ABSTRACT
Objective:To investigate the progression pattern of acquired resistance to osimertinib and the treatment method as well as the therapeutic effect of salvage therapy in advanced lung cancer patients with epidermal growth factor receptor (EGFR) sensitive mutation or T790M mutation after the treatment of tyrosine-kinase inhibitor (TKI).Methods:The data of 145 patients with advanced lung cancer treated with osimertinib in Jiangsu Cancer Hospital between April 2017 (the approval time of osimertinib in China) and May 2019 were collected. At the last follow-up (December 2019), a total of 87 (60.0%) patients had acquired resistance to osimertinib, 61 (70.1%) of whom received salvage treatment; for patients with dramatic progression after resistance, chemotherapy was mainly given in the salvage therapy; for patients with gradual or local progression after resistance, the continuing targeted drug therapy and the local therapy were given. Imaging evaluation and Kaplan-Meier method were used to analyze the progression pattern of acquired resistance to osimertinib and the survival status, and to compare the salvage treatment results among subgroups.Results:The median follow-up time of 61 patients receiving salvage therapy was 11 months (4-32 months), among which 58 (95.1%) patients again had resistance to osimertinib, and 24 (39.3%) patients died of lung cancer. The median progression-free survival (PFS) time and overall survival (OS) time for the whole cohort was 2.5 months (95% CI 2.1-3.0 months) and 19.0 months (95% CI 13.7-26.3 months), respectively. The 1-year and 2-year OS rate was 72.1% and 41.7%, respectively. Among 61 patients receiving salvage therapy, 8 (13.1%) , 30 (49.2%) and 23 (37.7%) cases had dramatic progression, gradual progression and local progression, respectively; when given timely and proper salvage treatment, there were no statistically differences in PFS and OS of the patients in the above three subgroups (all P>0.05). There were no statistically differences in PFS and OS between patients receiving local therapy (24 cases) and patients not receiving local therapy (37 cases) after the progression occurred (all P>0.05). Among 58 patients with resistance to osimertinib again after the salvage therapy, 6 patients with gradual or local progression had more than 6-mouth PFS after the salvage therapy. Conclusions:Dramatic, gradual and local progression are the main patterns in patients with acquired resistance to osimertinib. The therapeutic efficacy of salvage therapy still shows some disappointing results.
ABSTRACT
Objective To investigate the relationship between the incidence of radiation-induced brain stem injury after intensity-modulated radiotherapy (IMRT) and the radiation dose volume in patients with nasopharyngeal carcinoma.Methods A retrospective analysis was performed on the data of 258 patients newly diagnosed with nasopharyngeal carcinoma who received IMRT in our group from 2005 to 2013.The radiation dose per unit volume of brain stem was analyzed.The relationship between the incidence of brain stem injury induced by IMRT and the radiation dose volume was studied.The survival rate was calculated using the Kaplan-Meier method.The factors influencing the radiation-induced brain stem injury were analyzed using the Cox regression model.Results Two patients with stage T3 disease and three patients with T4 disease had radiation-induced brain stem injury.The 3-and 5-year injury incidence rates were 1.6％ and 2.4％,respectively.The latency ranged between 9 and 58 months,with a median latency of 19 months.The median D1％ and Dmax for the brain stem were 54.24 and 59.22 Gy in all patients,54.31 and 59.45 Gy in patients with stage T3 disease,and 61.29 and 66.37 Gy in patients with stage T4 disease,respectively.In the five patients with brain stem injury,the D1％ and Dmax were larger than 60 and 63 Gy,respectively.The univariate analysis showed that the incidence of radiation-induced brain stem injury was correlated with D1％,Dmax,D0.1 cm3,D0.5 cm3,and D1.0 cm3 (all P=0.01).The incidence of radiation-induced brain stem injury was significantly lower in patients with D1％,Dmax,D0.1 cm3,D0.5 cm3,and D1.0 cm3 no larger than 60,63,60,58,and 56 Gy,respectively (all P =0.00).Conclusions The incidence of radiation-induced brain stem injury after IMRT is relatively low in patients with nasopharyngeal carcinoma.Strict control of the dose to the brain stem may help to reduce the incidence of brain stem injury and improve the long-term quality of life.