Next-generation sequencing (NGS) is an efficient and sensitive method to detect mutations from ctDNA. Many features and clinical conditions could significantly affect the concordance between ctDNA and corresponding tumor tissues. Our goal was to systematically investigate the critical factors contributing to different concordance between ctDNA and corresponding tumor tissues. We recruited two groups of IIIB or IV lung cancer patients: The standard group to evaluate the accuracy of our method and the concordance between ctDNA and tumor tissues, and the study group with various clinical conditions. We applied our unique identification (UID) indexed capturing-based sequencing (UC-Seq) to ctDNA samples, and confirm the results by Droplet digital PCR (ddPCR). Considering mutations detected from NGS of tumor tissues as golden standard, UC-Seq achieved overall 93.6% sensitivity for SNVs and Indels, and 0.8 Pearson correlation between tumor TMB and bTMB. Efficacious treatments, long sampling date (more than 2 weeks) between tumor tissues and ctDNA and low concentrations of cfDNA (less than 9 ng/ml) could significantly decrease the concordance between ctDNA and tumor tissues. About 84% mutations showed shorter mutant fragment length than that of wild-type fragments, and the AFs of mutations could be significantly enriched in small-size ctDNA. In late-stage lung cancer patients, ctDNA generally has high concordance with tumor tissues. However it could be significantly affected by three clinical conditions which could dynamically change the content of ctDNA. Moreover, the detection limit could be further extended by enriching small-size ctDNA in the preparation of samples.

Purpose This study aimed to investigate the safety and short-term efficacy of irreversible electroporation (IRE) combined with allogenic natural killer (NK) cell immunotherapy in the treatment of patients with unresectable primary liver cancer. Materials and Methods Between October 2015 and December 2016, 40 patients were enrolled and randomly allocated to either the IRE group (n = 22) or the IRE–NK group (n = 18). All adverse events experienced by the patients were recorded; the changes in tumor biomarkers [AFP, CA 19-9, circulating tumor cells (CTCs)], lymphocyte number and function, quality of life, clinical response, progression-free survival (PFS) and overall survival (OS) were assessed. Results Patients who received combination therapy exhibited significantly longer median PFS and OS than who just received IRE (PFS 15.1 vs. 10.6 months, P < 0.05, OS 17.9 vs. 23.2 months, P < 0.05). The combination therapy of IRE and NK cell immunotherapy significantly reduced CTCs and increased immune function and Karnofsky performance status. Conclusion Our data suggest a novel, promising combination therapy using IRE and allogenic NK cell immunotherapy. Larger clinical trials are required to confirm these conclusions.

Rationale: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver that is the leading cause of cancer-related mortality worldwide. However, genetic alterations and mechanisms underlying HCC development remain unclear.

Three patients with nasopharyngeal carcinoma developed binaural secretory otitis media 12, 2, and 0.5 years after radiotherapy, respectively. The secretions subsided after conventional drug and drainage treatments, but hearing continued to deteriorate until severe loss was documented in both ears. After examination of the eardrum and tympanum, patients were enrolled in a clinical trial in the first half of 2019 (ClinicalTrials.gov: NCT03818347). After 0.5, 1 and 2 months of continuous hydrogen–oxygen therapy, our first three patients reported different levels of improvement in binaural hearing. This is the first report to show that, after treatment for nasopharyngeal carcinoma, hearing loss can be alleviated using hydrogen–oxygen therapy.