A Dutch phase III randomized multicenter trial: Whole brain radiotherapy versus stereotactic radiotherapy for 4-10 brain metastases

Dianne Hartgerink; Anna Bruynzeel; Danielle Eekers; Ans Swinnen; Coen Hurkmans; Ruud Wiggenraad; Annemarie Swaak-Kragten; Edith Dieleman; Peter Paul Van Der Toorn; Bing Oei; Lieneke Van Veelen; Joost Verhoeff; Frank Lagerwaard; Dirk De Ruysscher; Philippe Lambin; Jaap Zindler

doi:10.1093/noajnl/vdab021

A Dutch phase III randomized multicenter trial: Whole brain radiotherapy versus stereotactic radiotherapy for 4-10 brain metastases

Dianne Hartgerink, Anna Bruynzeel, Danielle Eekers, Ans Swinnen, Coen Hurkmans, Ruud Wiggenraad, Annemarie Swaak-Kragten, Edith Dieleman, Peter Paul Van Der Toorn, Bing Oei, Lieneke Van Veelen, Joost Verhoeff, Frank Lagerwaard, Dirk De Ruysscher, Philippe Lambin, Jaap Zindler^*

^*Corresponding author for this work

Radiotherapy

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background. The clinical value of whole brain radiotherapy (WBRT) for brain metastases (BM) is a matter of debate due to the significant side effects involved. Stereotactic radiosurgery (SRS) is an attractive alternative treatment option that may avoid these side effects and improve local tumor control. We initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS compared with WBRT in patients with multiple brain metastases. Methods. Patients with 4-10 BM were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). The primary endpoint was the difference in quality of life (QOL) at 3 months post-treatment. Results. The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions were 6 (range: 4-9) and the median total treatment volume was 13.0 cc3 (range: 1.8-25.9 cc3). QOL at 3 months decreased in the SRS group by 0.1 (SD = 0.2), compared to 0.2 (SD = 0.2) in the WBRT group (P = .23). The actuarial 1-year survival rates were 57% (SRS) and 31% (WBRT) (P = .52). The actuarial 1-year brain salvage-free survival rates were 50% (SRS) and 78% (WBRT) (P = .22). Conclusion. In patients with 4-10 BM, SRS alone resulted in 1-year survival for 57% of patients while maintaining quality of life. Due to the premature closure of the trial, no statistically significant differences could be determined.

Original language	English
Article number	vdab021
Journal	Neuro-Oncology Advances
Volume	3
Issue number	1
DOIs	https://doi.org/10.1093/noajnl/vdab021
Publication status	Published - 1 Jan 2021

Bibliographical note

Funding Information:
The funders provided financial support but had no other role in the study design, data collection, analysis, interpretation, or writing of the report. The MAASTRO Clinic has a research agreement with Varian Medial Systems, Palo Alto in which funding was provided for this trial. Varian was not involved in writing the study protocol or manuscript, the storage of data, nor the analysis of data. The Data Center was responsible for the collection and maintenance of the data. The authors acknowledge financial support from the Dutch Technology Foundation STW (grant n° 10696 DuCAT), which is the applied science division of NWO, and the Technology Programme of the Ministry of Economic Affairs. The authors also acknowledge financial support from the EU 7th framework program (ARTFORCE - n° 257144, REQUITE - n° 601826), SME Phase 2 (RAIL – n°673780), the European Program H2020-PHC-2015 (BD2decide - n°210274050), and Kankeronderzoekfonds Limburg from the Limburg Health Foundation. The corresponding author and principal investigator of the study had full access to all the data and final responsibility.

Publisher Copyright:
© The Author(s) 2021.

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A Dutch phase III randomized multicenter trial, whole brain radiotherapy versus stereotactic radiotherapy for 4–10 brain metastasesFinal published version, 306 KBLicence: CC BY-NC

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Hartgerink, D., Bruynzeel, A., Eekers, D., Swinnen, A., Hurkmans, C., Wiggenraad, R., Swaak-Kragten, A., Dieleman, E., Van Der Toorn, P. P., Oei, B., Van Veelen, L., Verhoeff, J., Lagerwaard, F., De Ruysscher, D., Lambin, P., & Zindler, J. (2021). A Dutch phase III randomized multicenter trial: Whole brain radiotherapy versus stereotactic radiotherapy for 4-10 brain metastases. Neuro-Oncology Advances, 3(1), Article vdab021. https://doi.org/10.1093/noajnl/vdab021

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title = "A Dutch phase III randomized multicenter trial: Whole brain radiotherapy versus stereotactic radiotherapy for 4-10 brain metastases",

abstract = "Background. The clinical value of whole brain radiotherapy (WBRT) for brain metastases (BM) is a matter of debate due to the significant side effects involved. Stereotactic radiosurgery (SRS) is an attractive alternative treatment option that may avoid these side effects and improve local tumor control. We initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS compared with WBRT in patients with multiple brain metastases. Methods. Patients with 4-10 BM were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). The primary endpoint was the difference in quality of life (QOL) at 3 months post-treatment. Results. The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions were 6 (range: 4-9) and the median total treatment volume was 13.0 cc3 (range: 1.8-25.9 cc3). QOL at 3 months decreased in the SRS group by 0.1 (SD = 0.2), compared to 0.2 (SD = 0.2) in the WBRT group (P = .23). The actuarial 1-year survival rates were 57% (SRS) and 31% (WBRT) (P = .52). The actuarial 1-year brain salvage-free survival rates were 50% (SRS) and 78% (WBRT) (P = .22). Conclusion. In patients with 4-10 BM, SRS alone resulted in 1-year survival for 57% of patients while maintaining quality of life. Due to the premature closure of the trial, no statistically significant differences could be determined. ",

author = "Dianne Hartgerink and Anna Bruynzeel and Danielle Eekers and Ans Swinnen and Coen Hurkmans and Ruud Wiggenraad and Annemarie Swaak-Kragten and Edith Dieleman and {Van Der Toorn}, {Peter Paul} and Bing Oei and {Van Veelen}, Lieneke and Joost Verhoeff and Frank Lagerwaard and {De Ruysscher}, Dirk and Philippe Lambin and Jaap Zindler",

note = "Funding Information: The funders provided financial support but had no other role in the study design, data collection, analysis, interpretation, or writing of the report. The MAASTRO Clinic has a research agreement with Varian Medial Systems, Palo Alto in which funding was provided for this trial. Varian was not involved in writing the study protocol or manuscript, the storage of data, nor the analysis of data. The Data Center was responsible for the collection and maintenance of the data. The authors acknowledge financial support from the Dutch Technology Foundation STW (grant n° 10696 DuCAT), which is the applied science division of NWO, and the Technology Programme of the Ministry of Economic Affairs. The authors also acknowledge financial support from the EU 7th framework program (ARTFORCE - n° 257144, REQUITE - n° 601826), SME Phase 2 (RAIL – n°673780), the European Program H2020-PHC-2015 (BD2decide - n°210274050), and Kankeronderzoekfonds Limburg from the Limburg Health Foundation. The corresponding author and principal investigator of the study had full access to all the data and final responsibility. Publisher Copyright: {\textcopyright} The Author(s) 2021.",

year = "2021",

month = jan,

day = "1",

doi = "10.1093/noajnl/vdab021",

language = "English",

volume = "3",

journal = "Neuro-Oncology Advances",

issn = "2632-2498",

publisher = "Oxford University Press",

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Hartgerink, D, Bruynzeel, A, Eekers, D, Swinnen, A, Hurkmans, C, Wiggenraad, R, Swaak-Kragten, A, Dieleman, E, Van Der Toorn, PP, Oei, B, Van Veelen, L, Verhoeff, J, Lagerwaard, F, De Ruysscher, D, Lambin, P & Zindler, J 2021, 'A Dutch phase III randomized multicenter trial: Whole brain radiotherapy versus stereotactic radiotherapy for 4-10 brain metastases', Neuro-Oncology Advances, vol. 3, no. 1, vdab021. https://doi.org/10.1093/noajnl/vdab021

TY - JOUR

T1 - A Dutch phase III randomized multicenter trial

T2 - Whole brain radiotherapy versus stereotactic radiotherapy for 4-10 brain metastases

AU - Hartgerink, Dianne

AU - Bruynzeel, Anna

AU - Eekers, Danielle

AU - Swinnen, Ans

AU - Hurkmans, Coen

AU - Wiggenraad, Ruud

AU - Swaak-Kragten, Annemarie

AU - Dieleman, Edith

AU - Van Der Toorn, Peter Paul

AU - Oei, Bing

AU - Van Veelen, Lieneke

AU - Verhoeff, Joost

AU - Lagerwaard, Frank

AU - De Ruysscher, Dirk

AU - Lambin, Philippe

AU - Zindler, Jaap

N1 - Funding Information: The funders provided financial support but had no other role in the study design, data collection, analysis, interpretation, or writing of the report. The MAASTRO Clinic has a research agreement with Varian Medial Systems, Palo Alto in which funding was provided for this trial. Varian was not involved in writing the study protocol or manuscript, the storage of data, nor the analysis of data. The Data Center was responsible for the collection and maintenance of the data. The authors acknowledge financial support from the Dutch Technology Foundation STW (grant n° 10696 DuCAT), which is the applied science division of NWO, and the Technology Programme of the Ministry of Economic Affairs. The authors also acknowledge financial support from the EU 7th framework program (ARTFORCE - n° 257144, REQUITE - n° 601826), SME Phase 2 (RAIL – n°673780), the European Program H2020-PHC-2015 (BD2decide - n°210274050), and Kankeronderzoekfonds Limburg from the Limburg Health Foundation. The corresponding author and principal investigator of the study had full access to all the data and final responsibility. Publisher Copyright: © The Author(s) 2021.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Background. The clinical value of whole brain radiotherapy (WBRT) for brain metastases (BM) is a matter of debate due to the significant side effects involved. Stereotactic radiosurgery (SRS) is an attractive alternative treatment option that may avoid these side effects and improve local tumor control. We initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS compared with WBRT in patients with multiple brain metastases. Methods. Patients with 4-10 BM were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). The primary endpoint was the difference in quality of life (QOL) at 3 months post-treatment. Results. The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions were 6 (range: 4-9) and the median total treatment volume was 13.0 cc3 (range: 1.8-25.9 cc3). QOL at 3 months decreased in the SRS group by 0.1 (SD = 0.2), compared to 0.2 (SD = 0.2) in the WBRT group (P = .23). The actuarial 1-year survival rates were 57% (SRS) and 31% (WBRT) (P = .52). The actuarial 1-year brain salvage-free survival rates were 50% (SRS) and 78% (WBRT) (P = .22). Conclusion. In patients with 4-10 BM, SRS alone resulted in 1-year survival for 57% of patients while maintaining quality of life. Due to the premature closure of the trial, no statistically significant differences could be determined.

AB - Background. The clinical value of whole brain radiotherapy (WBRT) for brain metastases (BM) is a matter of debate due to the significant side effects involved. Stereotactic radiosurgery (SRS) is an attractive alternative treatment option that may avoid these side effects and improve local tumor control. We initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS compared with WBRT in patients with multiple brain metastases. Methods. Patients with 4-10 BM were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). The primary endpoint was the difference in quality of life (QOL) at 3 months post-treatment. Results. The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions were 6 (range: 4-9) and the median total treatment volume was 13.0 cc3 (range: 1.8-25.9 cc3). QOL at 3 months decreased in the SRS group by 0.1 (SD = 0.2), compared to 0.2 (SD = 0.2) in the WBRT group (P = .23). The actuarial 1-year survival rates were 57% (SRS) and 31% (WBRT) (P = .52). The actuarial 1-year brain salvage-free survival rates were 50% (SRS) and 78% (WBRT) (P = .22). Conclusion. In patients with 4-10 BM, SRS alone resulted in 1-year survival for 57% of patients while maintaining quality of life. Due to the premature closure of the trial, no statistically significant differences could be determined.

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U2 - 10.1093/noajnl/vdab021

DO - 10.1093/noajnl/vdab021

M3 - Article

C2 - 33738451

AN - SCOPUS:85119257189

SN - 2632-2498

VL - 3

JO - Neuro-Oncology Advances

JF - Neuro-Oncology Advances

IS - 1

M1 - vdab021

ER -

A Dutch phase III randomized multicenter trial: Whole brain radiotherapy versus stereotactic radiotherapy for 4-10 brain metastases

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