Growth dynamics of brain metastases differentiate radiation necrosis from recurrence

Abstract

Background: Radiation necrosis (RN) is a frequent adverse event after fractionated stereotactic radiotherapy (FSRT) or single-session stereotactic radiosurgery (SRS) treatment of brain metastases (BMs). It is difficult to distinguish RN from progressive disease (PD) due to their similarities in the magnetic resonance images. Previous theoretical studies have hypothesized that RN could have faster, although transient, growth dynamics after FSRT/SRS, but no study has proven that hypothesis using patient data. Thus, we hypothesized that lesion size time dynamics obtained from growth laws fitted with data from sequential volumetric measurements on magnetic resonance images may help in discriminating recurrent BMs from RN events.

Methods: A total of 101 BMs from different institutions, growing after FSRT/SRS (60 PDs and 41 RNs) in 86 patients, displaying growth for at least 3 consecutive MRI follow-ups were selected for the study from a database of 1031 BMs. The 3 parameters of the Von Bertalanffy growth law were determined for each BM and used to discriminate statistically PDs from RNs.

Results: Growth exponents in patients with RNs were found to be substantially larger than those of PD, due to the faster, although transient, dynamics of inflammatory processes. Statistically significant differences (P < .001) were found between both groups. The receiver operating characteristic curve (AUC = 0.76) supported the ability of the growth law exponent to classify the events.

Conclusions: Growth law exponents obtained from sequential longitudinal magnetic resonance images after FSRT/SRS can be used as a complementary tool in the differential diagnosis between RN and PD.

Keywords: Brain metastases; mathematical oncology; radiation necrosis; stereotactic radiosurgery.

Figure 1.

Longitudinal dynamics were observed in (A) Lesion with progressive disease (PD) post-SRS and (B) an irradiated BM diagnosed with radiation necrosis (RN). SRS treatment times are marked with a vertical dashed line. White dots are the measured volumes, and the solid lines are the result of interpolating longitudinal volumetric data (shown only to guide the eye). Axial slices of the contrast-enhanced (CE) T1-weighted magnetic resonance imaging (MRI) sequences are displayed.

Figure 2.

(A) Fitting curves and the growth exponents obtained from Equation (1) for a number of brain metastases (BMs), where dots correspond to the volumes measured. (B) Box plots comparing the growth exponents β obtained for post-SRS recurrence of BM (PD, n = 60) vs radiation necrosis (RN) events (n = 41). (C) receiver operating characteristic curve for the distinction between recurrent BM post-SRS and RN. (D) Box plots showing the growth rates λ obtained for the same subgroups by an exponential fit Equation (2) choosing (A1) the first 2 time points (λ ₁) and (D2) the last 2 time points (λ ₂).

Figure 3.

Box plots comparing the growth exponents obtained for recurrence of BM vs radiation necrosis (RN) events and their respective receiver operating characteristic curves for: (A) brain metastases (BMs) with upfront WBRT (PD, n = 11; RN, n = 9), (B) BMs which received single-session SRS (PD, n = 30; RN, n = 32) and (C) BMs treated with fractionated SRT (PD, n = 30; RN, n = 9).