Abstract

PurposeSelective internal radiation therapy (SIRT) is an effective treatment strategy for unresectable hepatocellular carcinoma (HCC) patients. However, the prognoses of patients with portal vein thrombosis, extra-hepatic metastases, or residual tumors remain poor when treated with SIRT alone. In these patients, sequential external beam radiotherapy (EBRT) may offer a chance of salvage. Here, we reported the clinical outcomes and the detailed dosimetry analysis of 22 patients treated with combination therapy.MethodsBetween October 2011 and May 2015, 22 consecutive patients who underwent EBRT after yttrium-90 (90Y) SIRT were included in this study. The post-SIRT 90Y bremsstrahlung SPECT/CT of each patient was transferred to dose distribution by adopting the local deposition hypothesis. The patient-specific 3-dimensional biological effective dose distribution of combined SIRT and EBRT was generated. The overall survival and safety were evaluated. The relationship between dosimetric parameters and liver toxicity was analyzed.ResultsThe mean administered activity of SIRT was 1.50 GBq (range: 0.5–2.8). The mean prescribed dose of EBRT was 42.3 Gy (range: 15–63) in 14 fractions (range: 5–15) and was targeted to the residual liver tumor in 12 patients (55%), portal vein thrombosis in 11 patients (50%), and perihilar lymphadenopathies in 4 patients (18%). The overall 1-, 2-, and 3-year survival rates were 59.8%, 47.9%, and 47.9%, respectively. Overall, 8 patients (36%) developed > grade 2 liver toxicities, and the Child-Pugh score prior to EBRT strongly affected the toxicity risk. A dosimetry analysis restricted to 18 Child-Pugh A/B patients showed that the V100 (The fraction of normal liver exposed to more than 100 Gy) to V140 significance differed between patients who did or did not experience hepatotoxicity. The V110 was the strongest predictor of hepatotoxicity (18.6±11.6% vs 29.5±5.8%; P = 0.030).ConclusionCombined therapy is feasible and safe if patients are carefully selected. Specifically, 3-dimensional dosimetry is crucial for the evaluation of efficacy and toxicity. The normal liver V100 to V140 values of the combined dose should be as low as possible to minimize the risk of liver toxicity.

Highlights

  • Selective internal radiation therapy (SIRT) is an effective local treatment in hepatocellular carcinoma (HCC) patients not eligible for surgery[1,2]

  • A dosimetry analysis restricted to 18 Child-Pugh A/B patients showed that the V100 (The fraction of normal liver exposed to more than 100 Gy) to V140 significance differed between patients who did or did not experience hepatotoxicity

  • 3dimensional dosimetry is crucial for the evaluation of efficacy and toxicity

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Summary

Introduction

Selective internal radiation therapy (SIRT) is an effective local treatment in hepatocellular carcinoma (HCC) patients not eligible for surgery[1,2]. The presence of portal vein thrombosis (PVT), extra-hepatic lymphadenopathy, or residual tumor remains a poor prognostic factor after SIRT. In these circumstances, the combination of external beam radiotherapy (EBRT) is reasonable and may improve tumor control and survival. A delicate physical and biologic conversion yielded from a post-SIRT image can be used as a source of patient-specific 3-dimensional voxel-based dose reconstruction. These methods have gained popularity and have been applied to evaluate outcome in recent years[4]

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