FSRT vs. SRS in Brain Metastases-Differences in Local Control and Radiation Necrosis-A Volumetric Study.

Florian Putz,Hadi Siavooshhaghighi,Thomas Weissmann,Sabine Semrau,Sebastian Lettmaier,Christoph Bert,Johannes Roesch,Charlotte Schmitter,Manuel Alexander Schmidt,Dominik Oft,Benjamin Frey,Veit Mengling,Rainer Fietkau,Luitpold Valentin Distel,Irina Filimonova

doi:10.3389/fonc.2020.559193

Abstract

Background: While the role of stereotactic radiotherapy for brain metastases is increasing, evidence on the comparative efficacy and safety of fractionated stereotactic radiotherapy (FSRT) and single-session radiosurgery (SRS) is scarce.Methods: Longitudinal volumetric analysis was performed in a consecutive cohort of 120 patients and 190 brain metastases (>0.065 cm3 in volume / > ~5 mm in diameter) treated exclusively with FSRT (n = 98) and SRS (n = 92), respectively. A total of 972 tumor segmentations was used, averaging 5.1 time points per metastasis. Progression was defined using a volumetric extension of the RANO-BM criteria. Local control and radionecrosis were compared for lesions treated with FSRT and SRS, respectively.Results: Metastases treated with FSRT were significantly larger at baseline (mean, 4.66 vs. 0.40 cm3, p < 0.001). Biologically effective dose (BED) for metastases (α/β = 12, linear-quadratic-cubic model) was significantly associated with local control, whereas BED for normal brain (α/β = 2, linear-quadratic model) was significantly associated with radionecrosis. Median time to local progression was 22.9 months in the FSRT group compared to 14.5 months in the SRS group (p = 0.022). Overall radionecrosis rate at 12 months was 3.4% for FSRT and 14.8% for SRS (p = 0.010). Radionecrosis °IV requiring resection with histologic proof of radiation necrosis also was significantly reduced in the FSRT group (FSRT 0.0% vs. SRS 3.9%, p = 0.041). In multivariate analysis, FSRT was associated with reduced risk of progression (HR 0.47, p = 0.015) and reduced risk of radionecrosis (HR 0.18, p = 0.045).Conclusions: This volumetric study provides initial evidence that the improvements in therapeutic ratio expected for FSRT in larger brain metastases, might equally extend into the domain of smaller metastases, traditionally less considered for fractionated treatment. FSRT might constitute an important tool to further increase local control and reduce radionecrosis risk in stereotactic radiotherapy for brain metastases, that should be assessed in randomized intervention trials.

Highlights

Stereotactic radiotherapy (SRT) is one of the most important treatments for brain metastases, an increasingly common disease entity that occurs in up to 40% of patients with cancer [1]
In 190 brain metastases, 972 time points / MRI studies were available at baseline or following stereotactic radiotherapy (SRT) and segmented longitudinally corresponding to a mean of 5.1 segmentations per metastasis, which means that lesions were measured on an average of 5.1 separate MRI studies conducted at different points in time during follow-up and including one baseline measurement before treatment per lesion
972 whole-tumor segmentations were available after stereotactic radiotherapy and at baseline with a mean of 5.1 segmentations per metastasis, which means that lesions were measured on an average of 5.1 separate MRI studies conducted at different points in time during followup and including one baseline measurement before treatment per lesion

Summary

Introduction

Stereotactic radiotherapy (SRT) is one of the most important treatments for brain metastases, an increasingly common disease entity that occurs in up to 40% of patients with cancer [1]. Fractionated stereotactic radiotherapy (FSRT) may constitute an important option to increase the therapeutic ratio in comparison to single-session radiosurgery (SRS) in patients with brain metastases. As current radiobiologic understanding suggests that brain metastases have a very high α/β ratio of around 12, whereas surrounding normal brain tissue is characterized by a low α/β of 2-3, dose fractionation should—in theory—be able to optimize local control while avoiding increased risk for radionecrosis [8,9,10]. While the role of stereotactic radiotherapy for brain metastases is increasing, evidence on the comparative efficacy and safety of fractionated stereotactic radiotherapy (FSRT) and single-session radiosurgery (SRS) is scarce

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Results

Discussion

Conclusion