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Hepatobiliary scintigraphy may improve radioembolization treatment planning in HCC patients.

ABSTRACT: BACKGROUND:Routine work-up for transarterial radioembolization, based on clinical and laboratory parameters, sometimes fails, resulting in severe hepatotoxicity in up to 5% of patients. Quantitative assessment of the pretreatment liver function and its segmental distribution, using hepatobiliary scintigraphy may improve patient selection and treatment planning. A case series will be presented to illustrate the potential of this technique. Hepatocellular carcinoma patients with cirrhosis (Child-Pugh A and B) underwent hepatobiliary scintigraphy pre- and 3 months post-radioembolization as part of a prospective study protocol, which was prematurely terminated because of limited accrual. Included patients were analysed together with their clinical, laboratory and treatment data. RESULTS:Pretreatment-corrected 99mTc-mebrofenin liver uptake rates were marginal (1.8-3.0%/min/m2), despite acceptable clinical and laboratory parameters. Posttreatment liver functions seriously declined (corrected 99mTc-mebrofenin liver uptake rates: 0.6-2.4%/min/m2), resulting in lethal radioembolization-induced liver disease in two out of three patients. CONCLUSIONS:Hepatobiliary scintigraphy may be of added value during work-up for radioembolization, to estimate liver function reserve and its segmental distribution, especially in patients with underlying cirrhosis, for whom analysis of clinical and laboratory parameters may not be sufficient.

SUBMITTER: Braat MNGJA

PROVIDER: S-EPMC5215993 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Hepatobiliary scintigraphy may improve radioembolization treatment planning in HCC patients.

Braat Manon N G J A MNGJA de Jong Hugo W HW Seinstra Beatrijs A BA Scholten Mike V MV van den Bosch Maurice A A J MAAJ Lam Marnix G E H MGEH

EJNMMI research 20170105 1

<h4>Background</h4>Routine work-up for transarterial radioembolization, based on clinical and laboratory parameters, sometimes fails, resulting in severe hepatotoxicity in up to 5% of patients. Quantitative assessment of the pretreatment liver function and its segmental distribution, using hepatobiliary scintigraphy may improve patient selection and treatment planning. A case series will be presented to illustrate the potential of this technique. Hepatocellular carcinoma patients with cirrhosis ...[more]

PMID: 28058660

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Project description:Radioembolization is increasingly used as a bridge to resection (i.e., radiation lobectomy). It combines ipsilateral tumor control with the induction of contralateral hypertrophy to facilitate lobar resection. The aim of this pilot study was to investigate the complementary value of hepatobiliary scintigraphy (HBS) before and after radioembolization in the assessment of the future remnant liver. Methods: Consecutive patients with liver tumors who underwent HBS before and after 90Y radioembolization were included. Regional (treated/nontreated) and whole liver function and volume were determined on HBS and CT. Changes in regional liver function and volume were correlated with the functional liver absorbed doses, determined on 90Y PET/CT. In addition, the correlation between liver volume and function change was evaluated. Results: Thirteen patients (10 hepatocellular carcinoma, 3 metastatic colorectal carcinoma) were included. Liver function of the treated part declined after radioembolization (HBS-pre, 4.0%/min/m2; HBS-post, 1.9%/min/m2; P = 0.001), whereas the function of the nontreated part increased (HBS-pre, 1.4%/min/m2; HBS-post, 2.8%/min/m2; P = 0.009). Likewise, treated volume decreased (pretreatment, 1,118.7 cm3; posttreatment, 870.7 cm3; P = 0.003), whereas the nontreated volume increased (pretreatment, 412.7 cm3; posttreatment, 577.6 cm3; P = 0.005). Bland-Altman analysis revealed a large bias (29%) between volume decrease and function decrease in the treated part and wide limits of agreement (-7.7%-65.6%). The bias between volume and function change was smaller (±6.0%) in the nontreated part of the liver, but limits of agreement were still wide (-117.9%-106.7%). Conclusion: Radioembolization induces regional changes in liver function that are accurately detected by HBS. Limits of agreement between function and volume changes were wide, showing large individual differences. This finding indicates that HBS may have a complementary role in the management of patients for radiation lobectomy.

Project description:Background and aimsLocoregional therapies, including yttrium-90 radioembolization, play an important role in the treatment of unresectable HCC. The aim of the LEGACY (Local radioEmbolization using Glass Microspheres for the Assessment of Tumor Control with Y-90) study was to evaluate objective response rate (ORR) and duration of response (DoR) in patients with solitary unresectable HCC treated with yttrium-90 glass microspheres.Approach and resultsLEGACY is a multicenter, single-arm, retrospective study conducted at three sites that included all eligible, consecutive patients with HCC treated with radioembolization between 2014 and 2017. Eligibility criteria included solitary HCC ≤ 8 cm, Child-Pugh A cirrhosis, and Eastern Cooperative Oncology Group performance status 0-1. Primary endpoints were ORR and DoR based on modified Response Evaluation Criteria in Solid Tumors in the treated area (localized), as evaluated by blinded, independent, central review. Radioembolization was performed with intent of ablative-level dosimetry in a selective fashion when possible. Overall survival was evaluated using Kaplan-Meier and multivariate Cox proportional hazards. Among the 162 patients included, 60.5% were Eastern Cooperative Oncology Group 0, and the median tumor size was 2.7 cm (range: 1-8) according to blinded, independent, central review. Radioembolization served as neoadjuvant therapy for transplantation or resection in 21.0% (34 of 162) and 6.8% (11 of 162) of patients, respectively, and as primary treatment for all others. Median follow-up time was 29.9 months by reverse Kaplan-Meier. ORR (best response) was 88.3% (CI: 82.4-92.4), with 62.2% (CI: 54.1-69.8) exhibiting a DoR ≥ 6 months. Three-year overall survival was 86.6% for all patients and 92.8% for those neoadjuvant patients with resected or transplanted liver.ConclusionsIn this multicenter study of radioembolization, clinical meaningful response rates and prolonged DoR were observed in the treatment of unresectable, solitary HCC ≤ 8 cm.

Project description:BackgroundTo confirm the prognostic value of previously published baseline interleukin 6 (IL6) and IL8 cutoff values in survival and liver dysfunction in patients with advanced HCC undergoing 90Y radioembolization.MethodsA total of 83 patients (77 male) represented a subset of HCC patients undergoing 90Y radioembolization combined with sorafenib as part of the prospective multicenter phase II trial SORAMIC. IL6 and IL8 levels were determined in serum samples collected at baseline. In this post hoc analysis, we sought to confirm the prognostic value of baseline cutoff values of 6.53 pg/mL and 60.8 pg/mL for IL6 and IL8, respectively, in overall survival (OS) or liver dysfunction (grade 2 bilirubin increase) after treatment.ResultsMedian OS was 12.0 months. While low baseline albumin and high bilirubin values were associated with high IL6, liver cirrhosis, alcoholic liver disease, and portal vein infiltration were associated with high IL8. In univariate analysis, high baseline IL6 and IL8 were associated with significantly shorter overall survival (7.8 vs. 19.0 months for IL6 and 8.4 vs. 16.0 months for IL8). In addition to IL values, liver cirrhosis, Child-Pugh grade, baseline albumin (< 36 g/dL), and total bilirubin (≥ 17 µmol/L), and higher mALBI grade (2b &3) values were associated with OS. At multivariate analysis, high baseline IL6 was the only independent prognostic factor for OS (HR 2.35 [1.35-4.1], p = 0.002). Risk factors for liver dysfunction were high baseline IL6, albumin, and total bilirubin, and mALBI grade as found in univariate analysis. High baseline IL6 (HR 2.67 [1.21-5.94], p = 0.016) and total bilirubin ≥ 17 µmol/L (HR 3.73 [1.72-8.06], p < 0.001) were independently associated with liver dysfunction.ConclusionIn advanced HCC patients receiving 90Y radioembolization combined with sorafenib, baseline IL6 values proved to be prognostic, confirming previous findings in patients undergoing 90Yradioembolization. IL6 might be useful for patient selection or stratification in future trials.

Project description:PurposeInvestigate reproducibility of two segmentation methods for multicompartment dosimetry, including normal tissue absorbed dose (NTAD) and tumour absorbed dose (TAD), in hepatocellular carcinoma patients treated with yttrium-90 (90Y) glass microspheres.MethodsTARGET was a retrospective investigation in 209 patients with < 10 tumours per lobe and at least one tumour ≥ 3 cm ± portal vein thrombosis. Dosimetry was compared using two distinct segmentation methods: anatomic (CT/MRI-based) and count threshold-based on pre-procedural 99mTc-MAA SPECT. In a round robin substudy in 20 patients with ≤ 5 unilobar tumours, the inter-observer reproducibility of eight reviewers was evaluated by computing reproducibility coefficient (RDC) of volume and absorbed dose for whole liver, whole liver normal tissue, perfused normal tissue, perfused liver, total perfused tumour, and target lesion. Intra-observer reproducibility was based on second assessments in 10 patients ≥ 2 weeks later.Results99mTc-MAA segmentation calculated higher absorbed doses compared to anatomic segmentation (n = 209), 43.9% higher for TAD (95% limits of agreement [LoA]: - 49.0%, 306.2%) and 21.3% for NTAD (95% LoA: - 67.6%, 354.0%). For the round robin substudy (n = 20), inter-observer reproducibility was better for anatomic (RDC range: 1.17 to 3.53) than 99mTc-MAA SPECT segmentation (1.29 to 7.00) and similar between anatomic imaging modalities (CT: 1.09 to 3.56; MRI: 1.24 to 3.50). Inter-observer reproducibility was better for larger volumes. Perfused normal tissue volume RDC was 1.95 by anatomic and 3.19 by 99mTc-MAA SPECT, with corresponding absorbed dose RDC 1.46 and 1.75. Total perfused tumour volume RDC was higher, 2.92 for anatomic and 7.0 by 99mTc-MAA SPECT with corresponding absorbed dose RDC of 1.84 and 2.78. Intra-observer variability was lower for perfused NTAD (range: 14.3 to 19.7 Gy) than total perfused TAD (range: 42.8 to 121.4 Gy).ConclusionAnatomic segmentation-based dosimetry, versus 99mTc-MAA segmentation, results in lower absorbed doses with superior reproducibility. Higher volume compartments, such as normal tissue versus tumour, exhibit improved reproducibility.Trial registrationNCT03295006.

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Hepatobiliary scintigraphy may improve radioembolization treatment planning in HCC patients.

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Hepatobiliary scintigraphy may improve radioembolization treatment planning in HCC patients.

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