Chordoma is a rare primary bone tumor that exhibits insensitivity to radiotherapy and chemotherapy and has a poor prognosis. Currently, resection is the primary treatment for affected patients, but the subsequent rate of recurrence is high, and both overall survival (OS) and progression-free survival (PFS) are consequentially relatively short. This case report describes a patient who was diagnosed with metastatic chordoma that was found to possess the A1209fs mutation of the PBRM1 gene, which may be associated with beneficial responses to immunotherapies. The patient received pembrolizumab, an immune checkpoint inhibitor (ICI) that targets the PD-1 receptor of lymphocytes, as second-line therapy, which he tolerated well (the most frequent adverse events were abnormal liver function and hyperglycemia, both of which were only grades 1–2), and achieved a PFS duration of 9.3 months. We hope these results will promote further research that will clarify the mechanisms underlying this beneficial response and that will further explore the use of immunotherapies in this population.

BackgroundLung adenocarcinoma can transform into small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. Approximately 3% to 10% of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) could transform to SCLC. This phenomenon has been described in several case reports and small patient series. However, the characteristics and treatment outcomes of this population have not been comprehensively reported, and their clinical course is poorly characterized.MethodsWe performed a systematic review of the published literature to summarize the clinical and pathological features and prognosis of the reported cases and analyzed the demographics, disease features, and outcomes.ResultsA total of 72 patients (50 females and 22 males) initially diagnosed with lung adenocarcinoma were included. EGFR mutations included 19-deletion (75%), L858R (22%), and G719X (3%). All patients received EGFR-TKIs before SCLC transformation. The median time from diagnosis to transformation was 20.5 months (95% CI, 15.45 to 26.55 months). Of the 67 patients with post-translational gene test results, 58 maintained their EGFR mutation, and only 1 of 18 with prior T790M positivity retained T790M mutation. After the pathological transformation, both conventional chemotherapy regimen and chemotherapy combined targeted therapy yielded high response rates. The disease control rate of first-line therapy after transformation was 76%, while the objective response rate was 48%. The median overall survival (OS) since diagnosis was 27 months (95% CI, 22.90 to 31.10 months), whereas median OS since SCLC transformation was 8.5 months (95% CI, 5.50 to 11.60 months).ConclusionThe prognosis of transformed SCLC is worse than primary SCLC. The response rate to conventional chemotherapy was high. However, the progression-free survival and OS after transformation were short and the prognosis was poor with first-line therapies. New therapies are needed in the management of transformed SCLC.

Background: The aim of this study was to investigate the clinical features, immunohistochemistry (IHC), compound mutation, and prognosis of patients with non-small cell lung cancer (NSCLC) harboring exon 19 deletion-insertion mutations.Methods: This retrospective analysis included 4,666 NSCLC patients harboring epidermal growth factor receptor (EGFR) mutations in a multi-center study from January 2017 to December 2020, and 69 patients with EGFR exon 19 deletion-insertions were taken to account. Next-generation sequencing (NGS) was used to detect the subtype of EGFR exon 19 deletion-insertions. These mutations were correlated with clinical features, immunophenotype and molecular characteristics of tumors and outcomes of patients.Results: Sixty-nine patients with EGFR exon 19 deletion-insertions were analyzed in this study, comprising 24 cases (34.8%) with L747_P753delinsS, 9 cases (13.1%) with L747_A750delinsP, both 5 cases (7.2%) in E746_A750delinsQP, E746_S752delinsV and both 4 cases (5.8%) in E746_T751delinsA and L747_ T751delinsP. Twenty-nine males (42%) and 40 females (58%), with a median age of 59.7 years; 12 (21.7%) participants were smokers and 54 (78.3%) were nonsmokers. The compound mutations were tumor protein ^ ORCID: 0000-0003-2681-9893.

The Ritter-type reaction, without relying on a pre-installed functional group, is a highly efficient tool for the construction of amides. However, the intrinsic chemo-selectivity that determines the generation of amides...

Background The usefulness of metagenomic next-generation sequencing (mNGS) in identifying the prognosis of lung cancer with chromosomal instability (CIN) remains unclear. We aimed to analyze clinical characteristics and prognosis of patients in patients harboring CIN. Methods This retrospective cohort study included 668 patients diagnosed with suspected pulmonary infection or lung cancer whose samples underwent mNGS detection from January 2021 to January 2022. Difference between clinical characteristics were calculated by the Student’s t-test and the chi-square test. The subjects were followed-up from registered to September 2022. Survival curves were analyzed by the Kaplan-Meier method. Results Of 619 bronchoalveolar lavage fluid (BALF) samples collected by bronchoscopy, 30 CIN-positive samples were confirmed as malignant on histopathology, with a sensitivity of 61.22%, a specificity of 99.65%, and an 83.17% accuracy [cut-off values were established by the receiver operating characteristic (ROC) area under the curve (AUC) =0.804]. In 42 patients with lung cancer, mNGS detected 24 patients as CIN-positive and 18 as CIN-negative. There were no differences between two groups including ages, pathologic types, stage and metastases. In 25 cases, we detected 523 chromosomal copy number variants (CNVs) with forms including duplication (dup), deletion (del), mosaic (mos), and whole chromosome amplification or loss. A total of 243 duplication variants and 192 deletion variants occurred in all chromosomes. Duplications occurred in most chromosomes except for Chr9 and Chr13, in which CNV tended to delete. The median overall survival (OS) in patients with Chr5p15 duplication was 32.4 months [95% confidence interval (CI), 10.35–54.45 months]. The median OS differed significantly between the 5p15dup+ group and the combined group (32.4 vs. 8.63 months, P=0.049). In 29 patients with unresected lung cancer, the median OS of 18 cases in the CIN-positive group was 32.4 months (95% CI, 14.2–50.6 months) and the median OS of 11 cases in the CIN-negative group was 35.63 months (95% CI, 21.64–49.62 months; Wilcoxon, P=0.227). Conclusions Various forms of CIN detected by mNGS may predict prognosis of patients with lung cancer differentially. CIN with duplication or deletion deserves further study to guide clinical treatment.