Osimertinib Greatly Increase the Risk of Radiotherapy Pneumonitis when Concurrent with Thoracic Radiotherapy

Abstract

Osimertinib have prolonged the survival for NSCLC patients who harboring EGFR-TKI sensitizing or T790M resistance mutations. Osimetinib concurrent with thoracic radiotherapy is also a pattern for some people who experienced progression during the treatment of osimertinib or the transformation from first generation EGFR-TKI to osimertinib owe to the progression of primary lesion. But the risk of radiation pneumonitis (RP) for the concurrent osimertinib with thoracic radiotherapy have not been reported. We report a high rate of RP when concurrent osimertinib with thoracic radiotherapy. All patients from January 2017 to December 2019 at one institution were treated with concurrent osimertinib with thoracic radiotherapy were identified and all clinical records were reviewed. All people were treated with concurrent osimertinib with thoracic radiotherapy were included; the people who have a history of interstitial pneumonitis (ILD), immune checkpoint inhibitor therapy, thoracic radiotherapy was excluded. All patients were included treated with intensity-modulated radiotherapy, and osimertinib was administered orally at 80mg/d along with radiotherapy until the progression disease or intolerable toxicity. The diagnostic of RP was based on imaging manifestation of computed tomography, RP was graded from 1 to 5 according to CTCAE v5.0. Nine females and two males of lung adenocarcinoma patients harboring EGFR T790M treated with concurrent osimertinib and thoracic radiotherapy were included, nine of them experience progression disease of primary lesion during the treatment of first generation TKI and converted to osimertinib concurrent thoracic radiotherapy, two patients receive thoracic radiotherapy during the treatment of osimertinib because of the progression of primary lesion. The median age of 11 patients is 59 years old. The median follow time is 7.83 months, all 11 patients experience RP from grade 1 to grade 5. Seven patients (63.63%) developed to grade 2 or higher RP, 1 patient for grade 2, 5 patients for grade 3, 1 patient developed to fetal RP. The median dose for PTV is 60Gy (range 30-64Gy), the median fractioned dose is 2Gy (range 2-5Gy). The median volume for GTV is 11.70ml (range 2.50-247.71ml), PTV is 76.60ml (range 18.70-448.80ml). The median total-lung V5 is 29.92% (range 17.94-47.05%), V20 is 10.93% (range 6.26-28.06%), the median mean lung dose (MLD) is 6.40Gy (range 4.22-14.82Gy). We report up to 63.63% patients who receive concurrent osimertinib and thoracic radiotherapy developed to grade 2 or higher RP, and a patient developed to fetal RP, but they only have lower MLD and lesser V5, V20 compared to some patients who receive Concurrent Chemoradiation developed to RP. Compared with the 37.5% rate of RP for concurrent erlotinib and thoracic radiotherapy, our study pointed out a higher rate for osimertinib and come up with a warning for RP when concurrent osimertinib with thoracic radiotherapy.