Cyberknife Radiosurgery for Patients With Brain Metastases Diagnosed With Either SPACE or MPRAGE Sequence

NCT03303365 | Completed

• 1 other identifier: S-448/2017
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 1

Brief Summary

For patients with cerebral oligometastases who are in adequate clinical condition stereotactic radiosurgery (SRS) is the treatment of choice, being recommended by international guidelines for the treatment of one to four lesions. Newer findings have shown that for patients with more than four lesions SRS can be considered as a favorable alternative to whole-brain radiotherapy (WBRT), the currently established standard-of-care treatment. With modern techniques highly conformal SRS of multiple lesions has become feasible with comparable clinical effort and minimal toxicity as compared to WBRT. Developments in magnetic resonance imaging (MRI- imaging) have produced highly sensitive contrast-enhanced three-dimensional fast spin echo sequences such as SPACE that facilitate the detection of very small and early-stage lesions in a fashion superior to the established Magnetization Prepared Rapid Gradient Echo (MPRAGE) series. Since it has been established that the response of brain metastases to SRS is better for smaller lesions and that WBRT can come at the price of significant neurotoxicity, the investigators hypothesize that 1) earlier detection of small brain metastases and 2) early and aggressive treatment of those by SRS will result in an overall clinical benefit by delaying the failure of repeated localized therapy and thus preserving quality of life and potentially prolonging overall survival. On the other hand however, overtreatment might be a valid concern with this approach since it has yet to be proved that a clinical benefit can be achieved. The current study aims to stretch the boundaries of the term "cerebral oligometastases" by performing SRS for up to ten cerebral metastases, compared to the established clinical standard of four, given that existing data supports the non-inferiority of this approach and given that modern Cyberknife SRS facilitates the treatment of multiple lesions with minimal treatment-associated toxicity.

Conditions

Brain Metastases; Adult Solid Tumor

Keywords

Brain Metastases; WBRT (whole brain radiotherapy); SRS (stereotactic radiosurgery); CYBER-Knife

Outcome Measures

Primary Outcomes (1)

• Ineligibility for further cerebral SRS

  simultaneous new occurrence or progression of \> 10 brain metastases

  12 months after initial SRS

Secondary Outcomes (3)

• Overall survival (OS)

  12 months after initial SRS

• cognitive function

  6 months after initial SRS

• quality of life

  6 months after initial SRS

Study Arms (2)

Treatment based on SPACE MRI sequence

EXPERIMENTAL

Cyberknife SRS of all suspect intracranial lesions visible in SPACE up to 10 simultaneous lesions

Radiation: stereotactic radiosurgery (SRS)

Treatment based on MPRAGE

ACTIVE COMPARATOR

Cyberknife SRS of all suspect intracranial lesions visible in MPRAGE up to 10 simultaneous lesions

Radiation: stereotactic radiosurgery (SRS)

Interventions

stereotactic radiosurgery (SRS) RADIATION

All patients will receive a pre-treatment cranial MRI for diagnostic and treatment planning purposes. In Arm A, the contrast-based T1-weighted SPACE sequence is utilized for GTV definition. In Arm B, the contrast-based T1-weighted three-dimensional MPRAGE sequence is utilized for GTV definition. In both cases the GTV consists of all contrasted tissue associated with the target lesion and all additional tissue judged by an experienced physician to be part of the suspect target lesion. To the GTV a PTV margin of 1 mm is added by isotropic expansion that can be slightly modified if deemed necessary by the treating physician (e.g. intersection with adjoining OAR). Dose prescription to the PTV for target lesions will be as follows: * 20 Gy to the 70%-isodose (lesions \< 2 cm max. diameter) * 18 Gy to the 70%-isodose (lesions 2 - 3 cm max. diameter) * 6 x 5 Gy to the conformally surrounding isodose (lesions \> 3 cm max. diameter)

Treatment based on MPRAGE; Treatment based on SPACE MRI sequence

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• radiologically confirmed metastases of the brain with an underlying history of a malignant illness
• between one and ten suspect intracranial lesions, taking into consideration all available series of the pre-therapeutic MRI (performed at Heidelberg University Hospital and including SPACE sequence)
• age ≥ 18 years of age
• Karnofsky Performance Score (KPS) ≥ 70
• for women with childbearing potential, (and men) adequate contraception.
• ability to understand character and individual consequences of the clinical trial
• written informed consent (must be available before enrolment in the trial)

You may not qualify if:

• refusal of the patient to take part in the study
• Small-cell lung cancer (SCLC) as primary malignant illness
• More than 10 suspect intracranial lesions in the initial pre-therapeutic MRI imaging (performed at Heidelberg University Hospital and including SPACE sequence)
• metastasis so close to OAR that initial single-session SRS would be impossible due to lacking radiotolerance
• known contraindications against the performing of cranial MRI
• previous radiotherapy of the brain
• Patients who have not yet recovered from acute toxicities of prior therapies
• Pregnant or lactating women
• Participation in another clinical study or observation period of competing trials, respectively

Sponsors & Collaborators

• Juergen Debus: lead
• Heidelberg University: collaborator

Study Sites (1)

University Hospital of Heidelberg, Department of Radiation Oncology

Heidelberg, 69120, Germany

Location

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MeSH Terms

Conditions

Brain Neoplasms; Snyder Robinson syndrome

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Juergen Debus, Prof. Dr.Dr.

  Head of department Radiation Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr.Dr. Jürgen Debus

Study Record Dates

• First Submitted: October 2, 2017
• First Posted: October 6, 2017
• Study Start: February 1, 2018
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: November 3, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)