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Iodine-125 brachytherapy as upfront and salvage treatment for brain metastases

A comparative analysis

Jod-125-Brachytherapie als Primär- und Rezidivtherapie von intrakraniellen Metastasen

Eine Vergleichsstudie

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Abstract

Background

Outcome and toxicity profiles of salvage stereotactic ablative radiation strategies for recurrent pre-irradiated brain metastases are poorly defined. This study compared risk–benefit profiles of upfront and salvage iodine-125 brachytherapy (SBT) for small brain metastases. As the applied SBT treatment algorithm required histologic proof of metastatic brain disease in all patients, we additionally aimed to elucidate the value of biopsy before SBT.

Patients and methods

Patients with small untreated (n = 20) or pre-irradiated (n =28) suspected metastases intended for upfront or salvage SBT, respectively, were consecutively included. Temporary iodine-125 implants were used (median reference dose: 50 Gy, median dose rate: 15 cGy/h). Cumulative biologically effective doses (BED) were calculated and used for risk assessment. Treatment toxicity was classified according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria.

Results

Upfront SBT was initiated in 20 patients and salvage SBT in 23. In 5 patients, salvage SBT was withheld because of proven radiation-induced lesions. Treatment groups exhibited similar epidemiologic data except for tumor size (which was slightly smaller in the salvage group). One-year local/distant tumor control rates after upfront and salvage SBT were similar (94 %/65 % vs. 87 %/57 %, p = 0.45, respectively). Grade I/II toxicity was suffered by 2 patients after salvage SBT (cumulative BED: 192.1 Gy3 and 249.6 Gy3). No toxicity-related risk factors were identified.

Conclusion

SBT combines diagnostic yield with effective treatment in selected patients. The low toxicity rate in the salvage group points to protective radiobiologic characteristics of continuous low-dose rate irradiation. Upfront and salvage SBT are similarly effective and safe. Histologic reevaluation should be reconsidered after previous radiotherapy to avoid under- or overtreatment.

Zusammenfassung

Hintergrund

Daten zu Risiko und Effizienz ablativer stereotaktischer Rebestrahlungsstrategien zerebraler Metastasen sind kaum publiziert worden. Wir verglichen Risiko-Effizienz-Profile der Jod-125 Brachytherapie (SBT) als Primärtherapie kleiner Metastasen und als Rezidivtherapie nach vorausgegangener Bestrahlung. Voraussetzung für eine SBT war immer eine histologische Sicherung der Diagnose. Dieses einheitliche Vorgehen erlaubte, zusätzlich den Stellenwert bioptischer Verfahren zu analysieren.

Patienten und Methoden

Patienten mit kleinen unbehandelten (n = 20) oder vorbestrahlen (n = 28) metastasensuspekten Läsionen wurden konsekutiv eingeschlossen. Implantiert wurden temporäre Jod-125-Seeds (mediane Referenzdosis: 50 Gy, mediane Energiedosisleistung: 15 cGy/h). Für Risikoanalysen berechneten wir die kumulative biologische effektive Dosis (BED). Die Klassifikation der Neurotoxizität erfolgte entsprechend den Kriterien der RTOG/EORTC (Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer).

Ergebnisse

SBT als Initialtherapie wurde bei 20 Patienten und als Rezidivtherapie bei 23 Patienten durchgeführt. Fünf Patienten der Rezidivgruppe wiesen radiogene Gewebsveränderungen auf, sodass keine Behandlung erfolgte. Patienten mit Primär- und Rezidivtherapie waren bezüglich ihrer klinischen Parameter mit Ausnahme des Tumorvolumens vergleichbar (geringfügig kleinere Tumoren in der Rezidivgruppe). Die lokale/distante Einjahrestumorkontrollrate nach Primär- und Rezidiv-SBT war ähnlich (94 %/64 % vs. 87 %/57 %, p = 0,45). Eine Toxizität vom Grad I/II fand sich bei 2 Patienten (kumulative BED: 192,1 Gy3 und 249,6 Gy3).

Schlussfolgerung

SBT verbindet diagnostische Genauigkeit mit effektiver Behandlung. Die niedrige Toxizitätsrate unterstreicht die protektiven radiobiologischen Eigenschaften kontinuierlicher Bestrahlung mit niedriger Energiedosisleistung. SBT als Primär- und Rezidivtherapie ist sicher und effektiv. Die Indikation zur histologischen Reevaluation sollte nach vorausgegangener Bestrahlung immer erwogen werden, um Unter- oder Überbehandlungen zu vermeiden.

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Authors and Affiliations

  1. Department of Neurosurgery, Ludwig-Maximilians-University, Marchioninistr. 15, 81377, Munich, Germany

    Alexander Romagna MD, Christoph Schwartz MD, Jörg-Christian Tonn MD & Friedrich-Wilhelm Kreth MD

  2. Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany

    Rupert Egensperger MD

  3. Department of Radiation-Oncology, Ludwig-Maximilians-University, Munich, Germany

    Juliana Watson, Claus Belka MD & Silke Birgit Nachbichler MD

Authors
  1. Alexander Romagna MD
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  2. Christoph Schwartz MD
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  3. Rupert Egensperger MD
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  4. Juliana Watson
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  5. Jörg-Christian Tonn MD
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  6. Claus Belka MD
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  7. Friedrich-Wilhelm Kreth MD
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  8. Silke Birgit Nachbichler MD
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Corresponding author

Correspondence to Friedrich-Wilhelm Kreth MD.

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Conflict of interest

A. Romagna, C. Schwartz, R. Egensperger, J. Watson, J.-C. Tonn, C. Belka, F.-W. Kreth, and S.B. Nachbichler report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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). Informed consent was obtained from all patients included in studies.

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Romagna, A., Schwartz, C., Egensperger, R. et al. Iodine-125 brachytherapy as upfront and salvage treatment for brain metastases. Strahlenther Onkol 192, 780–788 (2016). https://doi.org/10.1007/s00066-016-1009-5

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  • DOI: https://doi.org/10.1007/s00066-016-1009-5

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