Concurrent Neoadjuvant Chemotherapy and Radiotherapy in Locally Advanced Breast Cancer

• Published in: International journal of radiation oncology, biology, physics
• Main Authors: Brackstone, Muriel, MD PhD, Palma, David, MD PhD, Tuck, Alan B., MD PhD, Scott, Leslie, MD, Potvin, Kylea, MD, Vandenberg, Theodore, MD, Perera, Francisco, MD, D’Souza, David, MD, Kornecki, Anat, MD, Taves, Donald, MD, Muscedere, Giulio, MD, Chambers, Ann F., PhD
• Format: Journal Article
• Language: English
• Published: 2017
• Subjects: Hematology, Oncology and Palliative Medicine; Radiology; pathological complete response; docetaxel; concurrent chemoradiation; radiosensitization; Neoadjuvant; locally advanced breast cancer
• ISSN: 0360-3016
• DOI: 10.1016/j.ijrobp.2017.06.005

Abstract Purpose Locally advanced breast cancer (LABC) patients have poor overall survival. We evaluated whether concurrent neoadjuvant radiation added to standard chemotherapy could increase the pathological complete response (pCR) to treatment. Methods and Materials This prospective phase-II trial recruited thirty-two LABC patients from 2009-2011. Patients received neoadjuvant q3 weekly 5-fluorouracil (500mg/m2 ), epirubicin (100mg/m2 ) and cyclophosphamide (500mg/m2 ) for 3 cycles, followed by weekly docetaxel (35mg/m2 ) for 9 cycles. Regional radiation (45Gy/25 plus 5.4Gy/5) was delivered concurrently with docetaxel, then modified radical mastectomy. Patients were matched post-hoc by a blinded statistician to a concurrent cohort treated with neoadjuvant chemotherapy, modified radical mastectomy and adjuvant regional radiation. Results Thirty of 32 patients completed treatment. Twenty-seven were successfully matched by propensity score to 81 control patients by age, stage and molecular subtype. The concurrent chemoradiation produced a significant increase in pCR (14% vs 22%, p<0.001), but no statistically significant difference in disease-free and overall survival at 3 years (69% vs 81%, p=0.186; Hazard Ratio 0.51; 74% vs 89%, p=0.162; Hazard Ratio 0.46). Toxicity included 25% of patients with grade 3 pneumonitis and 25% of patients with dermatitis, and one death. Conclusions Concurrent neoadjuvant radiation added to radiosensitizing chemotherapy significantly improved pCR. A prospective randomized clinical trial is warranted to exploit the improved response seen with concurrent therapy but using another radio sensitizing taxane in order to better minimize treatment related toxicity and determine its impact on overall survival.