P3-16-11: Prospective Evaluation of Radiation Pneumonitis in Neoadjuvant Concurrent Docetaxel and Radiation Therapy for Locally Advanced Breast Cancer.
Authors: Louie AV , Rodrigues G , Sathya A , Perera F , Ong M , D'Souza D , Chambers AF , Brackstone M 
Published: June 2012

Background: Taxanes are known to have radiosensitizing properties, by causing cell arrest in the G2 and M phases of the cell cycle. As taxanes have become integrated into routine oncologic use, concerns have arisen over the association between taxanes and radiation toxicities such as pneumonitis. Pneumonitis has been reported to occur both with taxane administration alone or, more commonly, with concurrent or sequential radiation. The purpose of this study is to evaluate radiation pneumonitis from our institutional phase I/II protocol of neoadjuvant FEC chemotherapy followed by weekly docetaxel concurrent with radiotherapy in the treatment of locally advanced breast cancer (LABC).

Materials and Methods: Since August 2009, thirty-two LABC patients with stage IIB, IIIA, IIIB, or IIIC invasive breast cancer were enrolled to receive protocol based treatment consisting of 3 cycles of intravenous (IV) fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2 (FEC) every 3 weeks. Following this, weekly IV docetaxel 35 mg/m2 was administered concurrently with locoregional external beam radiotherapy to a total dose of 45 Gy in 25 fractions followed by a boost of 5.4-9 Gy in 3–5 fractions to gross residual disease. Adverse events were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. A linear regression model was built used to evaluate potential parameters predictive of clinical pneumonitis (grade ≥2).

Results: Of the 32 patients enrolled on this prospective protocol, 7 were excluded from analysis (n = 6, follow-up &lt; 4 weeks; n = 1, converted to palliative radiotherapy due to metastatic disease). Twenty-five patients remained for analysis. The median age was 48 years (range 26 to 64). Thirteen patients were treated with intensity modulated radiation therapy while 12 were treated using 3D conformal radiotherapy. In total 13 patients (52%) experienced clinical pneumonitis with 6 of these patients (24%) transiently requiring supportive oxygen (grade 3). On linear regression modeling, the use of IMRT (p = 0.08), grade 3 skin toxicity (p = 0.08), and baseline left ventricular ejection fraction (LVEF, p = 0.05) were potentially predictive of symptomatic pneumonitis. Conversely, various heart and lung dose-volume histogram parameters, trastuzumab use, bolus use, disease laterality, total docetaxel dose, were not predictive of symptomatic pneumonitis (p &gt; 0.10). In multivariable modeling, the use of IMRT (p = 0.05) and baseline LVEF (0 = 0.03) remained predictive of symptomatic pneumonitis.

Conclusion: The use of concurrent weekly docetaxel-based chemoradiotherapy in LABC is associated with significant symptomatic pneumonitis and may be related to low baseline LVEF and the use of IMRT. However, conventional parameters of low dose volumes of lung and heart irradiated were not predictive of pneumonitis. The relationship of the use of IMRT and taxanes in the development of pnemonitis is likely complex and warrants further investigation.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-11.