A Phase I Study of Cyberknife® Partial Breast Irradiation (PBI) for Early Stage Breast Cancer
Subjects for this study will be enrolled by the Moncrief Radiation Oncology Department at the Simmons Cancer Center.
The primary objective is to escalate the dose of stereotactic radiotherapy utilizing the Cyberknife system to a tumorcidal dose to the lumpectomy cavity without exceeding the maximum tolerated dose in patients with early stage breast cancer.
The secondary objectives will be to determine the dose-limiting toxicity (if the maximum tolerated dose is reached) and cosmesis (as evaluated by an independent panel judging from serial photography)
The tertiary objectives will be to determine the ipsilateral breast recurrence rate, distant disease-free interval (defined as the time from registration to first diagnosis of distant disease), recurrence free survival (time from registration to first diagnosis of a local, regional, or distant recurrence), and overall survival (time from registration to death due to any cause) and cosmesis.
Number of patients = between 7-75 for phase I (depending on tolerance)
Patients in each dose cohort will all be treated as a single group for dose escalation. The starting dose for the dose escalation portion will be 6 Gy per fraction for 5 fractions (total dose = 30 Gy). Subsequent cohorts of patients will receive an additional 0.5 Gy per treatment (total 2.5 Gy per escalation). If significant toxicity is encountered at the starting dose, a de-escalation will occur (step -1) to 5.5 Gy per fraction for 5 fractions (total dose 27.5 Gy).
Step No. Fractions Dose per fraction (Gy) Total Dose (Gy) No. Patients
1 5 5.5 27.5 7-15
0 (starting) 5 6 30.0 7-15
1 5 6.5 32.5 7-15
2 5 7 35.0 7-15
3 5 7.5 37.5 7.15
4 5 8 40 7-15
Minimum waiting periods will be assigned between each dose cohort to observe toxicity. The phase I study will be completed when dose limiting toxicity is reached or when a sufficiently high dose level (i.e. 7 Gy per fraction, 35 Gy total) is attained to consider the therapy likely to be efficacious.
All patients must be willing and capable to provide informed consent to participate in the protocol.
DCIS or invasive ductal, medullary, papillary, mucinous (colloid), or tubular histologies. Eligible patients must have appropriate staging studies identifying them as AJCC stage T0 , T1 or T2 (≤3 cm) treated with lumpectomy and axillary node dissection with at least 6 nodes sampled or sentinel node biopsy. Patients with up to 3 positive nodes without microscopic or macroscopic evidence of extracapsular extension are eligible.Patients with DCIS are not required to have axillary staging
The patient’s Zubrod performance status must be 0-2.
Patients must be ≥ 18 years of age.
If chemotherapy is planned, it must begin no earlier than two weeks following completion of radiation therapy.
Unifocal breast cancer (no evidence of gross multifocal disease, multicentric, or bilateral disease.
Negative margins after lumpectomy (re-excision for initial positive margins is.allowed-negative margins defined as >≥2 mm clear of tumor in all directions). Histological negative margins closer than 2 mm are permitted in the circumstance where the margin of excision is limited by adjacent tissues such as pectoral muscle or skin, but in the opinion of the surgeon and radiation oncologist an oncologically adequate excision was achieved
Negative post- lumpectomy mammography if malignancy-associated microcalcifications were initially present.
The target lumpectomy cavity must be clearly delineated.
Patients must complete appropriate pretreatment evaluation as detailed in section 4.0 including post-lumpectomy mammogram if microcalcifications were initially present to confirm complete removal