V5 Does Not Predict Pulmonary Toxicity of Intensity Modulated Radiation Therapy for Adjuvant Whole-Breast/Chest-Wall and Regional Nodal Irradiation

Abstract

Adjuvant regional nodal irradiation (including the ipsilateral internal mammary chain) confers a disease-free- and distant-metastasis-free-survival benefit among both node-positive and high-risk/node-negative breast cancer patients. Multi-field IMRT and volumetric-modulated arc therapy (VMAT) can improve target coverage compared to conventional planning techniques, but result in increased low-dose lung exposure (V5). The clinical significance of the V5 remains uncertain. Moreover, the ongoing NSABP-51 limits the ipsilateral lung V5 to 65% and the contralateral lung V5 to 5%, thereby effectively precluding the use of IMRT/VMAT. Here, we update the long term pulmonary outcomes of patients treated with IMRT/VMAT since our initial report of early toxicity in 2013. Between 2010 and 2012, we prospectively enrolled 106 patients to receive adjuvant chest-wall and regional-nodal irradiation following mastectomy for invasive breast cancer. Radiation was administered to a total dose of 50Gy in 2Gy daily fractions using multi-field IMRT or VMAT techniques, typically without a chest wall or scar boost. The median age was 49 (range 25-76) with a median follow-up of 3.2 years. Among the overall cohort, median D95 to the planning target volume (PTV) was 48.1Gy (range 47.0 – 50.2Gy; prescription dose = 50Gy). Pulmonary metrics included a median ipsilateral lung V5 of 100% (range 77-100%), median V20 of 29% (range 22.5-31%) and median ipsilateral mean lung dose of 19.3Gy (range 6.6-21.5Gy). The contralateral lung received a median V5 of 79.3% (range 0 - 99.9%), median V20 of 0.65% (range 0 – 21.4%), and the median contralateral mean lung dose was 7.1Gy (range 4.4 – 11.5 Gy). Early evaluation at 6 months revealed 11 patients with any pulmonary toxicity, one of whom had grade 3 pneumonitis. By 3 years of follow-up, only five patients (4.7%) were noted to have mild respiratory symptoms (limited to cough or dyspnea), none requiring intervention, and none definitively attributed to radiotherapy. This prospective study demonstrates that multi-field IMRT/VMAT results in excellent tumor target coverage, but with a high V5 of the lungs. Despite relatively high lung V5 values, the rates of pulmonary toxicity were low overall. The clinical significance of the lung V5 to predict pulmonary toxicity in breast cancer does not apply to IMRT-based planning.