title: Phase 1 clinical trial of stereotactic body radiation therapy concomitant with neoadjuvant chemotherapy for breast cancer.
abstract: OBJECTIVE
  Stereotactic body radiation therapy (SBRT) allows stereotactic irradiation of thoracic tumors. It may have a real impact on patients who may not otherwise qualify for breast-conserving surgery. We conducted a phase 1 trial that tested 5 dose levels of SBRT concomitant with neoadjuvant chemotherapy (NACT) before to surgery. The purpose of the current dose escalation study was to determine the maximum tolerable dose of SBRT in the treatment of breast cancer.
  
  
  METHODS
  To define toxicity, we performed dermatologic examinations that included clinical examinations by 2 separate physicians and technical evaluations using colorimetry, dermoscopy, and skin ultrasonography. Dermatologic examinations were performed before NACT, 36 and 56 days after the beginning of NACT, and before surgery. Surgery was performed 4 to 8 weeks after the last chemotherapy session. Efficacy, the primary endpoint, was determined by the pathologic complete response (pCR) rate.
  
  
  RESULTS
  Maximum tolerable dose was not reached. Only 1 case of dose-limiting toxicity was reported (grade 3 dermatologic toxicity), and SBRT was overall well tolerated. The pCR rate was 36%, with none being observed at the first 2 dose levels, and the highest rate being obtained at dose level 3 (25.5 Gy delivered in 3 fractions). Furthermore, the breast-conserving surgery rate was up to 92% compared with an 8% total mastectomy rate. No surgical complications were reported.
  
  
  CONCLUSIONS
  This study demonstrates that SBRT can be safely combined with NACT. Regarding the efficacy endpoints, this trial showed promising results in terms of pCR rate (36%) and breast-conserving rate (92%). The findings provide a strong rationale for extending the study into a phase 2 trial. In view of the absence of correlation between dose and pCR, and given that the data from dose level 3 met the statistical requirements, a dose of 25.5 Gy in 3 fractions should be used for the phase 2 trial.
authors: Department of Radiotherapy, Centre Antoine Lacassagne, Nice, France. pierre-yves.bondiau@nice.unicancer.fr
authors: Pierre-Yves
authors: PY
authors: Bondiau
authors: Adel
authors: A
authors: Courdi
authors: Phillipe
authors: P
authors: Bahadoran
authors: Emmanuel
authors: E
authors: Chamorey
authors: Catherine
authors: C
authors: Queille-Roussel
authors: Michel
authors: M
authors: Lallement
authors: Isabelle
authors: I
authors: Birtwisle-Peyrottes
authors: Claire
authors: C
authors: Chapellier
authors: Sandrine
authors: S
authors: Pacquelet-Cheli
authors: Jean-Marc
authors: JM
authors: Ferrero
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D005260:Female; D057918:Fiducial Markers; D006801:Humans; D015412:Mastectomy, Segmental / Q000706:statistics & numerical data; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D011855:Radiodermatitis / Q000209:etiology / Q000473:pathology; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D016896:Treatment Outcome