Abstract OT2-04-05: Phase II trial of pre-operative stereotactic ablative radiotherapy (SABR) in early-stage breast cancer
Authors: Liveringhouse CL , Diaz R , Ahmed KA , Lee MC , Czerniecki B , Laronga C , Khakpour N , Weinfurtner RJ , Rosa M , Montejo ME 
Published: May 2019

Background:

Post-operative accelerated partial breast irradiation (APBI) has demonstrated efficacy in preventing in-breast tumor recurrence. Pre-operative administration of APBI may be advantageous as an intact breast tumor is smaller than its corresponding lumpectomy cavity, is easier to distinguish on treatment-planning images, and results in smaller and more accurately delineated target volumes. Pre-operative APBI may reduce the incidence of positive margins following breast-conserving surgery (BCS). Investigation is needed in the correlation of MR imaging with pathologic response 6 weeks after SABR. Also, evidence suggests that SABR induces immune activation in the tumor microenvironment; evaluation of excised tumor tissue will give insight into these processes.

Trial Design:

Treatment Planning and Delivery: CT simulation and treatment are performed in the prone position. Diagnostic MRI is fused to planning CT. GTV is delineated on registered breast MRI and includes the intact breast tumor. CTV is 15mm expansion of GTV. PTV is 3 mm expansion of CTV. VMAT or IMRT are permitted. Daily image-guidance aligning to tumor and biopsy-fiducial is mandatory. All subjects undergo pre-operative SABR to 28.5 Gy in 3 fractions of 9.5 Gy on different days separated by ≤48 hours. CTCAE v4 is used to assess toxicity 4-5 weeks after SABR. Pre-operative diagnostic MRI is performed 5-6 weeks following SABR. Imaging parameters to be evaluated include changes in tumor size, enhancement, and tumor margin description. BCS will be 6-8 weeks following SABR.

Tissue pathology: Margin status and degree of pathologic response are recorded from breast-conserving excisions, specimens are archived for future analysis.

Eligibility Criteria:

Inclusion criteria are women age ≥50 with biopsy proven invasive breast adenocarcinoma with tumor size ≤2cm on MRI, cN0 M0, ER+/HER2-, without history of invasive malignancy or prior breast/thoracic radiotherapy.

Exclusion criteria are active scleroderma or lupus erythematosus with skin involvement, MRI defined tumor within 10 mm of skin, implanted hardware prohibiting appropriate treatment planning or delivery, neoadjuvant chemotherapy, carrier of BRCA1 or 2 gene mutation, pregnancy.

Specific Aims:

The primary endpoint is pathologic complete response (pCR) in the breast tumor, secondary endpoints are incidence of adequate surgical margins (defined as “no tumor on ink”) and MRI response following SABR. Analyses of tumor immune response and microenvironment on pathologic specimens following SABR will also be performed.

Statistical Methods:

Fisher's exact test will be performed to examine associations between patient/tumor characteristics and pCR and surgical margins; these associations will be explored with multivariable logistic and linear regressions.

Accrual:

Present accrual is 9 subjects.

Expected accrual is 22 subjects; if ≥3 pCR are noted in the initial cohort, accrual will be expanded to 40 subjects.

Citation Format: Liveringhouse CL, Diaz R, Ahmed KA, Lee MC, Czerniecki B, Laronga C, Khakpour N, Weinfurtner RJ, Rosa M, Montejo ME. Phase II trial of pre-operative stereotactic ablative radiotherapy (SABR) in early-stage breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-04-05.