PMID- 28463160 OWN - NLM STAT- MEDLINE DCOM- 20170726 LR - 20181113 IS - 1879-355X (Electronic) IS - 0360-3016 (Print) IS - 0360-3016 (Linking) VI - 98 IP - 2 DP - 2017 Jun 1 TI - Predictors of Radiation Therapy-Related Gastrointestinal Toxicity From Anal Cancer Dose-Painted Intensity Modulated Radiation Therapy: Secondary Analysis of NRG Oncology RTOG 0529. PG - 400-408 LID - S0360-3016(17)30332-2 [pii] LID - 10.1016/j.ijrobp.2017.02.005 [doi] AB - PURPOSE: NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). METHODS AND MATERIALS: NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structure receiving doses >/=5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade >/=2 acute and late GI AEs, and grade >/=3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). RESULTS: Among 52 evaluable patients, grade >/=2 acute, grade >/=2 late, and grade >/=3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P<.05) toward statistically significant associations were observed between grade >/=2 acute GI AEs and small bowel dose (V20-V40), grade >/=2 late GI AEs and APC dose (V60), grade >/=3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size >4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade >/=2 GI AEs. CONCLUSIONS: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Olsen, Jeffrey R AU - Olsen JR AD - University of Colorado Denver, Aurora, Colorado. Electronic address: Jeffrey.R.Olsen@ucdenver.edu. FAU - Moughan, Jennifer AU - Moughan J AD - NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania. FAU - Myerson, Robert AU - Myerson R AD - Washington University, St. Louis, Missouri. FAU - Abitbol, Andre AU - Abitbol A AD - Baptist Hospital of Miami, Miami, Florida. FAU - Doncals, Desiree E AU - Doncals DE AD - Summa Akron City Hospital accruals for Akron City Hospital, Akron, Ohio. FAU - Johnson, Douglas AU - Johnson D AD - Florida Radiation Oncology Group-Baptist Regional, Jacksonville, Florida. FAU - Schefter, Tracey E AU - Schefter TE AD - University of Colorado Denver, Aurora, Colorado. FAU - Chen, Yuhchyau AU - Chen Y AD - University of Rochester Medical Center, Rochester, New York. FAU - Fisher, Barbara AU - Fisher B AD - London Regional Cancer Program-University of Western Ontario, London, Ontario, Canada. FAU - Michalski, Jeff AU - Michalski J AD - Washington University, St. Louis, Missouri. FAU - Narayan, Samir AU - Narayan S AD - Michigan Cancer Research Consortium CCOP, Ann Arbor, Michigan. FAU - Chang, Albert AU - Chang A AD - University of California San Francisco, San Francisco, California. FAU - Crane, Christopher H AU - Crane CH AD - Memorial Sloan Kettering Cancer Center, New York, New York. FAU - Kachnic, Lisa AU - Kachnic L AD - Vanderbilt University Medical Center, Nashville, Tennessee. LA - eng GR - U10 CA180868/CA/NCI NIH HHS/United States GR - UG1 CA189867/CA/NCI NIH HHS/United States GR - U10 CA180834/CA/NCI NIH HHS/United States GR - U24 CA081647/CA/NCI NIH HHS/United States GR - U10 CA037422/CA/NCI NIH HHS/United States GR - U10 CA021661/CA/NCI NIH HHS/United States GR - U10 CA180833/CA/NCI NIH HHS/United States GR - U10 CA180822/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20170213 PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 RN - 0 (Antineoplastic Agents) RN - 50SG953SK6 (Mitomycin) RN - U3P01618RT (Fluorouracil) SB - IM MH - Acute Disease MH - Adult MH - Age Factors MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/*adverse effects/therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use MH - Anus Neoplasms/diagnostic imaging/pathology/*therapy MH - Carcinoma, Squamous Cell/pathology/*therapy MH - Chemoradiotherapy/*adverse effects/methods MH - Colon/diagnostic imaging MH - Feasibility Studies MH - Female MH - Fluorouracil/administration & dosage/adverse effects MH - Humans MH - Intestine, Small/diagnostic imaging/*radiation effects MH - Male MH - Middle Aged MH - Mitomycin/administration & dosage/adverse effects MH - Organs at Risk/diagnostic imaging/pathology/radiation effects MH - Pelvis/diagnostic imaging MH - Proportional Hazards Models MH - ROC Curve MH - Radiotherapy Dosage MH - Radiotherapy, Intensity-Modulated/*adverse effects/methods MH - Regression Analysis MH - Tumor Burden PMC - PMC5639877 MID - NIHMS865818 COIS- Conflicts of Interest: Dr. Olsen reports grants and speaking fees from ViewRay, Inc., outside the submitted work. Dr. Doncals reports grants from federal government thru RTOG, during the conduct of the study; grants from RTOG, ECOG, NSABP, GOG, NRG, CTSU for the hospital to conduct their studies, outside the submitted work. Dr. Crane reports consulting fees from Vertex, outside the submitted work. EDAT- 2017/05/04 06:00 MHDA- 2017/07/27 06:00 PMCR- 2018/06/01 CRDT- 2017/05/03 06:00 PHST- 2016/06/22 00:00 [received] PHST- 2017/01/03 00:00 [revised] PHST- 2017/02/06 00:00 [accepted] PHST- 2017/05/03 06:00 [entrez] PHST- 2017/05/04 06:00 [pubmed] PHST- 2017/07/27 06:00 [medline] PHST- 2018/06/01 00:00 [pmc-release] AID - S0360-3016(17)30332-2 [pii] AID - 10.1016/j.ijrobp.2017.02.005 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):400-408. doi: 10.1016/j.ijrobp.2017.02.005. Epub 2017 Feb 13.