Pulmonary toxicity after radiotherapy in primary breast cancer patients: results from a randomized chemotherapy study

Abstract

Purpose : Pulmonary toxicity was prospectively evaluated within a randomized trial for breast cancer patients at high risk for relapse, who postoperatively received as adjuvant therapy either 9 cycles of tailored chemotherapy (20 patients) (cyclophosphamide, epirubicin, 5-fluorouracil [FEC]) or standard FEC × 3 followed by high-dose chemotherapy (cyclophosphamide, thiotepa, carboplatin [CTCb]) supported by peripheral blood stem cell transplantation (14 patients). After high-dose chemotherapy or tailored FEC, all patients received locoregional radiotherapy (50 Gy/5 weeks), plus tamoxifen for 5 years. Methods and Materials : Lung function tests (FVC, FEV1, and DL CO) were performed before chemotherapy and 9 months after radiotherapy. Computed tomography of the lungs was performed before radiotherapy and 6 weeks, 3 months, and 9 months after radiotherapy. Results : Clinical signs of suspected pneumonitis were noted in 29% of patients, but only 1 patient needed symptomatic therapy. Radiologic changes were detected in 68% of patients, and they were most frequent at 3 months after radiotherapy. FVC decreased in both groups (tailored FEC: mean difference, −6.5%, p = 0.0005; CTCb: −2.0%, p = 0.21; tailored FEC vs. CTCb: −4.5%, p = 0.05). DL CO decreased significantly in both groups (tailored FEC: mean difference, −11.2%, p < 0.0001; CTCb: −5.6%, p = 0.02; tailored FEC vs. CTCb: −5.6%, p = 0.07). FEV1 decreased by 7.3% in patients treated with tailored FEC ( p < 0.0001) and by 2.5% in patients treated with CTCb ( p = 0.03) (tailored FEC vs. CTCb: 3.7%, p = 0.08). Conclusions : Changes in pulmonary function were thus detected in both groups, although to a greater extent in the tailored FEC group. The clinical significance of these findings should be balanced carefully against the improved, statistically significant relapse-free survival achieved with the tailored FEC regimen compared to high-dose CTCb + peripheral blood stem cell transplantation (PSCT).