Whole Brain Radiotherapy (WBRT) Versus Stereotactic Radiosurgery (SRS) for 4 Upto 10 Brain Metastases

Overview

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.

Full Title of Study: “Whole Brain Radiotherapy vs. Stereotactic Radiosurgery for 4 – 10 Brain Metastases:a Phase III Randomized Multicenter Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2019

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.

Interventions

  • Radiation: Stereotactic Radiosurgery
    • Stereotactic Radiosurgery for patients with 4 up to 10 brain metastases
  • Radiation: Whole Brain Radiotherapy
    • Whole Brain Radiotherapy for patients with 4 up to 10 brain metastases

Arms, Groups and Cohorts

  • Experimental: Stereotactic Radiosurgery
    • Stereotactic Radiosurgery for patients with 4 up to 10 brain metastases:
  • Other: Whole Brain Radiotherapy
    • Whole Brain Radiotherapy for patients with 4 up to 10 brain metastases:

Clinical Trial Outcome Measures

Primary Measures

  • Quality of life in patients with 4 – 10 brain metastases comparing WBRT and SRS
    • Time Frame: Change in quality of life measured from baseline to 3 months after radiotherapy
    • Quality of life is measured by the EQ-5D-5L, a descriptive system of health-related quality of life states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression)

Secondary Measures

  • Overall survival steroid use (mg), toxicity including hair loss and fatigue.
    • Time Frame: 1 year
    • Overall survival
  • Time that patient is functioning independently (Karnofsky ≥ 70)
    • Time Frame: Change in Karnofsky index from baseline to 3 months after radiotherapy
    • Time that patient is functioning independently (Karnofsky ≥ 70)
  • Steroid use
    • Time Frame: Change in steroid use from baseline to 3 months after radiotherapy
    • Steroid use in mg over time
  • Toxicity measured by hair loss and fatigue
    • Time Frame: Change in toxicity from baseline to 3 months after radiotherapy
    • Toxicity measured by hair loss and fatigue using CTCAE version 4.0
  • Degree of independence
    • Time Frame: Change in independence from baseline to 3 months after radiotherapy
    • Degree of independence of patients using the Barthel index

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Maastricht Radiation Oncology
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Philippe Lambin, Prof. Dr., Principal Investigator, Maastro Clinic, The Netherlands

Citations Reporting on Results

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.

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.

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.

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.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.