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Title: Intraoperative electron boost radiation followed by moderate doses of external beam radiotherapy in limb-sparing treatment of patients with extremity soft-tissue sarcoma

Abstract

Purpose: To analyze long-term prognosis and morbidity after limb-sparing treatment of patients with extremity soft-tissue sarcoma, with intraoperative electron boost radiotherapy (IOERT) followed by a moderate dose of external beam radiotherapy (EBRT). Methods and Materials: A total of 153 patients who were treated in a single center from 1991 to 2004 were evaluated. Median IOERT dose was 15 Gy, mean EBRT dose 43 Gy (range, 40-50.4 Gy) in conventional fractionation (1.8-2 Gy). Median duration of follow-up was 33 months. Acute toxicity was assessed with Common Toxicity Criteria; late toxic effects were scored according to European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. Results: Five-year overall survival and 5-year local control rates were 77% and 78%, respectively. Whereas tumor size, patient age, and EBRT dose did not significantly affect outcome, resection status and grading were significant for survival; resection status and IOERT dose were significant for local control. Extremity salvage until death or time of follow-up was achieved in 90% of our patients, 86% of whom showed excellent limb function without impairment in activities of daily life. Acute toxicity Grade 2-4 was observed in 23% and late toxicity Grade 2-4 in 17% of patients. Conclusions: Treatment withmore » IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity soft-tissue sarcoma.« less

Authors:
 [1];  [1];  [2];  [1];  [1];  [1];  [1];  [1];  [1];  [3];  [4];  [5];  [4];  [2];  [1];  [6]
  1. Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany)
  2. Department of Orthopedics, University of Heidelberg, Heidelberg (Germany)
  3. Department of Radiation Oncology, German Cancer Research Center, Heidelberg (Germany)
  4. Department of Surgery, University of Heidelberg, Heidelberg (Germany)
  5. Department of Radiation Oncology, RWTH Aachen University, Aachen (Germany)
  6. Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany). E-mail: robert_krempien@med.uni-heidelberg.de
Publication Date:
OSTI Identifier:
20793427
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2005.10.009; PII: S0360-3016(05)02812-9; 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; BEAMS; DEATH; FRACTIONATED IRRADIATION; LIMBS; PATIENTS; PRESERVATION; RADIATION DOSES; RADIOTHERAPY; SARCOMAS; TOXICITY

Citation Formats

Oertel, Susanne, Treiber, Martina, Zahlten-Hinguranage, Angelika, Eichin, Steffen, Roeder, Falk, Funk, Angela, Hensley, Frank W., Timke, Carmen, Niethammer, Andreas G., Huber, Peter E., Weitz, Juergen, Eble, Micheal J., Buchler, Markus W., Bernd, Ludger, Debus, Juergen, and Krempien, Robert C. Intraoperative electron boost radiation followed by moderate doses of external beam radiotherapy in limb-sparing treatment of patients with extremity soft-tissue sarcoma. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.1.
Oertel, Susanne, Treiber, Martina, Zahlten-Hinguranage, Angelika, Eichin, Steffen, Roeder, Falk, Funk, Angela, Hensley, Frank W., Timke, Carmen, Niethammer, Andreas G., Huber, Peter E., Weitz, Juergen, Eble, Micheal J., Buchler, Markus W., Bernd, Ludger, Debus, Juergen, & Krempien, Robert C. Intraoperative electron boost radiation followed by moderate doses of external beam radiotherapy in limb-sparing treatment of patients with extremity soft-tissue sarcoma. United States. doi:10.1016/J.IJROBP.2005.1.
Oertel, Susanne, Treiber, Martina, Zahlten-Hinguranage, Angelika, Eichin, Steffen, Roeder, Falk, Funk, Angela, Hensley, Frank W., Timke, Carmen, Niethammer, Andreas G., Huber, Peter E., Weitz, Juergen, Eble, Micheal J., Buchler, Markus W., Bernd, Ludger, Debus, Juergen, and Krempien, Robert C. Sat . "Intraoperative electron boost radiation followed by moderate doses of external beam radiotherapy in limb-sparing treatment of patients with extremity soft-tissue sarcoma". United States. doi:10.1016/J.IJROBP.2005.1.
@article{osti_20793427,
title = {Intraoperative electron boost radiation followed by moderate doses of external beam radiotherapy in limb-sparing treatment of patients with extremity soft-tissue sarcoma},
author = {Oertel, Susanne and Treiber, Martina and Zahlten-Hinguranage, Angelika and Eichin, Steffen and Roeder, Falk and Funk, Angela and Hensley, Frank W. and Timke, Carmen and Niethammer, Andreas G. and Huber, Peter E. and Weitz, Juergen and Eble, Micheal J. and Buchler, Markus W. and Bernd, Ludger and Debus, Juergen and Krempien, Robert C.},
abstractNote = {Purpose: To analyze long-term prognosis and morbidity after limb-sparing treatment of patients with extremity soft-tissue sarcoma, with intraoperative electron boost radiotherapy (IOERT) followed by a moderate dose of external beam radiotherapy (EBRT). Methods and Materials: A total of 153 patients who were treated in a single center from 1991 to 2004 were evaluated. Median IOERT dose was 15 Gy, mean EBRT dose 43 Gy (range, 40-50.4 Gy) in conventional fractionation (1.8-2 Gy). Median duration of follow-up was 33 months. Acute toxicity was assessed with Common Toxicity Criteria; late toxic effects were scored according to European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. Results: Five-year overall survival and 5-year local control rates were 77% and 78%, respectively. Whereas tumor size, patient age, and EBRT dose did not significantly affect outcome, resection status and grading were significant for survival; resection status and IOERT dose were significant for local control. Extremity salvage until death or time of follow-up was achieved in 90% of our patients, 86% of whom showed excellent limb function without impairment in activities of daily life. Acute toxicity Grade 2-4 was observed in 23% and late toxicity Grade 2-4 in 17% of patients. Conclusions: Treatment with IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity soft-tissue sarcoma.},
doi = {10.1016/J.IJROBP.2005.1},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 64,
place = {United States},
year = {Sat Apr 01 00:00:00 EST 2006},
month = {Sat Apr 01 00:00:00 EST 2006}
}
  • Purpose: To perform a joint analysis of data from 3 contributing centers within the intraoperative electron-beam radiation therapy (IOERT)-Spanish program, to determine the potential of IOERT as an anticipated boost before external beam radiation therapy in the multidisciplinary treatment of pediatric extremity soft-tissue sarcomas. Methods and Materials: From June 1993 to May 2013, 62 patients (aged <21 years) with a histologic diagnosis of primary extremity soft-tissue sarcoma with absence of distant metastases, undergoing limb-sparing grossly resected surgery, external beam radiation therapy (median dose 40 Gy) and IOERT (median dose 10 Gy) were considered eligible for this analysis. Results: After a median follow-up ofmore » 66 months (range, 4-235 months), 10-year local control, disease-free survival, and overall survival was 85%, 76%, and 81%, respectively. In multivariate analysis after adjustment for other covariates, tumor size >5 cm (P=.04) and R1 margin status (P=.04) remained significantly associated with local relapse. In regard to overall survival only margin status (P=.04) retained association on multivariate analysis. Ten patients (16%) reported severe chronic toxicity events (all grade 3). Conclusions: An anticipated IOERT boost allowed for external beam radiation therapy dose reduction, with high local control and acceptably low toxicity rates. The combined radiosurgical approach needs to be tested in a prospective trial to confirm these results.« less
  • Background: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. Methods and Materials: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). Results: From 1986 to 2012, a totalmore » of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically involved margin resection status (P=.04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P=.03). Conclusion: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy.« less
  • Purpose: To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT). Methods and Materials: Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors. Mean dose to bone, RT field sizemore » (FS), maximum dose to a 2-cc volume of bone, and volume of bone irradiated to >=40 Gy (V40) were compared. Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the dose distribution. Results: For fracture patients, mean dose to bone was 45 +- 8 Gy (mean dose at fracture site 59 +- 7 Gy), mean FS was 37 +- 8 cm, maximum dose was 64 +- 7 Gy, and V40 was 76 +- 17%, compared with 37 +- 11 Gy, 32 +- 9 cm, 59 +- 8 Gy, and 64 +- 22% for nonfracture patients. Differences in mean, maximum dose, and V40 were statistically significant (p = 0.01, p = 0.02, p = 0.01). Leg fractures were more common above the knee joint. Conclusions: The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy. There was a trend toward lower mean FS for nonfracture patients.« less
  • 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
  • Purpose: The goal of this study was to determine the effect of combination of intratumoral administration of dendritic cells (DC) and fractionated external beam radiation (EBRT) on tumor-specific immune responses in patients with soft-tissue sarcoma (STS). Methods and Material: Seventeen patients with large (>5 cm) high-grade STS were enrolled in the study. They were treated in the neoadjuvant setting with 5,040 cGy of EBRT, split into 28 fractions and delivered 5 days per week, combined with intratumoral injection of 10{sup 7} DCs followed by complete resection. DCs were injected on the second, third, and fourth Friday of the treatment cycle.more » Clinical evaluation and immunological assessments were performed. Results: The treatment was well tolerated. No patient had tumor-specific immune responses before combined EBRT/DC therapy; 9 patients (52.9%) developed tumor-specific immune responses, which lasted from 11 to 42 weeks. Twelve of 17 patients (70.6%) were progression free after 1 year. Treatment caused a dramatic accumulation of T cells in the tumor. The presence of CD4{sup +} T cells in the tumor positively correlated with tumor-specific immune responses that developed following combined therapy. Accumulation of myeloid-derived suppressor cells but not regulatory T cells negatively correlated with the development of tumor-specific immune responses. Experiments with {sup 111}In labeled DCs demonstrated that these antigen presenting cells need at least 48 h to start migrating from tumor site. Conclusions: Combination of intratumoral DC administration with EBRT was safe and resulted in induction of antitumor immune responses. This suggests that this therapy is promising and needs further testing in clinical trials design to assess clinical efficacy.« less