title: Patterns and challenges of treatment sequencing in patients with hepatocellular carcinoma: Experience from a German referral center.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers. Several local and systemic therapies are available for patients with HCC depending on the stage of the disease. In clinical practice, treatment decision-making, and sequencing may be very heterogeneous.
  
  
  METHODS
  In this study, we retrospectively analyzed treatment algorithms in 2101 patients with HCC treated from 2000 to 2015 at Hannover Medical School, Germany.
  
  
  RESULTS
  Transarterial chemoembolization was the most common initial treatment (n = 545; 25.9%), followed by resection (n = 435, 20.7%), local-ablative procedures (n = 283, 13.5%), systemic therapies (n = 275, 13.1%), and liver transplantation (n = 52; 2.5%). Most patients were treated only once (n = 960; 59.6%). A total of 433 (26.9%) and 160 (9.9%) patients received a second line and third line treatment after recurrent or progressive disease. Patients with more than one treatment line were diagnosed at significantly earlier disease stages (P < 0.001). Using binary logistic regression, AFP ≤ 200 μg/L, albumin > 36 g/L, and small tumor size (≤50 mm) were identified as predictors of achieving more than one treatment line. Subsequent treatment stage migration to a therapy suggested for the next advanced stage occurred only in 56.9%, whereas 43.1% received treatments suggested for earlier disease stages. Only 16% of all treated patients received systemic therapy in the salvage setting.
  
  
  CONCLUSIONS
  Most patients were treated only once, and only a minority of patients received systemic treatment. The high dropout rate for subsequent therapies needs to be considered within therapy decision-making. There is an urgent need for prospective studies to define the best time point when to switch patients from local to systemic therapies.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Martha M
authors.initials: MM
authors.lastname: Kirstein
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Schweitzer
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Winter
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Katerina
authors.initials: K
authors.lastname: Lappas
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Graen
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Kunstmann
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Voigtländer
authors.affiliation: Institute for Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Reineke-Plaaß
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Lehner
authors.affiliation: Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rodt
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Vogel
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000706:statistics & numerical data; D000066491:Clinical Decision-Making; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D042241:Early Diagnosis; D005260:Female; D005858:Germany; D006498:Hepatectomy / Q000706:statistics & numerical data; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D016031:Liver Transplantation / Q000706:statistics & numerical data; D008297:Male; D009367:Neoplasm Staging; D012189:Retrospective Studies; D062606:Tertiary Care Centers
keywords: TACE; liver transplantation; radiofrequency ablation; sorafenib; treatment lines