Neoadjuvant Stereotactic Radiotherapy for Brain Metastasis (NeoSTROBE)

Neoadjuvant Stereotactic Radiotherapy for Brain Metastasis - Prospective Trial NeoSTROBE

This multicentre proof-of-concept study, involving 4 centers, aims to establish the value of fractionated neoadjuvant stereotactic radiotherapy (NaSRT) as a new treatment paradigm for brain metastases (BM) in the frame of the Czech neurooncology network. Most relevant studies published to date used single-fraction radiotherapy and dealt with the inherent bias related to their retrospective nature. The researchers aim to increase the level of evidence for this treatment paradigm together with other similar ongoing studies.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: Neoadjuvant Stereotactic Radiotherapy (NaSRT); Radiation: Postoperative Stereotactic Radiotherapy (SRT)

Detailed Description

The prospective study will evaluate the efficacy and toxicity of neoadjuvant stereotactic radiotherapy (NaSRT) in patients with brain metastases (BM). Clinical data gathered will include local control (LC), the incidence of leptomeningeal disease (LMD), radiological and clinical signs of radiation necrosis (RN), overall survival, and incidence of metachronous brain metastases. The magnetic resonance imaging (MRI) characteristics of irradiated and subsequently resected BM will be obtained according to the usual protocol and specified time intervals. Clinical monitoring will comprise neurological findings, Karnofsky performance status, and quality of life (FACT-Br/EORTC QLQ-C30 questionnaire and EORTC QLQ-BN20 questionnaire. These questionnaires are designed to measure cancer patients' physical, psychological, and social functions. The questionnaires are composed of multi-item scales and single items). The data obtained from the retrospective control group (estimated for 160 patients) will include the same parameters monitored in the consecutive group of patients who underwent surgery at centers included in our study, with or without adjuvant radiotherapy (RT). Formation of this control group corresponding to the NaSRT group will enable the efficacy and risks of NaSRT to be determined in comparison with established treatment modalities.

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiří Hynčica; Phone Number: 2587 0042059737; Email: jiri.hyncica@fno.cz

Study Locations

• Czechia
  • Brno, Czechia, 65653
    • Recruiting
    • Masaryk Memorial Cancer Institute
    • Contact: Tomáš Kazda, Assoc. Prof., MD, PhD; Phone Number: 0509 0042072544; Email: tomas.kazda@mou.cz
    • Principal Investigator: Tomáš Kazda, Assoc. Prof., MD, PhD
  • Hradec Králové, Czechia, 50005
    • Recruiting
    • University hospital Hradec Králové
    • Contact: Igor Sirák, Assoc. Prof., MD, PhD; Phone Number: 00420608100251; Email: igor.sirak@fnhk.cz
    • Principal Investigator: Igor Sirák, Assoc. Prof., MD, PhD
  • Olomouc, Czechia, 77900
    • Recruiting
    • University Hospital Olomouc
    • Contact: Martin Doležel, prof., MD, PhD; Phone Number: 0111 0042073713; Email: dolezelm@email.cz
    • Principal Investigator: Martin Doležel, prof., MD, PhD
  • Moravian-Silesian Region
    • Ostrava, Moravian-Silesian Region, Czechia, 70852
      • Recruiting
      • University Hospital Ostrava
      • Contact: Jiří Hynčica; Phone Number: 2587 0042059737; Email: jiri.hyncica@fno.cz
      • Principal Investigator: Jakub Cvek, Assoc.Prof.,MD, Ing., PhD, MBA
      • Sub-Investigator: Štefan Reguli, MD, PhD
      • Sub-Investigator: Jana Jackaninová, MD
      • Sub-Investigator: Lukáš Knybel, Ing., PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Karnofsky Performance Status ≥ 60
• Histologically verified primary cancer disease
• MRI findings indicating BM
• Target BM indicated for surgical resection and any other metastases suitable for radical SRT.
• Target BM between 1 cm and 7 cm at the longest diameter on T1 post-contrast MR imaging

Exclusion Criteria:

• Confirmed hematological malignity
• Small-cell (lung) carcinoma
• Peracute condition requiring immediate neurosurgical intervention
• History of whole-brain radiotherapy (WBRT)
• History of stereotactic radiotherapy to a target brain metastasis
• Pregnancy
• Inability to perform surgical resection of the target BM within 7 days after NaSRT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant NaSRT - prospective; Patients undergoing neoadjuvant NaSRT will be enrolled prospectively in this study arm.	Radiation: Neoadjuvant Stereotactic Radiotherapy (NaSRT); Neoadjuvant Stereotactic Radiotherapy (NaSRT) gives radiotherapy before surgery from many different angles around the body. The beams meet at the tumor. This means the tumor receives a high dose of radiation and the tissues around it receive a much lower dose. This lowers the risk of side effects.
Active Comparator: Postoperative SRT - retrospective; Patients who underwent postoperative SRT in the past will be analyzed retrospectively in this study arm.	Radiation: Postoperative Stereotactic Radiotherapy (SRT); Postoperative Stereotactic Radiotherapy (SRT) gives radiotherapy after surgery from many different angles around the body. The beams meet at the tumor. This means the tumor receives a high dose of radiation and the tissues around it receive a much lower dose. This lowers the risk of side effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Toxicity	Acute Toxicity will be assessed in the study subjects according to Common Terminology Criteria for Adverse Events (CTCAE) ver. 5 to 10%.	3 months
Quality of Life Questionnaire (FACT-Br/EORTC QLQ-C30)	Quality of Life will be assessed in the study subjects using the FACT-Br/EORTC QLQ-C30 questionnaire.	3 months
Quality of Life Questionnaire (EORTC QLQ-BN20)	Quality of Life will be assessed in the study subjects using the EORTC QLQ-BN20 questionnaire.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from NaSRT to local progression	Time from NaSRT to local progression will be assessed.	3 years
Time from NaSRT to detection of LMD	Time from NaSRT to detection of LMD will be assessed.	3 years
Time from NaSRT to the onset of RN	Time from NaSRT to the onset of RN will be assessed.	3 years
Time from NaSRT to detection of distant parenchymal metastasis	Time from NaSRT to detection of distant parenchymal metastasis will be assessed.	3 years
Overall Survival	Overall survival from NaSRT to death from any reason will be assessed.	3 years

Collaborators and Investigators

• Sponsor: University Hospital Ostrava
• Collaborators: University Hospital Olomouc; Masaryk Memorial Cancer Institute; University Hospital Hradec Kralove
• Investigators: Principal Investigator: Jakub Cvek, Assoc.Prof., MD, Ing, PhD, MBA, University Hospital Ostrava

Publications and helpful links

General Publications

• Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol. 2005 Oct;75(1):5-14. doi: 10.1007/s11060-004-8093-6.
• DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989 Jun;39(6):789-96. doi: 10.1212/wnl.39.6.789.
• Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004 Jul 15;22(14):2865-72. doi: 10.1200/JCO.2004.12.149.
• CHAO JH, PHILLIPS R, NICKSON JJ. Roentgen-ray therapy of cerebral metastases. Cancer. 1954 Jul;7(4):682-9. doi: 10.1002/1097-0142(195407)7:43.0.co;2-s. No abstract available.
• Linskey ME, Andrews DW, Asher AL, Burri SH, Kondziolka D, Robinson PD, Ammirati M, Cobbs CS, Gaspar LE, Loeffler JS, McDermott M, Mehta MP, Mikkelsen T, Olson JJ, Paleologos NA, Patchell RA, Ryken TC, Kalkanis SN. The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010 Jan;96(1):45-68. doi: 10.1007/s11060-009-0073-4. Epub 2009 Dec 4.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 3, 2025
• First Submitted That Met QC Criteria: April 10, 2025
• First Posted (Actual): April 18, 2025

Study Record Updates

• Last Update Posted (Actual): May 4, 2025
• Last Update Submitted That Met QC Criteria: May 1, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Quality of Life; Brain Metastases; Overall Survival; Leptomeningeal Disease; Acute Toxicity; Neoadjuvant Stereotactic Radiotherapy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: ONK-NeoSTROBE; NW25-03-00278 (Other Grant/Funding Number: Ministry of Health of the Czech Republic)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make individual participant data available to other researchers. The data may be provided upon request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No