title: Regional hyperthermia for high-risk soft tissue sarcoma treatment: present status and next questions.
abstract: Recent developments of neo-adjuvant chemotherapy treatment strategies for high-risk soft tissue sarcoma (STS) with special emphasis on regional hyperthermia (RHT) are reviewed.
  
  
  
  Attempts to improve outcomes using up-front strategies in addition to surgery have essentially focused on neo-adjuvant and adjuvant chemotherapy or preoperative radiochemotherapy. Unfortunately, the results are either confounded by retrospective analyses of nonrandomized studies with small sample size or are negative showing no substantial clinical benefit in the few randomized trials. RHT targets the region of tumor burden by heat. The pleotropic effects on malignant cells and tumor stroma to counteract tumor growth and progression have been recently summarized as hallmarks of hyperthermia. An updated analysis of a completed EORTC-ESHO Intergroup randomized phase 3 trial for the most common types of high-risk STS demonstrates a significantly improved long-term overall survival for patients receiving RHT in combination with neo-adjuvant chemotherapy added to standard surgery and postoperative radiation.
  
  
  
  By comparison with other strategies, RHT combined with preoperative and postoperative chemotherapy improves overall survival and adds an important but underused standard for high-risk STS.
authors.affiliation: Ludwig-Maximilian University of Munich, Campus Grosshadern, Medical Clinic III, Munich, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Issels
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lindner
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D020360:Neoadjuvant Therapy; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery / Q000628:therapy*