Dynamic Contrast-Enhanced CT and MRI to Evaluate Response in Neuroendocrine Liver Metastases Treated With Everolimus and Radiation

Abstract

<h3>Purpose/Objective(s)</h3> The optimal method to evaluate response in neuroendocrine liver metastases (NELM) treated with radiotherapy (RT) is unknown; tumor perfusion parameters were measured by dynamic contrast-enhanced CT and MRI (DCE-CT and -MRI) to evaluate changes with treatment and correlate with efficacy in a pilot study combining everolimus with RT for NELM. <h3>Materials/Methods</h3> Fourteen patients with oligoprogressive (< 4) NELM received everolimus (up to a max of 7.5 mg daily) for 28 days prior to, concurrent with, and 14 days following RT. All patients received external-beam RT (30Gy in 10 fractions) or SBRT (up to 60Gy in 3-5 fractions over 1-2 weeks), with the preference for SBRT. Each patient had a DCE-CT and -MRI at baseline (t₀), prior to RT (t₁) and 7 days after RT (t₂). Per lesion response was evaluated by RECIST v1.1. Perfusion parameters of blood flow (BF) and blood volume (BV) by DCE-CT, and the volume transfer constant (K_trans) and extravascular extracellular space (v_e) by DCE-MRI were correlated with the change in size of NELM at the 12-month follow-up (12mo). NELM not treated with RT served as internal controls. Statistics were performed using Wilcoxon Signed-Rank Test and Spearman's coefficient. <h3>Results</h3> Twenty-one and 14 treated NELM were evaluable by DCE-CT and -MRI respectively. Compared to t₀, BV by DCE-CT increased at t₁ by 11% (-15, +37%) (median (quartiles)), then significantly decreased after RT from t₁ to t₂ by -20% (-37, +2%) with <i>P</i> < 0.01. Compared to t₀, BF by DCE-CT decreased at t₁ by -7% (-25, +33%) and decreased further after RT from t₁ to t₂ by -13% (-25, +25%) with <i>P</i> = 0.35. Trend of increased BV in internal controls at each time point supports that the effect seen is due to RT. Compared to t₁, the decrease in BV by DCE-CT after RT correlated with the max % change in the size of the treated NELM at 12mo (rs = -0.45, <i>P</i> = 0.04). v_e by DCE-MRI increased between t₀ and t₁ from 0.25 (0.21, 0.35) to 0.32 (0.21, 0.42), <i>P</i> = 0.59 and dropped after RT between t₁ to t₂ to 0.28 (0.21, 0.32) with <i>P</i> = 0.02, whereas v_e continued to increase in untreated control data. A similar trend was observed for K_trans. Conventional ORR was 33%; no progression was seen within 12mo. <h3>Conclusion</h3> Changes in DCE-CT and -MRI are observed in patients receiving everolimus and everolimus+RT for NELM, with BV and v_e decreasing significantly post-RT. Given the challenges in assessing response in NELM using traditional RECIST in any context, DCE-CT and -MRI appear to be promising modalities; further studies are required.