Matthew M Poppe1, Zeinab A Yehia2, Christopher Baker3, Sharad Goyal4, Deborah Toppmeyer2, Laurie Kirstein5, Chunxia Chen6, D F Moore6, Bruce G Haffty2, Atif J Khan5. 1. Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah. Electronic address: matthew.poppe@hci.utah.edu. 2. Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. 3. Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah. 4. George Washington University, Washington, DC. 5. Memorial Sloan Kettering Cancer Center, New York City, New York. 6. Rutgers School of Public Health, Piscataway, New Jersey.
Abstract
PURPOSE: Hypofractionation in the setting of postmastectomy radiation (PMRT) is not currently the standard of care in most countries. Here we present a 5-year update of our multi-institutional, phase 2 prospective trial evaluating a novel 15-day hypofractionated PMRT regimen. METHODS AND MATERIALS: Patients were enrolled to receive 3.33 Gy daily to the chest wall (or reconstructed breast) and regional lymphatics in 11 fractions with an optional 4-fraction mastectomy scar boost. The primary endpoint was freedom from grade 3 or higher late non-reconstruction-related radiation toxicities. Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0. Secondary endpoints included local and locoregional recurrence rates, cosmesis, and reconstruction complications. RESULTS: After enrolling 69 patients with stage II-IIIa breast cancer, 67 women were eligible for analysis. At a median follow up of 54 months, there were no acute or late grade 3 and 4 nonreconstruction reported toxicities. The grade 2 or greater late toxicity rate was only 12% and comprised grade 2 pain, fatigue, and lymphedema that persisted beyond 6 months after completion of radiation therapy. Only 3 women (4.6%) experienced a chest wall or nodal recurrence as a first site of relapse. Freedom from local failure, including local failure after distant relapse, was 92% at 5 years, and the 5-year overall survival was 90%. CONCLUSIONS: This is the first prospective trial conducted in the United States to demonstrate the safe and effective use of hypofractionated PMRT. We have demonstrated a low complication rate while achieving excellent local control. Toxicity was better than anticipated based on previously published series of PMRT toxicities. Although our fractionation was novel, the radiobiological equivalent dose is similar to other hypofractionation schedules. This trial was the basis for the creation of Alliance A221505 (RT CHARM), which is currently accruing patients in a phase 3 randomized design.
RCT Entities:
PURPOSE: Hypofractionation in the setting of postmastectomy radiation (PMRT) is not currently the standard of care in most countries. Here we present a 5-year update of our multi-institutional, phase 2 prospective trial evaluating a novel 15-day hypofractionated PMRT regimen. METHODS AND MATERIALS: Patients were enrolled to receive 3.33 Gy daily to the chest wall (or reconstructed breast) and regional lymphatics in 11 fractions with an optional 4-fraction mastectomy scar boost. The primary endpoint was freedom from grade 3 or higher late non-reconstruction-related radiation toxicities. Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0. Secondary endpoints included local and locoregional recurrence rates, cosmesis, and reconstruction complications. RESULTS: After enrolling 69 patients with stage II-IIIa breast cancer, 67 women were eligible for analysis. At a median follow up of 54 months, there were no acute or late grade 3 and 4 nonreconstruction reported toxicities. The grade 2 or greater late toxicity rate was only 12% and comprised grade 2 pain, fatigue, and lymphedema that persisted beyond 6 months after completion of radiation therapy. Only 3 women (4.6%) experienced a chest wall or nodal recurrence as a first site of relapse. Freedom from local failure, including local failure after distant relapse, was 92% at 5 years, and the 5-year overall survival was 90%. CONCLUSIONS: This is the first prospective trial conducted in the United States to demonstrate the safe and effective use of hypofractionated PMRT. We have demonstrated a low complication rate while achieving excellent local control. Toxicity was better than anticipated based on previously published series of PMRTtoxicities. Although our fractionation was novel, the radiobiological equivalent dose is similar to other hypofractionation schedules. This trial was the basis for the creation of Alliance A221505 (RT CHARM), which is currently accruing patients in a phase 3 randomized design.
Authors: J Ragaz; S M Jackson; N Le; I H Plenderleith; J J Spinelli; V E Basco; K S Wilson; M A Knowling; C M Coppin; M Paradis; A J Coldman; I A Olivotto Journal: N Engl J Med Date: 1997-10-02 Impact factor: 91.245
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Authors: M Overgaard; P S Hansen; J Overgaard; C Rose; M Andersson; F Bach; M Kjaer; C C Gadeberg; H T Mouridsen; M B Jensen; K Zedeler Journal: N Engl J Med Date: 1997-10-02 Impact factor: 91.245
Authors: Atif J Khan; Matthew M Poppe; Sharad Goyal; Kristine E Kokeny; Thomas Kearney; Laurie Kirstein; Deborah Toppmeyer; Dirk F Moore; Chunxia Chen; David K Gaffney; Bruce G Haffty Journal: J Clin Oncol Date: 2017-05-01 Impact factor: 44.544
Authors: P McGale; C Taylor; C Correa; D Cutter; F Duane; M Ewertz; R Gray; G Mannu; R Peto; T Whelan; Y Wang; Z Wang; S Darby Journal: Lancet Date: 2014-03-19 Impact factor: 79.321
Authors: Casey L Liveringhouse; Iman R Washington; Roberto Diaz; Rachel B Jimenez; Eleanor E Harris; Rachel Rabinovitch; Wendy A Woodward; Javier F Torres-Roca; Kamran A Ahmed Journal: Adv Radiat Oncol Date: 2021-05-28
Authors: David Krug; René Baumann; Stephanie E Combs; Marciana Nona Duma; Jürgen Dunst; Petra Feyer; Rainer Fietkau; Wulf Haase; Wolfgang Harms; Thomas Hehr; Marc D Piroth; Felix Sedlmayer; Rainer Souchon; Vratislav Strnad; Wilfried Budach Journal: Strahlenther Onkol Date: 2021-01-28 Impact factor: 3.621