title: Predicting disease progression after regional therapy for in-transit melanoma.
abstract: OBJECTIVE
  Although approximately 30% to 50% of patients experience a complete response after regional chemotherapy for in-transit melanoma, a subset of patients will develop rapidly progressive disease. In the current era of an expanding armamentarium, including both regional and systemic options for treating advanced melanoma, identifying perioperative factors that predict disease progression may obviate unnecessary morbidity associated with regional therapy and avoid delays in systemic therapy.
  
  
  OBJECTIVE
  To identify patient-related clinical and pathological variables, as well as procedural factors, that correlate with disease progression.
  
  
  METHODS
  Using a prospectively maintained database, we identified patients who either underwent first-time melphalan-based isolated limb infusion (ILI) or first-time hyperthermic isolated limb perfusion (HILP) for in-transit melanoma. Response was defined using modified Response Evaluation Criteria in Solid Tumors for cutaneous disease at 3 months after treatment. Survival analyses were performed using the Kaplan-Meier method, with the differences in survival curves compared using a log-rank test. Potential preoperative and procedural predictors of in-field progressive disease were analyzed using logistic regression.
  
  
  METHODS
  Of the 258 patients included in the database, 215 were identified as having undergone first-time regional therapy. Of these 215 patients, 134 underwent ILI, and 81 underwent HILP.
  
  
  METHODS
  Regional therapy (ILI or HILP).
  
  
  METHODS
  Complete response or progressive disease.
  
  
  RESULTS
  Of 134 patients who underwent ILI, 43 (32.1%) experienced in-field progressive disease. Of 81 patients who underwent HILP, 9 (11.1%) experienced in-field progressive disease. The median survival for patients with in-field progressive disease was 20.3 months for the ILI cohort and 15.0 months for the HILP cohort. In general, patients with progressive disease were younger, with advanced-stage melanoma and increased tumor burden. Compared with patients who experienced a complete response, patients with in-field progressive disease after ILI were younger (odds ratio, 1.06 [95% CI, 0.90-0.98]; P = .002). For patients who underwent HILP, no clinically relevant preoperative predictors of in-field progressive disease were identified. Procedural variables, including chemotherapeutic dosing, degree of acidosis or base deficit achieved, and peak temperature attained, were not predictors of in-field progressive disease after ILI or HILP.
  
  
  CONCLUSIONS
  Patient, clinical, and procedural factors are unreliable predictors of in-field progressive disease after regional therapy in patients with in-transit melanoma. Defining the potential utility of molecular markers in predicting response or failure of regional therapy should be the focus of future research efforts.
authors.affiliation: Department of Surgery, Duke University Medical Center, 2301 Erwin Rd, Durham, NC 27710, USA. michael.lidsky@duke.edu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Lidsky
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Turley
authors.forename: Georgia M
authors.initials: GM
authors.lastname: Beasley
authors.forename: Ketan
authors.initials: K
authors.lastname: Sharma
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Tyler
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008558:Melphalan / Q000008:administration & dosage / Q000493:pharmacokinetics; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan
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