title: Multi-disciplinary Concurrent Management of Recurrent Hepatocellular Therapy is Superior to Sequential Therapy.
abstract: Recurrent hepatocellular carcinoma after a patient's initial therapy, whether it is transplantation, resection, or ablation, remains a challenging clinical problem. Since recurrence occurs in 70% of all initially treated disease within 5 years, optimal management to treat this recurrence is needed. Currently, a bias exists toward mono-therapy (i.e., ablation alone, hepatic arterial therapy alone, or sorafenib therapy alone) instead of concurrent sequential therapy-as is common in other primary and metastatic disease to the liver. Thus, the aim of our study was to evaluate the overall survival of recurrent HCC based on either mono-therapy or multimodality therapy.
  
  
  
  A review of our prospective 2245 patient hepato-pancreatico-biliary database was performed for all patients who underwent treatment with curative intent for hepatocellular carcinoma and had complete recurrence treatment data from June 2002 to May 2015. Mono-therapy was defined as initiation of a solitary therapy until disease progression or intolerance. Multimodality therapy was defined as at least 2 therapies that occurred simultaneously or within 4 weeks of each therapy.
  
  
  
  A total of 281 patients underwent treatment with curative intent for hepatocellular carcinoma, in which 192 experienced recurrence. These patients were treated with either thermal ablation or liver resection (LR) (N = 51), transarterial chemoembolization (TACE) or radiation (N = 68), systemic therapy (N = 26), or multimodality therapy (N = 47). The extent of the first recurrence was similar in regard to the number of tumors (median 1), the type of radiologic HCC, gender, BMI, and percentage of liver involvement. They differed in regard to size (MMT largest, median 5.6 cm, p = 0.02), and MMT had higher Hepatitis C involvement (37% of patients, p = 0.001). In evaluation of first recurrence treatment, after a median follow-up of 24 months, multimodality therapy has a significant improvement in overall survival (median 40 months, range 8-85), when compared to LR/Ablation (27 months, range 4-75), TACE/XRT (13 months, range 4-68), and systemic (26 months, range 3-59) (p = 0.003).
  
  
  
  Multimodality therapy should be considered in all patients with recurrent HCC based on tumor biology and underlying hepatic reserve. Hepatocellular cancer should be treated like other hepatic malignancies in which concurrent therapies are utilized simultaneously to optimize oncologic effects (response rates and overall survival) and minimize quality-of-life side effects. Multimodality therapy can lead to far superior overall survival and is well tolerated in the majority of recurrent HCC patients.
authors.affiliation: University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Tyler D
authors.initials: TD
authors.lastname: Fields
authors.affiliation: University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Prejesh
authors.initials: P
authors.lastname: Philips
authors.affiliation: University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Scoggins
authors.affiliation: University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Cliff
authors.initials: C
authors.lastname: Tatum
authors.affiliation: University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kelly
authors.affiliation: University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McMasters
authors.affiliation: University of Louisville School of Medicine, Louisville, KY, USA. robert.martin@louisville.edu.
authors.forename: Robert C G
authors.initials: RCG
authors.lastname: Martin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000628:therapy*; D017115:Catheter Ablation; D016461:Chemoembolization, Therapeutic; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000628:therapy*; D018714:Radiotherapy, Adjuvant; D055815:Young Adult