RET rearrangement has been proven as an oncogenic driver in patients with lung cancer. However, the prevalence, clinical characteristics, molecular features and therapeutic options in RET-rearranged patients remain unclear, especially in Chinese lung cancers. We retrospectively collected 6125 Chinese lung cancer patients who have been profiled using next-generation sequencing (NGS). The clinical demographics and molecular features of RET rearrangement-positive patients were analyzed. RET rearrangements were identified in 84 patients with proportion of 1.4% in our cohort. The median age at diagnosis was 58 years and it mainly occurred in females with adenocarcinoma histology. KIF5B-RET was the most frequently fusion type and accounted for 53.8% (57/106) of all RET fusions identified, with K15-R12 as the most frequent variant (71.9%). Among 47 RET-positive patients profiled with larger panels, 72.3% (34/47) harbored concurrent alterations. TP53 ranked as the most common concurrent alteration and concomitant EGFR oncogenic alterations were identified in 7 patients. Moreover, we presented an adenocarcinoma patient harboring concurrent RET fusion and EGFR L858R responded to combinatorial treatment of cabozantinib and osimertinib, with a progression-free survival of 5 months. Our study improved knowledge of clinical characteristics and molecular features of RET-rearranged Chinese lung cancers. It might be helpful for guiding clinicians for more effective personalized diagnostic and therapeutic approaches.

Rationale:Primary cardiac tumors are very rare, and angiosarcoma accounts for about 33% of all primary malignant cardiac tumors. Primary cardiac epithelioid angiosarcoma is a highly aggressive and difficult to diagnose tumor, with early systemic metastasis and poor prognosis.Patient concerns:A 35-year-old Han male experienced sudden severe palpitation and moderate dyspnea. The patient received a whole body F-18 fluoro-deoxyglucose positron emission tomography (18F-FDG PET)/computed tomography (CT) scan, the scan showed a large mass in the right atrium (RA) and numerous pulmonary nodules in both lungs.Diagnoses:The patient was diagnosed as right atrial epithelioid angiosarcoma with multiple pulmonary metastasis by pulmonary biopsy through CT-guided percutaneous transthoracic fine needle aspiration.Interventions:The patient received a cycle of chemotherapy with docetaxel and gemcitabine, followed by another cycle with epirubicin and ifosfamide.Outcomes:The chemotherapy was ineffective. After the two cycles, the bilateral pleural effusion steadily increased, the patient had severe dyspnea and palpitation, and died three weeks later, with an overall survival of 2.5 months.Lessons:Primary angiosarcoma of heart is a very rare and aggressive disease, and its diagnosis and treatment are difficult. Most patients may have systemic metastasis at diagnosis, and have a very short survival without surgical resection. Hence, early diagnosis and surgical resection is extremely important to treat this disease.