title: Primary tumor necrosis predicts distant control in locally advanced soft-tissue sarcomas after preoperative concurrent chemoradiotherapy.
abstract: OBJECTIVE
  Various neoadjuvant approaches have been evaluated for the treatment of locally advanced soft-tissue sarcomas. This retrospective study describes a uniquely modified version of the Eilber regimen developed at the University of Chicago.
  
  
  METHODS
  We treated 34 patients (28 Stage III and 6 Stage IV) with locally advanced soft-tissue sarcomas of an extremity between 1995 and 2008. All patients received preoperative therapy including ifosfamide (2.5 g/m2 per day for 5 days) with concurrent radiation (28 Gy in 3.5-Gy daily fractions), sandwiched between various chemotherapy regimens. Postoperatively, 47% received further adjuvant chemotherapy.
  
  
  RESULTS
  Most tumors (94%) were Grade 3, and all were T2b, with a median size of 10.3 cm. Wide excision was performed in 29 patients (85%), and 5 required amputation. Of the resected tumor specimens, 50% exhibited high (> or =90%) treatment-induced necrosis and 11.8% had a complete pathologic response. Surgical margins were negative in all patients. The 5-year survival rate was 42.3% for all patients and 45.2% for Stage III patients. For limb-preservation patients, the 5-year local control rate was 89.0% and reoperation was required for wound complications in 17.2%. The 5-year freedom-from-distant metastasis rate was 53.4% (Stage IV patients excluded), and freedom from distant metastasis was superior if treatment-induced tumor necrosis was 90% or greater (84.6% vs. 19.9%, p = 0.02).
  
  
  CONCLUSIONS
  This well-tolerated concurrent chemoradiotherapy approach yields excellent rates of limb preservation and local control. The resulting treatment-induced necrosis rates are predictive of subsequent metastatic risk, and this information may provide an opportunity to guide postoperative systemic therapies.
authors: Department of Radiation & Cellular Oncology, University of Chicago, Chicago, IL 60637, USA.
authors: Dhara M
authors: DM
authors: MacDermed
authors: Luke L
authors: LL
authors: Miller
authors: Terrance D
authors: TD
authors: Peabody
authors: Michael A
authors: MA
authors: Simon
authors: Hue H
authors: HH
authors: Luu
authors: Rex C
authors: RC
authors: Haydon
authors: Anthony G
authors: AG
authors: Montag
authors: Samir D
authors: SD
authors: Undevia
authors: Philip P
authors: PP
authors: Connell
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005121:Extremities; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D015996:Survival Rate; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D015251:Epirubicin; D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide