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

Lisa A. Kachnic, Kathryn Winter, Robert J. Myerson, Michael D. Goodyear, John Willins, Jacqueline Esthappan, Michael Haddock, Marvin Rotman, Parag J. Parikh, Howard Safran, Christopher G. Willett

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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.

Original languageEnglish (US)
Pages (from-to)27-33
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume86
Issue number1
DOIs
StatePublished - May 1 2013

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canals
Mitomycin
Fluorouracil
radiation therapy
grade
Radiotherapy
cancer
Morbidity
dosage
evaluation
Anus Neoplasms
planning
tumors
pretreatment
Radiation
Neoplasms
assurance
radiation
Anal Canal Carcinoma
toxicity

ASJC Scopus subject areas

  • Radiation
  • Medicine(all)
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

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. / Kachnic, Lisa A.; Winter, Kathryn; Myerson, Robert J.; Goodyear, Michael D.; Willins, John; Esthappan, Jacqueline; Haddock, Michael; Rotman, Marvin; Parikh, Parag J.; Safran, Howard; Willett, Christopher G.

In: International Journal of Radiation Oncology Biology Physics, Vol. 86, No. 1, 01.05.2013, p. 27-33.

Research output: Contribution to journalArticle

Kachnic, Lisa A. ; Winter, Kathryn ; Myerson, Robert J. ; Goodyear, Michael D. ; Willins, John ; Esthappan, Jacqueline ; Haddock, Michael ; Rotman, Marvin ; Parikh, Parag J. ; Safran, Howard ; Willett, Christopher G. / 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. In: International Journal of Radiation Oncology Biology Physics. 2013 ; Vol. 86, No. 1. pp. 27-33.
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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.",
author = "Kachnic, {Lisa A.} and Kathryn Winter and Myerson, {Robert J.} and Goodyear, {Michael D.} and John Willins and Jacqueline Esthappan and Michael Haddock and Marvin Rotman and Parikh, {Parag J.} and Howard Safran and Willett, {Christopher G.}",
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T2 - 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

AU - Kachnic, Lisa A.

AU - Winter, Kathryn

AU - Myerson, Robert J.

AU - Goodyear, Michael D.

AU - Willins, John

AU - Esthappan, Jacqueline

AU - Haddock, Michael

AU - Rotman, Marvin

AU - Parikh, Parag J.

AU - Safran, Howard

AU - Willett, Christopher G.

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N2 - 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.

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