Combined Yttrium-90 microsphere selective internal radiation therapy and external beam radiotherapy in patients with hepatocellular carcinoma: From clinical aspects to dosimetry

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.

Twenty Years of Radiation Therapy of Unresectable Intrahepatic Cholangiocarinoma: Internal or External? A Systematic Review and Meta-Analysis

“…While SIRT studies often report in GBy, EBRT reports total delivered doses and BEDs (Tables 1, 2). BED of SIRT has been calculated with the consideration of time factors, despite downsides such as single-photon emission computed tomography being less accurate than PET/CT [72,73]. The development of a conversion algorithm may be needed to characterize the relationship of radiation dosage and clinical outcomes in future studies comparing EBRT and SIRT.…”

Stereotactic Inverse Dose Planning After Yttrium-90 Selective Internal Radiation Therapy in Hepatocellular Cancer

“…8 Wang et al reported for the first time, 90 Y dosimetry and outcomes for 22 hepatocellular carcinoma (HCC) patients treated with SIRT and EBRT. 9 The main finding of this important study was that, with careful patient selection, the combination was feasible and safe. As acknowledged by the authors, the potential limitations of this study include the use of single photon emission computed tomography (SPECT) imaging as the basis for dose calculation as it has inferior spatial resolution compared to positron emission tomography (PET).…”

“… 6 , 7 Bodey et al 8 considered combination therapy of EBRT with iodine-131-metaiodobenzylguanidine or -NaI and found improvement in the dose distribution compared with either single therapy. Wang et al 9 reported for the first time 90 Y dosimetry and outcomes for 22 patients with hepatocellular carcinoma (HCC) treated with SIRT and EBRT. The main finding of this important study was that, with careful patient selection, the combination was feasible and safe.…”

Potential alternative treatment approach for pediatric patient with diffusely infiltrative primary rhabdomyosarcoma of the liver

“…Due to this progression, she was considered for EBRT which had been reported to be safe after Y-90 in adults [11]. Decision was made to proceed with definitive EBRT to all known disease, including 42 Gy in 14 fractions to the extrahepatic disease and a dose-reduction to 30 Gy in 10 fractions to the intrahepatic tumor due to the prior Y-90 treatment (Fig.…”

“…Dose constraints used for external beam radiation therapy (eBrt) treatment. Liver dose constraints adopted from[11]. Kidney and spinal cord constraints were department standard dose constraints, as adopted from QUaNtec[19] …”