Short-term Safety and Quality of Life Outcomes Following Radioembolization in Primary and Secondary Liver Tumours: a Multi-centre Analysis of 200 Patients in France

Romaric Loffroy, Maxime Ronot, Michel Greget, Antoine Bouvier, Charles Mastier, Christian Sengel, Lambros Tselikas, Dirk Arnold, Geert Maleux, Jean-Pierre Pelage, Olivier Pellerin, Bora Peynircioglu, Bruno Sangro, Niklaus Schaefer, María Urdániz, Nathalie Kaufmann, José Ignacio Bilbao, Thomas Helmberger, Valérie Vilgrain, CIRT-FR Principal Investigators, Gilles Piana, Julien Frandon, Jean-Pierre Tasu, Hicham Kobeiter, Romaric Loffroy, Maxime Ronot, Michel Greget, Antoine Bouvier, Charles Mastier, Christian Sengel, Lambros Tselikas, Dirk Arnold, Geert Maleux, Jean-Pierre Pelage, Olivier Pellerin, Bora Peynircioglu, Bruno Sangro, Niklaus Schaefer, María Urdániz, Nathalie Kaufmann, José Ignacio Bilbao, Thomas Helmberger, Valérie Vilgrain, CIRT-FR Principal Investigators, Gilles Piana, Julien Frandon, Jean-Pierre Tasu, Hicham Kobeiter

Abstract

Purpose: Radioembolization has emerged as a treatment modality for patients with primary and secondary liver tumours. This observational study CIRT-FR (CIRSE Registry for SIR-Spheres Therapy in France) aims to evaluate real-life clinical practice on all patients treated with transarterial radioembolization (TARE) using SIR-Spheres yttrium-90 resin microspheres in France. In this interim analysis, safety and quality of life data are presented. Final results of the study, including secondary effectiveness outcomes, will be published later. Overall, CIRT-FR is aiming to support French authorities in the decision making on reimbursement considerations for this treatment.

Methods: Data on patients enrolled in CIRT-FR from August 2017 to October 2019 were analysed. The interim analysis describes clinical practice, baseline characteristics, safety (adverse events according to CTCTAE 4.03) and quality of life (according to EORTC QLQ C30 and HCC module) aspects after TARE.

Results: This cohort included 200 patients with hepatocellular carcinoma (114), metastatic colorectal cancer (mCRC; 38) and intrahepatic cholangiocarcinoma (33) amongst others (15). TARE was predominantly assigned as a palliative treatment (79%). 12% of patients experienced at least one adverse event in the 30 days following treatment; 30-day mortality was 1%. Overall, global health score remained stable between baseline (66.7%), treatment (62.5%) and the first follow-up (66.7%).

Conclusion: This interim analysis demonstrates that data regarding safety and quality of life generated by randomised-controlled trials is reflected when assessing the real-world application of TARE.

Trial registration: Clinical Trials.gov NCT03256994.

Keywords: Interim analysis; Radioembolization; SIR-spheres; SIRT; Transarterial radioembolization; Yttrium-90.

Conflict of interest statement

RL, MG reported consultancy to SIRTEX Medical; LT received speaker fees from SIRTEX Medical and fees from Boston Scientific, Amgen, Ipsen and GE healthcare as well as grants from BMS and Terumo Medical; DA received consulting fees and speaker honoraria from Terumo, Boston Scientific, SIRTEX Medical and Biocompatibles; GM and JIB reported to act as proctor and speaker for SIRTEX; J-PP was speaker at the SIRTEX symposium and investigator of SIRFLOX and SARAH studies, consultant for Merit Medical, Terumo and Guerbet and received research grants from Guerbet and Merit Medical; BP reported occasional proctor activities for SIRTEX Medical; BS received lecture and/or consulting fees from Adaptimmune, Bayer, BMS, BTG, Eisai, Ipsen, Lilly, Roche and Sirtex, research fees from BMS and SIRTEX Medical. VV received speaker fees from SIRTEX Medical, Supersonic Imagine, Canon, as well as grants from Guerbet. MR, AB, CM, CS, OP, NS, MU, NK, TH declared no conflict of interest. All authors report no conflict of interest directly related to the submitted work.

Figures

Fig. 1
Fig. 1
Health-related quality of life over time (EORTC-QLQ 30). Shows HRQOL score of 46 patients (A-F) and 25 patients (G, H) collected at baseline (before the first treatment), right after treatment (within 1 week later) and at the first follow-up (13 weeks after treatment on average) by analysing global health (A, B), functionality (C, D), symptoms (E, F) and HCC18 module (G, H) score according to EORTC-QLQ30 version 3.0 and the EORTC QLQ-HCC18 version 2.0. For the global health and the functional score, a high score indicates high health and for the symptoms and HCC18 scale a low score indicates few symptoms and better HRQOL, respectively. For general comparisons between baseline to right after treatment and baseline to the first follow-up, boxplots were used (A, C, E, G). The difference between baseline to right after treatment (black) and baseline to first follow-up (light colour) was plotted for individual patients using a waterfall diagram (B, D, F, H). Cut-offs (dashed line) for clinically significant improvement were set at + 10 for global health, functional score, − 10 for symptoms score, HCC18 module and at -10 for global health, functional score and + 10 for symptoms score, HCC18 module for deterioration

References

    1. Golfieri R. SIR-Spheres yttrium-90 radioembolization for the treatment of unresectable liver cancers. Hepatic Oncol. 2014;1:265–283. doi: 10.2217/hep.14.6.
    1. Mosconi C, Cappelli A, Pettinato C, Golfieri R. Radioembolization with Yttrium-90 microspheres in hepatocellular carcinoma: Role and perspectives. World J Hepatol. 2015;7:738–752. doi: 10.4254/wjh.v7.i5.738.
    1. Vogel A, Cervantes A, Chau I, et al. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018;29:iv238–iv255. 10.1093/annonc/mdy308
    1. Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386–1422. doi: 10.1093/annonc/mdw235.
    1. Memon K, Lewandowski RJ, Kulik L, et al. Radioembolization for primary and metastatic liver cancer. Semin Radiat Oncol. 2011;21:294–302. doi: 10.1016/j.semradonc.2011.05.004.
    1. Salem R, Lewandowski RJ, Gates VL, et al. Research reporting standards for radioembolization of hepatic malignancies. J Vasc Interv Radiol. 2011;22:265–278. doi: 10.1016/j.jvir.2010.10.029.
    1. Galle PR, Forner A, Llovet JM, et al. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236. doi: 10.1016/j.jhep.2018.03.019.
    1. Helmberger T, Arnold D, Bilbao JI, et al. Clinical application of radioembolization in hepatic malignancies: Protocol for a prospective multicenter observational study. J Med Internet Res. 2020;22: 10.2196/16296.
    1. Helmberger T, Golfieri R, Pech M, et al. Clinical Application of TARE in Hepatic Malignances in Eurpoe: first results from the prospective multicentre observational study CIRSE Registry for SIR-Spheres Therapy (CIRT). Cardiovasc Interv Radiol 2020 (in press)
    1. Vilgrain V, Pereira H, Assenat E, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2017;18:1624–1636. doi: 10.1016/S1470-2045(17)30683-6.
    1. Chow PKH, Gandhi M, Tan SB, et al. SIRveNIB: Selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol. 2018;36:1913–1921. doi: 10.1200/JCO.2017.76.0892.
    1. Fayers P, Bottomley A. Quality of life research within the EORTC—The EORTC QLQ-C30. Eur J Cancer. 2002;38:125–133. doi: 10.1016/s0959-8049(01)00448-8.
    1. NCI, NIH D (2009) Common Terminology Criteria for Adverse Events v4.0. NIH Publ 2009:0–71
    1. Blazeby JM, Currie E, Zee BCY, et al. Development of a questionnaire module to supplement the EORTC QLQ-C30 to assess quality of life in patients with hepatocellular carcinoma, the EORTC QLQ-HCC18. Eur J Cancer. 2004;40:2439–2444. doi: 10.1016/j.ejca.2004.06.033.
    1. Cocks K, King MT, Velikova G, et al. Evidence-based guidelines for determination of sample size and interpretation of the European organisation for the research and treatment of cancer quality of life questionnaire core 30. J Clin Oncol. 2011;29:89–96. doi: 10.1200/JCO.2010.28.0107.
    1. Kolligs FT, Bilbao JI, Jakobs T, et al. Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma. Liver Int. 2015;35:1715–1721. doi: 10.1111/liv.12750.
    1. Ricke J, Bulla K, Kolligs F, et al. Safety and toxicity of radioembolization plus Sorafenib in advanced hepatocellular carcinoma: analysis of the European multicentre trial SORAMIC. Liver Int. 2015;35:620–626. doi: 10.1111/liv.12622.
    1. Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, Mulcahy MF, Baker T, Abecassis M, Miller F, Yaghmai V, Sato K, Desai K, Thornburg B, Benson AB. RE: Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2017;152:1625–1626. doi: 10.1053/j.gastro.2016.09.069.
    1. White J, Carolan-Rees G, Dale M, et al. Yttrium-90 transarterial radioembolization for chemotherapy-refractory intrahepatic cholangiocarcinoma: a prospective, observational study. J Vasc Interv Radiol. 2019;30:1185–1192. doi: 10.1016/j.jvir.2019.03.018.
    1. Salem R, Lewandowski RJ, Kulik L, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011;140:497–507.e2. doi: 10.1053/j.gastro.2010.10.049.
    1. White J, Carolan-Rees G, Dale M, et al. Analysis of a national programme for selective internal radiation therapy for colorectal cancer liver metastases. Clin Oncol. 2019;31:58–66. doi: 10.1016/j.clon.2018.09.002.
    1. Gangi A, Shah J, Hatfield N, et al. Intrahepatic cholangiocarcinoma treated with transarterial Yttrium-90 glass microsphere radioembolization: results of a single institution retrospective study. J Vasc Interv Radiol. 2018;29:1101–1108. doi: 10.1016/j.jvir.2018.04.001.
    1. Bourien H, Palard X, Rolland Y, et al. Yttrium-90 glass microspheres radioembolization (RE) for biliary tract cancer: a large single-center experience. Eur J Nucl Med Mol Imaging. 2019;46:669–676. doi: 10.1007/s00259-018-4199-5.
    1. Khor AYK, Toh Y, Allen JC, et al. Survival and pattern of tumor progression with yttrium-90 microsphere radioembolization in predominantly hepatitis B Asian patients with hepatocellular carcinoma. Hepatol Int. 2014;8:395–404. doi: 10.1007/s12072-014-9533-9.
    1. Kim DY, Park BJ, Kim YH, et al. Radioembolization with Yttrium-90 resin microspheres in hepatocellular carcinoma: a multicenter prospective study. Am J Clin Oncol Cancer Clin Trials. 2015;38:495–501. doi: 10.1097/COC.0b013e3182a78dba.
    1. Sangro B, Carpanese L, Cianni R, et al. Survival after Yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology. 2011;54:868–878. doi: 10.1002/hep.24451.
    1. Salem R, Gilbertsen M, Butt Z, et al. Increased quality of life among hepatocellular carcinoma patients treated with radioembolization, compared with chemoembolization. Clin Gastroenterol Hepatol. 2013;11:1358–1365.e1. doi: 10.1016/j.cgh.2013.04.028.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe