Individualised dosimetry and safety of SIRT for intrahepatic cholangiocarcinoma

Kathy P Willowson, Enid M Eslick, Dale L Bailey, Kathy P Willowson, Enid M Eslick, Dale L Bailey

Abstract

Background: The aim of this study was to investigate the safety and efficacy of selective internal radiation therapy (SIRT) with 90Y resin microspheres for the treatment of Intrahepatic Cholangiocarcinoma (ICC). A total of 23 SIRT procedures from 18 ICC subjects were analysed to determine a lesion-based dose/response relationship with absorbed dose measures from 90Y PET and metabolic response as measured on [18F]FDG PET. Average absorbed dose (Davg), minimum dose to 70% of the volume (D70), volume receiving at least 50 Gy (V50), biological effective dose (BED) and equivalent uniform dose (EUD), were compared to changes in metabolic volume, maximum standardised uptake value (SUVmax) and total lesion glycolysis (TLG). Dose to normal liver was assessed with changes in liver uptake rate as measured with [99mTc]mebrofenin scintigraphy for a cohort of 20 subjects with primary liver malignancy (12 ICC, 8 hepatocellular carcinoma (HCC)).

Results: Thirty-four lesions were included in the analysis. A relationship was found between metabolic response and both Davg and EUD similar to that seen previously in metastatic colorectal cancer (mCRC), albeit trending towards a lower response plateau. Both dose and SUV coefficient of variation within the lesion (CoVdose and CoVSUV), baseline TLG and EUD were found to be mildly significant predictors of response. No strong correlation was seen between normal liver dose and change in [99mTc]mebrofenin liver uptake rate; low baseline uptake rate was not indicative of declining function following SIRT, and no subjects dropped into the 'poor liver function' category.

Conclusions: ICC lesions follow a similar dose-response trend as mCRC, however, despite high lesion doses a full metabolic response was rarely seen. The CoV of lesion dose may have a significant bearing on response, and EUD correlated more tightly with metabolic response compared to Davg. SIRT in primary liver malignancy appears safe in terms of not inducing a clinically significant decline in liver function, and poor baseline uptake rate is not predictive of a reduction in function post SIRT.

Keywords: Cholangiocarcinoma; Radioembolisation; SIRT.

Conflict of interest statement

The authors have no existing or potential conflicts of interest to declare.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Linear relationship between CoVdose and lesion response (R2 = 0.48)
Fig. 2
Fig. 2
The relationship between average dose (a) and equivalent uniform dose (b) and lesion response, as measured by reduction in TLG. The line of fit in a is represented by the equation y = 103.4–3656.9/x, with a R2 value of 0.49; and for (B) y = 104.2–3642.7/x, with a R2 value of 0.57
Fig. 3
Fig. 3
Comparison of baseline Bilirubin measures in blood and baseline global liver uptake rate as measured by 99mTc-mebrofenin dynamic scintigraphy
Fig. 4
Fig. 4
Change in liver function, as measured by the global liver uptake rate (%/min) from 99mTc-mebrofenin dynamic scintigraphy, with the mean absorbed dose to healthy liver parenchyma following SIRT (R2 of linear fit is 0.104)

References

    1. Dhanasekaran R, Hemming AW, Zendejas I, et al. Treatment outcomes and prognostic factors of intrahepatic cholangiocarcinoma. Oncol Rep. 2013;29(4):1259–1267. doi: 10.3892/or.2013.2290.
    1. Mouli S, Memon K, Baker T, et al. Yttrium-90 radioembolization for intrahepatic cholangiocarcinoma: safety, response, and survival analysis. J Vasc Intervent Radiol: JVIR. 2013 doi: 10.1016/j.jvir.2013.02.031.
    1. Zhen YA-O, Liu BA-O, Chang ZA-O, Ren HA-O, Liu ZA-OX, Zheng JA-O. A pooled analysis of transarterial radioembolization with yttrium-90 microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma. OncoTargets Therapy. 2019;12:4489. doi: 10.2147/OTT.S202875.
    1. Manceau V, Palard X, Rolland Y, et al. A MAA-based dosimetric study in patients with intrahepatic cholangiocarcinoma treated with a combination of chemotherapy and 90Y-loaded glass microsphere selective internal radiation therapy. Eur J Nucl Med Mol Imaging. 2018;45(10):1731–1741. doi: 10.1007/s00259-018-3990-7.
    1. Lam MGEH, Banerjee A, Goris ML, et al. Fusion dual-tracer SPECT-based hepatic dosimetry predicts outcome after radioembolization for a wide range of tumour cell types. Eur J Nucl Med Mol Imaging. 2015;42(8):1192–1201. doi: 10.1007/s00259-015-3048-z.
    1. Levillain HA-OX, Duran Derijckere I, Ameye L, et al. Personalised radioembolization improves outcomes in refractory intra-hepatic cholangiocarcinoma: a multicenter study. Eur J Nucl Med Mol Imaging. 2019;46:2270–2279. doi: 10.1007/s00259-019-04427-z.
    1. Wondergem M, Smits M, Elschot M, et al. Tc-99m-macroaggregated albumin poorly predicts the intrahepatic distribution of Y-90 resin microspheres in hepatic radioembolization. J Nucl Med: Off Publ Soc Nucl Med. 2013 doi: 10.2967/jnumed.112.117614.
    1. Lhommel R, Elmbt L, Goffette P, et al. Feasibility of 90Y TOF PET-based dosimetry in liver metastasis therapy using SIR-spheres. Eur J Nucl Med Mol Imaging. 2010;37(9):1654–1662. doi: 10.1007/s00259-010-1470-9.
    1. Song YS, Paeng JC, Kim H-C, et al. PET/CT-based dosimetry in 90Y-microsphere selective internal radiation therapy: single cohort comparison with pretreatment planning on (99m)Tc-MAA imaging and correlation with treatment efficacy. Medicine (Baltimore) 2015;94(23):e945–e1045. doi: 10.1097/MD.0000000000000945.
    1. Willowson K, Hayes A, Bernard E, Maher R, Bailey D. Image based prognostic factors in predicting response to Y-90 SIRT. J Nucl Med. 2017;58(supplement 1):114.
    1. Levillain H, Duran Derijckere I, Marin G, et al. (90)Y-PET/CT-based dosimetry after selective internal radiation therapy predicts outcome in patients with liver metastases from colorectal cancer. EJNMMI Res. 2018;8(1):60–60. doi: 10.1186/s13550-018-0419-z.
    1. Kafrouni M, Allimant C, Fourcade M, et al. Analysis of differences between 99mTc-MAA SPECT- and 90Y-microsphere PET-based dosimetry for hepatocellular carcinoma selective internal radiation therapy. EJNMMI Res. 2019;9(1):62. doi: 10.1186/s13550-019-0533-6.
    1. Levillain HA-OX, Bagni OA-O, Deroose CA-O, et al. International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres. Eur J Nucl Med Mol Imaging. 2021;48:1570–1584. doi: 10.1007/s00259-020-05163-5.
    1. Willowson KP, Tapner M, Team Q, Bailey DL. A multicentre comparison of quantitative (90)Y PET/CT for dosimetric purposes after radioembolization with resin microspheres: the QUEST phantom study. Eur J Nucl Med Mol Imaging. 2015;42(8):1202–22. 10.1007/s00259-015-3059-9
    1. Cremonesi M, Chiesa C, Strigari L, et al. Radioembolization of hepatic lesions from a radiobiology and dosimetric perspective. Fron Oncol. 2014;4:210.
    1. d’Abadie P, Hesse M, Jamar F, Lhommel R, Walrand S. (90)Y TOF-PET based EUD reunifies patient survival prediction in resin and glass microspheres radioembolization of HCC tumours. Phys Med Biol. 2018;63:245010. doi: 10.1088/1361-6560/aaf205.
    1. Willowson KP, Schembri GP, Bernard EJ, Chan DL, Bailey DL. Quantifying the effects of absorbed dose from radioembolisation on healthy liver function with [99mTc]Tcmebrofenin. Eur J Nucl Med Mol Imaging. 2020;47(4):838–848. doi: 10.1007/s00259-020-04686-1.
    1. Tann M, Woolen S, Swallen A, Nelson A, Fletcher J. Establishing a normal reference range for mebrofenin clearance rate (MCR) for overall liver function assessment. J Nucl Med. 2015;56:A49.
    1. Dewaraja YK, Devasia T, Kaza RK, et al. Prediction of tumor control in 90Y radioembolization by logit models with PET/CT-based dose metrics. J Nucl Med. 2020;61(1):104. doi: 10.2967/jnumed.119.226472.
    1. Tao R, Krishnan S, Bhosale PR, et al. Ablative radiotherapy doses lead to a substantial prolongation of survival in patients with inoperable intrahepatic cholangiocarcinoma: a retrospective dose response analysis. J Clin Oncol. 2016;34:219. doi: 10.1200/JCO.2015.61.3778.
    1. Abbott EM, Falzone N, Lee BQ, et al. The impact of radiobiologically-informed dose prescription on the clinical benefit of yttrium-90 SIRT in colorectal cancer patients. J Nucl Med. 2020 doi: 10.2967/jnumed.119.233650.
    1. Gholami Y, Willowson K, Forwood N, et al. Comparison of radiobiological parameters for 90Y radionuclide therapy (RNT) and external beam radiotherapy (EBRT) in vitro. EJNMMI Phys. 2018 doi: 10.1186/s40658-018-0217-8.
    1. Craciun L, de Wind R, Demetter P, et al. Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy. BMC Cancer. 2020;20(1):135–235. doi: 10.1186/s12885-020-6613-1.

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