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Breathing-motion-compensated robotic guided stereotactic body radiation therapy

Patterns of failure analysis

Atembewegungskompensierte, robotergeführte stereotaktische Körperstammstrahlentherapie

Analyse der Rezidivmuster

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Abstract

Purpose

We retrospectively evaluated the patterns of failure for robotic guided real-time breathing-motion-compensated (BMC) stereotactic body radiation therapy (SBRT) in the treatment of tumors in moving organs.

Patients and methods

Between 2011 and 2016, a total of 198 patients with 280 lung, liver, and abdominal tumors were treated with BMC-SBRT. The median gross tumor volume (GTV) was 12.3 cc (0.1–372.0 cc). Medians of mean GTV BEDα/β = 10 Gy (BED = biological effective dose) was 148.5 Gy10 (31.5–233.3 Gy10) and prescribed planning target volume (PTV) BEDα/β = 10 Gy was 89.7 Gy10 (28.8–151.2 Gy10), respectively. We analyzed overall survival (OS) and local control (LC) based on various factors, including BEDs with α/β ratios of 15 Gy (lung metastases), 21 Gy (primary lung tumors), and 27 Gy (liver metastases).

Results

Median follow-up was 10.4 months (2.0–59.0 months). The 2‑year actuarial LC was 100 and 86.4% for primary early and advanced stage lung tumors, respectively, 100% for lung metastases, 82.2% for liver metastases, and 90% for extrapulmonary extrahepatic metastases. The 2‑year OS rate was 47.9% for all patients. In uni- and multivariate analysis, comparatively lower PTV prescription dose (equivalence of 3 × 12–13 Gy) and higher average GTV dose (equivalence of 3 × 18 Gy) to current practice were significantly associated with LC. For OS, Karnofsky performance score (100%), gender (female), and SBRT without simultaneous chemotherapy were significant prognostic factors. Grade 3 side effects were rare (0.5%).

Conclusions

Robotic guided BMC-SBRT can be considered a safe and effective treatment for solid tumors in moving organs. To reach sufficient local control rates, high average GTV doses are necessary. Further prospective studies are warranted to evaluate these points.

Zusammenfassung

Zweck

Wir führten eine retrospektive Untersuchung der Rezidivmuster bei der Behandlung von Tumoren in bewegten Organen mittels robotergeführter in Echtzeit atembewegungskompensierter (EAK) stereotaktischer Körperstammstrahlentherapie (SBRT) durch.

Patienten und Methoden

Zwischen 2011 und 2016 wurden insgesamt 198 Patienten mit 280 Lungen‑, Leber- und Abdominaltumoren mit EAK-SBRT behandelt. Das mediane makroskopische Tumorvolumen (GTV) lag bei 12,3 cm3 (0,1–372,0 cm3). Die mediane mittlere GTV-BEDα / β = 10 Gy lag bei 148,5 Gy10 (31,5–233,3 Gy10; BED = biologisch effektive Dosis) und die verschriebene PTV-BEDα / β = 10 Gy bei 89,7 Gy10 (28,8–151,2 Gy10; PTV = Planungszielvolumen). Wir analysierten das Gesamtüberleben (GÜ) und die lokale Kontrolle (LK) basierend auf verschiedenen Faktoren, einschließlich BED mit α/β-Verhältnissen von 15 Gy (Lungenmetastasen), 21 Gy (primäre Lungentumoren) und 27 Gy (Lebermetastasen).

Ergebnisse

Die mediane Nachbeobachtungszeit betrug 10,4 Monate (2,0–59,0 Monate). Die 2‑Jahres-LK betrug 100 und 86,4 % für primäre Lungentumoren im Früh- bzw. fortgeschrittenen Stadium, 100 % für Lungenmetastasen, 82,2 % für Lebermetastasen und 90 % für extrapulmonale, extrahepatische Metastasen. Die 2‑Jahres-GÜ-Rate über alle Patienten betrug 47,9 %. In der uni- und multivariaten Analyse wurde die LK vor allem durch eine zur üblichen Praxis vergleichsweise niedrige PTV-Verschreibungsdosis (äquivalent zu 3‑mal 12–13 Gy) sowie durch höhere mittlere GTV-Dosen (äquivalent zu 3‑mal 18 Gy) beeinflusst. Für ein hohes GÜ waren ein hoher Karnofsky-Index (100 %), das Geschlecht (weiblich) und die SBRT ohne gleichzeitige Chemotherapie prognostisch signifikant. Grad-3-Nebenwirkungen waren selten (0,5 %).

Schlussfolgerungen

Die robotergeführte EAK-SBRT kann als eine sichere und wirksame Behandlung für solide Tumoren in beweglichen Organen angesehen werden. Für eine ausreichend hohe lokale Kontrollrate sind hohe mittlere GTV-Dosen erforderlich. Weitere prospektive Studien sind nötig, um diese Punkte zu evaluieren.

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Acknowledgements

The authors would kindly thank Rainer Klement (Schweinfurt, Germany) for his helpful comments and discussions on biological effective dose calculation. The authors would also like to thank Prof. Dr. Jost Philipp Schäfer (Kiel, Germany), PD Dr. Peter Hunold (Lübeck, Germany), Dr. Gunnar Gaffke (Güstrow, Germany), Dr. Klaus-Rainer Bogun (Rostock, Germany), Prof. Dr. Norbert Hosten (Greifswald), PD Dr. Nikolaos Tselis (Frankfurt, Germany) and Prof. Thomas Vogl (Frankfurt, Germany) for implanting the fiducials.

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Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany

    Susanne Stera MD, Panagiotis Balermpas MD, Christian Keller MD, Detlef Imhoff & Claus Rödel MD

  2. Saphir Radiosurgery Center, Frankfurt, Germany

    Panagiotis Balermpas MD, Christian Keller MD & Oliver Blanck PhD

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

    Mark K. H. Chan PhD, Jürgen Dunst MD & Oliver Blanck PhD

  4. Saphir Radiosurgery Center, Güstrow, Germany

    Stefan Huttenlocher MD, Stefan Wurster MD & Oliver Blanck PhD

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

    Stefan Wurster MD

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

    Dirk Rades MD

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

    Jürgen Dunst MD

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

    Guido Hildebrandt MD

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  1. Susanne Stera MD
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  2. Panagiotis Balermpas MD
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  12. Oliver Blanck PhD
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Corresponding author

Correspondence to Susanne Stera MD.

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Conflict of interest

S. Stera, P. Balermpas, M.K.H. Chan, S. Huttenlocher, S. Wurster, C. Keller, D. Imhoff, D. Rades, J. Dunst, C. Rödel, G. Hildebrandt and O. Blanck declare that they have no competing interests.

Ethical standards

This retrospective analysis was approved by the local ethics committee of the medical faculty of the university Frankfurt (477/15), Rostock (A2016-0008) and Lübeck (13–218 A).

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Stera, S., Balermpas, P., Chan, M.K.H. et al. Breathing-motion-compensated robotic guided stereotactic body radiation therapy. Strahlenther Onkol 194, 143–155 (2018). https://doi.org/10.1007/s00066-017-1204-z

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