Preoperative Partial Breast Irradiation in Early-Stage Breast Cancer

Impact of Preoperative Stereotactic Partial Breast Irradiation on Treatment Response, Treatment-related Toxicity, and Cosmetic Outcomes in Early-stage Breast Cancer: A Prospective, Phase II Clinical Trial

In the management of early breast cancer patients, postoperative radiotherapy following breast-conserving surgery has been established as the standard treatment. Over the past two decades, significant changes have occurred in radiotherapy for breast cancer, encompassing dose fractionation methods, radiotherapy techniques, and delineation of the radiation field. Hypofractionated radiotherapy has been reported in numerous randomized phase 3 studies to show equivalent tumor control rates, reduced acute side effects, and similar late side effects compared to conventional fractionation. Among hypofractionated radiotherapy approaches, particularly in early-breast cancer, accelerated partial breast irradiation (APBI) may be chosen over whole breast irradiation (WBI). This approach is based on data indicating that the majority of local recurrences in breast cancer occur around the site of the primary tumor. By targeting radiation to the involved breast region, it becomes possible to increase the dose per fraction while shortening the overall treatment duration due to the smaller radiation treatment volume. While careful patient selection is crucial, multiple clinical studies have demonstrated that APBI, particularly after breast-conserving surgery, yields satisfactory local control rates comparable to WBI. This is accompanied by reduced side effects, improved convenience, enhanced quality of life, and potential cost savings.

Traditionally, APBI has been administered after surgery, but there is a recent trend to explore preoperative APBI. The rationale for performing preoperative APBI includes several considerations. Firstly, compared to postoperative APBI, the precise location of visually identifiable tumors allows for more accurate and targeted radiation therapy, minimizing the impact on adjacent normal tissues and achieving superior cosmetic results. Secondly, reducing the size of the preoperative lesion may enable more conservative surgery, decreasing the extent of the surgical procedure. Thirdly, it can serve as a preparatory treatment to assess tumor responsiveness. Fourthly, in some cases, it may be administered for definitive purposes, especially in elderly or frail women who may find it challenging to undergo standard treatment due to concurrent health issues.

Several clinical studies have reported the effectiveness and validity of preoperative PBI in a few cases of early breast cancer. These studies have shown low rates of acute and chronic toxicity, with excellent cosmetic outcomes. While accumulating evidence supports preoperative PBI, there is currently a lack of comparative studies with postoperative PBI. Therefore, this study aims to compare and evaluate the overall clinical advantages, including safety and efficacy, of preoperative PBI and postoperative PBI in early breast cancer patients.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Invasive Breast Cancer; Ductal Carcinoma in Situ
• Intervention / Treatment: Radiation: Preoperative PBI

Detailed Description

This study is a phase II clinical trial consisting of a single experimental group (preoperative PBI group).

- Experimental Group: Preoperative Partial Breast Irradiation (Preoperative PBI)

The objective is to prove that preoperative partial breast irradiation (PBI) is not inferior in terms of radiotherapy-related side effects compared to postoperative PBI in early breast cancer patients.

Treatment outcomes, treatment-related complications, quality of life, degree of breast fibrosis, and breast aesthetics will be prospectively observed. Up to 47 patients will be enrolled over a period of 2 years, with a maximum follow-up observation of 1 years.

Evaluation of acute radiotherapy-related complications will be conducted at least once within 2 weeks from the start of radiotherapy. Additional assessments for acute complications and surgery-related complications will be performed at least once after 6 months of radiotherapy. Evaluation of late radiotherapy-related complications will occur 12 months after radiotherapy.

Patient's quality of life will be measured using self-reported questionnaires at (1) before radiotherapy, (2) 6 months after radiotherapy, and (3) 12 months after radiotherapy.

Breast aesthetics assessment using BCCT. Score software will be conducted at (1) before radiotherapy, (2) 6 months after radiotherapy, and (3) 12 months after radiotherapy. Evaluation of breast fibrosis will utilize the Tissue Compliance Meter device at (1) before radiotherapy, (2) 6 months after radiotherapy, and (3) 12 months after radiotherapy.

Preoperative PBI will be administered within 6 weeks of the patient's first registration, and surgery will be performed within 8 to 12 weeks after radiotherapy. Throughout radiotherapy, immediate, post-treatment, and follow-up observations at 6-month to 1-year intervals for up to 1 years will assess complications, surgical outcomes, cosmetic effects, and disease status.

• Study Type: Interventional
• Enrollment (Estimated): 47
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yong Bae Kim; Phone Number: 82-2-2228-8106; Email: ybkim3@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Department of Radiation Oncology, Yonsei University College of Medicine
    • Contact: Yong Bae Kim; Email: ybkim3@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed ductal carcinoma in situ (DCIS) and invasive breast cancer.
• Age ≥ 45
• cT1/cN0, tumor size ≤ 2.5cm
• ECOG 0~2 -ER+, HER2-

Exclusion Criteria:

• cN+
• Tumor located too close to the skin or chest wall (within 5 mm)
• With previous treatment history for breast cancer
• Neoadjuvant chemotherapy
• Multicentric disease
• Diffuse microcalcification
• BRCA mutation
• Paget's disease
• In cases where tumor delineation is not achievable on CT/MRI images

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preoperative PBI; PBI before surgery	Radiation: Preoperative PBI; Preoperative PBI: 21 Gy * 1 fraction Preoperative PBI is administered within 6 weeks of the patient's initial registration, and surgery is scheduled within 8 to 12 weeks after PBI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of grade 2 or higher acute toxicities	The grade of toxicities should be evaluated according to CTCAE version 5.0.	Within 6 months after the start of radiotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	12 months
Pathologic complete response (CR) rate	At the time of surgery
Rate of any grade acute toxicities	Within 6 months after the start of radiotherapy
Rate of any gade late toxicities	6 months after the start of radiotherapy
Rate of grade 2 or higher late toxicities	6 months after the start of radiotherapy
BCCT.core software score	Baseline (before radiotherapy), at 6 months, 12 months after radiotherapy
Change of Quality of life score	Baseline (before radiotherapy), at 6 months, 12 months after radiotherapy
Tissue compliance meter score	Baseline (before radiotherapy), at 6 months, 12 months after radiotherapy
Disease-free survival	12 months
breast cancer specific survival	12 months

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Yong Bae Kim, Department of Radiation Oncology, Yonsei University College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2023
• Primary Completion (Estimated): October 12, 2025
• Study Completion (Estimated): October 12, 2026

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: November 6, 2024
• First Posted (Estimated): November 7, 2024

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 6, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Breast Carcinoma In Situ; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Skin Diseases; Breast Diseases; Carcinoma; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating
• Other Study ID Numbers: 4-2023-1112

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No