Improved effectiveness of stereotactic radiosurgery in large brain metastases by individualized isotoxic dose prescription: an in silico study

Jaap D Zindler,Jacqueline Schiffelers,Aswin L Hoffmann,Philippe Lambin

doi:10.1007/s00066-018-1262-x

Abstract

IntroductionIn large brain metastases (BM) with a diameter of more than 2 cm there is an increased risk of radionecrosis (RN) with standard stereotactic radiosurgery (SRS) dose prescription, while the normal tissue constraint is exceeded. The tumor control probability (TCP) with a single dose of 15 Gy is only 42%. This in silico study tests the hypothesis that isotoxic dose prescription (IDP) can increase the therapeutic ratio (TCP/Risk of RN) of SRS in large BM.Materials and methodsA treatment-planning study with 8 perfectly spherical and 46 clinically realistic gross tumor volumes (GTV) was conducted. The effects of GTV size (0.5–4 cm diameter), set-up margins (0, 1, and 2 mm), and beam arrangements (coplanar vs non-coplanar) on the predicted TCP using IDP were assessed. For single-, three-, and five-fraction IDP dose–volume constraints of V12Gy = 10 cm3, V19.2 Gy = 10 cm3, and a V20Gy = 20 cm3, respectively, were used to maintain a low risk of radionecrosis.ResultsIn BM of 4 cm in diameter, the maximum achievable single-fraction IDP dose was 14 Gy compared to 15 Gy for standard SRS dose prescription, with respective TCPs of 32 and 42%. Fractionated SRS with IDP was needed to improve the TCP. For three- and five-fraction IDP, a maximum predicted TCP of 55 and 68% was achieved respectively (non-coplanar beams and a 1 mm GTV-PTV margin).ConclusionsUsing three-fraction or five-fraction IDP the predicted TCP can be increased safely to 55 and 68%, respectively, in large BM with a diameter of 4 cm with a low risk of RN. Using IDP, the therapeutic ratio of SRS in large BM can be increased compared to current SRS dose prescription.

Highlights

In large brain metastases (BM) with a diameter of more than 2 cm there is an increased risk of radionecrosis (RN) with standard stereotactic radiosurgery (SRS) dose prescription, while the normal tissue constraint is exceeded
Since in clinical practice the gross tumor volumes (GTV) of BM are not perfectly spherical and the plan quality may slightly vary due to inter- and intratreatment planner differences, we compared the isotoxic dose prescription (IDP) dose levels obtained from the 48 treatment plans with perfectly spherical GTVs to those of clinical treatment plans comprising 46 consecutive patients who had been treated with SRS for a single BM at our institution between January 2013 and June 2014 with a dose of 15–24 Gy in 1–3 fractions
For BM with a 4 cm diameter, using a 1 mm GTV-planning target volume (PTV) margin and a non-coplanar beam arrangement, the predicted tumor control probability (TCP) was increased from 23% using single fraction IDP to 55 and 68% using a threefraction IDP and five-fraction IDP respectively (Fig. 4). In this in silico study, the potential of IDP was investigated for improving the TCP from 42% with a single fraction of 15 Gy in large BM up to 4 cm diameter, while simultaneously respecting an acceptably low normal tissue complication probability (NTCP) limit

Summary

Introduction

In large brain metastases (BM) with a diameter of more than 2 cm there is an increased risk of radionecrosis (RN) with standard stereotactic radiosurgery (SRS) dose prescription, while the normal tissue constraint is exceeded. SRS is used for inoperable BM up to a diameter of 4 cm The consequence of this PTV size-based dose prescription protocol is a 12month local tumor control probability (TCP) of about 86% in small BM and a TCP of around 40% in large BM [4, 5]. The IDP concept is different from the PTV sizebased dose prescription approach, where fixed prescription doses are used that solely depend on the size of the target volume and for large BM do not respect the predefined dose–volume constraint for normal tissue. Apart from being dependent on the tumor prescription dose, the V12Gy depends on the gross tumor volume-to-planning target-volume (GTV-PTV) margin used as well as on the beam arrangement (i. e., coplanar vs non-coplanar) that affect the degree of dose conformity and the steepness of the dose gradient at the outer rim of the PTV [17]

Methods

Results

Conclusion