American College Of Surgeons - Inspiring Quality: Highest Standards, Better Outcomes

CRP Investigator Webinar: Breast (NRG BR005 and A221505)

A Surgical Investigators Meeting Webinar focusing on Ongoing Breast Cancer Trials.

Sponsored by the ALLIANCE/American College of Surgeons Clinical Research Program.

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Recorded October 11, 2017

Presentation Slides

Moderator: Judy C. Boughey, MD, FACS Education Committee, ACS CRP

Speakers: Terry Mamounas, MD, MPH, FACS, Matthew Poppe, MD, Jamie Wagner, DO, FACOS

Trials Covered: NRG BR005 and A221505

NRG BR005

Assessing the Accuracy of Tumor Biopsies After Chemotherapy to Determine if Patients Can Avoid Breast Surgery

NRG BR005 is a two-stage Phase II trial study to assess the accuracy of post-neoadjuvant systemic therapy (NST) image-directed tumor bed biopsy for pathologic complete response (pCR), defined as resolution of both invasive disease and DCIS, in cases of clinical and radiologic complete response with tri-modality imaging. The primary objective of the study is to estimate the biopsy detection rate among breast cancer patients treated with neoadjuvant therapy who fail to achieve pCR at surgery after having clinical/radiologic CR and tumor bed biopsy. This will be accomplished by undertaking a two-stage design that would accrue 175 patients who have clinical/radiologic CR, perform tumor bed biopsy and surgery on these patients, determine the results of biopsy, and compare the results of biopsy with the findings at surgery in terms of pCR. There will be one interim analysis at the time that there are 27 patients who failed to achieve pCR at surgery. If 18 or fewer of these 27 patients had a positive biopsy, the study will be terminated. If 19 or more of these 27 patients had a positive biopsy, the study will continue until 35 patients who failed to achieve pCR at surgery are accrued. If at least 25 positive biopsies are observed among the 35 patients who fail to achieve pCR at surgery (at least 71.4%), breast conserving treatment without surgery in patients who have clinical/radiologic CR and negative tumor bed biopsy would be considered feasible.

The protocol was opened for accrual on June 22, 2017. The first patient was registered to the study on August 25, 2017. As of August 31, 2018, 51 patients had been accrued.

NRG BR005 Study Schema

BR005 Study Schema

A221505

Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer (RT-CHARM)

This study is being conducted to determine if short course (hypofractionated) is as safe and effective as conventional radiation in the setting of post mastectomy radiation with breast reconstruction. Short course radiation has been shown in multiple randomized trials to be equivalent to traditional longer course of radiation but only the setting of node negative breast cancer and lumpectomy. There is data, although limited, suggesting that this should hold true in the setting of mastectomy, reconstruction and node positive breast cancer. The primary outcome is the reconstruction complication rate, which includes: capsular contracture, failure of implant/flap, unplanned admission or operation related to a reconstruction complication, including need for IV antibiotics. This does not include “routine,” cosmetic revisions.

All techniques and timing of reconstruction will be allowed on this trial, and secondary analyses will examine the effect of reconstruction techniques and timing on complications, photographic outcomes and patient satisfaction. Additional secondary endpoints include: incidence of acute and late CTCAE toxicities associated with radiation, local and local regional recurrence rates, lymphedema and cost effectiveness.

Key Inclusion Criteria

  • Clinical or pathological N1 or N2 invasive breast cancer
  • Post mastectomy with plans for breast reconstruction
  • Radiation oncologist planning to treat regional nodes and not use a boost dose of radiation
  • AJCC Stage IIa–IIIa *T4, N3 and involved internal mammary disease (N1b, N1c, and N2b) will not be allowed.
  • Negative inked histologic margins of mastectomy
  • Chemo allowed neoadjuvant or adjuvant (before or after RT)
  • Planned chest wall reconstruction is required with intent declared for autologous or implant based reconstruction before randomization
  • Reconstruction can take place before or after post mastectomy radiation

Key Exclusion Criteria

  • No history of prior breast cancer or concurrent bilateral breast cancer
  • No active collagen vascular disease
  • No significant post mastectomy complications (unplanned re-operation, or IV antibiotics)
  • No malignancy of malignancy within 5 years and live expectancy > 5 years

Surgery

  • Total, simple, skin sparing, nipple sparing or modified radical mastectomy
  • Margins should be negative, defined as no tumor on ink. Focally positive deep margin will be acceptable if the deep margin is the pectoralis fascia and the pectoralis fascia was noted as removed in the operative description or pathology report.
  • Lymph nodes must be evaluated by sentinel node biopsy or axillary dissection.
  • Mastectomy and nodal evaluation must be completed within 56 days of the completion of neoadjuvant chemotherapy.
  • If contralateral breast surgery, no invasive disease

Reconstruction

  • Reconstruction of the breast may occur before or after radiation.
  • Tissue expander may be placed before or after radiation and maybe inflated or deflated for radiation
  • Plastic surgeon may use any combination of allograft, implant or tissue flap for reconstruction.
  • Reconstruction intent must be stated at the time of registration

A221505 Schema

A221505 Schema

Estimated enrollment: 880
Start date: Jan 2018
Estimated end date: Dec 2021

About the Speakers and Program

More about Terry Mamounas, MD, MPH, FACS

Terry P. Mamounas is medical director of the Comprehensive Breast Program at Orlando Health UF Health Cancer Center, Professor of Surgery at University of Central Florida and clinical professor of clinical sciences at Florida State University. He is past chair of the NSABP Breast Committee and current chair of the NRG Oncology Breast Committee.

Dr. Mamounas received his medical degree from the University of Athens Medical School in Athens, Greece, and a Masters of Public Health degree in Epidemiology from the University of Pittsburgh. He completed his surgical residency at Mckeesport Hospital in Mckeesport, PA, an oncology research fellowship at the University of Pittsburgh and a surgical oncology fellowship at Roswell Park Cancer Institute in Buffalo, New York.

Dr. Mamounas has authored or coauthored more than 350 abstracts, manuscripts, and book chapters, and he has given numerous presentations on breast cancer at various regional, national, and international symposia. His clinical research has focused on the surgical and adjuvant treatment of early-stage breast cancer. He is a member of several professional societies including the American College of Surgeons, the Society of Surgical Oncology, the American Society of Clinical Oncology and the American Society of Breast Surgeons. Dr. Mamounas is a member of the NCI Breast Cancer Steering Committee. He serves on several editorial boards and he is past associate editor for the Journal of Clinical Oncology. Dr. Mamounas is a past member of the Scientific Advisory Council for the Susan G. Komen for the Cure.

More about Matthew Poppe, MD

Matthew Poppe is a radiation oncologists specializing in breast and pediatric cancer treatment. Dr. Poppe is an associate professor and residency directory at the University of Utah, Huntsman Cancer Hospital, in Salt Lake City, UT. His research focuses on improving radiation treatment techniques for women with breast cancer, ultimately improving quality of life while decreasing treatment cost and patient burden. He is currently the PI of A221505 (RT CHARM), looking at the safety and efficacy of short course radiation after reconstruction and mastectomy. He also runs several prospective breast cancer trials at his institution, including NOVEMBER, a phase II 9 day trial of whole breast radiation. He is the co-chair of the Alliance Local Control committee and Vice Chair of the Alliance Breast Committee. He also serves as a member of the National Cancer Institute (NCI) Breast Cancer Committee’s BOLD Task Force.

More about Jamie Wagner, DO, FACOS

Jamie Wagner is an associate professor in the department of surgery at the University of Kansas Cancer Center. She serves as the chief of the division of breast surgical oncology and director of the breast program at the Women’s Cancer Center. After graduating from Kirksville College of Osteopathic Medicine, she went on to complete a general surgery residency at Plaza Medical Center in Fort Worth, TX, and a breast surgical oncology fellowship at the University of Texas, MD Anderson Cancer Center. Dr. Wagner continues to pursue her research interest in breast cancer-related lymphedema, nodal surgery and de-escalation treatment in breast cancer. She is the institutional principal investigator for the Alliance for Clinical Trials and an active member of the prevention committee.

More about Judy C. Boughey, MD, FACS, Education Committee, ACS CRP

Judy C. Boughey is professor of surgery and vice chair for research in the Department of Surgery and medical director of clinical research in the department of surgery. Dr. Boughey is the program director for the Multidisciplinary Breast Surgery Fellowship at Mayo. She is chair of the Publications Committee for the American Society of Breast Surgeons and Chair of the Education Committee for the American College of Surgeons Clinical Research Program. Dr. Boughey has led multiple national clinical trials funded by National Cancer Institute; ACOSOG Z1071 evaluating SLN surgery in patients with node positive breast cancer treated with neoadjuvant chemotherapy, ACOSOG Z11102 evaluating breast conservation in women with multiple ipsilateral breast tumors and ALLIANCE A11202 comparing axillary dissection to axillary radiation for patients with node positive disease after neoadjuvant chemotherapy.

More about ALLIANCE/ACS Clinical Research Program

The mission of the ALLIANCE/American College of Surgeons Clinical Research Program (ACS CRP) is to reduce the impact of cancer by increasing knowledge and awareness of new evidence and practice standards; increasing the participation of community oncology surgeons in cancer research and cancer care activities; developing and implementing evidence-based practices in surgical oncology; and creating opportunities for meaningful health services research.