title: Acute gastrointestinal toxicity and bowel bag dose-volume parameters for preoperative radiation therapy for retroperitoneal sarcoma.
abstract: OBJECTIVE
  Acute gastrointestinal (GI) toxicity has been studied in GI and gynecological (GYN) cancers, with volume receiving 15 Gy (V15) <830 mL, V25 <650 mL, and V45 <195 mL identified as dose constraints for the peritoneal space (bowel bag [BB]). There are no reported constraints derived from retroperitoneal sarcoma (RPS), and prospective trials for RPS have adopted some of the GI and GYN constraints. This study quantified GI toxicity during preoperative radiation therapy (RT) for RPS, assessed toxicity using published constraints, and evaluated predictors for toxicity.
  
  
  METHODS
  From 2003 to 2013, 56 patients with RPS underwent preoperative RT at 2 institutions. Toxicity was scored using Radiation Therapy Oncology Group criteria for upper and lower acute GI toxicity. BB was contoured on planning computed tomography scans per Radiation Therapy Oncology Group atlas guidelines with review by a radiologist. Relationships among toxicity, clinical factors, and BB dose were analyzed.
  
  
  RESULTS
  Three patients (5%) developed grade ≥3 acute GI toxicity: 2 grade 3 toxicities (anorexia and nausea) and 1 grade 5 toxicity (tumor-bowel fistula). Thirty-six patients (64%) had grade 2 toxicity (nausea, 55%; diarrhea, 23%; pain, 20%). Tumor size was the only significant clinical predictor of grade ≥2 acute GI toxicity. Larger mean BB volumes predicted for grade ≥2 toxicity (P = .001). On receiver operating characteristics analysis, V30 was the best discriminator for toxicity (P = .0001). Median BB V15 was 1375 mL; 75% of patients had V15 ≥830 mL. Median V25 was 1083 mL; 68% had V25 ≥650 mL. Median V45 was 575 mL; 82% had V45 ≥195 mL. V25 ≥650 mL was significantly associated with grade ≥2 toxicity (P = .01).
  
  
  CONCLUSIONS
  Among patients treated with preoperative RT for RPS, significant acute GI toxicity was very low despite BB dose exceeding established constraints for most cases. Acceptable dose constraints for RPS may be higher than those for GI or GYN cancers. Further assessment of dose-volume constraints for RPS is needed.
authors.affiliation: Harvard Radiation Oncology Program, Boston, Massachusetts; Department of Radiation Oncology, Boston Medical Center, Boston, Massachusetts.
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Mak
authors.affiliation: Harvard Radiation Oncology Program, Boston, Massachusetts; Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: John G
authors.initials: JG
authors.lastname: Phillips
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Constance M
authors.initials: CM
authors.lastname: Barysauskas
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Leslie K
authors.initials: LK
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Edward G
authors.initials: EG
authors.lastname: Mannarino
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Liam
authors.initials: L
authors.lastname: Van Benthuysen
authors.affiliation: Division of Surgical Oncology, Brigham and Women's Hospital, Boston, Massachusetts; Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Chandrajit P
authors.initials: CP
authors.lastname: Raut
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: John T
authors.initials: JT
authors.lastname: Mullen
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Mark
authors.initials: M
authors.lastname: Fairweather
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: DeLaney
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts; Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Electronic address: ebaldini@partners.org.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Baldini
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D011879:Radiotherapy Dosage; D012186:Retroperitoneal Neoplasms / Q000532:radiotherapy*; D012509:Sarcoma / Q000532:radiotherapy*; D055815:Young Adult