EF5 binding and clinical outcome in human soft tissue sarcomas.
OBJECTIVE
To study the 2-nitroimidazole agent EF5 as a surrogate for measuring hypoxia in a series of patients with soft tissue sarcomas, and to determine whether hypoxia measured with this technique was associated with patient outcome.


METHODS
Patients with soft tissue sarcomas of the head and neck, extremity, trunk, or retroperitoneum for whom surgical excision was the initial treatment of choice, were given 21 mg/kg EF5 24-48 hours before surgery. Biopsy specimens were stained for EF5 binding with fluorescence-labeled monoclonal antibodies, and the images were analyzed quantitatively. Endpoints included the relationship between EF5 binding, clinically important prognostic factors, and patient outcome.


RESULTS
Two patients with recurrent and 14 patients with de novo sarcomas were studied. There were seven low-grade, one intermediate-grade, and eight high-grade tumors. No relationship was found between EF5 binding and patient age, sex, hemoglobin level, or tumor size. In de novo tumors, the presence of mitoses and histologic grade were positively correlated with hypoxia. High-grade and -stage de novo tumors had higher levels of EF5 binding compared with low-grade and -stage tumors. Patients with de novo tumors containing moderate to severe hypoxia (> or = 20% EF5 binding), high grade, or > or = 7% mitoses were more likely to develop metastases.


CONCLUSIONS
Further studies in a larger cohort of patients are necessary to determine whether hypoxia, as measured by EF5 binding, is an independent prognostic factor for outcome in high-grade sarcomas. Such data should be useful to identify high-risk patients for clinical trials to determine whether early chemotherapy will influence the occurrence of metastasis.
Evans
Sydney M
SM
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. sydevans@mail.med.upenn.edu
Fraker
Douglas
D
Hahn
Stephen M
SM
Gleason
Kristen
K
Jenkins
W Timothy
WT
Jenkins
Kevin
K
Hwang
Wei-Ting
WT
Zhang
Paul
P
Mick
Rosemarie
R
Koch
Cameron J
CJ
D000328:Adult; D000368:Aged; D015687:Cell Hypoxia / Q000502:physiology*; D017341:Etanidazole / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism*; D007202:Indicators and Reagents / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D016896:Treatment Outcome; D005466:Fluorocarbons
D017341:Etanidazole; D006845:Hydrocarbons, Fluorinated; D007202:Indicators and Reagents; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons