title: Burden of disease predicts response to isolated limb infusion with melphalan and actinomycin D in melanoma.
abstract: BACKGROUND
  Isolated limb infusion (ILI) with melphalan is a minimally invasive, effective treatment for in transit melanoma. We hypothesized that burden of disease (BOD) would correlate to treatment response.
  
  
  METHODS
  We retrospectively analyzed a prospectively collected database from two academic centers. BOD was stratified as high or low (low ≤ 10 lesions, none >2 cm). Response rates were measured 3 months post-ILI. Multivariable analysis (MV) was used to evaluate the association between the response and BOD. Kaplan-Meier methods with log-rank tests and MV Cox proportional hazard models were used to analyze overall survival (OS) and progression free survival (PFS).
  
  
  RESULTS
  Sixty (38 %) patients had low and 100 (62 %) high BOD. Patients with low BOD had an overall response rate (ORR) of 73 % with 50 % CR, compared with an ORR of 47 % with 24 % CR in patients with high BOD (p = 0.002). MV analysis of preoperative, intraoperative, and postoperative parameters showed no significant impact on 3-month response. Patients with a CR at 3 months demonstrated improved PFS over the remainder of the cohort, but OS was similar. Low BOD patients had an increased median PFS of 6.9 versus 3.8 months (p = 0.047) and a increased median OS of 38.4 versus 30.9 months (p = 0.146).
  
  
  CONCLUSIONS
  Lower BOD is associated with an increased ORR and CR rate with statistically significantly improved PFS in patients undergoing ILI for in transit extremity melanoma. BOD provides useful prognostic information for patient counseling and serves as a marker to stratify patient risk groups.
authors.affiliation: Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Diego J
authors.initials: DJ
authors.lastname: Muilenburg
authors.forename: Georgia M
authors.initials: GM
authors.lastname: Beasley
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Thompson
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Tyler
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Zager
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods; D003609:Dactinomycin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007866:Leg; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D015999:Multivariate Analysis; D009366:Neoplasm Seeding; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D003609:Dactinomycin; D008558:Melphalan