PMID- 23154075 OWN - NLM STAT- MEDLINE DCOM- 20130611 LR - 20220409 IS - 1879-355X (Electronic) IS - 0360-3016 (Print) IS - 0360-3016 (Linking) VI - 86 IP - 1 DP - 2013 May 1 TI - RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. PG - 27-33 LID - S0360-3016(12)03601-2 [pii] LID - 10.1016/j.ijrobp.2012.09.023 [doi] AB - PURPOSE: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. METHODS AND MATERIALS: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy 3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator's ability to perform DP-IMRT. RESULTS: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. CONCLUSIONS: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Kachnic, Lisa A AU - Kachnic LA AD - Department of Radiation Oncology, Boston University Medical Center, Boston, Massachusetts 02118, USA. lisa.kachnic@bmc.org FAU - Winter, Kathryn AU - Winter K FAU - Myerson, Robert J AU - Myerson RJ FAU - Goodyear, Michael D AU - Goodyear MD FAU - Willins, John AU - Willins J FAU - Esthappan, Jacqueline AU - Esthappan J FAU - Haddock, Michael G AU - Haddock MG FAU - Rotman, Marvin AU - Rotman M FAU - Parikh, Parag J AU - Parikh PJ FAU - Safran, Howard AU - Safran H FAU - Willett, Christopher G AU - Willett CG LA - eng GR - U24 CA081647/CA/NCI NIH HHS/United States GR - CCOP U10 CA3742/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 - RTOGU10 CA21661/CA/NCI NIH HHS/United States GR - ATC U24 CA 81647/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural DEP - 20121112 PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 RN - 50SG953SK6 (Mitomycin) RN - U3P01618RT (Fluorouracil) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Anal Canal MH - Analysis of Variance MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Anus Neoplasms/diagnostic imaging/pathology/*therapy MH - Carcinoma, Squamous Cell/diagnostic imaging/pathology/*therapy MH - Carcinoma, Transitional Cell/pathology/*therapy MH - Chemoradiotherapy/adverse effects/*methods MH - Dose Fractionation, Radiation MH - Drug Administration Schedule MH - Female MH - Fluorouracil/administration & dosage/adverse effects MH - Gastrointestinal Tract/radiation effects MH - Humans MH - Male MH - Middle Aged MH - Mitomycin/administration & dosage/adverse effects MH - Neoplasm Staging MH - Radiation Injuries/prevention & control MH - Radiography MH - Radiotherapy Planning, Computer-Assisted/standards MH - Radiotherapy, Intensity-Modulated/adverse effects/*methods MH - Urogenital System/radiation effects PMC - PMC3619011 MID - NIHMS423041 COIS- Conflict of Interest to Disclose: The authors have no conflicts of interest to report. EDAT- 2012/11/17 06:00 MHDA- 2013/06/12 06:00 PMCR- 2014/05/01 CRDT- 2012/11/17 06:00 PHST- 2012/06/29 00:00 [received] PHST- 2012/09/14 00:00 [revised] PHST- 2012/09/18 00:00 [accepted] PHST- 2012/11/17 06:00 [entrez] PHST- 2012/11/17 06:00 [pubmed] PHST- 2013/06/12 06:00 [medline] PHST- 2014/05/01 00:00 [pmc-release] AID - S0360-3016(12)03601-2 [pii] AID - 10.1016/j.ijrobp.2012.09.023 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 2013 May 1;86(1):27-33. doi: 10.1016/j.ijrobp.2012.09.023. Epub 2012 Nov 12.