Multimodal Theranostic Nanoparticles for Necrosis Targeting, Fluorescence/SPECT Imaging, and Radiotherapy of Residual Tumors after Hepatocellular Carcinoma Ablation.

Thermal ablation has been commonly used as an effective treatment for hepatocellular carcinoma; however, peri-necrotic tumor residues after ablation play a significant role in tumor recurrence and poor prognosis. Therefore, developing agents that can effectively target and eliminate residual tumors is critically needed. Necrosis targeting strategies have potential implications for evaluating tumor necrosis areas and treating the surrounding residual tumors. To address this issue, we have developed a biodegradable nanoparticle with necrosis avidity that is compatible with fluorescence imaging, single photon emission computed tomography (SPECT) imaging, and necrosis targeted radiotherapy. The nanoparticles were synthesized using iodine-131-labeled hypericin (131I-Hyp) as the core and amphiphilic copolymer poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) as the shell. The developed nanoparticle, PNP@(131I-Hyp), has a uniform spherical morphology with a size of 33.07 ± 3.94 and 45.93 ± 0.58 nm determined by cryogenic transmission electron microscopy (cryo-TEM) and dynamic light-scattering analysis (polydispersity index = 0.19 ± 0.01), respectively, and having a good stability and blood compatibility in vitro. In mouse subcutaneous ablated-residual tumor models, fluorescence and SPECT imaging demonstrated that PNP@(131I-Hyp) prominently accumulated in the tumor and was retained for as long as 168 h following intravenous injection. Moreover, ex vivo analyses showed that PNP@(131I-Hyp) mainly gathered in the necrotic zones of subcutaneous tumors and inhibited residual tumors by radiotherapy. In addition, histological examination of harvested organs and hematological analysis demonstrated that intravenous injection of 5 mCi/kg nanoparticles caused no gross abnormalities. This multifunctional nanoparticle, therefore, has necrosis imaging and targeted therapeutic effects on residual tumors after thermal ablation of hepatocellular carcinoma, showing potential for clinical application.

Nomogram-based development and evaluation for predictions of 30-day and 1-year survival in patients with spontaneously ruptured hepatocellular carcinoma.

BACKGROUND: Accurately predicting the prognosis of patients with spontaneously ruptured hepatocellular carcinoma (HCC) is crucial for effective clinical management. The aim of the present study was to establish and evaluate prediction models for 30-day and 1-year survival in patients with spontaneously ruptured HCC. METHODS: A total of 118 patients with spontaneous rupture HCC were enrolled. Univariate and multivariate analyses were performed using logistic-regression model and Cox proportional-hazard model. The identified indicators were used to establish prediction models, the performance of which we compared with those of commonly used liver disease scoring models. The survival possibilities of different risk categories were calculated using the newly developed models. RESULTS: Largest tumor size (LTS), serum albumin (ALB), total bilirubin (TBil), and serum creatinine were identified as independent predictors, which were used to establish a 30-day survival prediction model. LTS, BCLC staging, ALB, TBil, hepatectomy at rupture, and TACE during follow-up were identified as independent predictors of 1-year survival model. The 30-day survival model had sensitivity of 79.3%, specificity of 87.1%, and an AUC of 0.879, exhibiting better predictive performance than scores for Chronic Liver Failure Consortium Acute Decompensation score (CLIF-C ADs) and Model for End-stage Liver Disease (MELD). The 1-year survival model had sensitivity of 66.7%, specificity of 94.6%, and an AUC of 0.835, showing better predictive performance than Albumin-Bilirubin (ALBI), Child-Pugh, CLIF-C ADs, and MELD. After stratification, survival possibilities were 90.9 and 21.1% in low- and high-risk groups within 30 days, respectively, and 43.90, 4.35%, and 0 in low-, intermediate-, and high-risk groups at 1 year, respectively. CONCLUSIONS: The established models exhibited good performance in predicting both 30-day and 1-year survival in patients with spontaneously ruptured HCC.

Radioiodinated hypericin as a tracer for detection of acute myocardial infarction: SPECT-CT imaging in a swine model.

PURPOSE: Hypericin (Hyp) is a natural compound with a newly discovered necrosis-avidity, which can be exploited as a necrosis-avid tracer once labeled with radioactive iodine as has been tested in rodent models. This study was to evaluate the effect of radioiodinated Hyp (131I-Hyp) for imaging detection of acute myocardial infarction (AMI) in conditions closer to clinical scenarios. METHODS: We established swine AMI models (n = 6) which were intravenously given 131I-Hyp and 99mTc-sestamibi and underwent SPECT-CT imaging with high- and low-energy collimators. The acquired SPECT images were fused with cardiac CT images and correlated with postmortem autoradiography and macro- and microscopic pathology. Tissue γ counting was performed to determine biodistribution of 131I-Hyp. RESULTS: 131I-Hyp based SPECT indicated clearly hot regions on ventricular walls which were all histologically proved as AMI. Complementally, the hot AMI regions on 131I-Hyp SPECT (infarct/myoc ratio of 15.3 ± 7.7) were inversely cold regions on 99mTc-sestamibi SPECT (infarct/myoc ratio of 0.029 ± 0.021). Autoradiography of heart slices showed 9.8 times higher 131I-Hyp uptake in infarcted over normal myocardium. With γ counting, the mean 131I-Hyp uptake in infarcts was 10.69 ID%/g, 12.05 times of that in viable myocardium. CONCLUSION: 131I-Hyp shows a potential for clinical detection of AMI once I-131 is substituted by its isotope like I-124 or I-123 for PET or SPECT, respectively.

Scalable Synthesis of Porous SiFe@C Composite with Excellent Lithium Storage.

Utilizing cost-effective raw materials to prepare high-performance silicon-based anode materials for lithium-ion batteries (LIBs) is both challenging and attractive. Herein, a porous SiFe@C (pSiFe@C) composite derived from low-cost ferrosilicon is prepared via a scalable three-step procedure, including ball milling, partial etching, and carbon layer coating. The pSiFe@C material integrates the advantages of the mesoporous structure, the partially retained FeSi2 conductive phase, and a uniform carbon layer (12-16 nm), which can substantially alleviate the huge volume expansion effect in the repeated lithium-ion insertion/extraction processes, effectively stabilizing the solid-electrolyte interphase (SEI) film and markedly enhancing the overall electronic conductivity of the material. Benefiting from the rational structure, the obtained pSiFe@C hybrid material delivers a reversible capacity of 1162.1 mAh g-1 after 200 cycles at 500 mA g-1 , with a higher initial coulombic efficiency of 82.30 %. In addition, it shows large discharge capacities of 803.1 and 600.0 mAh g-1 after 500 cycles at 2 and 4 A g-1 , respectively, manifesting an excellent electrochemical lithium storage. This work provides a good prospect for the commercial production of silicon-based anode materials for LIBs with a high lithium-storage capacity.

Brachytherapy with Iodine-125 seeds for treatment of portal vein-branch tumor thrombus in patients with hepatocellular carcinoma.

BACKGROUND: There is currently no widely-accepted consensus for the management of hepatocellular carcinoma with portal vein tumor thrombus. We evaluate the safety and efficacy of ultrasound-guided percutaneous brachytherapy with iodine-125 seeds for the treatment of hepatocellular carcinoma with portal vein-branch tumor thrombus (PVBTT). METHODS: Sixty-nine hepatocellular carcinoma patients with PVBTT were enrolled; 34 received transarterial chemoembolization (TACE) combined with iodine-125 seeds implanted in the PVBTT; 35 were treated with TACE alone. Adverse events, objective response rate, disease control rate, progression-free survival, and overall survival were compared between the two groups. Tumor responses of PVBTT and intrahepatic tumor were correlated. Multivariate and subgroup analyses were conducted for overall survival. RESULTS: No grade 3 or 4 adverse events were recorded, and there was no difference in grade 1 or 2 adverse events between the two groups. Objective response rate and disease control rate for PVBTT were 58.9 and 91.2%, respectively, in the combined treatment group, which were significantly greater than the 5.7 and 54.3% rates, respectively, in the TACE-alone group (both p's ≤ 0.001). Intrahepatic tumor response was positively correlated with the PVBTT response (γ = 0.782, p < 0.01). Survival outcomes were better in the combined treatment group than in the TACE-alone group: the median progression-free survival for PVBTT was 9 months versus 3 months (HR = 0.187 [95% CI: 0.101, 0.345], p < 0.001), and the median overall survival was 11 months versus 7 months (HR = 0.448 [95% CI: 0.265, 0.758], p = 0.003). Multivariate analysis revealed that application of brachytherapy and lower grade PVBTT (Vp1 + Vp2 vs. Vp3) were protective predictors of overall survival. In stratified analysis, the benefit of overall survival was more significant in the subgroup of PVBTT Vp1 + Vp2 rather than in Vp3. CONCLUSIONS: The combination of iodine-125 seed brachytherapy guided by ultrasound and TACE is a convenient, safe, and effective treatment for patients with HCC and PVBTT, conferring a better survival benefit than TACE alone.

Intraoperative radiotherapy vs concurrent chemoradiotherapy in the treatment of patients with locally advanced pancreatic cancer.

PURPOSE: The purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated. RESULTS: Most factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0-17.6 months) and 13.8 months (95% CI, 11.0-16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%-80.2%) and 60.9% in Arm B (95% CI, 46.4%-75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458). CONCLUSION: Our results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.

Porous Si-Cu3 Si-Cu Microsphere@C Core-Shell Composites with Enhanced Electrochemical Lithium Storage.

Low-cost Si-based anode materials with excellent electrochemical lithium storage present attractive prospects for lithium-ion batteries (LIBs). Herein, porous Si-Cu3 Si-Cu microsphere@C composites are designed and prepared by means of an etching/electroless deposition and subsequent carbon coating. The composites show a core-shell structure, with a porous Si/Cu microsphere core surrounded by the N-doped carbon shell. The Cu and Cu3 Si nanoparticles are embedded inside porous silicon microspheres, forming the porous Si/Cu microsphere core. The microstructure and lithium storage performance of porous Si-Cu3 Si-Cu microsphere@C composites can be effectively tuned by changing electroless deposition time. The Si-Cu3 Si-Cu microsphere@C composite prepared with 12 min electroless deposition delivers a reversible capacity of 627 mAh g-1 after 200 cycles at 2 A g-1 , showing an enhanced lithium storage ability. The superior lithium storage performance of the Si-Cu3 Si-Cu microsphere@C composite can be ascribed to the improved electronic conductivity, enhanced mechanical stability, and better buffering against the large volume change in the repeated lithiation/delithiation processes.

Pictorial Imaging-Histopathology Correlation in a Rabbit with Hepatic VX2 Tumor Treated by Transarterial Vascular Disrupting Agent Administration.

Cancer vasculature is immature, disorganized and hyperpermeable and can serve as a target for anti-cancer therapies. Vascular disrupting agents (VDAs) are tubulin protein binding and depolymerizing agents that induce rapid tumoral vascular shutdown and subsequent cancer necrosis. However, two clinical problems exist with all VDAs, i.e. 1) incomplete anticancer effect and 2) dose-dependent toxicity. To tackle these problems, in our ongoing research, a novel VDA C118P is applied by transarterial administration of half the intravenous dose in rabbits with implanted VX2 liver tumor to assess its therapeutic efficacy. Nearly complete tumor necrosis was achieved by only a single arterial dose of C118P at 5 mg/kg, which was documented in a representative case by in vivo digital subtraction arteriogram (DSA) and magnetic resonance imaging (MRI), and further confirmed by ex vivo microangiogram and histopathology. This convincing and promising preliminary outcome would warrant further comprehensive studies to explore the potentials of VDAs by transarterial administration either in mono-drug or in combination for management of solid cancers.

CT-Guided Percutaneous Needle Biopsy of Retroperitoneal and Pelvic Lymphadenopathy: Assessment of Technique, Diagnostic Yield, and Clinical Value.

PURPOSE: To assess the technical success rate, diagnostic yield, and clinical value of computed tomography (CT)-guided percutaneous needle biopsy (PNB) for retroperitoneal and pelvic lymphadenopathy. MATERIALS AND METHODS: This retrospective study included 344 patients evaluated for safety and technique and 334 patients evaluated for diagnostic yield and clinical analyses. PNBs were performed with fine-needle aspiration (FNA) in 315 patients and with core biopsy in 333 patients. Follow-up analyses, including repeat biopsy, open surgery, imaging, and clinical indicators, were conducted for 94 patients who had nonspecific malignant or benign results. Diagnostic yields were calculated based on biopsy and follow-up results. Factors associated with final diagnoses were compared and modeled by multivariate analysis. RESULTS: Technical success rate was 99.7%. Thirty-nine patients (11.3%) had minor complications. From biopsy results and follow-up analyses, final malignant diagnoses were determined for 281 patients (84.1%). Overall sensitivity, specificity, and accuracy rates of PNB were 91.5%, 100%, and 92.8%, respectively. For patients with a history of malignancy, the likelihood of nodal involvement was 84.6% and that of a new, different malignancy was 3.7%. Older age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.00-1.05), history of malignancy (OR, 3.44; 95% CI, 1.71-6.92), multiple lymph nodes (LNs; OR, 2.65; 95% CI, 1.38-5.09), and new or enlarging LNs (OR, 2.62; 95% CI, 1.25-5.48) were independent risk factors for malignancy diagnosis. CONCLUSIONS: CT-guided PNB is a safe, effective procedure that can achieve high diagnostic yields for patients with retroperitoneal and pelvic lymphadenopathy.

Layered MoS2 Hollow Spheres for Highly-Efficient Photothermal Therapy of Rabbit Liver Orthotopic Transplantation Tumors.

Combining photothermal therapy (PTT) with clinical technology to kill cancer via overcoming the low tumor targeting and poor therapy efficiency has great potential in basic and clinical researches. A brand-new MoS2 nanostructure is designed and fabricated, i.e., layered MoS2 hollow spheres (LMHSs) with strong absorption in near-infrared region (NIR) and high photothermal conversion efficiency via a simple and fast chemical aerosol flow method. Owing to curving layered hollow spherical structure, the as-prepared LMHSs exhibit unique electronic properties comparing with MoS2 nanosheets. In vitro and in vivo studies demonstrate their high photothermal ablation of cell and tumor elimination rate by single NIR light irradiation. Systematic acute toxicity study indicates that these LMHSs have negligible toxic effects to normal tissues and blood. Remarkably, minimally invasive interventional techniques are introduced to improve tumor targeting of PTT agents for the first time. To explore PTT efficiency on orthotopic transplantation tumors, New Zealand white rabbits with VX2 tumor in liver are used as animal models. The effective elimination of tumors is successfully realized by PTT under the guidance of digital subtraction angiography, computed tomography, and thermal imaging, which provides a new way for tumor-targeting delivery and cancer theranostic application.

Photochemical fabrication of 3D hierarchical Mn3O4/H-TiO2 composite films with excellent electrochemical capacitance performance.

We herein report a novel, energy-saving and environmentally benign photodeposition approach to fabricate a manganese oxide film on hydrogenated TiO2 (H-TiO2) nanotube arrays using a Mn(2+)-containing solution as a precursor. Mn(2+) ions are oxidized to Mn3O4 by the photogenerated holes during the photodeposition. The preferential growth of Mn3O4 on the nucleation sites leads to the formation of Mn3O4 nanorods on each H-TiO2 nanotube, forming a 3D hierarchical Mn3O4/H-TiO2 composite film. The as-fabricated 3D hierarchical Mn3O4/H-TiO2 composite film electrode delivers a high specific capacitance of 508 F g(-1) at a current of 0.7 A g(-1). The composite film electrode still shows a specific capacitance of 228 F g(-1) even at a high rate of 35.7 A g(-1), demonstrating its prominent rate capability. Remarkably, the composite film electrode shows no obvious capacitance decay after 10,000 charge/discharge cycles at a current density of 3.6 A g(-1), revealing its superior electrochemical cycling stability. The prominent pseudocapacitive performance of the composite film electrode can be attributed to its unique structure characteristics. The as-constructed energy-saving and environmentally benign photodeposition method can be used as a general and efficient route to prepare other composite materials with controlled morphologies and dimensions.

Shape-Dependent Genotoxicity of Mesoporous Silica Nanoparticles and Cellular Mechanisms.

Although mesoporous silica nanoparticles (MSNs) are widely used in food products, cosmetics and nanomedicines as vector for drug delivery, data on their potential genotoxocity are limited. The aim of this study was to investigate the cytotoxic and genotoxic potentials of MSNs of different shapes, and to establish a high-throughput screening method for nanoparticles. We used functional macrophage receptor with collagenous structure (MARCO)-expressing DNA repair deficient chicken DT40 cells, which are designed to internalize nanoparticles and to be deficient in several specific DNA repair pathways. In addition, we verified the validity of this assay by analyzing and characterizing the genotoxicity of sphere- or rod-shaped MSNs. We demonstrated that both sphere- and rod-shaped MSNs were cytotoxic, and that this effect was greater in FEN1(-/-) and REV3(-/-) cells compared with wild-type cells. Effects of rod-shaped MSNs were more severe compared with sphere-shaped MSNs. Furthermore, MSNs induced oxidative damage and a larger number of mitotic chromosomal aberrations in repair-deficient cells compared with repair-proficient cells. Taken together, this assay system using the chimeric receptor-expressing DNA repair-deficient DT40 cells provides a sensitive method to screen for genotoxicity of MSNs.

Radiopharmaceutical study on Iodine-131-labelled hypericin in a canine model of hepatic RFA-induced coagulative necrosis.

PURPOSE: Hypericin (HYP) has been found avid to necrosis in small animal studies. We sought to evaluate the tissue distribution of (131)I-HYP in a large animal model and to explore the theranostic utilities of (131)I-HYP after radiofrequency ablation (RFA). MATERIALS AND METHODS: This animal experiment was approved by the institutional ethics committee. Twenty-five male dogs were enrolled and subjected to transabdominal hepatic RFA. (131)I-HYP was prepared by an electrophilic substitution method and intravenously administered at 0.5 mCi/kg. Systemic and regional distributions of (131)I-HYP were monitored dynamically by single-photon emission computed tomography/computed tomography (SPECT-CT), gamma counting, autoradiography, and fluorescent and light microscopy at different time points up to 14 days. Experimental data were quantified and statistically analysed. RESULTS: Most of the tissues and organs retained (131)I-HYP only transiently. (131)I-HYP was mainly metabolised in the liver and excreted into the bile. (131)I-HYP gradually accumulated in the RFA-induced necrosis with a peak concentration occurring within 2 days and lasting over 2 weeks as visualised by in vivo SPECT-CT and ex vivo autoradiography and fluorescent microscopy, and quantified by radioactivity and fluorescence measurements. Accumulation of (131)I-HYP was low in both the necrosis centre and normal liver tissue. CONCLUSION: (131)I-HYP showed persistent high affinity to hepatic thermo-coagulative necrosis, but only a transient uptake by normal liver in dogs. Necrosis caused by RFA could be indicated by (131)I-HYP on nuclear imaging, which suggests a supplementary measure for tumour detection and therapy.

The Impact of Combined Transarterial Chemoembolization on the Overall Survival of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib.

BACKGROUND/AIMS: Sorafenib has been proved to prolong survival of patients with advanced hepatocellular carcinoma (HCC), but with moderate efficacy. The present study aimed to evaluate the prognostic factors for overall survival (OS) in Chinese patients with advanced HCC treated with sorafenib who had been refractory to transarterial chemoembolization (TACE) and identify the impact of combined TACE on OS. METHODOLOGY: 29 cases with advanced HCC treated with sorafenib between Feb 2009 and Sep 2012 who had been treated with TACE and finally failed to respond to TACE were included in the analysis. The survival was analysed by Kaplan-Meier Method. The clinical parameters were analysed by univariate and multivariate analysis to determine the prognostic factors of OS. RESULTS: Median OS of the whole cohort was 11.867 months. Combined TACE and ALB > 39.4 g/L were the independent prognostic factors associated with improved OS while Barcelona Clinic Liver Cancer (BCLC) stage C was associated with reduced OS. The overall incidence of sorafenib-related adverse effects was 82.8% and most were mild. CONCLUSION: Albumin and combined TACE is associated with improved OS in patients with advanced HCC treated with sorafenib who had been refractory to TACE. While, BCLC stage C is an independent negative prognostic factor for the OS.

[Efficacy and safety of combination of sorafenib and transarterial chemoembolization in treating primary hepatocellular carcinoma].

OBJECTIVE: To evaluate the efficacy and safety of the combination of sorafenib and transarterial chemoembolization (TACE)in the treatment of primary hepatocellular carcinoma (HCC). METHODS: The clinical data of 10 patients with unresectable HCC treated by sorafenib combined with TACE in the Department of Radiology, the First Hospital of China Medical University were retrospectively analyzed. The efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors assessment. Survival was analyzed by Kaplan-Meier method. Safety was evaluated according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0. RESULTS: Among the 10 patients, 2 achieved complete response, 3 achieved partial response, 3 achieved stable disease, and 2 experienced progressive disease. The median overall survival of the cohort was 29.5 months. Different degree of adverse drug reactions (ADRs) occurred in 9 patients but all were at grade 3 or lower. The most common ADRs were hand-foot skin reaction (7/10) and diarrhea (6/10). CONCLUSION: The combination of sorafenib and TACE is an effective and safe treatment for HCC.

Hepatic arterial infusion chemotherapy with implantable arterial access port for advanced-stage hepatocellular carcinoma: a case report.

Background: Hepatocellular carcinoma (HCC) is a common gastrointestinal malignancy characterized by high incidence rates and a poor prognosis. Common treatment modalities include surgery, ablation, and transarterial chemoembolization (TACE). Hepatic arterial infusion chemotherapy (HAIC) has long been used in the treatment of unresectable liver cancer. In recent years, the combination of anti-angiogenesis therapy and immune checkpoint inhibitors has shown significant advances in the treatment of middle- and advanced-stage liver cancer. This report presents a case of HCC in which sustained benefits are achieved through a combination of HAIC of infusional oxaliplatin, leucovorin, and fluorouracil (FOLFOX), targeted therapy, and immunotherapy. Main body: A 64-year-old male patient was diagnosed with a parenchymal mass in the liver by a three-dimensional color ultrasound one month before admission, prompting consideration of liver cancer. Subsequently, computed tomography (CT) imaging performed at our hospital identified mass shadows in the right lobe of the liver and diffuse nodules throughout the liver, suggesting malignant lesions. Upon admission, the patient presented poor general health and baseline indicators. Following symptomatic treatment, the patient underwent a therapeutic regimen that combined transarterial infusion port FOLFOX-HAIC with Lenvatinib and Sintilimab. This combined treatment resulted in significant liver tumor necrosis and effectively managed the patient's condition. Conclusion: The combined approach of using FOLFO-HAIC transarterial infusion alongside anti-angiogenesis therapy and immune checkpoint inhibitors has shown promising results that provide substantial benefits. This combined regimen has demonstrated the potential to improve treatment compliance among certain patients. Given these encouraging outcomes, further investigation into this combination therapy regimen is warranted to understand better its efficacy and potential broader applications in clinical settings.

TACE plus tyrosine kinase inhibitors and immune checkpoint inhibitors versus TACE plus tyrosine kinase inhibitors for the treatment of patients with hepatocellular carcinoma: a meta-analysis and trial sequential analysis.

BACKGROUND: We conducted a meta-analysis and trial sequential analysis (TSA) to compare the therapeutic efficacy and adverse events (AEs) between the following treatment strategies for patients with hepatocellular carcinoma (HCC): TACE plus tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) (TACE + T + I) versus TACE plus TKIs (TACE + T). METHODS: We systematically searched PubMed, the Web of Science, the Cochrane Library, and Embase for studies comparing TACE + T + I and TACE + T for the treatment of BCLC intermediate- or advanced-stage HCC. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and AEs were included as outcomes. We used a fixed- or random-effects model based on the results of a heterogeneity evaluation and performed a meta-analysis using Review Manager 5.3 and Stata 16.0. We then carried out the TSA. RESULTS: Five studies examining a total of 425 patients were included in this study. Our meta-analysis revealed that, compared to TACE + T, TACE + T + I significantly improved the ORR (risk ratio [RR] = 1.53, 95% confidence interval [CI] = 1.27-1.85, p < 0.01) and extended both the median PFS (mean difference [MD] = 4.51 months, 95% CI = 2.16-6.87, p < 0.01) and median OS (MD = 5.75 months, 95% CI = 4.03-7.48, p < 0.01). These results were tested to be true by the TSA without requiring a larger information size. Among AEs, hypertension tended to occur more often in patients treated with TACE + T + I than in those treated with TACE + T (RR = 1.58, 95% CI = 1.05-2.40, p < 0.05). However, the TSA suggested that additional cases are necessary to confirm this difference. Regarding the other AEs, no significant differences were detected between the two groups. CONCLUSION: TACE + T + I showed better effects on the ORR, PFS, and OS than TACE + T as a treatment for BCLC stages B and C HCC, without an obvious increase in the AEs. Based on these findings, well-designed, large RCTs are suggested.

A New Automated Prognostic Prediction Method Based on Multi-Sequence Magnetic Resonance Imaging for Hepatic Resection of Colorectal Cancer Liver Metastases.

Colorectal cancer is a prevalent and life-threatening disease, where colorectal cancer liver metastasis (CRLM) exhibits the highest mortality rate. Currently, surgery stands as the most effective curative option for eligible patients. However, due to the insufficient performance of traditional methods and the lack of multi-modality MRI feature complementarity in existing deep learning methods, the prognosis of CRLM surgical resection has not been fully explored. This paper proposes a new method, multi-modal guided complementary network (MGCNet), which employs multi-sequence MRI to predict 1-year recurrence and recurrence-free survival in patients after CRLM resection. In light of the complexity and redundancy of features in the liver region, we designed the multi-modal guided local feature fusion module to utilize the tumor features to guide the dynamic fusion of prognostically relevant local features within the liver. On the other hand, to solve the loss of spatial information during multi-sequence MRI fusion, the cross-modal complementary external attention module designed an external mask branch to establish inter-layer correlation. The results show that the model has accuracy (ACC) of 0.79, the area under the curve (AUC) of 0.84, C-Index of 0.73, and hazard ratio (HR) of 4.0, which is a significant improvement over state-of-the-art methods. Additionally, MGCNet exhibits good interpretability.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.