Multi-Institutional Trial of Phase I Dose Escalation Using Single Fraction Stereotactic Partial Breast Irradiation (S-PBI) for Early Stage Breast Cancer

Abstract

We report on our early experience of a phase I dose escalation study of single fraction stereotactic partial breast irradiation (S-PBI) for early stage breast cancer after partial mastectomy using a robotic stereotactic radiation system. Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior to simulation, 3-4 gold fiducials were placed around the lumpectomy cavity to be used for real-time tracking during treatments. Dose limiting toxicity (DLT) was defined as grade ≥ 3 toxicity by CTCAE (version 4) deemed definitely related to treatment for: skin, ribs/bone (fracture), pulmonary (radiation pneumonitis), or neurological (intercostal or brachial plexus nerves) or any grade 4 or 5 toxicity definitely attributed to therapy. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires using a 4-point scale ranging from excellent, good, fair, or poor. Initial dose cohort was 22.5 Gy delivered in single fraction, and dose cohorts 2 and 3 (26.5 Gy and 30 Gy in single fraction, respectively). Dose escalation was permitted provided that one or fewer of the first seven, or two or fewer of nine patients experienced a DLT within 90 days of treatment within each dose group. If more patients had DLT in a given dose cohort, the maximum tolerable dose (MTD) would have been exceeded. From 4/2016 to 1/2020, 11, 8, and 8 patients were treated on cohorts 1, 2 and 3 respectively. Of these, data from 19 evaluable patients from cohorts 1 and 2 with at least 12 months of follow up are reported. Median f/u for cohort 1 was 27.3 m (r 24-36m), and cohort 2 was 15 m (r 12-18m). Average age was 65 (r 47-84). Histology included 9 DCIS, and 10 invasive carcinomas. Of 9 DCIS, 8 were ER+, and 1 was ER-. All 10 invasive tumors were ER+. 17/19 patients received endocrine therapy, and no patient received chemotherapy. In cohorts 1 and 2, no patients experienced grade 3 or higher treatment related toxicity in the acute period (≤ 90 days), and MTD was not reached. There were two delayed grade 3 toxicities, one in each cohort (one patient had breast pain, and another had mastitis, at 12 months and 9 months). No patients experienced grade 4 or 5 toxic events. Four patients developed fat necrosis diagnosed at 10 and 12 mo. in cohort 1, and 9 and 10 months after radiation treatments (with only 1 being painful and others asymptomatic). Physicians scored cosmesis excellent or good in 100%, 100%, 100%, and 100%, respectively, at baseline, 3, 6, and 12 months post S-PBI, while patients scored the same periods 89.5%, 95%, 100%, and 90.9%. There has been no report of disease recurrences. Dose was escalated to 30 Gy in single fraction without a DLT, and the majority of patients maintained good or excellent cosmetic outcome. Continued analysis of all cohorts is in progress.