Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma

Riad Salem*, Andrew C. Gordon, Samdeep K Mouli, Ryan M Hickey, Joseph Kallini, Ahmed Gabr, Mary Frances Mulcahy, Talia Baker, Michael Messod Abecassis, Frank H Miller, Vahid Yaghmai, Kent T Sato, Kush R Desai, Bartley Garver Thornburg, Al B Benson III, Alfred W Rademaker, Daniel R Ganger, Laura M Kulik, Robert J Lewandowski

*Corresponding author for this work

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122 Citations (Scopus)

Abstract

Background & Aims Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. Methods From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50% Child–Pugh A) or cTACE (n = 21; 71% Child–Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan–Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses. Results Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P =.0012) (hazard ratio, 0.122; 95% confidence interval [CI], 0.027–0.557; P =.007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P =.031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group; P <.001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) (P =.433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3–not calculable) vs 18.6 months for the Y90 group (95% CI, 7.4–32.5) (P =.99). Conclusions In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930.

Original languageEnglish (US)
Pages (from-to)1155-1163.e2
JournalGastroenterology
Volume151
Issue number6
DOIs
StatePublished - Dec 1 2016

Fingerprint

Yttrium
Carcinoma
Hepatocellular Carcinoma
Liver Neoplasms
Confidence Intervals
Necrosis
Hypoalbuminemia
Neoplasms
Intention to Treat Analysis
Survival
Liver Transplantation
Blood Vessels
Diarrhea
Therapeutics
Transplantation

Keywords

  • Chemoembolization
  • Liver Cancer
  • Radioembolization
  • Randomized Trial

ASJC Scopus subject areas

  • Gastroenterology

Cite this

@article{2712d05e194d4facbda8c95086fd1fbc,
title = "Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma",
abstract = "Background & Aims Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. Methods From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50{\%} Child–Pugh A) or cTACE (n = 21; 71{\%} Child–Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan–Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses. Results Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P =.0012) (hazard ratio, 0.122; 95{\%} confidence interval [CI], 0.027–0.557; P =.007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21{\%}) than in the Y90 group (0{\%}; P =.031) or hypoalbuminemia (58{\%} in the cTACE group vs 4{\%} in the Y90 group; P <.001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74{\%} in the cTACE group vs 87{\%} in the Y90 group) (P =.433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95{\%} CI, 8.3–not calculable) vs 18.6 months for the Y90 group (95{\%} CI, 7.4–32.5) (P =.99). Conclusions In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930.",
keywords = "Chemoembolization, Liver Cancer, Radioembolization, Randomized Trial",
author = "Riad Salem and Gordon, {Andrew C.} and Mouli, {Samdeep K} and Hickey, {Ryan M} and Joseph Kallini and Ahmed Gabr and Mulcahy, {Mary Frances} and Talia Baker and Abecassis, {Michael Messod} and Miller, {Frank H} and Vahid Yaghmai and Sato, {Kent T} and Desai, {Kush R} and Thornburg, {Bartley Garver} and {Benson III}, {Al B} and Rademaker, {Alfred W} and Ganger, {Daniel R} and Kulik, {Laura M} and Lewandowski, {Robert J}",
year = "2016",
month = "12",
day = "1",
doi = "10.1053/j.gastro.2016.08.029",
language = "English (US)",
volume = "151",
pages = "1155--1163.e2",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "6",

}

TY - JOUR

T1 - Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma

AU - Salem, Riad

AU - Gordon, Andrew C.

AU - Mouli, Samdeep K

AU - Hickey, Ryan M

AU - Kallini, Joseph

AU - Gabr, Ahmed

AU - Mulcahy, Mary Frances

AU - Baker, Talia

AU - Abecassis, Michael Messod

AU - Miller, Frank H

AU - Yaghmai, Vahid

AU - Sato, Kent T

AU - Desai, Kush R

AU - Thornburg, Bartley Garver

AU - Benson III, Al B

AU - Rademaker, Alfred W

AU - Ganger, Daniel R

AU - Kulik, Laura M

AU - Lewandowski, Robert J

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Background & Aims Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. Methods From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50% Child–Pugh A) or cTACE (n = 21; 71% Child–Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan–Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses. Results Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P =.0012) (hazard ratio, 0.122; 95% confidence interval [CI], 0.027–0.557; P =.007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P =.031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group; P <.001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) (P =.433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3–not calculable) vs 18.6 months for the Y90 group (95% CI, 7.4–32.5) (P =.99). Conclusions In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930.

AB - Background & Aims Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. Methods From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50% Child–Pugh A) or cTACE (n = 21; 71% Child–Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan–Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses. Results Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P =.0012) (hazard ratio, 0.122; 95% confidence interval [CI], 0.027–0.557; P =.007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P =.031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group; P <.001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) (P =.433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3–not calculable) vs 18.6 months for the Y90 group (95% CI, 7.4–32.5) (P =.99). Conclusions In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930.

KW - Chemoembolization

KW - Liver Cancer

KW - Radioembolization

KW - Randomized Trial

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U2 - 10.1053/j.gastro.2016.08.029

DO - 10.1053/j.gastro.2016.08.029

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VL - 151

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JO - Gastroenterology

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