Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept

Abstract

PurposeTo evaluate the impact of dosimetry based on MAA SPECT/CT for the prediction of response, toxicity and survival, and for treatment planning in patients with hepatocellular carcinoma (HCC) treated with 90Y-loaded glass microspheres (TheraSphere®).MethodsTheraSphere® was administered to 71 patients with inoperable HCC. MAA SPECT/CT quantitative analysis was used for the calculation of the tumour dose (TD), healthy injected liver dose (HILD), and total injected liver dose. Response was evaluated at 3 months using EASL criteria. Time to progression (TTP) and overall survival (OS) were evaluated using the Kaplan-Meier method. Factors potentially associated with liver toxicity were combined to construct a liver toxicity score (LTS).ResultsThe response rate was 78.8 %. Median TD were 342 Gy for responding lesions and 191 Gy for nonresponding lesions (p < 0.001). With a threshold TD of 205 Gy, MAA SPECT/CT predicted response with a sensitivity of 100 % and overall accuracy of 90 %. Based on TD and HILD, 17 patients underwent treatment intensification resulting in a good response rate (76.4 %), without increased grade III liver toxicity. The median TTP and OS were 5.5 months (2–9.5 months) and 11.5 months (2–31 months), respectively, in patients with TD <205 Gy and 13 months (10–16 months) and 23.2 months (17.5–28.5 months), respectively, in those with TD >205 Gy (p = 0.0015 and not significant). Among patients with portal vein thrombosis (PVT) (n = 33), the median TTP and OS were 4.5 months (2–7 months) and 5 months (2–8 months), respectively, in patients with TD <205 Gy and 10 months (6–15.2 months) and 21.5 months (12–28.5 months), respectively, in those with TD >205 Gy (p = 0.039 and 0.005). The median OS was 24.5 months (18–28.5 months) in PVT patients with TD >205 Gy and good PVT targeting on MAA SPECT/CT. The LTS was able to detect severe liver toxicity (n = 6) with a sensitivity of 83 % and overall accuracy of 97 %.ConclusionDosimetry based on MAA SPECT/CT was able to accurately predict response and survival in patients treated with glass microspheres. This method can be used to adapt the injected activity without increasing liver toxicity, thus defining a new concept of boosted selective internal radiation therapy (B-SIRT). This new concept and LTS enable fully personalized treatment planning with glass microspheres to be achieved.

Multiagent imaging of liver tumors with reference to intra-arterial radioembolization

“…All published studies found a dose-efficacy correlation: with resin spheres, both in HCC [31] and in CRC metastases [32,33], and with glass spheres in HCC [34,35]. Statistically significant differences in the most important oncological end points, i.e., overall survival, progression-free survival and time to progression, were correlated with lesion absorbed doses higher or lower than about 200 Gy with glass spheres in HCC [36,37]. As regards radio-induced liver toxicity, Sangro et al [38] found that the threshold for RE-induced liver disease (REILD) with resin spheres is an activity greater than 0.8 GBq/L, which corresponds to 50 Gy kg/ GBq 9 0.8 GBq/1 kg = 40 Gy mean absorbed dose to non-tumoral parenchyma.…”

Radioembolization with 90Y-loaded microspheres: high clinical impact of treatment simulation with MAA-based dosimetry

“…In this study, response rate was significantly higher when using personalized dosimetry, at 86 % compared to only 55 % while using the standard dosimetric approach aiming to deliver 120 ±20 Gy to the treated liver, regardless of the TD (p=0.001) [11]. In a cohort of 41 PVT patients treated with personalized dosimetry, with intensification in 37 %, the median OS was 18 months [95 % confidence interval (CI) 11-25 months], highly impacted by TD.…”

“…ATD exceeding 205 Gy has also been reported as the only parameter associated with response on multivariate analysis, correlating with OS, especially in PVT patients [10]. In the case of unilobar treatment, HILD alone was not correlated with liver toxicity, yet a HILD>120 Gy combined with a small hepatic reserve (<30 %) highly correlated with permanent liver toxicities (p<0.0001) [11].…”

“…Due to the high effectiveness achieved with MAA single photon emission computed tomography (SPECT)/CT-based dosimetry, the concept of personalized dosimetry, with intensification when necessary, in order to achieve a TD>205 Gy has recently been reported with interesting results [11]. In this study, response rate was significantly higher when using personalized dosimetry, at 86 % compared to only 55 % while using the standard dosimetric approach aiming to deliver 120 ±20 Gy to the treated liver, regardless of the TD (p=0.001) [11].…”

A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy

“…They determined a threshold dose of 205 Gy which enabled a response prediction with 91% accuracy and 100% sensitivity [108]. Using this threshold in a cohort of 71 patients, the group detailed 17 patients who underwent treatment intensification to achieve D T > 205 Gy while maintaining D NL <120 Gy [109]. They show an OS of 11.5 months and 23.2 months for D T < 205 Gy and > 205 Gy respectively.…”