Phase I dose escalation trial using stereotactic body radiation therapy (SBRT) for partial breast irradiation (PBI).

1057 Background: To evaluate tolerability of escalating doses of 5 fraction SBRT PBI in treating early stage breast cancer after partial mastectomy on a phase I dose escalation trial. The primary objective was to escalate the PBI dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose (MTD). Methods: Eligible patients included DCIS or invasive ductal histologies, AJCC stage 0-II with tumor size < 3cm, and margins ≥ 2mm. Prior to simulation 3-4 four gold fiducials were placed around the lumpectomy cavity for real-time respiratory tracking. Dose limiting toxicity (DLT) equaled grade ≥ 3 toxicity by CTCAE deemed definitely related to treatment for: skin, bone (fracture), pulmonary, neurological (intercostal or brachial plexus nerves) or any grade 4/ 5 toxicity definitely attributed to therapy. Both patients and physicians completed baseline and subsequent cosmesis questionnaires using a four point scale – excellent, good, fair, poor. Starting dose was 30 Gy in 5 fractions. Dose was escalated by 2.5 Gy total, provided 4 or fewer of 15 patients experienced a DLT within 90 days of treatment within each dose group. If more patients had DLT in a given dose cohort, the MTD would be exceeded. Results: 68 patients (15 per dose cohort (cohort 5 -8 patients)) enrolled with median age 62 years. Median follow-up for cohorts 1,2,3,4, and 5 were - 36.3, 26.4, 16, 8.8, and 2.3 months. The first 3 dose cohorts completed 90 day follow-up without DLTs. There was 1 focal grade 3 dermatitis DLT at 37.5 Gy. DLT follow-up is still ongoing in cohort 5. There were 72 grade 1 toxicity events, 2 grade 2 toxicities (rib fracture and breast pain), and 2 grade 3 radiation dermatitis toxicities. Physicians scored cosmesis as excellent or good in 94.9%, 100%, 97.7%, and 100% respectively (p = 0.28), at baseline, 6, 12, and 24 months post SBRT, while patients scored the same periods 82.7%, 96.2%, 95.4%, and 92.8% (p = 0.04). Conclusions: Dose is escalated to 37.5 Gy in 5 fractions without MTD thus far. Soon we are completing dose escalation for 40Gy in 5 fractions PBI, hoping to increase the likelihood of long term tumor control while evaluating toxicity and cosmesis of this innovative therapy. Clinical trial information: NCT01162200.