Hypofractionated Versus Single Fraction Stereotactic Adjuvant Radiotherapy to the Resection Cavity of Brain Metastases (SATURNUS)

Hypofractionated Stereotactic Radiotherapy Versus Single Fraction Stereotactic Radiosurgery to the Resection Cavity of Brain Metastases After Surgical Resection - A Prospective, Randomized, Controlled, Monocentric Phase III Trial

This prospective, randomized, controlled, monocentric clinical phase III study focuses on stereotactic irradiation of resection cavities of brain metastases after surgical resection and seeks to demonstrate the superiority of fractionated irradiation schemes in terms of local control.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases; Resection Cavity
• Intervention / Treatment: Radiation: Hypofractionated stereotactic radiotherapy (HFSRT) versus single fraction stereotactic radiotherapy radiosurgery (SRS)

Detailed Description

There is a growing scientific focus on single fraction stereotactic (SRS) and hypofractionated stereotactic irradiation (HFSRT) after surgical resection of brain metastasis and its use is more frequently recommended in international guidelines. Despite intensive research, the optimal fractionation scheme and dose prescription for adjuvant irradiation of the resection cavity remains unclear.

Based on our own institutional data [Cit.1] and a recently published metaanalysis [Cit.2], we hypothesize that local control (LC) after HFSRT is superior compared to SRS in terms of LC. To evaluate the hypothesis in a prospective, randomized, controlled setting we designed the SATURNUS study.

A total of 126 patients will be randomized 1:1 to either HFSRT (dose 6-7 x 5 Gy) or SRS (dose 1 x 12-20 Gy). If further unresected brain metastases are present, they will be treated with SRS (1 x 14 - 22 Gy). Irradiation is carried out with a Gamma Knife or a Linear Accelerator. In line with current clinical practice, the choice of positioning method for SRS with the Gamma Knife (mask or stereotactic frame) is left to the patient. In the case of SRS with the Linear Accelerator or HFSRT, fixation is done with a mask as technically not otherwise feasible. Follow-up-MRI will be at least carried out 6 weeks and 3, 6, 9 and 12 months after treatment. Primary endpoint of the study is local control (LC) at the irradiated resection cavity after 12 months. Locoregional control (LRC) and overall survival (OS) as well as salvage-treatments, irradiation-associated toxicities (especially rate of radionecrosis) and quality-of-life parameters are investigated as secondary endpoints.

To the best of our knowledge, the SATURNUS study is the only randomized phase III study comparing different techniques of postoperative stereotactic radiotherapy after resection of brain metastases adequately powered to detect a superiority of HSFRT regarding LC.

• Study Type: Interventional
• Enrollment (Anticipated): 126
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria Waltenberger; Phone Number: +49-89-4140-8281; Email: maria.waltenberger@mri.tum.de
• Study Contact Backup: Name: Stephanie E Combs, Prof. Dr.; Phone Number: +49-89-4140-4501; Email: direktion.radonk@mri.tum.de

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81675
      • Recruiting
      • Dept. Radiation Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed solid tumor disease
• One to three resected brain metastases
• Consent to perform adjuvant irradiation by an interdisciplinary tumor board
• Completed wound healing
• Resection within the last six weeks at the time of study inclusion
• Diameter of the resection cavity ≤ 4 cm (on Planning MRI)
• Age > 18 years
• KPS > 60%
• Adequate contraceptive measures for fertile women / men
• Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria:

• Contraindication for repetitive contrast enhanced MRI
• Leptomeningeal disease
• Small cell histology, hematological malignancies and / or germ cell malignancies
• Previous irradiation of the brain
• Pregnant and lactating women
• Inability to understand the character and consequences of the study
• Withdrawal of consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Arm A: HSFRT; Hypofractionated stereotactic radiotherapy to the resection cavity, dose prescription: 6-7 x 5 Gy	Radiation: Hypofractionated stereotactic radiotherapy (HFSRT) versus single fraction stereotactic radiotherapy radiosurgery (SRS); intervention description see above
ACTIVE_COMPARATOR: Arm B: SRS; Single fraction stereotactic radiotherapy to the resection cavity, dose prescription: 1 x 12-20 Gy	Radiation: Hypofractionated stereotactic radiotherapy (HFSRT) versus single fraction stereotactic radiotherapy radiosurgery (SRS); intervention description see above

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local control	Local control at the resected site(s)	12 months after adjuvant radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LC	Local control at all treated site(s)	12 months after adjuvant radiotherapy
LRC	Locoregional control=CNS progression free survival	12 months after adjuvant radiotherapy
OS	Overall survival	12 months after adjuvant radiotherapy
Salvage-free survival	Overall survival	12 months after adjuvant radiotherapy
Intracranial salvage therapy	Number and kind of intracranial salvage treatments	12 months after adjuvant radiotherapy
Pseudoprogression	Rate of pseudoprogression	up to 12 months after adjuvant radiotherapy
Irradiation-related toxicity	according to CTCAE v4.03, especially rate of radionecrosis	up to 12 months after adjuvant radiotherapy
QoL	Quality of life according to EORTC QLQ-C30 and EORTC QLQ-B20	up to 12 months after adjuvant radiotherapy
Time to loss of independence	defined as decrease in Barthel index by > 20 points	up to 12 months after adjuvant radiotherapy

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Study Director: Maria Waltenberger, Technical University Munich, Germany

Publications and helpful links

General Publications

• Specht HM, Kessel KA, Oechsner M, Meyer B, Zimmer C, Combs SE. HFSRT of the resection cavity in patients with brain metastases. Strahlenther Onkol. 2016 Jun;192(6):368-76. doi: 10.1007/s00066-016-0955-2. Epub 2016 Mar 10.
• Akanda ZZ, Hong W, Nahavandi S, Haghighi N, Phillips C, Kok DL. Post-operative stereotactic radiosurgery following excision of brain metastases: A systematic review and meta-analysis. Radiother Oncol. 2020 Jan;142:27-35. doi: 10.1016/j.radonc.2019.08.024. Epub 2019 Sep 25.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2021
• Primary Completion (ANTICIPATED): August 1, 2025
• Study Completion (ANTICIPATED): August 1, 2025

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (ACTUAL): December 16, 2021

Study Record Updates

• Last Update Posted (ACTUAL): December 16, 2021
• Last Update Submitted That Met QC Criteria: December 6, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Radiotherapy; Brain Metastases; Gamma Knife; Resection Cavity; Stereotactic Irradiation
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: RadOnc MRI TUM - 2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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