Clinical trial NCT00182728: Radiation Therapy During Surgery in Treating Older Women With Invasive Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: invasive ductal breast carcinoma
stage I breast cancer
stage II breast cancer
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2005-09-16
Enrollment: 89
Sex: FEMALE
Minimum age (years): 48
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rates of Good/Excellent Cosmesis as Measured by the Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale - Rated by Physician
timeFrame: 1 year follow up visit
measure: Rates of Good/Excellent Cosmesis as Measured by the Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale - Rated by Patients
timeFrame: 1 year follow up visit
measure: Incidence of Grade 3/4 Toxicity
timeFrame: 3 months
measure: Ipsilateral Breast Recurrence
timeFrame: 5 years
Secondary outcomes:
measure: 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
timeFrame: 3 months
measure: Association of Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NFkB) Expression in Tumor and Normal Tissue Before and After IORT
timeFrame: 3 months
measure: Association of Nuclear p53 Expression in Tumor and Normal Tissue Before and After IORT
timeFrame: 3 months
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: David Olilla, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.