Kearla Bentz Protocol Summary 1

Introduction
The Alliance for Clinical Trials in Oncology sponsored the clinical trial A221505: RT
CHARM (NCT03414970), a phase III randomized trial of hypofractionated (HF) post
mastectomy radiation therapy (PMRT) with breast reconstruction.1 This trial was initiated to test
if a shorter course of radiation is as safe as the current standard of care for PMRT. There has
been a recent shift to shorter, more cost effective, and convenient treatment course.2 Previous
studies have established HF radiation therapy (RT) as a standard of care for most early-stage
breast cancer, but the use of HF RT for PMRT is under investigation.3 This trial was intended to
resolve the questions of radiation-related complication rates of PMRT using HF RT, and if HF is
safe when treating regional nodal volumes.2
Trial Schema
For this trial the patient was required to have a mastectomy with nodal
evaluation/dissection, with or without adjuvant chemotherapy, with planned breast
reconstruction. The reconstruction could occur immediately following the mastectomy or within
8 months following RT. The patient was then randomized to either arm 1 or arm 2. Arm 1 was
the conventional PMRT of 50 Gy in 25 fractions, once daily over 5-6 weeks. Arm 2 was the HF
PMRT of 42.5 Gy in 16 fractions, once daily over 3-4 weeks.2
Objectives
The primary objective of this trial was to evaluate whether the reconstruction
complication rate at 24 months post radiation is non-inferior with HF. It also evaluated the rate
of complications and recurrence based on reconstruction method and timing. Additionally, it
compared photographic cosmetic scores, incidence of lymphedema, patient satisfaction, and
costs between the 2 treatment arms.1,4
Eligibility
In order to be eligible for this trial the patient had to be at least 18 years of age with
histologically confirmed invasive carcinoma of the breast (ductal, lobular, mammary, medullary,
or tubular cancers), metastatic breast cancer was not accepted. The patient was required to have
negative inked histologic margins and had to be planning on reconstruction and regional lymph
node RT, including the internal mammary nodes (IMN). Patients were ineligible if they had a
history of prior or concurrent contralateral invasive breast cancer or if they received prior
Kearla Bentz Protocol Summary 2

radiation to the chest, neck or axilla. They also were ineligible if they had other medical
conditions with life expectancy < 5 years.4
Treatment Plan
The treatment plan for this trial included surgery, reconstruction, RT, and optional
chemotherapy. Surgically the patients had to have either a total, simple, skin-sparing, nipple-
sparing, or modified radical mastectomy with pathological staging. They also had to have either
a sentinel node biopsy or axillary dissection. Reconstruction of the chest wall had to occur
immediately following the mastectomy or within 8 months of completing PMRT. Depending on
the arm of the trial the patient was in they received conventional PMRT or HF RT within 84 days
of the mastectomy or adjuvant chemo, no RT boost plans were to be incorporated. Chemotherapy
was optional and could be neoadjuvant or adjuvant, but could not be concurrent with RT. There
had to be at 21 days between chemotherapy and RT and the mastectomy had to occur within 56
days of finishing neoadjuvant chemotherapy.2
Radiation Therapy
In either of the trial treatment arms photons or electrons could be used, no proton
treatments, and either 3D-CRT or IMRT were allowed. A 3-dimensional treatment planning CT
was required post-mastectomy with the patient in the supine position and optimally position per
the physician’s discretion. Methods to minimize cardiac exposure and the use of bolus were
allowed at the discretion of the physician. Radio-opaque markers had to be placed on the
mastectomy scar and “at risk” chest wall. If an expander was placed prior to the simulation it had
to remain in the same expansion as the scan until completion of RT, unless it was an air expander
then it had to be deflated for the planning scan and all treatments.5
Targets that had to be contoured on the 3D treatment planning scan had to include the
chest wall and regional nodes, including the undissected axilla nodes, supraclavicular nodes, and
IMN. The OAR that were required for this protocol were the ipsilateral and contralateral long,
the contralateral breast, the heart, and the thyroid. Specific compliance to dosimetric constraints
had to be followed per protocol or variation acceptable. There were dose requests for the chest
wall PTV, supraclavicular PTV, axillary PTV, and IMN PTV to receive optimal coverage
without significant dose above the prescription. Additionally, each OAR had strict dose
constraints in this protocol that had to be followed per protocol or variation acceptable.4
Outcomes
Kearla Bentz Protocol Summary 3

The outcomes of this study have not been posted. This study started accrual in February
of 2018. After an accrual of 897 patients the study was closed in September of 2021. The
primary completion date is estimated to be February of 2024. The study and results are estimated
to be compete in August of 2035.4
Kearla Bentz Protocol Summary 4

References
1. Alliance for Clinical Trials in Oncology. Closed to accrual: alliance A221505 (RT
CHARM). E-Newsletter. September 2021. Accessed July 15, 2023.
[Link]
Public/News-Closed-Sept2021
2. Poppe M.M. Alliance A221505: RT CHARM: Phase III randomized trial of
hypofractionated post mastectomy radiation with breast reconstruction. Huntsman Cancer
Hospital, University of Utah. Accessed July 15, 2023.
[Link]
Annual%20Meeting/files/[Link]
3. Sayan M., Yehia Z.A., Ohri N., Haffty B.G. Hypofractionated postmastectomy radiation
therapy. Adv Radiat Oncol. 2020;6(1):100618. Published November 21, 2020. Accessed
July 18, 2023. [Link]
4. National Institute of Health. Hypofractionated radiation therapy after mastectomy in
preventing recurrence in patient with stage IIa-IIIa breast cancer. Accessed July 20, 2023.
[Link]
5. Alliance for Clinic Trials in Oncology. Clinical protocol document for trial A221505:
hypofractionated post mastectomy radiation with breast reconstruction.