiteren wurden signifikant verbesserte Dosisgradienten und folglich ein steilerer Dosisabfall für die SRS in FFF-Technik (−1,1 %, −29,6 %; p ≤ 0,003) festgestellt. Dagegen zeigte die SRS in FF-Technik einen leicht verbesserten Konformitätsindex (−1,3 %; p = 0,001). Bei einer medianen Nachbeobachtungzeit von 5,1 Monaten betrug das 6‑Monats-Gesamtüberleben 63,3 %. Bei den behandelten 25 Hirnmetastasen (96 %) waren 24 ohne lokalen Progress.

Schlussfolgerung

SRS in FFF-Technik ist zeiteffizient und ermöglicht gleiche Planqualität sowie eine leicht reduzierte Dosisbelastung des gesunden Hirngewebes im Vergleich zur SRS in FF-Technik. Entsprechend vielversprechend sind die ersten klinischen Ergebnisse bei moderater Toxizität.

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Acknowledgements

This work was supported by the Medical Faculty providing a research grant for JR.

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Authors and Affiliations

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

    J. Rieber, E. Tonndorf-Martini, O. Schramm, B. Rhein, S. Stefanowicz, K. Lindel, J. Debus & S. Rieken

  2. Heidelberg Institute of Radiation Oncology, Heidelberg, Germany

    J. Rieber, E. Tonndorf-Martini, O. Schramm, B. Rhein, S. Stefanowicz, K. Lindel, J. Debus & S. Rieken

  3. Translational Research Unit, Thoraxklinik, Heidelberg University, Heidelberg, Germany

    J. Kappes & H. Hoffmann

  4. Department of Pneumology, Thoraxklinik, Heidelberg University, Heidelberg, Germany

    J. Kappes

  5. Department of Thoracic Surgery, Thoraxklinik, Heidelberg University, Heidelberg, Germany

    H. Hoffmann

  6. Translational Lung Research Centre Heidelberg (TLRC-H), Member of the German Centre for Lung Research (DZL), Heidelberg, Germany

    J. Kappes & H. Hoffmann

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  1. J. Rieber
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Correspondence to S. Rieken.

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Conflict of interest

J. Rieber, E. Tonndorf-Martini, O. Schramm, B. Rhein, S. Stefanowicz, J. Kappes, H. Hoffmann, K. Lindel, J. Debus and S. Rieken 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. Informed consent was obtained from all individual participants included in the study. Ethical approval was obtained from the local Ethics Committee  (S-140/2016).

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Rieber, J., Tonndorf-Martini, E., Schramm, O. et al. Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases. Strahlenther Onkol 192, 789–796 (2016). https://doi.org/10.1007/s00066-016-1012-x

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