Should All Limited-Stage Small Cell Lung Cancer Be Treated Alike? Impact of AJCC Stage on Brain Metastasis, Survival, and Patterns of Failure

Abstract

Purpose/Objective(s): To determine if higher irradiated lung dose rather than irradiated lung volume or mean lung dose (MLD) is more critical for induction of radiation pneumonitis (RP) symptoms. Materials/Methods: We retrospectively analyzed the clinical and dosimetric data from 275 esophageal cancer cases treated with thoracic radiation therapy using IMRT, proton, or 3D-CRT. RP symptoms were evaluated using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4). For each patient, the percentage lung volume irradiated, mean irradiated lung dose (MILD), mean lung dose (MLD), lung dose regions (low dose volume, 10 Gy or CGE, Vlow; moderatedose volume, > 10-40 Gy or CGE, Vmod; and high dose volume > 40 Gy or CGE, Vhigh), as well as V5 to V50 were determined. The effects of MILV, MILD, MLD, lung dose regions, percentage lung volume irradiated, dosimetric parameters, patient and treatment characteristics, or metabolic radiation dose response (PMRR) with pulmonary toxicity were studied using logistic regression. Results: Proton therapy irradiated less lung volume (> 0.1 Gy or CGE) than IMRT (3.711 L in IMRT, 1.261 L in proton and 3.058 L in 3D-CRT) but the mean irradiated lung dose is higher in the proton versus IMRT group (12.04 Gy in IMRT, 17.21 CGE in proton and 11.70 Gy in 3D-CRT), despite the lower MLD received by the proton group (11.26 Gy in IMRT, 6.09 CGE in proton, and 10.62 Gy in 3D-CRT). We found the rate of symptomatic radiation pneumonitis is 2 times higher for proton than IMRT (25% in proton, 13.6% in IMRT, and 27.8% in 3DCRT). The PMRR was significantly different between the three modalities (0.15 in proton, 0.10 in IMRT, and 0.10 in 3DCRT, p Z 0.044 Kruskal-Wallis test). Conclusions: Despite smaller irradiated lung volumes, subjects treated with proton therapy (vs IMRT) were two times more likely to develop symptomatic RP. The higher mean irradiated lung dose resulting in a more intense local response is the likely culprit. Author Disclosure: N. Pham: None. R. Castillo: None. R. Castillo: None. B. Hobbs: None. T. Guerrero: None.