Breast Reconstruction and Neoadjuvant Radiotherapy

NCT05216900 | Recruiting DMC

• 1 other identifier: 80252
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose the BRENAR pilot study is to assess acute post-surgical complications following mastectomy and immediate breast reconstruction after neoadjuvant radiotherapy (NART). The investigators hypothesize that NART will avoid the negative effects of postmastectomy radiotherapy (PMRT) on the capsule of an implant, or on the skin and underlying tissue of an autologous flap, and would therefore lead to better cosmetic results, better quality of life and less complications compared to PMRT. If this hypothesis is confirmed, NART would allow more patients to undergo an immediate reconstruction resulting in superior cosmetic results and quality of life. Furthermore, the use of RT in a neoadjuvant setting could potentially result in a shorter overall loco-regional treatment time from diagnosis to receiving the last locoregional treatment. However, this pilot study will mainly assess whether or not the post-surgical complications of breast reconstruction with NART are acceptable. Further study to investigate long term quality of life and oncologic follow-up results will be conducted after this pilot study, if complication rates are acceptable.

Conditions

Breast Cancer

Keywords

Breast reconstruction; Neoadjuvant radiotherapy

Outcome Measures

Primary Outcomes (1)

• Acute post-surgical complication rate at 3 months following mastectomy and immediate breast reconstruction after NART in the treatment of breast cancer.

  Surgical complications are defined as any complication requiring surgical intervention necessary (excluding percutaneous drainage and antibiotic treatment for inflammation in cases without need for open drainage) within a period up to three months after the final reconstruction, defined and scored using the Clavien-Dindo Classification of Surgical Complications (C-DC)37: - Infection - Hematoma - Loss of implant/expander/flap - (Fat)Necrosis

  3 months following mastectomy and immediate breast reconstruction (latest intervention, being either autologous recosntruction or silicone implant)

Secondary Outcomes (5)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Within 3 months after both breast reconstruction and radiotherapy

• Patient-reported Satisfaction with Breasts, Physical, emotional and sexual well-being (as measured using BREAST-Q)

  At baseline and 3 months after definitive treatment (definitive breast reconstruction).

• The Aesthetic Items Scale; Physician-reported cosmetic results of the reconstructed breast

  3 months after definitive breast reconstruction surgery

• Timely initiation of (possible) adjuvant therapy

  In three months after mastectomy

• Pathological complete response (pCR) assessed in mastectomy specimen

  Within 2 weeks after mastectomy

Study Arms (1)

Neoadjuvant radiotherapy group

EXPERIMENTAL

Twenty breast cancer patients will be included after they have given informed consent. Patients are eligible if they have an indication for mastectomy and RT, and a wish for an immediate reconstruction, either implant-based or autologous, in UMCU, Alexander Monro hospital, St Antonius Hospital, ZiekenhuisGroep Twente, Haagladen Medical Center and Amsterdam UMC.

Radiation: Neoadjuvant radiotherapy

Interventions

Neoadjuvant radiotherapy RADIATION

The study examines the delivery NART. In case of neoadjuvant chemotherapy, RT will start 6-8 weeks after the last course of chemotherapy. A dose of 15 x 2.67 Gy 5 fractions per week, or a biologically equivalent dose will be applied. A mastectomy and a direct breast reconstruction will be performed, approximately 2-6 weeks after latest radiotherapy treatment. Breast reconstruction can be separated in the types of reconstruction, either reconstruction with a silicone implant or with only autologous tissue, of which the most common flap used is the Deep Inferior Epigastric Perforator (DIEP) flap.

Neoadjuvant radiotherapy group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Females at least 18 years of age.
• WHO performance scale ≤2
• Adequate communication and understanding skills of the Dutch language
• Able to understand and sign Dutch written informed consent
• Stage III (cT3N1, cT0-2N2-3) or cN1 with more than 3 suspicious nodes at initial diagnosis
• A positive SN/TAD\* pre- breast surgery in case of:
• cT1-2N0 and less than 3 RF\*\* at initial diagnosis and cCR on imaging\*\*\*
• cT3N0 and no risk factor at initial diagnosis
• If the indication for radiotherapy is not yet clear, and is only indicated when there is a pathological lymph node present, a sentinel node procedure or targeted axillary dissection (TAD) will be performed first to check for the lymph node status. A sentinel node procedure (SNP) will be performed under general anesthesia in order to explore regional lymph nodes. For cT1-3N0 patients, it is known that about 25% has a positive axillary node after neoadjuvant chemotherapy (50);for patients with cT1-3N+ breast cancer, about 55-70% still have positive nodes after neoadjuvant chemotherapy, which is dependent of receptor status 29,30,31,32,33. Consequently, we may have to ask for informed consent 2-4 times more patients than we would need for this pilot study.
• risk factors are: angio invasion, Grade III, Age ≤ 40 yrs, triple negative \*\*\* In patients with cT1-2N0 with at least 3 RF a tumour biopsy can be considered prior to surgery in case of neoadjuvant chemotherapy, since in case of no pCR the indication for RT is already set, and an SN or TAD prior to breast surgery is not required.

You may not qualify if:

• study:
• Legal incapacity
• Not able to understand and sign Dutch written informed consent
• Previous history of breast cancer or another malignancy for which radiotherapy of the breast or axilla
• Collagen synthesis disease
• MRI absolute contraindications as defined by the Radiology Department
• Age \< 18 year
• Pregnant or lactating.
• Smoking
• BMI \> 35 kg/m2
• cT4 tumour (and skin sparing mastectomy not possible)
• If NAC in cT1-2N0 and 3 RF: in triple negative or Her2 positive (with concern for under treatment of adjuvant therapy) and no tumor cells in preoperative biopsy\*
• NB: If neoadjuvant chemotherapy is given, and if the indication for adjuvant systemic treatment is dependent on the presence or absence of a pathological complete response pCR (such as in patients with a triple negative or Her2 positive tumour), centres can choose A) to exclude these patients, or B) only to include these patients when a non-pCR is proven via a biopsy prior to the start of the RT. Earlier studies in partial breast RT showed that pCR rate of NART only, followed by surgery \< 6-8 weeks is very low in the general breast cancer population (17 of the 110), whilst it seems to be higher in patients with triple negative (6/8) and Her2 positive (1/1) (personal communication Sophie Bosma, trial on Preoperative Accelerated Partial Breast Irradiation, PAPBI trial 34.

Sponsors & Collaborators

• UMC Utrecht: lead
• Alexander Monro Hospital, Bilthoven: collaborator
• Amsterdam UMC: collaborator
• Cancer Center Amsterdam grant for innovative research: collaborator

Study Sites (1)

Maarse Wiesje

Bilthoven, Utrecht, 3722 AG, Netherlands

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Central Study Contacts

Wies Maarse, PhD, MD

CONTACT

+31626598153; w.maarse@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: The study will be conducted as a prospective multicenter single arm interventional pilot study. The primary endpoint is post-surgical complications at three months after the latest patient has received the final reconstructive surgery.

Study Record Dates

• First Submitted: December 28, 2021
• First Posted: February 1, 2022
• Study Start: April 1, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 4, 2026
• Last Updated: June 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)