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Linac-based radiosurgery or fractionated stereotactic radiotherapy with flattening filter-free volumetric modulated arc therapy in elderly patients

A mono-institutional experience on 110 brain metastases

Linac-basierte Radiochirurgie oder fraktionierte stereotaktische Strahlentherapie mit flattening-filter-freier volumenmodulierter Rotationsbestrahlung bei älteren Patienten

Eine monoinstitutionelle Erfahrung bei 110 Hirnmetastasen

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Abstract

Aim

The aim of this study was to analyze the feasibility and clinical results of linear accelerator (linac-)based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SFRT) with flattening filter-free (FFF) volumetric modulated arc therapy (VMAT) in elderly patients affected by brain metastases (BMs).

Patients and methods

Patients selected for the present analysis were ≥65 years old with a life expectancy of >3 months, a controlled or synchronous primary tumor, and <10 BMs with a diameter <3 cm. All patients were treated with FFF linac-based SRS/SFRT. The prescribed total dose (15–30 Gy/1–5 fractions) was based on BM size and proximity to organs at risk (OAR). Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. MedCalc v18.2 (MedCalc Software, Ostend, Belgium) was used for statistical analysis.

Results

From April 2014 to December 2017, 40 elderly patients with 110 BMs were treated by FFF linac-based SRS/SFRT. With a median follow-up of 28 months (range 6–50 months), median and 1‑year overall survival were 9 months and 39%, respectively; median intracranial progression-free survival was 6 months. At the time of the analysis, local control was reported in 109/110 BMs (99.1%): 12 BMs had a complete response; 51 a partial response; 46 showed stable disease. One BM (0.9%) progressed after 2 months. BM volume (<1 cc) and higher SRS/SFRT dose correlated to treatment response (p = 0.01 and p = 0.0017, respectively). No adverse events higher than grade 2 were observed.

Conclusion

The present findings highlight the feasibility, safety, and effectiveness of FFF linac-based SRS/SFRT in elderly patients with BMs.

Zusammenfassung

Hintergrund

Ziel der Studie ist es, die Machbarkeit und erste klinische Ergebnisse einer linearbeschleuniger-(linac-)basierten stereotaktischen Radiochirurgie (SRS) oder fraktionierten stereotaktischen Strahlentherapie (SFRT) mit flattening-filter-freier (FFF) volumenmodulierter Rotationsbestrahlung (VMAT) für ältere Patienten mit Hirnmetastasen (HM) zu analysieren.

Materialien und Methoden

Für die vorliegende Analyse wurden Patienten mit einem Alter >65 Jahren und einer Lebenserwartung von >3 Monaten bei kontrolliertem oder synchronem Primärtumor ausgewählt, die bei <10 HM mit einem Durchmesser <3 cm mit FFF linac-basierter SRS/SFRT behandelt wurden. Die applizierte Gesamtdosis (15–30 Gy/1–5 Fraktionen) war von der Größe der HM sowie deren Lage zu Risikoorganen abhängig. Für jeden Patienten wurde ein FFF-VMAT-Plan erstellt. Die Toxizität wurde nach den Common Terminology Criteria for Adverse Events (CTCAE) v4.0 bewertet. MedCalc v18.2 (MedCalc Software, Ostend, Belgien) wurde für die statistische Analyse verwendet.

Ergebnisse

Von April 2014 bis Dezember 2017 wurden 40 ältere Patienten mit 110 HM mit FFF linac-basierter SRS/SFRT behandelt. Bei einer medianen Nachbeobachtungszeit von 28 Monaten (Spanne 6–50 Monate) betrug das mediane und 1‑Jahres-Gesamtüberleben 9 Monate bzw. 39 % und das mediane intrakranielle progressionsfreie Überleben 6 Monate. Zum Zeitpunkt der Analyse waren 109/110 HM (99,1 %) lokal kontrolliert: 12 HM hatten eine vollständige Remission, 51 eine partielle Remission und 46 eine stabile Erkrankung. Eine HM (0,9 %) hatte nach 2 Monaten einen lokalen Progress. Das Volumen der HM (<1 cm3) und eine höhere SRS/SFRT-Dosis korrelierten mit dem Therapieansprechen (jeweils p = 0,01 und p = 0,0017). Es wurden keine Nebenwirkungen >Grad 2 beobachtet.

Schlussfolgerung

Die Ergebnisse der Studie bestätigen die Machbarkeit, Sicherheit und Wirksamkeit von FFF linac-basierter SRS/SFRT bei älteren Patienten mit HM.

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Authors and Affiliations

  1. Department of Radiation Oncology, IRCCS, Sacro Cuore Don Calabria Hospital, Via don A. Sempreboni 5, 37024, Negrar, Verona, Italy

    Fabiana Gregucci MD, Alba Fiorentino, Vanessa Figlia, Rosario Mazzola, Francesco Ricchetti, Ruggero Ruggieri & Filippo Alongi

  2. Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany

    Stefanie Corradini

  3. University of Brescia, Piazza del Mercato 15, 25121, Brescia, Italy

    Filippo Alongi

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  1. Fabiana Gregucci MD
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  2. Alba Fiorentino
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  3. Stefanie Corradini
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  4. Vanessa Figlia
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Correspondence to Fabiana Gregucci MD.

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Conflict of interest

F. Gregucci, A. Fiorentino, S. Corradini, V. Figlia, R. Mazzola, F. Ricchetti, R. Ruggieri, and F. Alongi 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.

Additional information

F. Gregucci and A. Fiorentino contributed equally to the manuscript.

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Gregucci, F., Fiorentino, A., Corradini, S. et al. Linac-based radiosurgery or fractionated stereotactic radiotherapy with flattening filter-free volumetric modulated arc therapy in elderly patients. Strahlenther Onkol 195, 218–225 (2019). https://doi.org/10.1007/s00066-018-1405-0

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