title: Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial.
abstract: OBJECTIVE
  We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume.
  
  
  METHODS
  Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years.
  
  
  RESULTS
  In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001).
  
  
  CONCLUSIONS
  The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS.
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC. Dian_Wang@Rush.edu.
authors: Dian
authors: D
authors: Wang
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: Qiang
authors: Q
authors: Zhang
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: Burton L
authors: BL
authors: Eisenberg
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: John M
authors: JM
authors: Kane
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: X Allen
authors: XA
authors: Li
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: David
authors: D
authors: Lucas
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: Ivy A
authors: IA
authors: Petersen
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: Thomas F
authors: TF
authors: DeLaney
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: Carolyn R
authors: CR
authors: Freeman
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: Steven E
authors: SE
authors: Finkelstein
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: Ying J
authors: YJ
authors: Hitchcock
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: Manpreet
authors: M
authors: Bedi
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: Anurag K
authors: AK
authors: Singh
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: George
authors: G
authors: Dundas
authors: Dian Wang, Rush University Medical Center, Chicago, IL; Qiang Zhang, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Burton L. Eisenberg, Hoag/University of Southern California Norris Cancer Center, Los Angeles, CA; John M. Kane and Anurag K. Singh, Roswell Park Cancer Institute, Buffalo, NY; X. Allen Li and Manpreet Bedi, Medical College of Wisconsin, Milwaukee, WI; David Lucas, University of Michigan, Ann Arbor, MI; Ivy A. Petersen, Mayo Clinic, Rochester, MN; Thomas F. DeLaney, Massachusetts General Hospital, Boston, MA; Carolyn R. Freeman, McGill University Health Centre, Montreal, Quebec; George Dundas, Cross Cancer Institute, Edmonton, Alberta, Canada; Steven E. Finkelstein, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Ying J. Hitchcock, University of Utah, Salt Lake City, UT; and David G. Kirsch, Duke University Medical Center, Durham, NC.
authors: David G
authors: DG
authors: Kirsch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059186:Chemoradiotherapy, Adjuvant; D018450:Disease Progression; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005121:Extremities; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D009656:North America; D011446:Prospective Studies; D011832:Radiation Injuries / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D018714:Radiotherapy, Adjuvant; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D061089:Radiotherapy, Image-Guided / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods; D012307:Risk Factors; D012509:Sarcoma / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden / Q000528:radiation effects*; D055815:Young Adult