title: Prospective evaluation of patients with early-/intermediate-stage hepatocellular carcinoma with disease progression following arterial locoregional therapy: candidacy for systemic treatment or clinical trials.
abstract: OBJECTIVE
  During the course of cancer treatment, patients whose disease progresses despite therapy are offered alternative options. Similarly, patients with hepatocellular carcinoma (HCC) whose disease progresses following arterial locoregional therapies (LRTs) cross over to undergo systemic therapies or participate in clinical trials. Per current guidelines, patients must meet inclusion criteria (most importantly Child-Pugh class A status) to qualify for systemic options. The present study analyzed the candidacy for systemic agents or clinical trials of patients whose disease progresses despite LRTs.
  
  
  METHODS
  A total of 245 patients with HCC were treated with LRTs (chemoembolization, n = 123; yttrium-90 [(90)Y] radioembolization, n = 122) as part of a previously published comparative effectiveness study; 96 patients exhibiting disease progression were followed prospectively. Modes of progression (cancer stage, Child-Pugh class) were analyzed to determine candidacy for systemic therapy or clinical trials, as well as assess ultimate treatment(s) received.
  
  
  RESULTS
  Among the 96 patients with disease progression, 52% and 48% had Child-Pugh class A and class B/C disease, respectively, thereby substantially limiting the latter group's eligibility for systemic therapy and/or clinical trials. Of those whose disease progressed who had advanced-stage HCC, 63% had Child-Pugh class B/C disease. By size and necrosis criteria, the local disease progression rate was higher with chemoembolization than with (90)Y radioembolization (P = .006 and P = .016, respectively). Of the 96 patients with disease progression, only 13 (13%) ultimately received systemic agents or entered clinical trials.
  
  
  CONCLUSIONS
  Most patients with advanced HCC that progresses following LRTs were not candidates for clinical trials or systemic agents. There is a need for future research efforts directed at treatment options or novel trial designs that will permit inclusion of patients with progressive liver disease and suboptimal liver function.
authors.affiliation: Department of Radiology, Section of Interventional Radiology, and Division of Interventional Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Khairuddin
authors.initials: K
authors.lastname: Memon
authors.forename: Laura
authors.initials: L
authors.lastname: Kulik
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lewandowski
authors.forename: Ramona
authors.initials: R
authors.lastname: Gupta
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ryu
authors.forename: Frank H
authors.initials: FH
authors.lastname: Miller
authors.forename: Michael
authors.initials: M
authors.lastname: Vouche
authors.forename: Rohi
authors.initials: R
authors.lastname: Atassi
authors.forename: Daniel
authors.initials: D
authors.lastname: Ganger
authors.forename: Mary F
authors.initials: MF
authors.lastname: Mulcahy
authors.forename: Riad
authors.initials: R
authors.lastname: Salem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016461:Chemoembolization, Therapeutic; D016009:Chi-Square Distribution; D002986:Clinical Trials as Topic / Q000379:methods*; D018450:Disease Progression; D004608:Eligibility Determination; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes
keywords: BCLC; Barcelona Clinic Liver Cancer; EASL; European Association for the Study of the Liver; HCC; LRT; NCT; National Clinical Trials; PD; TTP; UNOS; United Network for Organ Sharing; WHO; World Health Organization; hepatocellular carcinoma; locoregional therapy; progressive disease; time to progression