Clinical trial NCT02353000: Whole Brain Radiotherapy (WBRT) Versus Stereotactic Radiosurgery (SRS) for 4 Upto 10 Brain Metastases
Official title: Whole Brain Radiotherapy vs. Stereotactic Radiosurgery for 4 - 10 Brain Metastases:a Phase III Randomized Multicenter Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Neoplasm Metastasis
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
First posted: 2015-02-02
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Recently stereotactic radiosurgery (SRS) in 5 up to 10 brain metastases showed to have equal survival as in 2 up to 4 brain metastases. Whole brain radiotherapy (WBRT) is currently the gold standard for patients with more than 3 brain metastases, but has significant side effects. In this prospective randomized phase III trial WBRT is compared to SRS for patients with 4 up to 10 BM.

Detailed description: Dutch guideline advices stereotactic radiosurgery (SRS) for patients with 1 up to 3 brain metastases (BM) and whole brain radiotherapy (WBRT) for patients with 4 or more BM. The interim analysis from the QUARTZ study showed that WBRT did not provide benefit in quality of life nor survival over best supportive care. WBRT has significant side effects, such as hair loss, fatigue, and cognitive dysfunction which may impair quality of life. A recently published study showed that SRS in patients with 5 up to 10 BM had a comparable survival to patients treated with 2 up to 4 BM. Many systemic therapies do not have a satisfactory intracranial response, because of the blood-brain barrier. The potential advantages of SRS i.e, limiting radiation doses to the uninvolved brain and a high rate of local tumour control by just a single treatment. Next logic step would be to compare WBRT with SRS alone in patients with 4-10 BM and evaluate whether SRS is superior to WBRT with regard to QOL.

Eligibility criteria: Inclusion Criteria:

* Minimal 4 up to a maximum of 10 BM on diagnostic MRI scan
* Max diameter of single GTV 2.5cm
* Max cumulative GTV of 30cm3
* Karnofsky performance status ≥ 70
* Any solid primary tumour. Small cell lung carcinoma, germinoma, and lymphoma are excluded
* Ability to provide written informed consent

Exclusion Criteria:

* Contra-indication for MRI
* Prior treatment for BM (i.e. surgery, SRS or WBRT)
* Concurrent use of systemic therapy
* Maximum cumulative GTV of more than 30cm3 on planning-MRI
* More than 10 BM on planning-MRI
* A brainstem metastasis with a PTV of more than 20 cm3

Primary outcomes:
measure: Quality of life in patients with 4 - 10 brain metastases comparing WBRT and SRS
timeFrame: Change in quality of life measured from baseline to 3 months after radiotherapy
Secondary outcomes:
measure: Overall survival steroid use (mg), toxicity including hair loss and fatigue.
timeFrame: 1 year
measure: Time that patient is functioning independently (Karnofsky ≥ 70)
timeFrame: Change in Karnofsky index from baseline to 3 months after radiotherapy
measure: Steroid use
timeFrame: Change in steroid use from baseline to 3 months after radiotherapy
measure: Toxicity measured by hair loss and fatigue
timeFrame: Change in toxicity from baseline to 3 months after radiotherapy
measure: Degree of independence
timeFrame: Change in independence from baseline to 3 months after radiotherapy
Other outcomes:
measure: Brain salvage during follow-up
timeFrame: 1 year
measure: Verbal learning
timeFrame: Change in verbal recall and verbal recognition from baseline to 3 months after radiotherapy
measure: Quality of life of cancer patients
timeFrame: Change in Quality of life from baseline to 3 months after radiotherapy
measure: Quality of life of cancer patients with brain neoplasms
timeFrame: Change in Quality of life from baseline to 3 months after radiotherapy
measure: Quality of life of cancer patients measuring cancer-related fatigue
timeFrame: Change in Quality of life from baseline to 3 months after radiotherapy
Locations:
city: Amsterdam
country: Netherlands
facility: VUmc
city: Amsterdam
country: Netherlands
facility: AMC
city: Den Haag
country: Netherlands
facility: Haaglanden MC
city: Maastricht
country: Netherlands
facility: Maastricht Radiation Oncology (MAASTRO clinic)
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Tilburg
country: Netherlands
facility: Instituut Verbeeten
city: Vlissingen
country: Netherlands
facility: ZRTI
Study officials:
affiliation: Maastro Clinic, The Netherlands
name: Philippe Lambin, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gijtenbeek JM, Ho VK, Heesters MA, Lagerwaard FJ, de Graeff A, Boogerd W. [Practice guideline 'Brain metastases' (revision)]. Ned Tijdschr Geneeskd. 2011;155(52):A4141. Dutch.
citation: Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Takanashi M, Mori Y, Takakura K, Saeki N, Kunieda E, Aoyama H, Momoshima S, Tsuchiya K. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014 Apr;15(4):387-95. doi: 10.1016/S1470-2045(14)70061-0. Epub 2014 Mar 10.
citation: Zindler JD, Rodrigues G, Haasbeek CJ, De Haan PF, Meijer OW, Slotman BJ, Lagerwaard FJ. The clinical utility of prognostic scoring systems in patients with brain metastases treated with radiosurgery. Radiother Oncol. 2013 Mar;106(3):370-4. doi: 10.1016/j.radonc.2013.01.015. Epub 2013 Mar 20.
citation: Langley RE, Stephens RJ, Nankivell M, Pugh C, Moore B, Navani N, Wilson P, Faivre-Finn C, Barton R, Parmar MK, Mulvenna PM; QUARTZ Investigators. Interim data from the Medical Research Council QUARTZ Trial: does whole brain radiotherapy affect the survival and quality of life of patients with brain metastases from non-small cell lung cancer? Clin Oncol (R Coll Radiol). 2013 Mar;25(3):e23-30. doi: 10.1016/j.clon.2012.11.002. Epub 2012 Dec 2.
citation: Hartgerink D, Bruynzeel A, Eekers D, Swinnen A, Hurkmans C, Wiggenraad R, Swaak-Kragten A, Dieleman E, van der Toorn PP, van Veelen L, Verhoeff JJC, Lagerwaard F, de Ruysscher D, Lambin P, Zindler J. Quality of life among patients with 4 to 10 brain metastases after treatment with whole-brain radiotherapy vs. stereotactic radiotherapy: a phase III, randomized, Dutch multicenter trial. Ann Palliat Med. 2022 Apr;11(4):1197-1209. doi: 10.21037/apm-21-1545. Epub 2021 Nov 18.
citation: Zindler JD, Bruynzeel AME, Eekers DBP, Hurkmans CW, Swinnen A, Lambin P. Whole brain radiotherapy versus stereotactic radiosurgery for 4-10 brain metastases: a phase III randomised multicentre trial. BMC Cancer. 2017 Jul 25;17(1):500. doi: 10.1186/s12885-017-3494-z.