Radiation-induced lung damage in patients treated with stereotactic body radiotherapy after EGFR-TKIs: is there any difference from stereotactic body radiotherapy alone?

Abstract

Background: To quantitatively evaluate lung damage after treatment of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and stereotactic body radiotherapy (SBRT) in patients with nonsmall cell lung cancer (NSCLC), and compare that of SBRT only treatment.Methods: Eligible patients from an IRB-approved prospective clinical trial had one month of EGFR-TKIs treatment followed by SBRT (TKI + SBRT) and with 3-month follow-up high resolution CT. NSCLC patients treated with SBRT alone during the same time period without EGFR-TKIs or other systemic therapies were identified as controls. The lung damage was assessed clinically by pneumonitis and quantitatively using by CT intensity (Hounsfield unit, HU) changes. The mean HU values were extracted for regions of the lungs receiving the same dose range at 10 Gy intervals to generate dose-response curves (DRC). The relationship of HU changes and radiation dose was modeled using a Probit model.Results: Four out of 20 (25%) TKI + SBRT patients and none of 19 (0%) SBRT alone patients had developed grade 2 and above pneumonitis (P=0.053), respectively. Sixty percent of TKI + SBRT patients and 30% SBRT alone patients had HU changes of the normal lung density >200 HU, respectively. There were significant differences in the DRC and in lung HU changes between the two groups (all P<0.05). The physical dose for a 50% complication risk (TD 50 ) of CT lung damage was 52 Gy (CI: 46-59) in TKI + SBRT group versus 72 Gy (CI: 58-107) in SBRT alone group (P<0.01).Conclusions: Compared to patients treated with SBRT alone, patients treated with EGFR-TKIs followed by SBRT were more incline to develop radiation pneumonitis, and resulted in greater lung CT intensity changes and steeper dose-CT lung damage response relationship at 3 months post treatment. Future study with larger number of patients and longer follow-up period is warranted to validate this finding.

Prediction of the Mechanism of Sodium Butyrate against Radiation-Induced Lung Injury in Non-Small Cell Lung Cancer Based on Network Pharmacology and Molecular Dynamic Simulations

“…Given that previous studies have reported that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) combined with radiotherapy were more inclined to develop RILI ( 33 , 34 ), we further explored the correlation between the 5 core target genes and EGFR using the TIMER 2.0 database. We found that the expression of EGFR was closely associated with AKT1, NOTCH1, SIRT1 and PTEN ( P <0.05), but not TP53 ( P >0.05) ( Figure 4 ).…”

Predicting the Efficacy of SBRT for Lung Cancer with 18F-FDG PET/CT Radiogenomics

“…The results of a prospective, single-arm, Phase II study suggest that the early SBRT of a primary lesion after EGFR-TKI therapy is a potentially safe and effective new approach for treating EGFR-mutant advanced NSCLC [45]. However, Tang et al [46] found that, compared with patients treated with SBRT alone, patients treated with EGFR-TKIs combined with SBRT were more likely to develop radiation pneumonitis. The safety and efficacy of SBRT combined with targeted therapy must be further studied.…”

Local therapy treatment conditions for oligometastatic non-small cell lung cancer

“…Of these examples, lung injury may be a potentially fatal event. A recent prospective clinical trial ( 59 ) showed that patients treated with EGFR-TKIs + stereotactic body radiation therapy (SBRT) were more likely to develop radiation pneumonitis (25% vs. 0%) when compared with the SBRT alone treatment group, with 4/20 patients developing grade 2 and above pneumonia. However, due to the small number of patients and no observed statistical differences, it was difficult to conclude that EGFR-TKIs combined with Radiation Therapy (RT) increased the risk of radiation-induced lung injury.…”