Persistent response of furmonertinib plus anlotinib in a lung adenocarcinoma patient with an EGFR exon 20 insertion mutation: A case report.

Insertions in exon 20 represent the third most common type of EGFR mutation following in-frame deletions in exon 19 and the point mutation L858R in exon 21. They are generally associated with primary resistance to EGFR-TKIs. Although mobocertinib and amivantamab were approved for adult patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, the efficacy of these two agents was rather moderate. Therefore, other more potent targeted agents are urgently needed. Here, we report a patient with advanced lung adenocarcinoma harboring an EGFR exon 20 insertion mutation (NM_005228: exon 20: c.2316_2321dup: p.773_774dup). After experiencing platinum-based chemotherapy, this patient received a combination of furmonertinib and anlotinib and achieved lasting stable disease (SD). The treatment was well tolerated, and only mild hand-foot syndrome was reported from the patient. To the best of our knowledge, this case firstly reported the encouraging efficacy of combined furmonertinib and anlotinib in an advanced lung adenocarcinoma patient with an EGFR exon 20 insertion mutation who was previously treated with platinum-based chemotherapy. In addition, we summarize the recent literature on therapies against NSCLC with EGFR exon 20 insertion mutations. This case might provide an alternative approach for clinical oncologists.

Case report: identification of EGFR R776H and FANCE R381H germline mutations in a patient with multiple pulmonary nodules.

Pulmonary nodules evaluation is clinically crucial because they may be the early predictors of lung cancer. Except for CT screening and serum tumor biomarkers testing, genetic alteration analysis by next-generation sequencing (NGS) technology can also help to find cancer earlier. In this study, we report a case of multiple pulmonary nodules patient with EGFR R776H and FANCE R381H germline mutations. Her father, paternal aunt, and elder uncle harbored either one or both two mutations and were found with multiple pulmonary ground-glass or sub-solid nodules. Her 7-year-old daughter also inherited the same two mutations.

Case Report: Triple Primary Malignant Tumors of the Esophagus, Stomach, and Colon in a Patient With Genetic Analysis.

The incidence of multiple primary malignant tumors (MPMTs) has increased greatly with the progress of tumor diagnosis and therapy technology. However, triple primary cancer is still very rare, and its genetic change is not clear yet. This case report described a 70-year-old Chinese male patient with triple primary cancers of the esophagus, stomach and right-sided colon. Pathological examination confirmed that each malignant tumor developed independently. Next-generation sequencing (NGS) using a 599-gene panel revealed five TP53 mutations in three tumor tissues. These variations might contribute to development of the triple primary malignant tumors in the patient. The patient underwent laparoscopic feeding jejunostomy and postoperative radiotherapy for synchronous esophageal and gastric carcinomas. Then, he underwent laparoscopic-assisted resection of right-sided colonic cancer and lysis of abdominal adhesions. By the time of submitting this manuscript, the patient had been well and no sign of recurrence or metastasis had been observed. To the best of our knowledge, this case is the first one to clarify the genetic abnormalities of triple primary cancers of esophagus, stomach and colon in a Chinese patient. It may contribute to understanding the molecular pathogenesis of multiple primary digestive malignancies and providing valuable treatment strategies for the similar patients in the future.

Unexpected favorable outcome to sintilimab plus bevacizumab in an EGFR-mutated non-small cell lung cancer patient: A case report.

A 53-year-old man diagnosed with disease stage IIIB pulmonary adenocarcinoma underwent chemotherapy and radiotherapy in the first-line setting. After disease progression, he received targeted therapy because of subsequent detection of EGFR exon 19 del mutation. Following an increase in his adrenal metastases, a combination of immunotherapy and antiangiogenic therapy (sintilimab plus bevacizumab) was commenced. After one month, imaging showed that the adrenal metastases had shrunk and a progression-free survival (PFS) of 6.0 months was achieved. In this case, we showed that the PD1 inhibitor sintilimab plus bevacizumab was effective in a refactory advanced EGFR-mutant NSCLC with positive PD-L1 expression. KEY POINTS: Our case report provides clinical evidence of the durable response of a patient with advanced EGFR-mutant lung adenocarcinoma to a combination of immunotherapy and anti-angiogenic agent, sintilimab and bevacizumab, as subsequent-line therapy. Sintilimab and bevacizumab combination therapy was well-tolerated and effective, resulting in dramatic tumor reduction and improvement in clinical symptoms.

Na(+) -Ca(2+) Exchanger, Leak K(+) Channel and Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Comediate the Histamine-Induced Excitation on Rat Inferior Vestibular Nucleus Neurons.

AIMS: Antihistaminergic drugs have traditionally been used to treat vestibular disorders in the clinic. As a potential central target for antihistaminergic drugs, the inferior vestibular nucleus (IVN) is the largest subnucleus of the central vestibular nuclear complex and is considered responsible for vestibular-autonomic responses and integration of vestibular, cerebellar, and multisensory signals. However, the role of histamine on the IVN, particularly the underlying mechanisms, is still not clear. METHODS: Using whole-cell patch-clamp recordings on rat brain slices, histamine-induced effect on IVN neurons and the underlying receptor and ionic mechanisms were investigated. RESULTS: We found that histamine remarkably depolarized both spontaneous firing neurons and silent neurons in IVN via both histamine H1 and histamine H2 receptors. Furthermore, Na(+) -Ca(2+) exchangers (NCXs) and background leak K(+) channels linked to H1 receptors and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to H2 receptors comediate the histamine-induced depolarization on IVN neurons. CONCLUSION: These results demonstrate the multiple ionic mechanisms underlying the excitatory modulation of histamine/central histaminergic system on IVN neurons and the related vestibular reflexes and functions. The findings also suggest potential targets for the treatment of vestibular disorders in the clinic, at the level of ionic channels in central vestibular nuclei.