Trial of Preoperative Radiosurgery Versus Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases

Официальное название

A Multicenter Prospective, Interventional, Randomized Trial of Preoperative Radiosurgery Compared With Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases

Обзор

The research question is whether a single fraction of preoperative radiosurgery can reduce the incidence of leptomeningeal disease 12 months following resection of a brain metastasis (BM) as compared with 5 fractions of postoperative stereotactic radiotherapy.

Подробное описание

Neurosurgical resection of a brain metastasis in patients with a diagnosis of cancer may be indicated however the recurrence rate approximates 50% and adjuvant radiotherapy is standard. Single fraction postoperative stereotactic radiosurgery (SRS) has been widely adopted as a standard therapy as it achieves equivalent survival and prevents loss of neurocognitive function as compared with whole brain radiotherapy and improves cavity local control rates as compared with observation. Hypofractionated stereotactic radiotherapy in 3 to 5 fractions (hfSRT) is also used in the postoperative setting.

Nodular leptomeningeal disease (nLMD) is a recognised pattern of failure after postoperative SRS and hfSRT. A 16.9% incidence of nodular LMD was seen after surgery and a similar incidence of 11%-28%is reported following postoperative SRS in retrospective series. These data suggest that postoperative SRS/hfSRT have no significant effect on the development of LMD following surgery.

The incidence of LMD following single fraction preoperative SRS is only 6.1% according to the largest retrospective series. Preoperative SRS takes advantage of the easier delineation of an intact BM and sterilizes tumor cells disseminated at surgery. Side effects are minimized by a smaller planning margin, a dose reduction and resection of the irradiated volume. In addition, there is no delay to systemic therapy due to wound healing/complications. Furthermore, a single fraction offers patient convenience.

This trial will randomise and compare intracranial outcomes between single fraction preoperative SRS and 5 fraction postoperative hFSRT.

Вмешательства

• Лучевая терапия preoperative radiosurgery
  single fraction radiosurgery
• Лучевая терапия postoperative hypofractionated stereotactic radiotherapy
  fractionated stereotactic radiotherapy /radiosurgery in 1 to 6 fractions according to local standard of care

Первичные конечные точки

• Leptomeningeal disease [Срок оценки: 12 months after intervention]

Вторичные конечные точки (4)

• Local control of the surgical cavity [Срок оценки: 12 months after intervention]
• Distant brain failure [Срок оценки: 12 months after intervention]
• Radionecrosis [Срок оценки: 12 months after intervention]
• Quality of life assessment [Срок оценки: 3,6,12 months after intervention]

Критерии участия

Критерии включения

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Age ≥18
• Karnofsky performance status ≥60
• Histological diagnosis of a malignant primary or metastatic tumour
• Ability to take steroids
• No contraindication to magnetic resonance imaging (MRI)
• MRI-diagnosis of a clearly demarcated contrast-enhancing brain metastasis up to 4.0 cm diameter indicated for neurosurgical resection (tumorboard decision). Up to 3 other brain metastases suitable for primary radiosurgery/ stereotactic radiotherapy
• Survival estimated by primary clinician > 12 months
• Platelet count > 100/ml, INR < 1.3, Hb > 7.5 g/dL

Критерии исключения

• Radiosensitive histology: germ cell tumour, lymphoma, multiple myeloma
• >10 mm midline shift, effacement of the 4th ventricle or other sign of raised intracranial pressure requiring urgent decompressive surgery
• More than 4 brain metastases or the diameter of the metastasis for resection >4.0 cm.
• More than 1 metastasis requiring resection
• Leptomeningeal disease in the CSF or on MRI (unless localized and can be irradiated then resected with the metastasis)
• Prior radiation to the brain (SRS/SRT to lesion to be resected and /or WBRT)
• Prior resection of a primary or secondary brain tumor
• Prior diagnosis of a non-meningioma brain tumor
• Prior radionuclide therapy within 30 days
• Prior anti-VEGF therapy within 6 weeks
• Unable to tolerate radiosurgery immobilization and treatment
• Inability to give informed consent
• Pregnancy or lactation
• Females of reproductive potential not willing to use effective contraception for at least 6 months after radiotherapy
• Males of reproductive potential not effective contraception for 3 months after radiotherapy
• Lack of likely compliance with protocol and follow-up

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Швейцария · 6 центров

• Kantonsspital Aarau — Aarau
• Inselspital, Universitätsklinik für Radio-Onkologie — Bern
• Kantonsspital Graubünden — Chur
• Luzerner Kantonsspital — Lucerne
• Kantonsspital St. Gallen — Sankt Gallen
• Kantonsspital Winterthur — Winterthur

Германия · 3 центра

• Knappschaft Kliniken, Universitätsklinikum Bochum GmbH — Bochum
• UKGM-Giessen — Giessen
• Universitätsklinikum Schleswig Holstein — Kiel

Австрия · 1 центр

• Tirol Kliniken Innsbruck — Innsbruck

Идентификаторы

NCT: NCT05124236 · 410.000.146

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗