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

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 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: Lisa A Kachnic, Kathryn Winter, Robert J Myerson, Michael D Goodyear, John Willins, Jacqueline Esthappan, Michael G Haddock, Marvin Rotman, Parag J Parikh, Howard Safran, Christopher G Willett
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 86 Issue 1 Pg. 27-33 (May 01 2013) ISSN: 1879-355X [Electronic] United States
• PMID: 23154075 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Mitomycin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Anal Canal
• Analysis of Variance
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Anus Neoplasms (diagnostic imaging, pathology, therapy)
• Carcinoma, Squamous Cell (diagnostic imaging, pathology, therapy)
• Carcinoma, Transitional Cell (pathology, therapy)
• Chemoradiotherapy (adverse effects, methods)
• Dose Fractionation, Radiation
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Gastrointestinal Tract (radiation effects)
• Humans
• Male
• Middle Aged
• Mitomycin (administration & dosage, adverse effects)
• Neoplasm Staging
• Radiation Injuries (prevention & control)
• Radiography
• Radiotherapy Planning, Computer-Assisted (standards)
• Radiotherapy, Intensity-Modulated (adverse effects, methods)
• Urogenital System (radiation effects)