Explore The Rate And Risk Factors For Radiation Pneumonitis In Non-small Cell Lung Cancer Patients Treated With EGFR-TKI And Thoracic Radiotherapy

Background:Epidermal Growth Factor Receptor-Tyrosine Kinase inhibitor(EGFR-TKI)is the first-line standard care for EGFR sensitive mutation non-small cell lung cancer(NSCLC).As previous study statement,addition of thoracic radiotherapy during the maintenance treatment of EGFR-TKI can significantly improve the prognosis for oligometastatic EGFR mutation NSCLC patients.However,Zhuang et al.found an 37.5%(9/24)patients developed grade 2 or worse radiation pneumonitis when simultaneous erlotinib and thoracic radiotherapy for EGFR mutation NSCLC patients.Meanwhile,several previous studies have shown that simultaneous EGFR-TKI and thoracic radiotherapy have high risk for grade 2 or worse radiation pneumonitis,but the risk factors for grade 2 or worse radiation pneumonitis when simultaneous EGFR-TKI and thoracic radiotherapy was rarely explored.In this study,we focus on the exact rate of grade 2 or worse radiation pneumonitis when simultaneous EGFR-TKI and thoracic radiotherapy for EGFR mutation NSCLC patients.Owe to the difference for mechanism between the third EGFR-TKI,osimertinib and first-generation EGFR-TKI,our study was divided into two part.In the first part,we explore the exactly rate of grade 2 or worse radiation pneumonitis when simultaneous osimertinib and thoracic radiotherapy;for second part,we focus on the rate and risk factors of grade 2 or worse radiation pneumonitis when simultaneous first-generation EGFR-TKI.Part 1:Explore the rate of radiation pneumonitis for NSCLC patients treated with osimertinib and thoracic radiotherapyAim:In this part we mainly explore the exact rate of grade 2 or worse radiation pneumonitis for patients treated with simultaneous osimertinib and thoracic radiotherapy.Method:This study screened the EGFR sensitive mutation or T790M resistance mutation NSCLC patients visited at Shandong tumor hospital form January 2018 to December 2019 respectively.NSCLC patients with stage ⅢB-ⅣB treated with simultaneous osimertinib and thoracic radiotherapy was included.The diagnosis and grade of radiation pneumonitis was depended on the symptom,imaging of computed tomography(CT),laboratory examination and prognosis of patients.The grading standard refers to CTCAE v5.0.Result:Eleven NSCLC patients treated with simultaneous osimertinib and thoracic radiotherapy was included,nine patients experienced progress disease(PD)after first-generation EGFR-TKI and switched to osimertinib and thoracic radiotherapy for second treatment,two patients experienced PD of primary lesion and thoracic radiotherapy was added to control the primary lesion.63.6%(7/11)patients developed grade 2 or worse radiation pneumonitis,among them,one patient for grade 2 radiation pneumonitis,five patients for grade 3 radiation pneumonitis,one patient was succumbed to radiation pneumonitis.Conclusion:In this part,we found 63.6%patients developed grade 2 or worse radiation pneumonitis when treated with simultaneous osimertinib and thoracic radiotherapy,which is much higher than 13-37%for patients treated with concurrent chemoradiotherapy.This result reminded us to be cautious when add thoracic radiotherapy during the maintenance of osimertinib.Part 2:Explore the rate and risk factor of radiation pneumonitis for NSCLC patients treated with first-generation EGFR-TKI and thoracic radiotherapyAim:In this part we mainly explore the rate and risk factors of grade 2 or worse radiation pneumonitis for NSCLC patients treated with simultaneous first-generation EGFR-TKI.Method:This study screened the EGFR sensitive mutation NSCLC patients visited at Shandong tumor hospital form January 2012 to December 2019 respectively.NSCLC patients with stage ⅢB-ⅣB treated with simultaneous first-generation EGFR-TKI and thoracic radiotherapy were included.The diagnosis and grade of radiation pneumonitis was depended on the symptom,imaging of computed tomography(CT),laboratory examination and prognosis of patients.The grading standard refers to CTCAE v5.0.Logistic Regression analysis was used to explore the risk factor of grade 2 or worse radiation pneumonitis.Result:Sixty-seven NSCLC patients treated with first-generation EGFR-TKI and thoracic radiotherapy was included.44.78%(30/67)patients developed grade 2 or worse radiation pneumonitis,among them 24 patients experienced grade 2 radiation pneumonitis,6 patients developed grade 3 radiation pneumonitis.Logistic Regression univariate analysis revealed the exposure dose of total lung and ipsilateral lung was significantly correlated with grade 2 or worse radiation pneumonitis.Besides,the GTV>20ml,PTV>120ml、dose per fraction<3Gy、ipsilateral lung V30>34%、overlap time between first-generation EGFR-TKI and thoracic radiotherapy>20 days、duration of thoracic radiotherapy>32 days was risk factors of grade 2 or worse radiation pneumonitis.Compared with gefitinib and erlotinib,icotinib have lower rate of grade 2 or worse radiation pneumonitis.Logistic Regression multivariate analysis found icotinib is an independent protect factor for grade 2 or worse radiation pneumonitis,ipsilateral lung V30>34%、overlap time between first-generation EGFR-TKI and thoracic radiotherapy>20 days is the independent risk factor of grade 2 or worse radiation pneumonitisConclusion:In this part,we found 44.78%patients developed grade 2 or worse radiation pneumonitis when simultaneous first-generation EGFR-TKI and thoracic radiotherpay,which is higher than 13-37%for concurrent chemoradiotherapy,lower than 63.6%for simultaneous osimertinib and thoracic radiotherapy.Further exploration about risk factors of grade 2 or worse radiation pneumonitis revealed that icotinib is an independent protective factors,and ipsilateral lung V30>34%、overlap time between first-generation EGFR-TKI and thoracic radiotherapy>20 days is the independent risk factor of grade 2 or worse radiation pneumonitisDiscussion:In our two study,we found simultaneous osimertinib and thoracic radiotherapy bring especially high rate of grade 2 or worse radiation pneumonitis,which is higher than concurrent chemoradiotherapy,simultaneous first-generation EGFR-TKI and thoracic radiotherapy.Logistic Regression multivariate analysis revealed overlap time between first-generation EGFR-TKI and thoracic radiotherapy>20 days is the independent risk factor of grade 2 or worse radiation pneumonitis,icotinib is an independent protective factors,these result also indicate EGFR-TKI play an important role in development of grade 2 or worse radiation pneumonitis.In summary,our study proved a high rate of grade 2 or worse radiation pneumonitis when simultaneous EGFR-TKI and thoracic radiotherapy,further exploration the risk factor of grade 2 or worse radiation pneumonitis in this treatment pattern,provided important references for management of EGFR mutation stage Ⅳ NSCLC patients.