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Retrospective analysis of linac-based radiosurgery for arteriovenous malformations and testing of the Flickinger formula in predicting radiation injury

Retrospektive Analyse linacbasierter Radiochirurgie bei arteriovenösen Fehlbildungen und Erprobung der Flickinger-Formel zur Vorhersage von Strahlenschäden

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Abstract

Background and purpose

The aim of the study was to validate the use of linac-based radiosurgery in arteriovenous malformation (AVM) patients and to predict complications using an integrated logistic formula (ILF) in comparison with clinical outcomes.

Patients and methods

The results of radiosurgery in 92 AVM patients were examined. All patients were treated with linac-based radiosurgery. Of these, 70 patients were followed for 12–45 months (median, 24 months) and were analyzed. The treated volume varied from 0.09 to 26.95 cm³ (median, 2.3 cm³) and the median marginal dose was 20 Gy (range, 10.4–22). The median 12-Gy volume was 9.94 cm³ (range, 0.74–60.09 cm³). Patients and lesion characteristics potentially affecting nidus obliteration and excellent outcome were evaluated by performing a log-rank test and univariate and multivariate analyses. The risk for radiation injury (RRI) was calculated with an integrated logistic formula. The predictive power of the RRI was assessed by calculating the area under the receiver operating characteristic (ROC) curve.

Results

Follow-up magnetic resonance (MR) angiography revealed complete AVM obliteration in 56 of 70 patients. The MR angiography confirmed an obliteration rate of 80%. The annual hemorrhage rate was 1.4% for the first 2 years after radiosurgery and 0% thereafter. The number of patients with an excellent outcome was 48 (68%). Factors associated with better obliteration were higher radiation dose to the lesion margins [12-Gy volume (V12) >10 cm³], small volume, and a Pollock-Flickinger score less than 1.49; those predicting excellent outcomes were V12<10 cm³, small volume, and Pollock-Flickinger score less than 1.49, as determined by multivariate analyses. Factors associated with radiation injury were V12>10 cm³ (p=0.03) and volume greater than 2 cm³ (p=0.001), as determined by a univariate analysis. The analyses showed an ROC of 0.66.

Conclusion

These data suggest that linac-based radiosurgery is effective. In terms of obliteration, excellent outcomes, and especially radiation injury, V12 and volume should be considered. The Flickinger formula seems to be applicable to Novalis-treated patients, but long-term follow-up is necessary for definite conclusions.

Zusammenfassung

Hintergrund und Zielsetzung

Das Ziel der Studie war es, die Verwendung der auf einem Linearbeschleuniger („“linear accelerator“, Linac) basierten Radiochirurgie bei Patienten mit arteriovenösen Malformationen (AVM) zu evaluieren und eine Vorhersage von Komplikationen mittels einer integrierten Logistikformel (ILF) im Vergleich mit klinischen Ergebnissen zu treffen.

Patienten und Methoden

Die Ergebnisse der Radiochirurgie bei 92 AVM-Patienten wurden untersucht. Alle Patienten wurden mit linacbasierter Radiochirurgie behandelt. Von diesen wurde bei 70 Patienten für 12–45 Monate (Median: 24) der Verlauf verfolgt und analysiert. Das behandelte Volumen variierte zwischen 0,09 und 26,95 cm3 (Median: 2,3 cm3) und die mittlere marginale Dosis betrug 20 Gy (Bereich: 10,4–22). Das mittlere 12-Gy-Volumen betrug 9,94 cm3 (Bereich: 0,74–60,09). Patienten- und Läsionenseigenschaften, die möglicherweise die Nidusauflösung und ein exzellentes Ergebnis beeinträchtigt haben, wurden mittels eines Log-Rank-Tests sowie univariater und multivariater Analysen ausgewertet. Das Risiko für Strahlenschäden (RRI) wurde mit einer ILF berechnet. Die Vorhersagekraft des RRI wurde durch Berechnung der Fläche unter der Receiver-Operating-Characteristic-(ROC)-Kurve beurteilt.

Ergebnisse

Die Nachsorge-Magnetresonanztomographie(MR)-Angiographie ergab eine vollständige AVM-Auflösung bei 56 von 70 Patienten. Die MR-angiographisch bestätigte Auflösung betrug 80%. Die jährliche Blutungsrate betrug während der ersten 2 Jahre nach Radiochirurgie 1,4% und danach null. Ein ausgezeichnetes Ergebnis wurde bei 48 Patienten (68%) erzielt. Die multivariate Analyse zeigte, dass folgende Faktoren mit einer besseren AVM-Auflösung assoziiert waren: höhere Strahlendosis auf den Läsionsgrenzen [12-Gy-Volumen (V12) >10 cm3], kleines Volumen, und Pollock-Flickinger-Score <1,49. Faktoren, die mit einem exzellenten Ergebnis in der multivariate Analyse assoziiert waren, waren ein V12 <10 cm3, ein kleines Volumen und ein Pollock-Flickinger-Score <1,49. Ein V12 >10 cm3 (p=0,03) und ein Volumen >2 cm3 (p=0,001) waren in einer univariaten Analyse mit Strahlenschäden assoziiert. Die Analysen zeigten eine ROC von 0,66.

Schlussfolgerung

Diese Daten lassen vermuten, dass linacbasierte Radiochirurgie wirksam ist. In Bezug auf die AVM-Auflösung, ein exzellentes Resultat und vor allem in Bezug auf Strahlenschäden zeigte sich, dass V12 und das Volumen evaluiert werden sollten. Die Flickinger-Formel scheint auf Patienten mit einer Novalis-Behandlung anwendbar zu sein. Jedoch ist eine Langzeituntersuchung für eine endgültige Beurteilung notwendig.

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On behalf of all authors, the corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology and Neurosurgery, Universitair Ziekenhuis Brussel, Brussels, Belgium

    I.A. Cetin, R. Ates, J. Dhaens & G. Storme

  2. Department of Radiation Oncology, Marmara University, Fevzı cakmak mah. Inonu cad. No:41, 34903, Ustkaynarca/Pendik, Turkey

    I.A. Cetin

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  1. I.A. Cetin
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Cetin, I., Ates, R., Dhaens, J. et al. Retrospective analysis of linac-based radiosurgery for arteriovenous malformations and testing of the Flickinger formula in predicting radiation injury. Strahlenther Onkol 188, 1133–1138 (2012). https://doi.org/10.1007/s00066-012-0180-6

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