Neoadjuvant Stereotactic Radiotherapy for Brain Metastasis

Official title

Neoadjuvant Stereotactic Radiotherapy for Brain Metastasis - Prospective Trial NeoSTROBE

Overview

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.

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.

Interventions

• 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.
• 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.

Primary outcome measures

• Acute Toxicity [Time frame: 3 months]
• Quality of Life Questionnaire (FACT-Br/EORTC QLQ-C30) [Time frame: 3 months]
• Quality of Life Questionnaire (EORTC QLQ-BN20) [Time frame: 3 months]

Secondary outcome measures (5)

• Time from NaSRT to local progression [Time frame: 3 years]
• Time from NaSRT to detection of LMD [Time frame: 3 years]
• Time from NaSRT to the onset of RN [Time frame: 3 years]
• Time from NaSRT to detection of distant parenchymal metastasis [Time frame: 3 years]
• Overall Survival [Time frame: 3 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Czechia · 4 centers

• University Hospital Ostrava — Ostrava
• Masaryk Memorial Cancer Institute — Brno
• University Hospital Hradec Králové — Hradec Králové
• University Hospital Olomouc — Olomouc

Publications

• 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. PMID 2725874
• 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. PMID 13172684
• Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol. 2005 Oct;75(1):5-14. doi: 10.1007/s11060-004-8093-6. PMID 16215811
• 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. PMID 15254054
• 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 Neuroonco PMID 19960227

Identifiers

NCT: NCT06933199 · ONK-NeoSTROBE · NW25-03-00278

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗