Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation

Int J Radiat Oncol Biol Phys. 2017 May 1;98(1):196-205.e2. doi: 10.1016/j.ijrobp.2017.01.020. Epub 2017 Jan 12.

Abstract

Purpose: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose.

Methods and materials: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohort to 40 Gy.

Results: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases.

Conclusion: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for early-stage breast cancer in the adjuvant setting.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Breast Carcinoma In Situ / diagnostic imaging
  • Breast Carcinoma In Situ / pathology
  • Breast Carcinoma In Situ / radiotherapy*
  • Breast Carcinoma In Situ / surgery
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • Breast Neoplasms / surgery
  • Carcinoma, Ductal, Breast / diagnostic imaging
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / radiotherapy*
  • Carcinoma, Ductal, Breast / surgery
  • Dose Fractionation, Radiation
  • Feasibility Studies
  • Female
  • Fiducial Markers
  • Humans
  • Mastectomy, Segmental
  • Middle Aged
  • Prospective Studies
  • Radiation Tolerance*
  • Radiosurgery / adverse effects
  • Radiosurgery / methods*
  • Radiotherapy, Adjuvant / methods
  • Treatment Outcome
  • Tumor Burden