Xingni Tang1, Yichao Shen1, Yinnan Meng1, Liqiao Hou1, Chao Zhou1, Changhui Yu1, Haijian Jia1, Wei Wang1, Ge Ren2, Jing Cai2, X Allen Li3, Haihua Yang4, Feng-Ming Spring Kong5. 1. Laboratory of Cellular and Molecular Radiation Oncology, Radiation Oncology Institute of Enze Medical Health Academy, Department of Radiation Oncology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, China. 2. Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China. 3. Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. 4. Laboratory of Cellular and Molecular Radiation Oncology, Radiation Oncology Institute of Enze Medical Health Academy, Department of Radiation Oncology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, China. yhh93181@hotmail.com. 5. Laboratory of Cellular and Molecular Radiation Oncology, Radiation Oncology Institute of Enze Medical Health Academy, Department of Radiation Oncology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou, China; Department of Clinical Oncology, Hong Kong University Shenzhen Hospital, Shenzhen, China; Hong Kong University LKS Medical School, Hong Kong, China; Department of Radiation Oncology, University Hospitals Cleveland Medical Center, Case Western University, Case Comprehensive Cancer Center, Cleveland, OH, USA. springenzert@163.com; kong0001@hku.hk.
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 EGFRTKIs 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 (TD50) 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.
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 EGFRTKIs treatment followed by SBRT (TKI + SBRT) and with 3-month follow-up high resolution CT. NSCLCpatients 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 (TD50) 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.
Entities:
Keywords:
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs); lung damage; normal tissue complication probability (NTCP); quantitative CT analysis; stereotactic body radiotherapy (SBRT)