Clinical trial NCT05160818: Hypofractionated Versus Single Fraction Stereotactic Adjuvant Radiotherapy to the Resection Cavity of Brain Metastases
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Brain Metastases
Resection Cavity
Keywords: Brain Metastases
Resection Cavity
Radiotherapy
Stereotactic Irradiation
Gamma Knife
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
First posted: 2021-12-16
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 Parallel Assignment
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Local control
timeFrame: 12 months after adjuvant radiotherapy
Secondary outcomes:
measure: LC
timeFrame: 12 months after adjuvant radiotherapy
measure: LRC
timeFrame: 12 months after adjuvant radiotherapy
measure: OS
timeFrame: 12 months after adjuvant radiotherapy
measure: Salvage-free survival
timeFrame: 12 months after adjuvant radiotherapy
measure: Intracranial salvage therapy
timeFrame: 12 months after adjuvant radiotherapy
measure: Pseudoprogression
timeFrame: up to 12 months after adjuvant radiotherapy
measure: Irradiation-related toxicity
timeFrame: up to 12 months after adjuvant radiotherapy
measure: QoL
timeFrame: up to 12 months after adjuvant radiotherapy
measure: Time to loss of independence
timeFrame: up to 12 months after adjuvant radiotherapy
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Dept. Radiation Oncology
state: Bavaria
Study officials:
affiliation: Technical University Munich, Germany
name: Maria Waltenberger
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.