Stereotactic Radiotherapy of the Resection Cavity of Brain Metastases vs. Post-operative Whole-brain Radiotherapy

Summary

In advanced cancer disease brain metastases are common, difficult to treat, and are associated with a poor prognosis. As new local and systemic therapies are eventually resulting in improved survival and quality of life for patients with brain metastases, negative neurocognitive effects of radiation therapy are becoming increasingly important as well as good loco-regional disease control of brain metastases.

Concerning treatment, brain metastases remain a major clinical problem and a multidisciplinary approach to management should be adopted. Neurosurgical resection with postoperative whole brain radiotherapy (WBRT) is one major treatment option in solitary or symptomatic brain metastases. Furthermore, WBRT is recommended for multiple brain metastases. For a limited number of brain metastases stereotactic radiosurgery (SRS) has been established as a highly effective treatment alternative.

Recently, a new treatment approach combing neurosurgery with postoperative stereotactic radiotherapy (SRT) of the resection cavity is emerging. Based on available evidence, postoperative SRT of the resection cavity improves local control following surgery, reduces the number of patients who require whole brain radiotherapy, and is well tolerated (1).

This protocol is aimed at primarily evaluating the safety and toxicity profile of SRT to the resection cavity following neurosurgical resection combined with SRT of potentially further unresected brain metastases, compared to postoperative whole-brain radiotherapy (WBRT). Secondary, the local effect of SRT in patients with brain metastases will be assessed by measuring time to local recurrence (LR), local and loco-regional progression-free survival (PFS).

Additional systemic treatment will be carried out according to the standards of the National Center for Tumor Therapy (NCT).

Conditions

• Brain Metastases, Adult

Interventions

RADIATION

post-operative stereotactic radiosurgery (SRS)

For radiosurgery, patients will be immobilized. Treatment planning including the MRI and planning CT should be performed 1 -2 weeks before SRT and treatment finished at latest 3-4 weeks after surgery. Planning should be as close to SRT as possible. Organs at risk such as the brain stem, optic nerves, chiasm and spinal cord will be contoured. The Clinical Target Volume 1 (CTV1) will be defined as the resection cavity based on MRI and CT including T1 contrast enhanced changes around the resection cavity. The Clinical Target Volume 2 (CTV2) will be defined as a 3mm margin added to CTV1 by isotropic expansion and slightly adjusted as deemed appropriated by the experienced contouring physician. The Planning Target Volume (PTV) will be an additional margin of 1mm added to CTV2 by isotropic expansion. Treatment planning will be performed using Accuray's Multiplan or subsequent approved treatment planning systems for Cyberknife.

RADIATION

Whole brain radiotherapy (WBRT)

For WBRT, an individual head fixation mask is manufactured for each patient, and treatment planning is performed as virtual simulation or 3D-conformal RT planning based on CT-imaging. The portals include the whole brain with special focus as including the skull base areas and lamina cribrosa. For low infratentorial lesions, the treatment volume may include the whole brain down to the second cervical vertbra. RT will be applied with two portals (e.g. 87°and 273°) using a 6 MeV linear accelerator. For WBRT, a total dose of 30 Gy in 3 Gy fractions will be applied.

Sponsors & Collaborators

• Heidelberg University

  collaborator OTHER

• Juergen Debus

  lead OTHER

Principal Investigators

• Juergen Debus, Prof. Dr. Dr. · Head of department Radiation Oncology

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-02-01

Primary Completion

2021-05-30

Completion

2021-07-08

Countries

• Germany

Study Locations