title: 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.
abstract: OBJECTIVE
  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
  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 or 54 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.
authors.affiliation: Department of Radiation Oncology, Boston University Medical Center, Boston, Massachusetts 02118, USA. lisa.kachnic@bmc.org
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Kachnic
authors.forename: Kathryn
authors.initials: K
authors.lastname: Winter
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Myerson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Goodyear
authors.forename: John
authors.initials: J
authors.lastname: Willins
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Esthappan
authors.forename: Michael G
authors.initials: MG
authors.lastname: Haddock
authors.forename: Marvin
authors.initials: M
authors.lastname: Rotman
authors.forename: Parag J
authors.initials: PJ
authors.lastname: Parikh
authors.forename: Howard
authors.initials: H
authors.lastname: Safran
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Willett
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001003:Anal Canal; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D002295:Carcinoma, Transitional Cell / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D011832:Radiation Injuries / Q000517:prevention & control; D011859:Radiography; D011880:Radiotherapy Planning, Computer-Assisted / Q000592:standards; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D014566:Urogenital System / Q000528:radiation effects
chemical_list: D016685:Mitomycin; D005472:Fluorouracil