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BACKGROUND: There has been no report to use camrelizumab with chemotherapy for advanced bladder cancer patients with positive programmed death-ligand 1 (PD-L1) expression and high tumor mutational burden (TMB). More effective predictors of bladder cancer immunotherapy have yet to be explored, and the combination of multiple factors may be more predictive than a single factor. CASE SUMMARY: We report the case of a 74-year-old male patient with recurrent metastatic bladder cancer, which demonstrated positive PD-L1 expression and high TMB. The immune checkpoint inhibitor camrelizumab was administered to the patient in combination with gemcitabine and cisplatin. The patient achieved a partial response with a progression-free survival of 11 mo. CONCLUSION: This is the first report to use camrelizumab with chemotherapy for advanced bladder cancer patients with positive PD-L1 expression and high TMB.
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INTRODUCTION: It has been well established that EGFR Thr790Met is one of the major resistance mechanisms to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). Nevertheless, whether EGFR Thr790Leu (T790L), which shares the mutation site of Thr790 with EGFR Thr790Met, mediates resistance to EGFR TKIs remains elusive. The treatment options for patients harboring this rare mutation have not been reported. METHODS: Capture-based targeted ultradeep sequencing was performed on tumor and plasma samples collected at various treatment milestones from three patients with advanced lung adenocarcinoma undergoing targeted therapy. RESULTS: Needle biopsy of lymph node metastasis from patient 1 revealed EGFR T790L at disease progression on first-line treatment of gefitinib. Patient 2 had EGFR T790L identified from needle biopsy of lung tissue at disease progression on icotinib treatment. This patient was subsequently treated with osimertinib and achieved stable disease with a progression-free survival of 9 months. For patient 3, at disease recurrence after surgery, resected lung tumor tissue was retrieved for molecular profiling and revealed EGFR exon 19 deletion and EGFR T790L. The patient subsequently received osimertinib treatment and continued to benefit for 16 months and counting. She has maintained stable disease at the time of submission of this manuscript. CONCLUSIONS: We revealed for the first time that EGFR T790L may serve as a potential resistance mechanism to first-generation EGFR TKIs. We also report the first clinical evidence of efficacy generated by osimertinib in patients with lung adenocarcinoma harboring primary or acquired EGFR T790L, shedding light on treatment options for this subset of patients.
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During the period from December 2012 to December 2014, three dripping water sites (S1, S2, S3) and one pool water site (SC) have been selected for a long-term monitoring of geochemical indexes in Naduo Cave, Guanling county of Guizhou Province, China. Based on the local meteorological data, this paper analyzed the seasonal change of hydro-geochemical indicators and their feedbacks to climate events. The results indicated that the hydro-geochemical type of cave water was HCO3â»-Ca²âº. Dripping water and pool water were in deposition all the year, except in the month with the maximum precipitation. There were some discrepancies of main ions' concentration among three dripping water sites due to the difference of the migration pathways and migration time. Affected by mixed water and high CO2 concentration of cave air, the ion concentration of pool water was higher than dripping water, and there was considerable fluctuation. The geochemistry indexes of water in Naduo Cave showed extraordinary seasonal variation rules and could perfectly respond to the external climate environment. The concentration of ions was sensitive to the response of the annual precipitation change caused by extreme climate events. During the rainy season, the concentrations of Ca²âº, Mg²âº and SO4²â» in 2013 were relatively higher and more stable than those in 2014. The response time and susceptivity of each monitoring site were inconsistent.