Partial Breast Irradiation (PBI) for Selected Patients With Early Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This study investigates the feasibility and safety of delivering radiation therapy only to part of the breast, (the tumor bed and selected areas) rather than the whole breast, for patients with early stage breast cancer.

Official Title
-----------------
Partial Breast Irradiation (PBI) for Selected Patients With Early Breast Cancer: A Phase I/II Feasibility Study

Conditions
-----------------
Breast Neoplasms

Intervention / Treatment
-----------------
* Radiation: Partial Breast Irradiation (PBI)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Histologic Documentation: Patients will have histologically confirmed Unicentric Stage I (T1 N0 M0) invasive ductal breast cancer. Histologically negative tumor margin 2 mm or more from any inked edges, or no tumor in a re-excision specimen or final shaved specimen. Tubular, mucinous and medullary variant histologies of infiltrating ductal carcinoma are permitted. Low-grade DCIS (I and II) of 2 cm or less with histologically negative margins of at least 2 mm margins (or a negative re-excision) are permitted. Women age 70 years or older with T1 invasive ductal carcinoma which are estrogen-receptor positive (ER+) with clinically negative axillary nodes who do not undergo surgical lymph node evaluation are also eligible if patient will take hormonal therapy. Patients with T1N0 (i+) tumors on sentinel lymph node mapping or dissection (i.e. is tumor deposit is 0.2mm or less, regardless of whether the deposit is detected by IHC or H&E staining) will also be eligible, provided that completion axillary dissection has been performed to confirm N0 status. In the case where invasive cancer is present, the invasive cancer's pathology will be used regardless if DCIS is also present. Prior Treatment: Patient may have been treated with adjuvant chemotherapy. Patients may be on adjuvant hormonal therapy or begin hormonal therapy following XRT at the discretion of the medical oncologist. Radiation therapy should begin within: 4-12 weeks from definitive surgical procedure 2-6 weeks after chemotherapy, if chemotherapy given first Radiation cannot be delivered concurrently with chemotherapy. Age >= 18 years of age ECOG Performance Status 0-2. Signed Informed Consent Exclusion Criteria The following guidelines are to assist physicians in selecting patients for whom protocol therapy is safe and appropriate. Physicians should recognize that the following may seriously increase the risk to the patient entering this protocol. Patients who meet the following criteria should not be entered in this study: 1a Multicentric IDC of the breast defined as discontiguous tumors separated by at least 5 cm of uninvolved tissue; alternatively, discontiguous tumors that are clinically or mammographically within separate breast quadrants or subareolar central region. b Multifocal IDC of the breast, defined as discontiguous discrete foci of invasive carcinoma, separated by uninvolved intervening tissue, but within an overall span of 5cm, or within the same breast quadrant or subareolar central region. Tumor > 2.0 cm, nodal involvement on H&E staining, or metastatic involvement Histological evidence of: Lymphovascular invasion: as defined by a tumor embolus present in an endothelial-lined space; cases with tumor emboli present in a space not lined by endothelial cells but otherwise very suspicious for an angiolymphatic space were also considered ineligible. EIC (Extensive Intraductal Component): defined as the presence of intraductal carcinoma both within the primary infiltrating ductal tumor (comprising at least 25% of the tumor area) and intraductal carcinoma present clearly beyond the edges of the invasive tumor, or as a predominantly intraductal tumor with one or more areas of focal invasion 7, 55. Invasive Lobular Carcinoma Infiltrating carcinoma with mixed ductal and lobular features: cases with ambiguous or mixed histologic features that showed positive E-cadherin staining throughout the tumor by immunohistochemistry were classified as ductal type and considered eligible 56, 57. Infiltrating papillary carcinoma Margins: In-situ or invasive carcinoma present less than 2 mm from the inked resection margin. History of cosmetic or reconstructive breast surgery Psychiatric illness which would prevent the patient from giving informed consent. Medical condition such as uncontrolled infection (including HIV), uncontrolled diabetes mellitus or connective tissue diseases (lupus, systemic sclerosis or other collagen vascular diseases) which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient. Patients with a currently active second malignancy other than non-melanoma skin cancers. Patients are not considered to have a currently active malignancy if they have completed therapy and considered by their physician to be at less than 5% risk of relapse within three years. Patients with diffuse (> 1 quadrant or > 5cm) suspicious microcalcifications Women who are pregnant.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (36 Gy)<br>36 Gy in 9 fractions BID x 4 1/2 treatment days | Radiation: Partial Breast Irradiation (PBI)<br> <br> |
| Experimental: Cohort 2 (40 Gy)<br>40 Gy in 10 fractions BID over 5 treatment days | Radiation: Partial Breast Irradiation (PBI)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of PBI Directed External Radiotherapy as Measured by Percentage of Participants Achieving a Dosimetrically Satisfactory Treatment Plan | -The study will be deemed infeasible if more than 4 patients cannot be given treatment because her tumor is such that a dosimetrically satisfactory treatment plan cannot be devised for her. | Within 1 year of protocol registration | 
| Feasibility of PBI Directed External Radiotherapy as Measured by Development of Histological Fat Necrosis or Other Grade 4 Skin or Grade 4 Subcutaneous Toxicity, or Requires Surgery for the Skin/Subcutaneous Toxicity | -The study will be deemed infeasible if more than 4 patients develop histological fat necrosis or other grade 4 skin or grade 4 subcutaneous toxicity, or requires surgery for her skin or subcutaneous toxicity | Within 1 year of protocol registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Cutaneous Toxicity | Uses RTOG/EORTC Late Radiation Morbidity Scoring Scheme Grade 0 = none Grade 1 = slight atrophy; pigmentation change; some hair loss Grade 2 = patch atrophy; moderate telangiectasia; total hair loss Grade 3 = marked atrophy; gross telangiectasia Grade 4 = ulceration Worst cutaneous toxicity grade is noted | Up to 5 years | 
| Incidence of Breast Fibrosis |  | Up to 5 years | 
| Incidence of Fat Necrosis | -Fat necrosis typically causes a painless mass located superficially in the breast, accompanied by retraction or dimpling of the overlying skin. The skin may be thickened clinically and radiologically. Fat necrosis is firm and relatively circumscribed on palpation. Mammography usually reveals a spiculated, often poorly defined mass that may contain punctate or large, irregular calcifications. Attachment to the skin, dimpling, and thickening of the skin are often evident. Less frequently, the lesion consists of a circumscribed, oil-filled, partly calcified cyst. Early in its development, fat necrosis has the appearance of hemorrhage in indurated fat. After several weeks, the affected area becomes demarcated, forming a distinct yellow-gray and focally reddish tumor. Cystic degeneration may develop in the center of such a lesion, resulting in a cavity that contains oily fluid or necrotic fat. | Up to 5 years | 
| Cosmetic Outcome | Excellent: little or no observable change Good: minimal but identifiable changes Fair: significant results of radiotherapy noted Poor: severe normal tissue sequelae | Up to 5 years | 
| Local Control Rate | -Local control rate for this study is the number of participants who remained free of disease in their breast. | Up to 5 years | 
| Regional Control Rate | -Regional control rate for this study is the number of participants who remained free from disease in the regional lymph nodes. The regional lymph nodes are the axilla, infraclavicular, supraclavicular, and internal mammary lymph node beds | Up to 5 years | 
| Distant Control Rate | -Distant control rate for this study is the number of participants who remained free of cancer at distant sites which is defined as all parts of the body that are not the ipsilateral breast or ipsilateral regional lymph nodes. | Up to 5 years |