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Title: EF5 binding and clinical outcome in human soft tissue sarcomas

Abstract

Purpose: 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 and Materials: 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 ({>=}20% EF5 binding), high grade, or {>=}7% mitoses were more likely to developmore » 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.« less

Authors:
 [1];  [2];  [2];  [2];  [2];  [3]
  1. Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States). E-mail: sydevans@mail.med.upenn.edu
  2. Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)|[Department of Surgery, University of Pennsylvania, Philadelphia, PA (United States)|[Department of Pathology, University of Pennsylvania, Philadelphia, PA (United States)|[Department of Biostatistics, University of Pennsylvania, Philadelphia, PA (United States)
  3. Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)|[Department of Surgery, University of Pennsylvania, Philadelphia, PA (United States)|[Department of Pathology, University of Pennsylvania, Philadelphia, PA (United States) [and others
Publication Date:
OSTI Identifier:
20793365
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2005.05.068; PII: S0360-3016(05)02823-3; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; BIOPSY; CHEMOTHERAPY; CLINICAL TRIALS; FLUORESCENCE; HEAD; HEMOGLOBIN; IMAGES; METASTASES; MONOCLONAL ANTIBODIES; NECK; PATIENTS; SARCOMAS; SURGERY

Citation Formats

Evans, Sydney M. V., Fraker, Douglas, Hahn, Stephen M., Gleason, Kristen, Jenkins, W. Timothy, and Jenkins, Kevin. EF5 binding and clinical outcome in human soft tissue sarcomas. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.0.
Evans, Sydney M. V., Fraker, Douglas, Hahn, Stephen M., Gleason, Kristen, Jenkins, W. Timothy, & Jenkins, Kevin. EF5 binding and clinical outcome in human soft tissue sarcomas. United States. doi:10.1016/J.IJROBP.2005.0.
Evans, Sydney M. V., Fraker, Douglas, Hahn, Stephen M., Gleason, Kristen, Jenkins, W. Timothy, and Jenkins, Kevin. Wed . "EF5 binding and clinical outcome in human soft tissue sarcomas". United States. doi:10.1016/J.IJROBP.2005.0.
@article{osti_20793365,
title = {EF5 binding and clinical outcome in human soft tissue sarcomas},
author = {Evans, Sydney M. V. and Fraker, Douglas and Hahn, Stephen M. and Gleason, Kristen and Jenkins, W. Timothy and Jenkins, Kevin},
abstractNote = {Purpose: 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 and Materials: 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 ({>=}20% EF5 binding), high grade, 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.},
doi = {10.1016/J.IJROBP.2005.0},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 64,
place = {United States},
year = {Wed Mar 01 00:00:00 EST 2006},
month = {Wed Mar 01 00:00:00 EST 2006}
}
  • Purpose: The present study was undertaken to determine factors predictive of toxicity, patterns of failure, and survival in 60 adult patients with soft tissue sarcomas of the extremity and superficial trunk treated with combined perioperative high-dose-rate brachytherapy and external beam radiotherapy. Methods and Materials: The patients were treated with surgical resection and perioperative high-dose-rate brachytherapy (16 or 24 Gy) for negative and close/microscopically positive resection margins, respectively. External beam radiotherapy (45 Gy) was added postoperatively to reach a 2-Gy equivalent dose of 62.9 and 72.3 Gy, respectively. Adjuvant chemotherapy with ifosfamide and doxorubicin was given to patients with advanced high-grademore » tumors. Results: Grade 3 toxic events were observed in 18 patients (30%) and Grade 4 events in 6 patients (10%). No Grade 5 events were observed. A location in the lower limb was significant for Grade 3 or greater toxic events on multivariate analysis (p = .013), and the tissue volume encompassed by the 150% isodose line showed a trend toward statistical significance (p = .086). The local control, locoregional control, and distant control rate at 9 years was 77.4%, 69.5%, and 63.8%, respectively. On multivariate analysis, microscopically involved margins correlated with local control (p = .036) and locoregional control (p = .007) and tumor size correlated with distant metastases (p = .004). The 9-year disease-free survival and overall survival rate was 47.0% and 61.5%, respectively. Multivariate analysis showed poorer disease-free survival rates for patients with tumors >6 cm (p = .005) and microscopically involved margins (p = .043), and overall survival rates decreased with increasing tumor size (p = .011). Conclusions: Grade 3 or greater wound complications can probably be decreased using meticulous treatment planning to decrease the tissue volume encompassed by the 150% isodose line, especially in lower limb locations. Microscopically involved margins remain a predictor of local and locoregional failure, despite radiation doses >70 Gy. Patients with tumors {>=}6 cm and microscopically involved margins are at high risk of treatment failure and death from the development of distant metastases.« less
  • PurposeTransarterial chemoembolization (TACE) is used to treat unresectable bone and soft tissue sarcoma (STS) and as a pre-surgical adjuvant treatment. However, its efficiency for advanced STS is undetermined. This study evaluated TACE’s efficiency in treating advanced STS and prognostic factors for patient survival.Materials and MethodsWe enrolled 39 patients with unresectable STS who underwent TACE as an alternative treatment during 2010–2014, with overall survival (OS) as the primary end point. Cancer pain was evaluated by visual analogue scores (VAS) before and after TACE procedures. Factors that affect survival were evaluated by multivariate analyses (Cox proportional hazard model).ResultsMean OS after TACE wasmore » 23.7 ± 2.1 months, with 1-year OS 71.5 %, 2-year OS 45.8 %, and 3-year OS 32.5 %. Lesion number and tumor stage were key predictors of survival. TACE was found to decrease cancer pain VAS and increase relapse interval. Size of polyvinyl alcohol (PVA) particle diameter (P = 0.03) and imaging response (P = 0.044) were also found to affect relapse interval.ConclusionTACE was an effective treatment for advanced STS, with a 32.5 % 3-year OS rate, and led to lower cancer pain VAS and longer relapse intervals than chemoinfusion only. Smaller PVA particles are preferable during the TACE procedure.« less
  • In a prospective study of forty-five patients, we evaluated the usefulness of bone and gallium scintigraphy prior to definitive surgery for a soft-tissue sarcoma in an extremity. Bone scintigraphy provides a baseline for staging and often reveals periosteal invasion that is not detected by routine radiographs. Blood-pool scintigraphy with bone tracers is very sensitive for a diagnosis of malignant disease. Gallium scintigraphy appeared to be a reliable preoperative indicator of malignant disease of soft tissue (sensitivity, 85 per cent; specificity, 92 per cent) and was useful for detecting the infrequent occult, non-pulmonary metastasis. Combined gallium and bone scintigraphy with blood-poolmore » imaging provided a reliable prediction of the presence or absence of a malignant lesion in patients with a soft-tissue mass in an extremity. We recommend that bone and gallium scintigraphy be routinely used in the initial clinical staging of soft-tissue sarcomas.« less
  • Purpose: To evaluate the clinical effects of transcatheter arterial embolization (TAE) on malignant bone and soft tissue tumors. Methods: TAE was performed in 10 patients with primary bone and soft tissue sarcomas and in 31 patients with metastatic bone tumors. The embolized arteries were the internal iliac artery in 30 cases, the intercostal artery in six cases, the lumbar artery in five cases, the suprascapular artery in three cases, and the iliolumbar artery, the internal pudendal artery, and the lateral sacral artery in one case each. The embolized material was gelatin sponge particles. The chemotherapeutic drugs were usually 20-40 mgmore » of doxorubicin for primary and metastatic tumors and 50-100 mg of cisplatin only for primary tumors. In addition, 50-60 Gy of 10-MV radiotherapy with or without radiofrequency (RF)-capacitive hyperthermia in four sessions was administered before TAE for primary tumors only. Results: Even though the pain score increased immediately after TAE, 30 of 38 (79%) patients with pain (8 of 9 with primary tumors, and 22 of 29 with metastases) achieved pain control after TAE. A necrotic low-density area shown by computed tomography (CT) after TAE was found in 31 of 41 (76%) tumors [8 of 10 (80%) with primary tumors, and 23 of 31 (74%) with metastatic tumors]. The tumor size decreased in 14 of 25 (56%) primary and metastatic tumors after 3 months. Osteosclerotic changes appeared in two cases of metastatic tumors after 6 months. In five tumors resected after TAE, large areas of necrosis within the tumor were confirmed histologically. Transient local pain and numbness appeared after TAE, but were relieved by drug treatment within 1 week. No severe complications except a case of gluteal muscle necrosis were encountered after TAE. The 1-year survival rate of the patients with primary tumors was 38.1%, and the median survival was 18 months. The longest survival was 84 months. The 1-year survival rate of the patients with metastatic bone tumors was 38.9%; the median survival was 12 months. The longest survival was 24 months. Conclusion: TAE could be an effective treatment for pain control and local control of malignant bone and soft-tissue tumors.« less
  • Purpose: To evaluate the clinical effects of transcatheter arterial embolization (TAE) on malignant bone and soft tissue tumors.Methods: TAE was performed in 10 patients with primary bone and soft tissue sarcomas and in 31 patients with metastatic bone tumors. The embolized arteries were the internal iliac artery in 30 cases, the intercostal artery in six cases, the lumbar artery in five cases, the suprascapular artery in three cases, and the iliolumbar artery, the internal pudendal artery, and the lateral sacral artery in one case each. The embolized material was gelatin sponge particles. The chemotherapeutic drugs were usually 20-40 mg ofmore » doxorubicin for primary and metastatic tumors and 50-100 mg of cisplatin only for primary tumors. In addition, 50-60 Gy of 10-MV radiotherapy with or without radiofrequency (RF)-capacitive hyperthermia in four sessions was administered before TAE for primary tumors only.Results: Even though the pain score increased immediately after TAE, 30 of 38 (79%) patients with pain (8 of 9 with primary tumors, and 22 of 29 with metastases) achieved pain control after TAE. A necrotic low-density area shown by computed tomography (CT) after TAE was found in 31 of 41 (76%) tumors [8 of 10 (80%) with primary tumors, and 23 of 31 (74%) with metastatic tumors]. The tumor size decreased in 14 of 25 (56%) primary and metastatic tumors after 3 months. Osteosclerotic changes appeared in two cases of metastatic tumors after 6 months. In five tumors resected after TAE, large areas of necrosis within the tumor were confirmed histologically. Transient local pain and numbness appeared after TAE, but were relieved by drug treatment within 1 week. No severe complications except a case of gluteal muscle necrosis were encountered after TAE. The 1-year survival rate of the patients with primary tumors was 38.1%, and the median survival was 18 months. The longest survival was 84 months. The 1-year survival rate of the patients with metastatic bone tumors was 38.9%; the median survival was 12 months. The longest survival was 24 months.Conclusion: TAE could be an effective treatment for pain control and local control of malignant bone and soft-tissue tumors.« less