Syndecan 4-c-ros oncogene 1 fusion as a mechanism of acquired resistance in epidermal growth factor receptor mutant lung adenocarcinoma

To the Editor:A 37-year-old Chinese woman,a nonsmoker,presented with adenocarcinoma of the left lung(stage IV)[Figure 1A],malignant pleural effusion,and multiple bone metastases in December 2014.Deoxyribonucleic acid sequencing of the tumor biopsy revealed an epidermal growth factor receptor(EGFR)exon 19 deletion,and treatment with gefitinib was consequently initiated in December 2014.There were no treatmentrelated side effects except for a grade 1 rash,and stable disease was achieved.Unfortunately,the patient did not experience long-term benefits and developed disease progression after only two months.A follow-up examination showed that extracranial disease and a small intracranial lesion had developed gradually.The patient then received whole-brain radiotherapy(30 Gy in ten fractions)and four cycles of single-agent pemetrexed in April 2015.Stable disease was achieved,which coincided with an improvement in the patient’s cough,shortness of breath,and general condition.The chemotherapy course was changed to two cycles of pemetrexed combined with cisplatin.A partial response(PR)was achieved,and the patient was treated with 14 cycles of pemetrexed alone as maintenance chemotherapy.The follow-up evaluations showed the patient’s condition to be stable;however,the patient’s disease progressed after 23 months.A computed tomography(CT)scan in March 2017 revealed that both the lung lesion and the malignant pleural effusion had increased in size[Figure 1B].The subsequent biopsy specimen was subjected to next-generation sequencing(NGS)and a Syndecan 4-c-ros oncogene 1(SDC4-ROS1)rearrangement was detected[Figure 1C].The patient then received crizotinib in April 2017,and a PR was achieved[Figure 1D].A CT scan done in August 2018 indicated the progression of the primary lesion in the left lung and malignant pleural effusion.However,the growth of the remaining lesions remained stable.