There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4–11.0) versus 8.0 months (95% CI, 6.6–9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1–27.3] vs. 15.7 months [13.0–20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Mn2+ doped perovskite nanocrystals (NCs) have important applications in the field of white light emitting diodes (WLEDs) due to their bright orange-red luminescence and large Stokes shift. However, the development...

Chemotherapy is widely used to treat patients with cancer. However, resistance to chemotherapeutic drugs remains a major clinical concern. The mechanisms of cancer drug resistance are extremely complex and involve such factors such as genomic instability, DNA repair, and chromothripsis. A recently emerging area of interest is extrachromosomal circular DNA (eccDNA), which forms owing to genomic instability and chromothripsis. eccDNA exists widely in physiologically healthy individuals but also arises during tumorigenesis and/or treatment as a drug resistance mechanism. In this review, we summarize the recent progress in research regarding the role of eccDNA in the development of cancer drug resistance as well as the mechanisms thereof. Furthermore, we discuss the clinical applications of eccDNA and propose some novel strategies for characterizing drug-resistant biomarkers and developing potential targeted cancer therapies.

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e16122 Background: The earlier randomized phase III RESORCE trial demonstrated that regorafenib improved overall survival in advanced hepatocellular carcinoma (HCC) patients progressing on sorafenib treatment, with a median survival of 10.6 months and a hazard ratio of 0.63 (95% CI 0.50-0.79, p < 0.0001). Meanwhile, more data were published from retrospective studies evaluating the sequence of single drug sorafenib and regorafenib in advanced HCC patients treated in real-world settings [eg, REFINE study (N = 1000; 100 from China)].We aimed to explore the efficacy and safety of regorafenib alone or in combinations in advanced HCC patients in a real-world setting. Methods: This retrospective multicenter study included pathologically or clinically diagnosed advanced HCC patients who received regorafenib alone or in combinations in first to fourth line settings for at least 28 consecutive days. The primary endpoints were objective response rate (ORR, RECIST 1.1 criteria) and progression-free survival (PFS). The secondary endpoints included overall survival (OS) rate at 6-month and 12-month, disease control rate (DCR) and safety. Kaplan-Meier method was used to calculate survival data. Results: A total of 61 advanced HCC patients (55 male vs. 6 female, 2 first-line recipients vs. 47 second-line recipients vs.11 third-line recipients vs. 1 fourth-line recipients, median age of 53.5 years) from 6 Chinese centers were included between January 2018 and June 2021. Most patients had BCLC stage C (96.7%) and a Child-Pugh A or B score in 23% or 57.4% of cases respectively. 23 (37.7%) patients received single drug regorafenib therapy, the remaining patients (62.3%) received different combination therapies, including regorafenib plus immune checkpoint inhibitors (ICIs) (29.5%), regorafenib combined with TACE (14.8%), and triple therapy (TKI, ICI, TACE) (18.0%). The ORR and DCR of 61 recipients were 71.7% and 83.3%, with a median PFS of 12.67 months (range 7.47-13.97). The 6-month, 12-month OS rates were 80.2% and 68.9%. In second-line recipients, the 6-month, and 12-month OS rates were 85.6% and 76.7%, with a PFS of 12.67 months. 36 recipients had treatment-related adverse events (TRAEs); most frequent TEAEs (≥5%) included fatigue (12.4%), abdominal pain (8.5%), anorexia (7%), rash (7%), diarrhea (6.2%), and hand-foot syndrome (6.2%). Conclusions: Regorafenib alone or in combination is effective and safe in advanced HCC patients, with a high response rate as well as long survival, especially in second-line recipients.