title: The treatment of high-grade soft tissue sarcomas with preoperative thermoradiotherapy.
abstract: OBJECTIVE
  To explore the use of a novel program of preoperative radiation and hyperthermia in the management of high-grade soft tissue sarcomas (STS).
  
  
  METHODS
  Eligible patients were adults over 18 with Grade 2 or 3 STS, surgically resectable without a local excision prior to referral to Duke University Medical Center and without distant metastases. Patients were staged generally with CT and/or MR imaging. The diagnosis was established with fine needle aspiration or incisional biopsy. Patients were then treated with 5000 to 5040 cGy, 180-200 cGy per fraction. Chemotherapy was usually not employed. Generally two hyperthermia treatments per week were given with a planned thermal dose of 10-100 CEM 43 degrees T90. Invasive thermometry and thermal mapping were done in all patients. Surgical resection was planned 4-6 weeks after the completion of radiation and hyperthermia.
  
  
  RESULTS
  Ninety-seven patients were treated on study between 1984 and 1996. Follow-up ranged from 12 to 155 months (median 32). All tumors were high-grade in nature, 44 greater than 10 cm in size (maximum tumor diameter), 43 5-10 cm in size, 10 less than 5 cm. Seventy-eight of the 97 tumors were located in an extremity. Of the 97 patients, 48 remain alive and continually free of disease following initial therapy. Of the remaining 49 patients, 44 have relapsed (34 dead, 10 living with disease), 3 have died secondary to complications of therapy, and 2 have died of unrelated causes. Ten-year actuarial overall survival, cause-specific survival, and relapse-free survival are 50, 47, and 47% respectively. The predominant pattern of failure has been distant metastases with only 2 patients developing local failure alone. Ten-year actuarial local control for extremity tumors is 94%, 63% for the 19 patients with tumors at sites other than the extremity. Of the 78 patients with extremity lesions, 63 have had limb preservation and remain locally controlled. Overall 38 patients experienced 57 major complications. There were 3 deaths, one due to adriamycin cardiomyopathy and two secondary to wound infections. Four patients required amputation secondary to postoperative wound healing problems. Complications directly attributable to hyperthermia occurred in 15 patients with 11 instances of second- or third-degree burns and two instances of subcutaneous fat necrosis. The hyperthermia complications were generally not severe and either healed readily or were excised at the time of surgical resection of the primary tumor.
  
  
  CONCLUSIONS
  For these aggressive high-grade soft tissue sarcomas, this treatment program of preoperative thermoradiotherapy provided excellent local regional control for extremity lesions (95%) and satisfactory local regional control (63%) of nonextremity sarcomas, but did not appear to influence the rate of distant metastases or survival. Complications were frequent but apart from the direct thermal burns, not too different from those reported for preoperative radiotherapy alone. More effective adjuvant systemic therapy is necessary to impact favorably on survival.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. prosnitz@radonc.duke.edu
authors.forename: L R
authors.initials: LR
authors.lastname: Prosnitz
authors.forename: P
authors.initials: P
authors.lastname: Maguire
authors.forename: J M
authors.initials: JM
authors.lastname: Anderson
authors.forename: S P
authors.initials: SP
authors.lastname: Scully
authors.forename: J M
authors.initials: JM
authors.lastname: Harrelson
authors.forename: E L
authors.initials: EL
authors.lastname: Jones
authors.forename: M
authors.initials: M
authors.lastname: Dewhirst
authors.forename: T V
authors.initials: TV
authors.lastname: Samulski
authors.forename: B E
authors.initials: BE
authors.lastname: Powers
authors.forename: G L
authors.initials: GL
authors.lastname: Rosner
authors.forename: R K
authors.initials: RK
authors.lastname: Dodge
authors.forename: L
authors.initials: L
authors.lastname: Layfield
authors.forename: R
authors.initials: R
authors.lastname: Clough
authors.forename: D M
authors.initials: DM
authors.lastname: Brizel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002056:Burns / Q000209:etiology; D002648:Child; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D016019:Survival Analysis; D017211:Treatment Failure