Radiation Therapy Boost Before Surgery for the Treatment of Non-metastatic Breast Cancer

A Single Center Phase II Prospective Clinical Trial to Assess the Feasibility of Preoperative Radiation Boost in Breast Cancer Patients

This phase II trial investigates the safety of delivering a part (boost) of radiation treatment before breast surgery in treating patients with breast cancer that has not spread to other places in the body (non-metastatic). Radiation therapy uses high energy photons/electrons to kill tumor cells and shrink tumors. Delivering a boost radiation treatment before surgery when doctors can still visualize the tumor on imaging may help to better target the tumor and decrease the volume of normal irradiated tissue. By so doing, doctors may achieve better cosmetic outcomes and possibly better tumor control.

PRIMARY OBJECTIVE: I. To demonstrate that the incidence of grade 3 or more wound complications in patients with non-metastatic node negative breast cancer who are eligible for breast conserving surgery (BCS) and treated with pre-operative radiation boost at 1 month after end of whole breast radiation is no worse than the rates in the current standard of care (6-20%). SECONDARY OBJECTIVE: I. To demonstrate that the physician reported cosmetic outcome at 1 and 3 years after the end of treatment is better than what has been reported for the current standard of practice for patients undergoing BCS and hypofractionated whole breast irradiation (WBI). TERTIARY/EXPLORATORY OBJECTIVES: I. To measure the acute and late radiation related toxicities such as radiation dermatitis, telangiectasia and fibrosis in this cohort of patients. II. To measure the pre-operative boost clinical target volume (CTV) and compare to the post-op CTV volume that would have been contoured as CTV if the boost was to be delivered post-operatively. III. To measure the incidence of fair/poor patient reported cosmetic outcome using the Breast Cancer Treatment Outcomes Scale (BCTOS) cosmetic scale. IV. To study the cancer biology before and after radiation treatment. OUTLINE: Prior to surgery, patients undergo radiation therapy boost over 4 fractions. Patients then undergo standard of care surgery 1-3 weeks from the last day of boost. 3 to 5 weeks after surgery, patients continue standard of care WBI in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1, 3, 6, 9, 12, 18, and 24 months

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Prior to surgery, patients undergo radiation therapy boost over 4 fractions. Patients then undergo standard of care surgery 1-3 weeks from the last day of boost. 3 to 5 weeks after surgery, patients continue standard of care WBI in the absence of disease progression or unacceptable toxicity.

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Change in wound status from baseline every 3-6 months after WBI to access incidence of grade 3 or more wound complications after breast conserving surgery.

Wound complications will be assessed by the surgeon and radiation oncologist and graded using descriptions and grading scales found in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5 (CTCAE v 5.0). This will be calculated as a proportion based on the number of events in the study. Will report the proportion with a 95% confidence interval (CI) using the Clopper-Pearson method.

Physician reported cosmesis will be assessed using the Harvard Cosmesis assessment Scale for Breast Cancer Patients which is a 4-point scale describing the breast cosmetic outcome (excellent, good, fair or poor).

Physician reported cosmesis will be assessed using the Harvard Cosmesis assessment Scale for Breast Cancer Patients which is a 4-point scale describing the breast cosmetic outcome (excellent, good, fair or poor).

Physician reported cosmesis will be assessed using the Harvard Cosmesis assessment Scale for Breast Cancer Patients which is a 4-point scale describing the breast cosmetic outcome (excellent, good, fair or poor). Will be reported as a proportion; CI will be calculated using the Clopper-Pearson model.

Rate of fibrosis, rate of telangiectasia formation and rate of radiation dermatitis will be assessed by the radiation oncologist using descriptions and grading scales found in the NCI CTCAE v5.0. Will also assess changes in pathology between the biopsy and the surgical specimen.

Patient reported cosmesis will be assessed by the patient using the Breast Cancer Treatment Outcomes Scale (BCTOS).

Patient reported cosmesis will be assessed by the patient using the Breast Cancer Treatment Outcomes Scale (BCTOS). Breast Cancer Treatment Outcome Scale is a questionnaire designed to assess women's subjective evaluation of both the aesthetic and functional outcome after breast cancer treatment. Patients are instructed to rate each item of the BCTOS questionnaire on a four-point scale evaluating the differences between the treated and the untreated breast (1 = no difference to 4 = large difference). Higher scores reflect worse outcomes.

Patient reported cosmesis will be assessed by the patient using the Breast Cancer Treatment Outcomes Scale (BCTOS). Breast Cancer Treatment Outcome Scale is a questionnaire designed to assess women's subjective evaluation of both the aesthetic and functional outcome after breast cancer treatment. Patients are instructed to rate each item of the BCTOS questionnaire on a four-point scale evaluating the differences between the treated and the untreated breast (1 = no difference to 4 = large difference). Higher scores reflect worse outcomes.

The difference between the pre-operative boost Clinical target volume (CTV) and the post-op Clinical target volume (CTV) volume that would have been contoured as Clinical target volume (CTV) if the boost was to be delivered post-operatively.

Another goal is to look into the histopathology of tumors before and after radiation to assess response and other immunologic changes to the tumor and the tumor environment elicited by the radiation treatment.

Inclusion Criteria: Breast cancer patients with biopsy proven invasive cancer Clinically and radiographically node negative No indication of metastatic disease Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Synchronous bilateral invasive cancer allowed Negative serum pregnancy test within one month from the radiation therapy (RT) boost delivery Willingness to participate in the clinical trial and adhere to the study protocol Individuals of all races, genders and ethnic groups are eligible for this trial Exclusion Criteria: Need for neoadjuvant chemotherapy Inflammatory breast cancer (cT4) Multicentric tumor Prior ipsilateral breast or thoracic RT Contraindication for baseline magnetic resonance imaging (MRI) Contraindication for surgery Distant metastatic disease Other synchronous cancer (besides bilateral breast) Contraindication to radiation therapy (presence of scleroderma or other collagen vascular disease) Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results