Radiation Therapy During Surgery in Treating Older Women With Invasive Breast Cancer (NRR)

Partial Breast Treatment Using Single Dose Intraoperative Radiotherapy for Patients With Early Stage Breast Cancer - A Feasibility Study With Molecular Analysis of Tumors and Normal Breast Epithelial Tissue

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation during surgery may be an effective treatment for breast cancer.

PURPOSE: This phase II trial is studying how well radiation therapy works in treating older women who are undergoing surgery for invasive breast cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: surgery; Procedure: therapy; Radiation: radiation therapy

Detailed Description

OBJECTIVES:

Primary

• Determine the feasibility of intraoperative partial breast radiotherapy prior to surgical resection in older women with low-risk early stage primary invasive ductal carcinoma of the breast. Feasibility will be determined by the rate of good/excellent cosmesis, as measured by the Radiation Therapy Oncology Group (RTOG) cosmetic rating scale, in patients treated with this regimen compared with that of patients treated with partial breast brachytherapy in clinical trial RTOG-9517.
• Determine the incidence of grade 3-4 toxicity of this regimen in these patients.
• Determine the rate of ipsilateral breast recurrence, including recurrence within the tumor bed as compared to elsewhere in the breast, in patients treated with this regimen.

Secondary

• Determine the radiation-induced activation of receptors and signal transduction pathways involved in radiation response in patients treated with this regimen.

OUTLINE: This is a non-randomized study.

Patients undergo intraoperative lymphatic mapping and sentinel lymphadenectomy OR standard level I, II axillary dissection to evaluate the lymph nodes followed by intraoperative breast ultrasonography to define the tumor target volume. Patients then undergo intraoperative single-dose partial breast radiotherapy followed by segmental mastectomy (i.e., lumpectomy) of the tumor. Patients with 1 or 2 tumor-involved surgical margins may undergo repeat segmental mastectomy. Patients with > 2 tumor-involved surgical margins undergo mastectomy. Patients determined to have a tumor size > 3 cm or an extensive intraductal component on final pathology evaluation undergo standard external beam radiotherapy after surgery.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 2 to 3 years.

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 118 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed primary invasive ductal carcinoma of the breast

  • Tumor size ≤ 3 cm
  • No extensive intraductal component
  • Tumor must not be attached to the skin, underlying muscle, or chest wall

• Candidate for breast-conserving therapy, as determined by the surgical and radiation oncologist

  • Tumor amenable to segmental mastectomy (i.e., lumpectomy)
• No bilateral breast cancer

• No clinical or radiographic multifocal disease not amenable to single segmental mastectomy

  • Patients with > 1 tumor mass in the same breast must have only 1 mass that is histologically malignant AND all other masses must be proven histologically benign

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 48 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• 0-2

Life expectancy

• At least 5 years

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant
• Fertile patients must use effective contraception
• No collagen vascular disease
• No medical condition that would preclude surgery

• Other prior malignancy allowed provided the following criteria are met:

  • Patient has undergone potential curative therapy for all prior malignancies
  • There is no evidence of any prior malignancy within the past 5 years
  • Patient is deemed to be at low risk for recurrence of prior malignancy, as determined by the treating physician

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for this malignancy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the breast

Surgery

• No breast implants

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: Intraoperative Radiation Arm; Intraoperative radiotherapy (radiation therapy) during surgery for tumor excision.	Procedure: surgery; conventional; Procedure: therapy; neoadjuvant; Radiation: radiation therapy; intraoperative radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of Good/Excellent Cosmesis as Measured by the Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale - Rated by Physician	Rates of good/excellent cosmesis was evaluated using the following criteria: Excellent - when compared to the untreated breast, there is minimal or no difference in the size, shape, or texture of the treated breast. There may be mild thickening or scar tissue within the breast or skin, but not enough to change the appearance. Good - there is mild asymmetry in the size or shape of the treated breast as compared to the normal breast. The thickening or scar tissue within the breast causes only a mild change in the shape.	1 year follow up visit
Rates of Good/Excellent Cosmesis as Measured by the Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale - Rated by Patients	Rates of good/excellent cosmesis was evaluated using the following criteria: Excellent - when compared to the untreated breast, there is minimal or no difference in the size, shape, or texture of the treated breast. There may be mild thickening or scar tissue within the breast or skin, but not enough to change the appearance. Good - there is mild asymmetry in the size or shape of the treated breast as compared to the normal breast. The thickening or scar tissue within the breast causes only a mild change in the shape.	1 year follow up visit
Incidence of Grade 3/4 Toxicity	Skin and subcutaneous toxicity were graded by a radiation oncologist according to the common terminology criteria for adverse events version 3.0. Toxicities directly, probably, or possibly related to the radiation were included. Grade refers to the severity of the AE. The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each adverse event (AE) based on this general guideline: Grade 1 Mild Adverse Event Grade 2 Moderate Adverse Event Grade 3 Severe Adverse Event Grade 4 Life-threatening or disabling Adverse Event Grade 5 Death related to Adverse Event	3 months
Ipsilateral Breast Recurrence	Percentage of participants who experienced a ipsilateral breast event (tumor bed recurrence versus elsewhere in breast).	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Association of Phosphorylated Epidermal Growth Factor Receptor (EGFR) , Human Epidermal Growth Factor Receptor 2 (HER2), p44/42 Mitogen-activated Protein Kinase (MAPK), and Protein Kinase B (Akt) in Breast Tumors and Normal Tissue Before and After IORT	3 months
Association of Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NFkB) Expression in Tumor and Normal Tissue Before and After IORT	3 months
Association of Nuclear p53 Expression in Tumor and Normal Tissue Before and After IORT	3 months

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Investigators: Principal Investigator: David Olilla, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

General Publications

• Ollila DW, Klauber-DeMore N, Tesche LJ, Kuzmiak CM, Pavic D, Goyal LK, Lian J, Chang S, Livasy CA, Sherron RF, Sartor CI. Feasibility of breast preserving therapy with single fraction in situ radiotherapy delivered intraoperatively. Ann Surg Oncol. 2007 Feb;14(2):660-9. doi: 10.1245/s10434-006-9154-1.
• Stitzenberg KB, Klauber-Demore N, Chang XS, Calvo BF, Ollila DW, Goyal LK, Meyers MO, Kim HJ, Tepper JE, Sartor CI. In vivo intraoperative radiotherapy: a novel approach to radiotherapy for early stage breast cancer. Ann Surg Oncol. 2007 Apr;14(4):1515-6. doi: 10.1245/s10434-006-9152-3.
• Kimple RJ, Klauber-DeMore N, Kuzmiak CM, Pavic D, Lian J, Livasy CA, Chiu WM, Moore DT, Sartor CI, Ollila DW. Local control following single-dose intraoperative radiotherapy prior to surgical excision of early-stage breast cancer. Ann Surg Oncol. 2011 Apr;18(4):939-45. doi: 10.1245/s10434-010-1392-6.
• Vanderwalde NA, Jones EL, Kimple RJ, Moore DT, Klauber-Demore N, Sartor CI, Ollila DW. Phase 2 study of pre-excision single-dose intraoperative radiation therapy for early-stage breast cancers: six-year update with application of the ASTRO accelerated partial breast irradiation consensus statement criteria. Cancer. 2013 May 1;119(9):1736-43. doi: 10.1002/cncr.27915. Epub 2013 Jan 29.
• Kimple RJ, Klauber-DeMore N, Kuzmiak CM, Pavic D, Lian J, Livasy CA, Esler L, Moore DT, Sartor CI, Ollila DW. Cosmetic outcomes for accelerated partial breast irradiation before surgical excision of early-stage breast cancer using single-dose intraoperative radiotherapy. Int J Radiat Oncol Biol Phys. 2011 Feb 1;79(2):400-7. doi: 10.1016/j.ijrobp.2009.10.032. Epub 2010 Apr 13.

Helpful Links

• University of North Carolina Lineberger Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2003
• Primary Completion (Actual): September 1, 2011
• Study Completion (Estimated): July 2, 2027

Study Registration Dates

• First Submitted: September 15, 2005
• First Submitted That Met QC Criteria: September 15, 2005
• First Posted (Estimated): September 16, 2005

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage I breast cancer; invasive ductal breast carcinoma
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: LCCC 0218