A new scoring system for predicting the outcome of hepatocellular carcinoma patients without microvascular invasion-a large-scale multicentre study.

BACKGROUND: The prognosis of HCC patients without MVI (so called M0) is highly heterogeneous and the need for adjuvant therapy is still controversial. METHODS: Patients with HCC with M0 who underwent liver resection (LR) or liver transplantation (LT) as an initial therapy were included. The Eastern Hepatobiliary Surgery Hospital (EHBH)-M0 score was developed from a retrospective cohort to form the training cohort. The classification which was developed using multivariate cox regression analysis was externally validated. RESULTS: The score was developed using the following factors: α-fetoprotein level, tumour diameter, liver cirrhosis, total bilirubin, albumin and aspartate aminotransferase. The score differentiated two groups of M0 patients (≤3, >3 points) with distinct long-term prognoses outcomes (median overall survival (OS), 98.0 vs. 46.0 months; p < 0.001). The predictive accuracy of the score was greater than the other commonly used staging systems for HCC. And for M0 patients with a higher score underwent LR. Adjuvant transcatheter arterial chemoembolization (TACE) was effective to prolong OS. CONCLUSIONS: The EHBH M0 scoring system was more accurate in predicting the prognosis of HCC patients with M0 after LR or LT. Adjuvant therapy is recommended for HCC patients who have a higher score.

Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial.

Hepatocellular carcinoma (HCC), particularly when accompanied by microvascular invasion (MVI), has a markedly high risk of recurrence after liver resection. Adjuvant immunotherapy is considered a promising avenue. This multicenter, open-label, randomized, controlled, phase 2 trial was conducted at six hospitals in China to assess the efficacy and safety of adjuvant sintilimab, a programmed cell death protein 1 inhibitor, in these patients. Eligible patients with HCC with MVI were randomized (1:1) into the sintilimab or active surveillance group. The sintilimab group received intravenous injections every 3 weeks for a total of eight cycles. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat population. Key secondary endpoints included overall survival (OS) and safety. From September 1, 2020, to April 23, 2022, a total of 198 eligible patients were randomly allocated to receive adjuvant sintilimab (n = 99) or undergo active surveillance (n = 99). After a median follow-up of 23.3 months, the trial met the prespecified endpoints. Sintilimab significantly prolonged RFS compared to active surveillance (median RFS, 27.7 versus 15.5 months; hazard ratio 0.534, 95% confidence interval 0.360-0.792; P = 0.002). Further follow-up is needed to confirm the difference in OS. In the sintilimab group, 12.4% of patients experienced grade 3 or 4 treatment-related adverse events, the most common of which were elevated alanine aminotransferase levels (5.2%) and anemia (4.1%). These findings support the potential of immune checkpoint inhibitors as effective adjuvant therapy for these high-risk patients. Chinese Clinical Trial Registry identifier: ChiCTR2000037655 .

Overall survival of patients with hepatocellular carcinoma treated with sintilimab and disease outcome after treatment discontinuation.

BACKGROUND: The use of Anti-PD-1 therapy has yielded promising outcomes in hepatocellular carcinoma (HCC). However, limited research has been conducted on the overall survival (OS) of patients with varying tumor responses and treatment duration. METHODS: This retrospective study analyzed HCC patients who received sintilimab between January 2019 and December 2020 at four centers in China. The evaluation of tumor progression was based on Response Evaluation Criteria in Solid Tumors version 1.1. The study investigated the correlation between tumor response and OS, and the impact of drug use on OS following progressive disease (PD). RESULTS: Out of 441 treated patients, 159 patients satisfied the inclusion criteria. Among them, 77 patients with disease control exhibited a significantly longer OS compared to the 82 patients with PD (median OS 26.0 vs. 11.3 months, P < 0.001). Additionally, the OS of patients with objective response (OR) was better than that of patients with stable disease (P = 0.002). Among the 47 patients with PD who continued taking sintilimab, the OS was better than the 35 patients who discontinued treatment (median OS 11.4 vs. 6.9 months, P = 0.042). CONCLUSIONS: In conclusion, the tumor response in HCC patients who received sintilimab affects OS, and patients with PD may benefit from continued use of sintilimab.

Linearly polarized fiber amplifier with narrow linewidth of 5†kW exhibiting a record output power and near-diffraction-limited beam quality.

In this work, a narrow-linewidth polarization-maintaining (PM) all-fiber amplifier with near-diffraction-limited beam quality and record output power is presented. First, a 4.45-kW PM fiber amplifier with a 3-dB linewidth of 0.08 nm and root mean square (rms) linewidth of 0.22 nm is achieved based on optimized phase modulation. However, the sideband of the spectrum broadens significantly during the amplification process, which is mainly caused by the additional intensity variation of the injected signal. Meanwhile, an up to 5.04-kW linearly polarized fiber laser with a relatively stable spectral bandwidth is achieved by effectively suppressing spectral broadening. At the maximum output power, the rms linewidth is 0.2 nm, the beam quality factor M2 is less than 1.3, the polarization extinction ratio (PER) is 16.5 dB, and the signal-to-noise ratio (SNR) is approximately 53 dB. The further power scaling of the amplifier is mainly limited by the pump power. To the best of our knowledge, this is the maximum output power of a narrow linewidth linearly polarized fiber amplifier to date.

Pharmacist-led iodinated contrast media infusion risk assessment service.

Background: With the increasing development of medical imaging, the use of iodinated contrast media has become more widespread. Adverse reactions caused by iodinated contrast media have drawn much attention. Despite this, there is still a lack of unified standards for the safe infusion process of iodinated contrast media in clinical practice both domestically and internationally. Objectives: Establishing a risk management service system to better predict the risks associated with iodinated contrast media infusion, reduce the incidence of adverse reactions and minimize patient harm. Method: A prospective interventional study was carried out from April 2021 to December 2021 at Nanjing Drum Tower Hospital in China. During this study, a service system was established to manage the risks associated with the infusion of iodinated contrast media. Personalized risk identification and assessment were performed by a pharmacist-led multidisciplinary team before iodinated contrast media infusion. Early warning, prevention, and adverse reaction management were performed according to different risk levels during and after infusion. Results: A multidisciplinary team led by pharmacists was established to evaluate the risks associated with infusion of iodinated contrast media. A total of 157 patients with risk factors related to the iodinated contrast media were screened out, which prevented 22 serious adverse events and enhanced the quality of medical care. All participants expressed high satisfaction with the service. Conclusion: Through practical exploration, the pharmacist-led multidisciplinary team can provide advance warning and effectively limit the risks of adverse reactions caused by iodinated contrast media to a preventable and controllable level. This approach serves as a valuable reference for developing strategies and schemes to reduce the incidence of such reactions. Therefore, we encourage the implementation of this intervention in other areas of China.

Gemcitabine and cisplatin or oxaliplatin chemotherapy combined with atezolizumab plus bevacizumab for advanced biliary tract cancers: a single-arm trial.

Advanced biliary tract cancer (BTC) has a poor prognosis, even after combined chemotherapy of gemcitabine and oxaliplatin (GEMOX). To investigate the efficacy and safety of GEMOX chemotherapy combining atezolizumab and bevacizumab in advanced BTC, the authors designed an open-label, single-arm, phase II clinical trial and will enroll patients with stage IV BTC. The participants will receive GEMOX chemotherapy combined with atezolizumab plus bevacizumab. The primary end point is objective response rate; the secondary end points are overall survival, disease control rate, progression-free survival, time to progression, duration of response and safety. The results of this trial are expected to provide novel, safe and effective treatment options for patients with advanced BTC, which could further improve their prognosis. Clinical Trial Registration: ChiCTR2100049830 (ChiCTR.org).

Efficacy and safety of a triple combination of atezolizumab, bevacizumab plus GEMOX for advanced biliary tract cancer: a multicenter, single-arm, retrospective study.

Background: Anti-programmed cell death ligand 1/vascular endothelial growth factor inhibition, coupled with chemotherapy, may potentiate antitumor immunity leading to enhanced clinical benefit, but it has not been investigated in advanced biliary tract cancer (BTC). Objectives: We investigated the efficacy and safety of atezolizumab, bevacizumab, and gemcitabine plus oxaliplatin (GEMOX) in advanced BTC and explore the potential biomarkers related to the response. Design: Multicenter, single-arm, retrospective study. Methods: Advanced BTC patients, who received a triple combination therapy at three medical centers between 18 March 2020 and 1 September 2021, were included. Treatment response was evaluated via mRECIST and RECIST v1.1. Endpoints included the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. The whole exome sequencing of pathological tissues was conducted for bioinformatic analysis. Results: In all, 30 patients were enrolled. The best ORR was 76.7% and the DCR was 90.0%. The median PFS was 12.0 months, and the median OS was not reached. During the treatment, 10.0% (3/30) of patients suffered from ⩾grade 3 treatment-related adverse events (TRAEs). Furthermore, fever (73.3%), neutropenia (63.3%), increased aspartate transaminase and alanine aminotransferase levels (50.0% and 43.3%, respectively) are the most common TRAEs. Bioinformatics analysis revealed patients with altered ALS2CL had a higher ORR. Conclusion: The triple combination of atezolizumab, bevacizumab, and GEMOX may be efficacious and safe for patients with advanced BTC. ALS2CL may be a potential predictive biomarker for the efficacy of triple combination therapy.

Early Experience of TACE Combined with Atezolizumab plus Bevacizumab for Patients with Intermediate-Stage Hepatocellular Carcinoma beyond Up-to-Seven Criteria: A Multicenter, Single-Arm Study.

Aim: Locoregional treatment, such as TACE, in combination with immunotherapy may elicit a synergistic anticancer effect. However, TACE combined with atezolizumab plus bevacizumab (atezo/bev) has not been investigated for patients with intermediate stage (BCLC B) HCC beyond the up-to-seven criteria. This study aims to evaluate the efficacy and safety of this treatment strategy in intermediate-stage HCC patients with large or multinodular tumors exceeding the up-to-seven criteria. Methods: This multicenter retrospective study included patients with intermediate stage (BCLC B) HCC beyond the up-to-seven criteria treated with TACE combined with atezo/bev from five centers in China from March to September 2021. The outcomes of this study included the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Treatment-related adverse events (TRAEs) were analyzed to assess safety. Results: A total of 21 patients were enrolled in this study, with a median follow-up duration of 11.7 months. According to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, the best ORR was 42.9% and the DCR was 100%. According to modified RECIST (mRECIST), the best ORR and DCR were 61.9% and 100%, respectively. The median PFS and OS were not reached. The most common TRAEs at all levels were fever (71.4%), and the most common grade 3/4 TRAE was hypertension (14.3%). Conclusions: TACE combined with atezo/bev showed encouraging efficacy and an acceptable safety profile, making it a promising treatment option for patients with BCLC B HCC beyond the up-to-seven criteria, which will be further investigated in a prospective single-arm trial.

Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study.

Background and aims: The efficacy and safety of systemic atezolizumab and bevacizumab (atezo/bev) in treatment of patients with unresectable hepatocellular carcinoma (HCC) have been demonstrated. However, the efficacy of this treatment in patients with HCC and extrahepatic portal vein tumor thrombus (ePVTT) is not satisfactory. This study aimed to study the efficacy and safety of combining intensity-modulated radiotherapy (IMRT) with systemic atezo/bev in treatment of these patients. Methods: This multicenter prospective study included patients with ePVTT treated with IMRT combined with atezo/bev from March to September 2021 in three centers in China. The outcomes of this study included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and association between response and tumor mutational burden (TMB). Treatment-related adverse events (TRAEs) were analyzed to assess safety. Results: Of 30 patients in this study, the median follow-up was 7.4 months. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, the ORR was 76.6%, the median OS for the entire cohort was 9.8 months, the median PFS was 8.0 months, and the median TTP was not reached. This study failed to establish a significant correlation between TMB with any of the following outcomes, including ORR, OS, PFS or TTP. The most common TRAEs at all levels were neutropenia (46.7%), and the most common grade 3/4 TRAE was hypertension (16.7%). There was no treatment-related deaths. Conclusions: IMRT combined with atezo/bev showed encouraging treatment efficacy with an acceptable safety profile, making this treatment to be a promising option for HCC patients with ePVTT. Further studies are required to support the findings of this preliminary study. Clinical trial registration: http://www.chictr.org.cn, Identifier ChiCTR2200061793.

Efficacy and safety of TACE combined with lenvatinib and PD-1 inhibitors for unresectable recurrent HCC: A multicenter, retrospective study.

BACKGROUND: There is no consensus on the optimal regimen for unresectable recurrent hepatocellular carcinoma (HCC), so this retrospective study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and PD-1 inhibitors (T-L-P) versus TACE combined with lenvatinib (T-L) or TACE alone. METHOD: Data were collected from 204 patients with unresectable recurrent HCC who received T-L-P, T-L, or TACE alone at three medical centers from January, 2019 to December, 2020 for analysis. The survival outcomes, tumor response, and adverse events were compared between three groups, and risk factors were further investigated. RESULTS: The median overall survival in the T-L-P, T-L, and TACE alone groups were not reached, 25.6, and 15.7 months, respectively (p < 0.001). The median progression-free survival in the T-L-P, T-L, and TACE alone groups were 24.1, 17.3, and 13.7 months, respectively (p < 0.001). The best objective response rate in the T-L-P, T-L, and TACE alone groups were 70.4%, 48.9%, and 42.5%, respectively. The best disease control rate in the T-L-P, T-L, and TACE alone groups were 100.0%, 97.8%, and 87.5%, respectively. There was no significant difference between the T-L-P and T-L groups for Grade 3/4 adverse events. CONCLUSION: T-L-P regimen was safe and superior to T-L or TACE alone in improving survival for unresectable recurrent HCC patients.

N6-Methyladenosine-Mediated Up-Regulation of FZD10 Regulates Liver Cancer Stem Cells' Properties and Lenvatinib Resistance Through WNT/ß-Catenin and Hippo Signaling Pathways.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, but there is a deficiency of early diagnosis biomarkers and therapeutic targets. Drug resistance accounts for most HCC-related deaths, yet the mechanisms underlying drug resistance remain poorly understood. METHODS: Expression of Frizzled-10 (FZD10) in liver cancer stem cells (CSCs) was identified by means of RNA sequencing and validated by means of real-time polymerase chain reaction and immunohistochemistry. In vitro and in vivo experiments were used to assess the effect of FZD10 on liver CSC expansion and lenvatinib resistance. RNA sequencing, RNA binding protein immunoprecipitation, and luciferase report assays were applied to explore the mechanism underlying FZD10-mediated liver CSCs expansion and lenvatinib resistance. RESULTS: Activation of FZD10 in liver CSCs was mediated by METTL3-dependent N6-methyladenosine methylation of FZD10 messenger RNA. Functional studies revealed that FZD10 promotes self-renewal, tumorigenicity, and metastasis of liver CSCs via activating ß-catenin and YAP1. The FZD10-ß-catenin/YAP1 axis is activated in liver CSCs and predicts poor prognosis. Moreover, FZD10-ß-catenin/c-Jun axis transcriptionally activates METTL3 expression, forming a positive feedback loop. Importantly, the FZD10/ß-catenin/c-Jun/MEK/ERK axis determines the responses of hepatoma cells to lenvatinib treatment. Analysis of patient cohort, patient-derived tumor organoids, and patient-derived xenografts further suggest that FZD10 might predict lenvatinib clinical benefit in patients with HCC. Furthermore, treatment of lenvatinib-resistant HCC with adeno-associated virus targeting FZD10 or a ß-catenin inhibitor restored lenvatinib response. CONCLUSIONS: Elevated FZD10 expression promotes expansion of liver CSCs and lenvatinib resistance, indicating that FZD10 expression is a novel prognostic biomarker and therapeutic target for human HCC.

Efficacy and safety of radiotherapy combined with atezolizumab plus bevacizumab in treating hepatocellular carcinoma with portal vein tumour thrombus: a study protocol.

INTRODUCTION: Vascular invasion and metastasis are poor prognostic factors in patients with hepatocellular carcinoma (HCC). The efficacy of available therapeutic regimens for unresectable HCC is not satisfactory in HCC with portal vein tumour thrombosis (PVTT). Therefore, this open-label, single-arm phase II clinical trial aims to investigate the efficacy and safety of radiotherapy combined with atezolizumab plus bevacizumab in treating HCC patients with PVTT. METHODS AND ANALYSIS: We plan to enrol patients diagnosed with unresectable HCC complicated by PVTT. Intensity-modulated radiotherapy (IMRT) combined with atezolizumab plus bevacizumab will be administered for treatment. Patients will initially receive radiotherapy, with each IMRT cycle lasting for 28 days and the total dose of tumour (DT) of 40 Gy/20 f/26 d. CT scan will be performed again, and the treatment plan will be reformulated after field constriction. The treatment will continue until the total DT is up to 54-56 Gy/27-28 f. The treatment with atezolizumab plus bevacizumab will be started at 3±1 days after the initiation of radiotherapy and will continue until unacceptable toxicity or disease progression. The primary endpoint is objective response rate (ORR), while the secondary endpoints include overall survival, disease control rate, progression-free survival, time to progression, duration of response and the rate of surgical conversions. Assuming an ORR of 47%, with a two-sided alpha error of 0.1, 90% power, and a 10% drop-out rate, the required number of evaluable patients is 42. ETHICS AND DISSEMINATION: This study will be conducted according to the standards of Good Clinical Practice and in compliance with the principles of the Declaration of Helsinki. The Ethics Committee of our Hospital has approved the protocol (EHBHKY2021-K-017). All participants are required to provide written informed consent. The results of the trial will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2100049831.

Iodine-based extracellular volume for evaluating myocardial status in patients undergoing percutaneous coronary intervention for acute myocardial infarction by using dual-layer spectral detector computed tomography: a comparison study with magnetic resonance.

Background: The myocardial status of patients who undergo percutaneous coronary intervention (PCI) must be evaluated accurately to enable treatment plans to be made for potential complications such as abrupt vessel closure, stent deformation, and myocardial chronic ischemia. This study examined the modality and clinical feasibility of iodine-based extracellular volume (ECV) assessment of the myocardium versus cardiovascular magnetic resonance (CMR) imaging in patients undergoing PCI. Methods: In all, 21 patients who underwent PCI were prospectively enrolled in the study. All patients underwent follow-up cardiac dual-layer spectral detector computed tomography (SDCT) and CMR imaging after PCI. Myocardial ECV was quantified by either computed tomography (ECVCT) or magnetic resonance (ECVMR) using iodine or T1-weighted mapping, respectively. The quality of SDCT and CMR images was independently assessed by two radiologists using a 4-point scale (1= poor and 4= excellent). Any patient with an image quality (IQ) score <2 was excluded. Consistency between radiologists was evaluated using intraclass correlation coefficients (ICC). Correlations between ECVCT and ECVMR values were analyzed using Pearson's test, and consistency was analyzed with Bland-Altman plots. Results: Nineteen of 21 patients completed both cardiac CT and CMR examinations, while three patients were excluded after IQ assessment (two with poor CMR IQ; one with a discontinuous coronary artery on CT images). The mean (±SD) IQ scores for CT and CMR images were 3.81±0.40 and 3.25±0.58, respectively, and interobserver agreement was good (ICC =0.93 and 0.92 for CT and CMR, respectively). The mean (±SD) ECVCT and ECVMR values were 35.93%±9.73% and 33.89%±7.51%, respectively, with good correlation (r=0.79, P<0.001). Bland-Altman analysis showed a difference of 2.04% (95% CI: -9.56%, 13.64%) between the ECVCT and ECVMR values. Conclusions: There is high correlation between iodine-based ECVCT and ECVMR values, which indicates that ECVCT is clinically feasible for evaluating the status of myocardial recovery in patients undergoing PCI.

Transcatheter arterial chemoembolization plus atezolizumab and bevacizumab for unresectable hepatocellular carcinoma: a single-arm, phase II trial.

The therapeutic effect of transcatheter arterial chemoembolization (TACE) is limited for patients with hepatocellular carcinoma (HCC). Herein, we designed an open-label, single-arm phase II clinical trial to investigate the efficacy and safety of TACE combined with atezolizumab plus bevacizumab for patients with Barcelona Clinic Liver Cancer (BCLC) stage-B HCC. Patients will initially receive TACE. Atezolizumab and bevacizumab will be initiated 2-14 days after the first TACE session. TACE will be repeated on demand. The primary endpoint is the objective response rate. The secondary end points include overall survival, disease control rate, progression-free survival, time-to-progression and safety. The study results will provide evidence for establishing a novel therapeutic regimen for patients with unresectable HCC. Clinical Trial Registration: ChiCTR2100049829 (ChiCTR.org).

A deep learning model with incorporation of microvascular invasion area as a factor in predicting prognosis of hepatocellular carcinoma after R0 hepatectomy.

INTRODUCTION: Microvascular invasion (MVI) is a known risk factor for prognosis after R0 liver resection for hepatocellular carcinoma (HCC). The aim of this study was to develop a deep learning prognostic prediction model by incorporating a new factor of MVI area to the other independent risk factors. METHODS: Consecutive patients with HCC who underwent R0 liver resection from January to December 2016 at the Eastern Hepatobiliary Surgery Hospital were included in this retrospective study. For patients with MVI detected on resected specimens, they were divided into two groups according to the size of the maximal MVI area: the small-MVI group and the large-MVI group. RESULTS: Of 193 patients who had MVI in the 337 HCC patients, 130 patients formed the training cohort and 63 patients formed the validation cohort. The large-MVI group of patients had worse overall survival (OS) when compared with the small-MVI group (p = 0.009). A deep learning model was developed based on the following independent risk factors found in this study: MVI stage, maximal MVI area, presence/absence of cirrhosis, and maximal tumor diameter. The areas under the receiver operating characteristic of the deep learning model for the 1-, 3-, and 5-year predictions of OS were 80.65, 74.04, and 79.44, respectively, which outperformed the traditional COX proportional hazards model. CONCLUSION: The deep learning model, by incorporating the maximal MVI area as an additional prognostic factor to the other previously known independent risk factors, predicted more accurately postoperative long-term OS for HCC patients with MVI after R0 liver resection.

Hazard rate for postoperative recurrence in patients with hepatocellular carcinoma at Barcelona Clinic Liver Cancer stage 0 or A1: A multicenter observational study.

AIM: Surgical treatment is the first-line treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A1 hepatocellular carcinoma (HCC), and postoperative monitoring improves long-term survival. We aimed to establish a reasonable short-interval follow-up duration for patients with HCC. METHODS: The cohort for this retrospective study included 1396 HCC patients with BCLC stage 0 or A1 disease who underwent curative resection from 2013 to 2016 at five centers in China. Hazard rates for recurrence were calculated using the hazard function. RESULTS: The recurrence rates in patients with BCLC stage 0 and A1 HCC were 46.4% and 58.0%, respectively. The hazard curve for stage 0 patients was relatively flat, and the hazard rate was consistently low (peak hazard rate 0.0163). The hazard rate curve for recurrence was initially high (peak hazard rate 0.0441) in patients with BCLC stage A1 disease and showed a rapid decreasing trend within 1 year, followed by a slow decreasing trend, reaching a low level (<0.0163) at approximately 36 months. The time to low risk was 47, 41, and 51 months in patients with cirrhosis, hepatitis B virus (HBV) infection, and satellite lesions, respectively. CONCLUSIONS: A short-interval follow-up of 1 year is sufficient for HCC patients with BCLC stage 0 disease, whereas a short-interval follow-up time of 3 years should be considered for patients with stage A1 disease. The follow-up period should be appropriately prolonged for patients with cirrhosis, HBV infection, and satellite lesions.

Transarterial chemoembolization plus a PD-1 inhibitor with or without lenvatinib for intermediate-stage hepatocellular carcinoma.

AIM: Transarterial chemoembolization (TACE) combined with a PD-1 inhibitor and TACE combined with a PD-1 inhibitor and lenvatinib have recently been reported as promising treatments to improve the prognosis of hepatocellular carcinoma (HCC) patients. This study aims to compare the efficacy of these two treatments. METHODS: A retrospective study was conducted, and patients were recruited from two centers in China. Progression-free survival (PFS) and overall survival (OS) were compared, and the objective response rate (ORR) and disease control rate (DCR) were evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Treatment-related adverse events (AEs) were analyzed to assess safety. RESULTS: The median follow-up for the entire cohort was 11.4 months. Of the 103 patients included in this study, 56 received triple therapy, and 47 received doublet therapy. PFS was significantly higher in the triple therapy group than in the doublet therapy group (mPFS 22.5 vs. 14.0 months, P < 0.001). Similar results were obtained in terms of OS (P = 0.001). The ORR and DCR were also better in the triple therapy group (64.3% vs. 38.3%, P = 0.010; 85.7% vs. 57.4%, P = 0.002). The most common AEs in the triple therapy group were decreased albumin (55.3%), decreased platelet count (51.8%) and hypertension (44.6%). CONCLUSIONS: The combination of TACE with a PD-1 inhibitor and lenvatinib in patients with BCLC stage B HCC might result in significantly improved clinical outcomes with a manageable safety profile compared with TACE with a PD-1 inhibitor.

Clinical feasibility of using effective atomic number maps derived from non-contrast spectral computed tomography to identify non-calcified atherosclerotic plaques: a preliminary study.

Background: To assess the clinical feasibility of using effective atomic number (Zeff) maps derived from non-contrast-enhanced computed tomography (NCECT) scans obtained by dual-layer spectral computed tomography (DLCT) to identify non-calcified atherosclerotic plaques. Methods: A total of 37 patients with 86 non-calcified atherosclerotic plaques confirmed by contrast-enhanced CT (CECT) were enrolled in this retrospective study. Both spectral-based-images (SBI) and conventional images (CI) were reconstructed from NCECT and CECT scans. The presence of plaques on NCECT Zeff maps and CIs were independently assessed by 2 radiologists. In CECT scans, plaques and regions of interest (ROIs) in vessel lumens were assessed with CT attenuation and Zeff values, and the proportion of plaques was determined as Area (plaque)/Area (vessel). The CT and Zeff values for plaques and blood were recorded from both CECT and NCECT scans. Contrast-to-noise ratios (CNRs) of the plaques were calculated and compared using CT attenuation and Zeff values. Finally, interobserver agreement was evaluated. Results: A total of 47 of the 86 (54.7%) plaques were identified on Zeff map images derived from the NCECT scans while only 7 (8.1%) plaques were identified on the CI. There was no significant difference between the mean vessel ROI area measured on CIs and that measured on Zeff map images (502.19 vs. 498.14 mm2; P=0.28), while the mean plaque ROI area was larger (81.45 vs. 75.46 mm2). The observer consensus of vessel and plaque ROI area measurements using both methods was excellent, with interclass correlation coefficients (ICCs) of 0.99 and 0.94, respectively. For the 7 plaques detected both by NCECT CI and Zeff mapping, the CT attenuation and Zeff blood values were both larger than the plaque values [42.00 vs. 25.67 Hounsfield unit (HU); 7.33 vs. 7.19 HU; both P<0.05]; the plaque ROI area measurement on the NCE Zeff map was smaller than that on the CE CI (48.73 vs. 77.76 mm2), but was much larger than that on the NCE CI (18.39 mm2). For all 47 plaques detected by NCE Zeff mapping, the CT attenuation and Zeff values of blood and plaques on the NCECT images showed no significant differences (42.53 vs. 35.14 HU; P=0.18; 7.32 vs. 7.31, P=0.71); however, the CNR of Zeff was significantly higher than the CT attenuation value (1.69 vs. 1.12; P<0.05) derived from the NCECT scans. Inter-reviewer agreement was good (ICC =0.78). Conclusions: Zeff map images derived from NCECT SBI with DLCT provide a potentially feasible approach for identifying non-calcified atherosclerotic plaques, which might be clinically useful for the screening of asymptomatic at-risk patients.

Effects of Stereotactic Body Radiation Therapy Plus PD-1 Inhibitors for Patients With Transarterial Chemoembolization Refractory.

Background and Aims: Patients with intermediate-stage hepatocellular carcinoma (HCC) who are refractory to transarterial chemoembolization (TACE) have a poor prognosis. This study aimed to explore whether stereotactic body radiation therapy (SBRT) combined with PD-1 inhibitors could improve the clinical outcomes of such patients. Methods: This retrospective cohort study included patients with intermediate-stage HCC who were diagnosed with TACE refractoriness between January 2019 and December 2020 in the Eastern Hepatobiliary Surgery Hospital and the First Affiliated Hospital of Wenzhou Medical University. The patients were divided into two groups: (1) those who switched from TACE to receive stereotactic body radiotherapy (SBRT) combined with PD-1 inhibitors; (2) those who continued TACE treatment and added PD-1 inhibitors. Progression-free survival (PFS), overall survival (OS), and tumour response were assessed in both groups after becoming refractory to TACE treatment. Results: Of the seventy-six patients included in this study, the median PFS was 19.6 months in the SBRT-IO group (n=31) and 10.1 months in the TACE-IO group (n=45, p<0.05). The SBRT-IO group also had a significantly higher OS than the TACE-IO group (p<0.05). The objective response rate (ORR) and disease control rate (DCR) were also better in the SBRT-IO group (ORR, 71.0% vs. 15.6%, OR=8.483, 95% CI 3.319-21.680, P < 0.001; DCR, 80.6% vs. 31.1%, OR=9.226, 95% CI 3.096-27.493, P < 0.001). Conclusions: SBRT combined with a PD-1 inhibitor improves PFS and OS in TACE-refractory patients with intermediate-stage HCC. Therefore, this therapy is a suitable option in cases of TACE treatment failure.

Image-matching digital macro-slide-a novel pathological examination method for microvascular invasion detection in hepatocellular carcinoma.

BACKGROUND: Microvascular invasion (MVI) is a prominent risk factor of postoperative recurrence for hepatocellular carcinoma (HCC). The MVI detection rate of conventional pathological examination approaches is relatively low and unsatisfactory. METHODS: By integrating pathological macro-slide with whole-mount slide imaging, we first created a novel pathological examination method called image-matching digital macro-slide (IDS). Surgical samples from eligible patients were collected to make IDS. The MVI detection rates, tumor recurrence rates and recurrence-free survival were compared among conventional 3-Point and 7-Point baseline sampling protocols and IDS. Additionally, biomarkers to recognize MVI false negative patients were probed via combining conventional pathological sampling protocols and IDS. Receiver operating characteristic curve (ROC) analysis was used to obtain the optimal cutoff of biomarkers to distinguish MVI false negative patients. RESULTS: The MVI detection rates were 21.98%, 32.97% and 63.74%, respectively, in 3-Point, 7-Point baseline sampling protocols and IDS (p < 0.001). Tumor recurrence rate of patients with MVI negative status in IDS (6.06%) was relatively lower than that of patients with MVI negative status in 3-Point (16.90%) and 7-Point (16.39%) sampling protocols. Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) were selected as potential biomarkers to distinguish MVI false negative patients. CONCLUSIONS: Our study demonstrated that IDS can help enhance the detection rate of MVI in HCC and refine the prediction of HCC prognosis. Alpha-fetoprotein is identified as a suitable and robust biomarker to recognize MVI false-negative patients in conventional pathological protocols.