Pneumonitis Rates Following Comprehensive Nodal Irradiation in Breast Cancer Patients: Results of a Phase 1 Feasibility Trial of Intensity Modulated Radiation Therapy

Abstract

To prospectively determine pneumonitis rates in breast cancer patients receiving comprehensive nodal irradiation with inverse-planned intensity modulated radiation therapy (IMRT) on protocol. Between May 2010 to December 2012, 106 women were enrolled on an IRB-approved study of inverse-planned IMRT to the breast or chest wall and regional lymph nodes. Internal mammary nodes were included in all cases. IMRT was delivered with 8-9 non-planar beams (50 Gy /25 fractions, +/- 10 Gy boost in patients with conserved breasts). Pulmonary function tests (PFTs) were performed prior to RT and 6 months following RT in all patients. Respiratory toxicities were routinely assessed at 6-8 weeks and 4-6 months after RT, utilizing the CTCAE v.3.0 scoring system. By February 2013, 86 patients had been followed for a minimum of 6 months and comprise the study population. Median age was 43 years. Seventy-six percent were stage III, 24% stage II. All patients received dose-dense chemotherapy (43% neoadjuvant, 57% adjuvant). Eighty-seven percent had mastectomy and 13% breast-conserving therapy. Mean values for ipsilateral lung V20, V30 and V40 in the entire cohort were 30%, 18% and 12%. Lung V05 was 100% in all patients. Percent change in post-treatment FEV1, FEV1/FVC and DLCO values in the entire cohort was -1%, -0.3% and -3%. The incidence of grade 1 respiratory toxicities was 7% (n = 6), grade 2 was 3.5% (n = 3), and ≥ grade 3 was 0%. Confounding variables for the development of pneumonitis were present in each of the 3 patients who developed grade 2 respiratory toxicities. Their mean ipsilateral lung V20, V30, and V40 were 28%, 19%, and 13%, with no detectable changes in post-treatment PFT parameters. The incidence of acute pneumonitis in patients who received dose-dense chemotherapy and comprehensive nodal irradiation with IMRT was low (3.5%). Changes in post-treatment PFT parameters at 6 months were undetectable. These results suggest that inverse-planned IMRT is a well-tolerated technique that minimizes the volume of lung and heart exposed to high doses of radiation.