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

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

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00325598

Enrollment

100

Registered

2006-05-15

Start date

2006-02-14

Completion date

2017-04-16

Last updated

2018-06-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Neoplasms

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.

Interventions

RADIATIONPartial Breast Irradiation (PBI)

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. 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. 2. 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. 3. Age \>= 18 years of age 4. ECOG Performance Status 0-2. 5. 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. 1. 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. 2. Tumor \> 2.0 cm, nodal involvement on H&E staining, or metastatic involvement 3. Histological evidence of: 1. 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. 2. 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. 3. Invasive Lobular Carcinoma 4. 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. 5. Infiltrating papillary carcinoma 6. Margins: In-situ or invasive carcinoma present less than 2 mm from the inked resection margin. 4. History of cosmetic or reconstructive breast surgery 5. 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. 6. 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. 7. Patients with diffuse (\> 1 quadrant or \> 5cm) suspicious microcalcifications 8. Women who are pregnant.

Design outcomes

Primary

Measure	Time frame	Description
Feasibility of PBI Directed External Radiotherapy as Measured by Percentage of Participants Achieving a Dosimetrically Satisfactory Treatment Plan	Within 1 year of protocol registration	-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.
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	Within 1 year of protocol registration	-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

Secondary

Measure	Time frame	Description
Incidence of Fat Necrosis	Up to 5 years	-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.
Cosmetic Outcome	Up to 5 years	* Excellent: little or no observable change * Good: minimal but identifiable changes * Fair: significant results of radiotherapy noted * Poor: severe normal tissue sequelae
Incidence and Severity of Cutaneous Toxicity	Up to 5 years	* 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
Regional Control Rate	Up to 5 years	-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
Distant Control Rate	Up to 5 years	-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.
Local Control Rate	Up to 5 years	-Local control rate for this study is the number of participants who remained free of disease in their breast.
Incidence of Breast Fibrosis	Up to 5 years	—

Countries

United States

Participant flow

Recruitment details

The study opened to participant enrollment on 02/14/2006 and closed to participant enrollment on 04/11/2012.

Participants by arm

Arm	Count
Cohort 1 (36 Gy) 36 Gy in 9 fractions BID x 4 1/2 treatment days Partial Breast Irradiation (PBI)	50
Cohort 2 (40 Gy) 40 Gy in 10 fractions BID over 5 treatment days Partial Breast Irradiation (PBI)	50
Total	100

Baseline characteristics

Characteristic	Cohort 1 (36 Gy)	Cohort 2 (40 Gy)	Total
Age, Continuous	56.5 years	59 years	58 years
Region of Enrollment United States	50 Participants	50 Participants	100 Participants
Sex: Female, Male Female	50 Participants	50 Participants	100 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	21 / 50	50 / 50	50 / 50	50 / 50
serious Total, serious adverse events	3 / 50	0 / 50	0 / 50	0 / 50

Outcome results

Primary

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

Time frame: Within 1 year of protocol registration

Arm	Measure	Value (NUMBER)
Cohort 1 (36 Gy)	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	0 percentage of participants
Cohort 2 (40 Gy)	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	4 percentage of participants

Primary

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.

Time frame: Within 1 year of protocol registration

Arm	Measure	Value (NUMBER)
Cohort 1 (36 Gy)	Feasibility of PBI Directed External Radiotherapy as Measured by Percentage of Participants Achieving a Dosimetrically Satisfactory Treatment Plan	100 percentage of participants
Cohort 2 (40 Gy)	Feasibility of PBI Directed External Radiotherapy as Measured by Percentage of Participants Achieving a Dosimetrically Satisfactory Treatment Plan	100 percentage of participants

Secondary

Cosmetic Outcome

* Excellent: little or no observable change * Good: minimal but identifiable changes * Fair: significant results of radiotherapy noted * Poor: severe normal tissue sequelae

Time frame: Up to 5 years

Population: 4 patients in Cohort 1 were not evaluable for this outcome measure because 2 patients did not have the cosmetic outcome performed, 1 patient withdrew consent, and 1 patient was lost to follow-up.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Cohort 1 (36 Gy)	Cosmetic Outcome	Excellent	6 Participants
Cohort 1 (36 Gy)	Cosmetic Outcome	Fair	9 Participants
Cohort 1 (36 Gy)	Cosmetic Outcome	Poor	1 Participants
Cohort 1 (36 Gy)	Cosmetic Outcome	Good	30 Participants
Cohort 2 (40 Gy)	Cosmetic Outcome	Fair	3 Participants
Cohort 2 (40 Gy)	Cosmetic Outcome	Excellent	11 Participants
Cohort 2 (40 Gy)	Cosmetic Outcome	Good	32 Participants
Cohort 2 (40 Gy)	Cosmetic Outcome	Poor	4 Participants

Secondary

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.

Time frame: Up to 5 years