Single Photon Emission Computed Tomography (SPECT) Functional Liver Imaging to Facilitate Reirradiation for Liver Malignancies: A Phase 1 Trial

Abstract

<h3>Purpose/Objective(s)</h3> Functional imaging, such as Tc-99m- sulfur colloid single photon emission computed tomography (SPECT), may allow preferential sparing of functional liver volume and facilitate safe reirradiation. The primary objective of this study is to evaluate the safety of hypofractionated reirradiation for patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHC) or liver metastases (LM) who received prior radiation with either external beam radiotherapy (EBRT) or yttrium-90 radioembolization (Y90 RE) when using SPECT functional liver imaging for planning. <h3>Materials/Methods</h3> This is a Phase I trial with a 3+3 design used to test three levels of dose constraints for safety. Eligible patients had a diagnosis of HCC, IHC or LM and received EBRT >/=12 months prior or Y90 RE >/=6 months prior. After giving informed consent, patients underwent simulation and subsequent SPECT scan in the treatment position. Functional liver was estimated based on 40% maximum intensity as threshold. The prescription dose was 45Gy-67.5Gy in 15 fractions. Composite constraints were bowel/duodenum/stomach Dmax <45Gy, esophagus Dmax <50Gy, common bile duct Dmax <60Gy, and V45Gy <10% for the heart. The mean functional liver dose constraint was <20Gy or 18Gy for patients treated with EBRT and Y90 RE, respectively. The volumetric dose constraint for functional liver volume receiving <22Gy depended on the dose level of trial enrollment: level 0 was ≥400cc, level -1 was 500cc and level +1 was 300cc. Dose limiting toxicities (DLTs), including grade 3 hypoalbuminemia, increase in INR, increase in bilirubin, ascites or hepatic failure as well as any grade 4 toxicity related to reirradiation, were assessed within 2 months after re-radiation. Any liver decompensation qualifying as a DLT was attributed to radiation therapy. The maximal dose constraint (MDC) is defined as the highest constraint level at which no more than one patient has experienced DLT in six patients treated at that dose constraint. <h3>Results</h3> A total of thirteen patients were enrolled between May 2018 and April 2021. The median [IQR] reirradiation GTV volume was 57cc [32-287cc]. The median [IQR] liver-minus-GTV and functional liver volumes were 1402cc [1141-1481cc] and 869 [784-1077], respectively. All plans spared >/=500ccs of functional liver from receiving ≥22Gy (median [IQR] 726 [637-783]). The median [IQR] mean function liver volume dose was 14.9Gy [10.4-18.6Gy]. The first 3 patients in dose level 0 and the next 3 patients treated in dose level +1 experienced no DLTs. Of the next seven patients treated using dose level +1 constraints, one developed a DLT possibly attributable to radiation. <h3>Conclusion</h3> SPECT functional imaging facilitates safe reirradiation for primary and metastatic liver tumors. Due to the ability to spare >/=500ccs of functional liver from >22Gy for all patients with only 1 of 13 patients experiencing DLT, we conclude this to be a reasonable constraint for reirradiation.