Whole Breast Irradiation vs Twice Daily vs. Once Daily Accelerated Partial Breast Irradiation

Not Applicable

• Conditions: Radiation Toxicity; Breast Cancer
• Interventions: Radiation: Whole Breast Irradiation; Radiation: Twice Daily APBI; Radiation: Once Daily APBI

• Registration Number: NCT03616626
• Lead Sponsor: National Cancer Institute, Egypt

Brief Summary

This is a randomized phase III trial in women with invasive carcinoma of the breast with negative axillary nodes treated by Breast Conserving Surgery (BCS). Eligible, patients will be randomly allocated to receive radiotherapy of 3 Dimensional Conformal Radiation Therapy (3DCRT) Whole Breast Irradiation (WBI) 50 Gray (Gy) in 25 daily fractions over 5 weeks or Accelerated Partial Breast Irradiation (APBI) 38.5 Gy in 10 daily fractions of 3.85Gy over two weeks or 38.5 Gy in 10 twice daily fractions of 3.85Gy over one week. Patients will be followed at 6, 12, 18 and 24 months post randomization. Cosmetic outcome will be measured using photographs and evaluated by a panel of trained radiation oncologists. Radiation toxicity will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).

Detailed Description

Women with invasive carcinoma of the breast less than 3 cm with negative axillary nodes , following BCS, who meet the inclusion criteria will be approached for potential study enrollment.

Eligible, consenting patients will be randomly allocated to receive radiotherapy of 3DCRT WBI 50 Gy in 25 fractions over 5 weeks or APBI 38.5 Gy in 10 once daily fractions of 3.85Gy over two weeks or 38.5 Gy in 10 twice daily fractions of 3.85 Gy over one week. Patients will be followed at 6, 12, 18 and 24 months post randomization. Cosmetic outcome will be measured using photographs and evaluated by a panel of trained radiation oncologists using the EORTC Breast Cosmetic Rating System. Radiation toxicity will be assessed using the NCI CTCAE version 4.0. The primary outcome is to compare the acute, late toxicities and adverse cosmetic outcomes at 6, 12 and 18 months among the three groups.

Study Timeline

• Study Start: 2013-07-01
• Primary Completion: 2018-06-30
• Study First Submitted: 2018-07-28
• Study First Submitted QC: 2018-08-03
• Study First Posted: 2018-08-06
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-27
• Last Update Posted: 2020-07-28
• Study Completion: 2021-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 91

Inclusion Criteria

Tumor characteristics

• Histologically confirmed invasive adenocarcinoma of the breast
• Tumors must be ≤ 3 cm. Gross disease must be unifocal. Negative lymph nodes
• Hormone receptor status:

Estrogen receptor (ER) status known Progesterone status known if ER analysis is negative Marginal or borderline results are considered positive Surgery

• Tumor removed with conservative breast surgery with adequate margin

• Re-excision of surgical margins allowed

• No prior breast implants

• Prior axillary staging required for patients including 1 of the following:

  • Sentinel node biopsy alone (if sentinel node is negative)
  • Sentinel node biopsy followed by axillary dissection if sentinel node is positive)
  • Axillary dissection alone with ≥ 6 axillary nodes

• Target lumpectomy cavity clearly delineated AND target lumpectomy/whole breast reference volume ≤ 30% based on postoperative pre-randomization CT scan

• Final surgery (i.e., lumpectomy, re-excision of margins, or axillary staging procedure) within the past 42 days

• No prior biologic therapy for this malignancy Chemotherapy

• No prior chemotherapy for this malignancy

• No concurrent chemotherapy during study radiotherapy Endocrine therapy

• No prior hormonal therapy for this malignancy

• Concurrent hormonal therapy allowed provided it is not administered during chemotherapy

• No concurrent raloxifene, tamoxifen, or other selective estrogen receptor modulating drugs

• No concurrent hormone replacement therapy Radiotherapy

• No prior radiotherapy for this malignancy

• No prior breast or thoracic radiotherapy

• No concurrent regional nodal irradiation Other

• No other concurrent anticancer therapy Menopausal status

• Premenopausal or postmenopausal Performance status

• WHO 0-1 Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective non-hormonal contraception

Exclusion Criteria

• Multicentric carcinoma in more than 1 quadrant or separated by ≥ 4 cm.
• Non-epithelial breast malignancies (e.g., sarcoma or lymphoma).
• Positive axillary nodes.
• Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes unless there is histologic confirmation that these nodes are negative for tumor.
• Suspicious microcalcifications, densities, or palpable abnormalities in the ipsilateral or contralateral breast unless biopsied and found to be benign
• Paget's disease of the nipple
• Previous history of invasive breast cancer or DCIS.
• Synchronous bilateral invasive or non-invasive breast cancer
• Collagen vascular disease (e.g., systemic lupus erythematosus or scleroderma), specifically dermatomyositis with a CPK level above normal, or active skin rash
• Psychiatric or addictive disorder that would preclude study therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Whole Breast Irradiation	Whole Breast Irradiation	Adjuvant 3D Conformal Radiation Therapy to a dose of 50 Gy in 25 fractions over 5 weeks. Boost is given as 10 Gy in 5 fractions over one week to patients with high grade tumors or age younger than 50 years
Twice Daily APBI	Twice Daily APBI	Adjuvant 3D Conformal Accelerated Partial Breast Irradiation to a dose of 38.5 Gy in 10 twice daily fractions given over 1 week
Once Daily APBI	Once Daily APBI	Adjuvant 3D Conformal Accelerated Partial Breast Irradiation to a dose of 38.5 Gy in 10 once daily fractions given over 2 weeks

Primary Outcome Measures

Name	Time	Method
Change in the Adverse cosmetic outcome using the EORTC Breast Cosmetic Rating System	prior to radiation, 6,12 and 18 months after radiation	The primary outcome is the change in the adverse cosmesis assessed prior to radiation, 6, 12 and 18 months after end of radiation. The cosmetic outcome will be assessed by a radiation oncologist who is unaware of treatment allocation, using the EORTC Breast Cosmetic Rating System.

Secondary Outcome Measures

Name	Time	Method
Disease Free Survival	throughout the study up to 5 years	defined as the time from randomization to the time of documented recurrent disease in the ipsilateral breast or regional nodes (supraclavicular, axillary or internal mammary) or distant sites (e.g. bone, liver, lung or brain).
Overall Survival	From date of randomization until the date of death up to 5 years	defined as the time from randomization to death from any cause
Ipsilateral Breast Tumor Recurrence (IBTR)	throughout the study up to 5 years	defined as recurrent invasive or in situ cancer in the ipsilateral breast. Histological evidence of local recurrence will be required.
Radiation Induced Early and late toxicities	during radiation and at 6, 12 and 18 months after radiation	using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.0

Trial Locations

Locations (1)

National Cancer Institute; 🇪🇬 Cairo, Egypt