Title
A Phase II Study of Real-Time MRI-Guided 3-Fraction Accelerated Partial Breast Irradiation in Early Breast Cancer (MAPBI)

Description
This trial will investigate a novel 3-fraction radiation regimen for participants undergoing breast-conserving therapy (BCT) for early breast cancer that will: 1) significantly reduce the duration of treatment and can be completed in one-week (5 working days) and 2) MRI-guided radiotherapy (MRIdian) would limit the volume of normal tissue radiated and therefore resultant toxicity. The hypothesis is that 3-fraction radiation therapy can be delivered safely without compromising the therapeutic ratio. Participants can expect to be on study for follow up up to 5 years.

Objective
Primary Objective
To evaluate physician reported 1-year cosmesis outcome using Harvard cosmesis scale for patients treated with 3-fraction APBI on MRIdian system.

Secondary Objectives
1. Evaluate patient quality of life (QOL) using BCTOS, convenience of care and MOS SF-36 forms at 1- and 3 -years
2. Physician evaluation of cosmesis will be done using Harvard cosmesis scale and objective evaluation of digital breast photographs at 1-year and 3-years.
3. Physician evaluation of fat necrosis will be performed using the Lövey et al., fat necrosis scale(51).
4. Acute and late radiation toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
5. Ipsilateral breast tumor recurrence (IBTR) defined as recurrent invasive or in situ cancer in the ipsilateral breast including the axillary tail at 5-years.
6. Ipsilateral regional nodal recurrence, defined as recurrent cancer in the ipsilateral axillary, supraclavicular, or internal mammary lymph nodes.
7. Disease free survival (DFS) defined as the time from start of radiation to the time of documented recurrent disease in the ipsilateral breast, regional nodes, or distant sites.
8. Overall survival (OS) defined as the time from start of radiation to death from any cause.

Treatment Experimental: 8.2 Gy Radiation Therapy
Accelerated partial breast irradiation using 3 x 8.2 Gy to the lumpectomy cavity with a 3mm PTV margin. Treatment duration will be 5-6 days and treatments will be on alternative weekdays, with a minimum interval of 40 hours between subsequent fractions.
Radiation: MRIdian Radiation Treatment Unit
partial breast irradiation using 3 x 8.2 Gy to the lumpectomy cavity with a 3mm planning tumor volume (PTV) margin

Key Eligibility Inclusion Criteria:
For all participants

Participants should have no contraindications to undergo MRI scan as part of radiotherapy planning and treatment.

Lumpectomy cavity must be clearly visible on CT and MRI scan at radiotherapy simulation.

Pregnancy test negative in women of child bearing potential (WOCBP).

The participant must consent to be in the study and must have signed an approved consent form conforming with institutional guidelines.

Participants with a history of non-breast malignancies are eligible if they have been disease-free for 5 or more years prior and are deemed by their physician to be at low risk for recurrence. Participants with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.

Suitable:



Age: >=50 years



Margins: Negative by at least 2 mm

T Stage: Tis or T1



Cautionary:


Age: 40-49 years



Margins: Negative by at least 2 mm

T Stage: Tis or T1 OR



Age: >=50 years IF participant has at least 1 of the pathologic factors below and does not have any "unsuitable" factors (below)



Pathologic Factors:



Size 2.1-3.0 cm (size of the invasive component)

T2

Close margins (<2 mm)

Limited/focal Lymphovascular Space Invasion (LVSI)

ER (-)

Clinically unifocal with total size 2.1-3.0 cm (Microscopic multifocality allowed, provided the lesion is clinically unifocal (a single discrete lesion by physical examination and ultrasonography/mammography) and the total lesion size (including foci of multifocality and intervening normal breast parenchyma) falls between 2.1 and 3.0 cm).

Invasive lobular histology

Extensive Intraductal Component (EIC) <=3 cm

Suitable Criteria, DCIS allowed if all of the following are met:



Screen-detected

Low to intermediate nuclear grade

Size <=2.5 cm

Resected with margins negative at >=3mm OR


Cautionary Criteria:



Pure DCIS <=3 cm if "suitable" criteria not fully met

Applicable Disease Sites
Breast

Participating Institutions
Johnson Creek, UW Cancer Center; UW Health Eastpark Medical Center; UW Health University Hospital