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

Phase III Randomized Study of Adjuvant Whole Breast Versus Partial Breast Irradiation Using Once Daily or Twice Daily Fractionation Scheme in Women With Stage I or II Breast Cancer

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).

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Radiation Toxicity
• Intervention / Treatment: Radiation: Whole Breast Irradiation; Radiation: Once Daily APBI; Radiation: Twice Daily APBI

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 Type: Interventional
• Enrollment (Actual): 91
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11796
    • National Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Radiation: 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
Experimental: 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	Radiation: 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
Experimental: 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	Radiation: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Adverse cosmetic outcome using the EORTC Breast Cosmetic Rating System	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.	prior to radiation, 6,12 and 18 months after radiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ipsilateral Breast Tumor Recurrence (IBTR)	defined as recurrent invasive or in situ cancer in the ipsilateral breast. Histological evidence of local recurrence will be required.	throughout the study up to 5 years
Disease Free Survival	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).	throughout the study up to 5 years
Overall Survival	defined as the time from randomization to death from any cause	From date of randomization until the date of death up to 5 years
Radiation Induced Early and late toxicities	using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.0	during radiation and at 6, 12 and 18 months after radiation

Collaborators and Investigators

• Sponsor: National Cancer Institute, Egypt
• Investigators: Principal Investigator: Rimoun Boutrus, M.D., Radiation Oncology Department, National Cancer Institute, Cairo University

Publications and helpful links

General Publications

• Hepel JT, Tokita M, MacAusland SG, Evans SB, Hiatt JR, Price LL, DiPetrillo T, Wazer DE. Toxicity of three-dimensional conformal radiotherapy for accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1290-6. doi: 10.1016/j.ijrobp.2009.01.009. Epub 2009 Apr 22.
• Jagsi R, Ben-David MA, Moran JM, Marsh RB, Griffith KA, Hayman JA, Pierce LJ. Unacceptable cosmesis in a protocol investigating intensity-modulated radiotherapy with active breathing control for accelerated partial-breast irradiation. Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):71-8. doi: 10.1016/j.ijrobp.2009.01.041.
• Vicini F, Winter K, Wong J, Pass H, Rabinovitch R, Chafe S, Arthur D, Petersen I, White J, McCormick B. Initial efficacy results of RTOG 0319: three-dimensional conformal radiation therapy (3D-CRT) confined to the region of the lumpectomy cavity for stage I/ II breast carcinoma. Int J Radiat Oncol Biol Phys. 2010 Jul 15;77(4):1120-7. doi: 10.1016/j.ijrobp.2009.06.067. Epub 2009 Nov 10.
• Chen PY, Wallace M, Mitchell C, Grills I, Kestin L, Fowler A, Martinez A, Vicini F. Four-year efficacy, cosmesis, and toxicity using three-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys. 2010 Mar 15;76(4):991-7. doi: 10.1016/j.ijrobp.2009.03.012. Epub 2009 Jun 8.
• Goyal S, Daroui P, Khan AJ, Kearney T, Kirstein L, Haffty BG. Three-year outcomes of a once daily fractionation scheme for accelerated partial breast irradiation (APBI) using 3-D conformal radiotherapy (3D-CRT). Cancer Med. 2013 Dec;2(6):964-71. doi: 10.1002/cam4.157. Epub 2013 Oct 31.
• DE Paula U, D'Angelillo RM, Barbara R, Caruso C, Gomellini S, Caccavari A, Costarelli L, Scavina P, Mauri M, Santini E, Antonaci A, Cavaliere F, LA Pinta M, Loreti A, Fortunato L. Once Daily Accelerated Partial Breast Irradiation: Preliminary Results with Helical Tomotherapy(R). Anticancer Res. 2016 Jun;36(6):3035-9.
• Bentzen SM, Yarnold JR. Reports of unexpected late side effects of accelerated partial breast irradiation--radiobiological considerations. Int J Radiat Oncol Biol Phys. 2010 Jul 15;77(4):969-73. doi: 10.1016/j.ijrobp.2010.01.059. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): June 30, 2018
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: July 28, 2018
• First Submitted That Met QC Criteria: August 3, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): July 28, 2020
• Last Update Submitted That Met QC Criteria: July 27, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Breast Cancer; Accelerated partial Breast Irradiation; Breast cosmesis; radiation Toxicity
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: NCI-BC-12/2012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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