Infusion Chemotherapy Research Articles

Transarterial infusion chemotherapy and embolization (TAICE) as a pre-operative therapy for patients with locally advanced gastric cancer (LAGC): A prospective, single-arm, pilot study.

436 Background: Interventional therapy is a local intensive therapy for tumor control, often utilized in palliative treatment for solid organ tumors. Yet, its application in tumors of hollow viscera still lacks evidence. Our previous retrospective study revealed transarterial infusion chemotherapy and embolization (TAICE) not only effectively managed tumor-related hemorrhage but also exhibited a notable anti-tumor efficacy in gastric cancer. This prospective study aims to further explore the feasibility and safety of TAICE as a pre-operative therapy for locally advanced gastric cancer (LAGC). Methods: Patients diagnosed with locally advanced adenocarcinoma of stomach and gastrointestinal junction (GEJ) with no distant metastasis (cT3-4N+M0) were enrolled. They were given 4 cycles of pre-operative treatments: 2 cycles of TAICE-SOX (Oxaliplatin [85mg/m 2 transarterial infusion on Day 1] and S-1 [40/50/60mg po bid on Day 1-14]) and 2 cycles of SOX (Oxaliplatin [130mg/m 2 IV on Day 1] and S-1 [same as above]), alternately. Then, they received D2 radical gastrectomy, and 4 cycles of SOX post-operatively. In brief, the TAICE procedure was summarized into 4 steps: 1) Celiac arteriography, 2) Super-selection of tumor feeding artery (TFA), 3) Infusion chemotherapy and embolization of TFA, 4) Celiac re-arteriography to ensure the success of embolization. The primary endpoint was pathological complete response (pCR) rate. Other endpoints included major pathological response (MPR) rate, overall survival (OS), progression-free survival (PFS), treatment-related adverse events (TRAEs). Results: Between December 2020 and June 2023, twenty patients were enrolled and all of them received TAICE. Among them, 18 (90.0%) patients received 2 cycles of TAICE. The pCR and MPR rate were 55.0% and 70.0%, respectively. The 1-year and 3-year OS rate were 100.0% and 82.6%. The 1-year and 3-year PFS rate were 90.0% and 67.3%. There was no difference in OS between the groups of high and low tumor residual rate with the threshold of 50%. Patients achieving low tumor residual rate had significantly longer PFS (NR vs. 12.17 months, p=0.018) than those with high rate after TAICE. Moreover, we divided TFA into two subtypes: dispersive and branching, depending on the vascular pattern presented in the angiography at the first cycle TAICE. Patients with dispersive TFA had higher risk of recurrence after TAICE (NR vs. 15.17 months, p=0.0264). All patients had TRAEs (vomiting, nausea, abdominal pain and fever) of grade 1 or 2 after the first cycle of TAICE. Only one patient experienced nausea of grade 3 after the second cycle of TAICE. The most common TRAEs were vomiting and nausea. Conclusions: TAICE is a promising pre-operative therapy for patients with LAGC for it displaying the satisfactory oncological effectiveness and safety profile. Clinical trial information: NCT05396326 .

Red light therapy for patients with chemotherapy-induced alopecia.

We have taken great interest in the topic of red light therapy (RLT) for the treatment of hair loss secondary to cancer therapies. On April 7, 2024, we searched through two private Facebook groups (Fig. 1) intended for patients who used scalp cooling for prevention of chemotherapy-induced hair loss. In these groups, we found several posts inquiring about the use of RLT (Fig.2). Posts ranged from patients asking if others in the group have used RLT, if RLT is safe to use while scalp cooling, and recommendations for how long to wait to initiate RLT after chemotherapy infusions are completed. Despite the rise in popularity of RLT for the management of hair loss, to date, only two clinical trials have included patients with cancer treatment-induced hair loss, which showed higher hair counts and increased quality of life in those who used RLT [1, 2]. Furthermore, no formal recommendations from oncologists or scalp cooling companies have been made to help guide patients when considering using RLT.

Lenvatinib and tislelizumab versus atezolizumab and bevacizumab in combination with TAE-HAIC for unresectable hepatocellular carcinoma with high tumor burden: a multicenter retrospective cohort study

BackgroundSystemic and locoregional combination therapy has demonstrated promising outcomes for unresectable hepatocellular carcinoma (HCC); However, the best combination option remains unknown. This study compared the efficacy and safety of lenvatinib and tislelizumab versus atezolizumab and bevacizumab in combination with transarterial embolization (TAE) plus hepatic artery infusion chemotherapy (HAIC) for unresectable HCC with high tumor burden.MethodsThis multicenter retrospective cohort study enrolled treatment-naive patients with unresectable HCC treated with TAE-HAIC plus lenvatinib and tislelizumab (THLP group) or TAE-HAIC plus atezolizumab and bevacizumab (THTA group). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), tumor response, and adverse events (AEs). Propensity score matching (PSM) was performed to reduce bias.ResultsOf the 240 patients enrolled, 153 and 51 patients were assigned to the THLP and THTA groups, respectively after PSM (3:1). The THLP group showed a longer median OS (22 months vs. 18.2 months; P = 0.412), whereas the median PFS was longer in the THTA group (8.1 months vs. 7 months; P = 0.723), with statistically insignificant intergroup differences. No statistical differences were observed in objective response rate (RECIST 1.1: 33.9 vs. 31.4%; mRECIST: 77.1% vs. 74.5%; P = 0.635), disease control rate (RECIST 1.1: 88.9% vs. 92.2; mRECIST: 92.2% vs. 94.1%; P = 0.716), and in grade 3/4 AEs. Gastrointestinal hemorrhage rate was significantly higher in the THTA group (9.1% vs. 1.6%; P = 0.007). All AEs were controllable and no treatment-related grade 5 AEs occurred.ConclusionsTAE-HAIC plus lenvatinib and tislelizumab or TAE-HAIC plus atezolizumab and bevacizumab showed similar outcomes for unresectable HCC with high tumor burden, and manageable safety. The results need further validation.

Lenvatinib plus hepatic arterial infusion chemotherapy of oxaliplatin, fluorouracil, and leucovorin versus lenvatinib alone for advanced hepatocellular carcinoma.

580 Background: Lenvatinib stands out as a first-line therapy for individuals with advanced hepatocellular carcinoma (HCC). Concurrently, hepatic arterial infusion chemotherapy comprising oxaliplatin, fluorouracil, and leucovorin (FOLFOX-HAIC) has emerged as a potential option for those with advanced HCC. It is necessary to investigate the efficacy and safety of lenvatinib plus FOLFOX-HAIC (lenvaHAIC) for advanced HCC in real-world situations. Methods: In this retrospective analysis, 127 consecutive patients underwent lenvaHAIC, while 184 patients received lenvatinib alone as first-line treatment at six Chinese academic centers between January 2019 and June 2022. Following 1:1 propensity-score matching, we established paired cohorts (113 patients in each group) for evaluating survival. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) evaluated by RECIST 1.1 and mRECIST criteria, and safety profiles were compared between the two groups. Results: The lenvaHAIC group exhibited significantly prolonged median PFS and OS than the lenvatinib group (PFS: 12.3 vs. 6.2 months; OS: 25.6 vs. 12.3 months; P < .001 for each). In the propensity-score matched cohorts (113 pairs), both PFS and OS were notably extended in the lenvaHAIC group compared with those in the lenvatinib group (P < .001). Multivariate analysis identified lenvaHAIC treatment as an independent factor for improved PFS (hazard ratio [HR] 0.45; P < .001) and OS (HR 0.38; P < .001). Grade 3-4 adverse events, including nausea, vomiting, diarrhea, thrombocytopenia, and neutropenia, were more prevalent in the lenvaHAIC group. Conclusions: LenvaHAIC may be a promising treatment in patients with advanced hepatocellular carcinoma, demonstrating enhanced OS, PFS, and ORR and an acceptable safety profile.

Comparison of efficacy and safety of PD-1 and PD-L1 antibodies in combination with hepatic arterial infusion chemotherapy and target therapy for unresectable intrahepatic cholangiocarcinoma: A multicenter retrospective study.

553 Background: Immune checkpoint inhibitors (ICIs) in combination with hepatic arterial infusion chemotherapy (HAIC) and target therapy have shown promising antitumor activity in unresectable intrahepatic cholangiocarcinoma (iCCA). The present study aimed to compare the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors in this setting. Methods: In this multicenter retrospective study, we included patients with iCCA who received ICIs + HAIC + target therapy from June 2018 to June 2023. Propensity score matching (PSM) was performed to reduce confounding factors. Patients were divided into two groups: those treated with PD-L1 antibody + HAIC + target therapy (Group A) and those treated with PD-1 antibody + HAIC + target therapy (Group B). Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were compared between the two groups. Adverse events were assessed according to CTCAE v5.0. Results: A total of 336 patients met the inclusion criteria and were enrolled for analysis. There were no significant differences in OS, PFS, or ORR between the two groups (median OS: 17.7 vs. 25.3 months, P=0.139; median PFS: 8.3 vs. 10.0 months, P=0.534; ORR: 48.4% vs. 31.1%, P=0.051). Following PSM (ratio = 3, caliper = 0.2), 30 patients in Group A and 83 patients in Group B were included. The ORR, according to the modified RECIST criteria, was significantly higher in Group A compared to Group B (50% vs. 28.9%, P=0.037). However, no significant difference in PFS (median 10.0 vs. 9.0 months, P=0.29) or OS (median 17.6 vs. 22.8 months, P=0.293) was observed between the two groups. Adverse events (AEs) occurred in all 113 patients (100%), wherein grade 3–4 AEs were reported for 12 (10.6%) patients in group A and 45 (39.8%) in group B. There was a tendency for Group A to have a lower incidence of grade 3–4 AEs compared to Group B (40.0% vs. 54.2%, P=0.182),although this difference was not statistically significant. Conclusions: This study found that in the treatment combining ICIs with HAIC and target therapy for unresectable iCCA, Group A demonstrated a superior tumor response and a more favorable safety profile.

Comparing the performance of ChatGPT and ERNIE Bot in answering questions regarding liver cancer interventional radiology in Chinese and English contexts: A comparative study.

This study aims to critically assess the appropriateness and limitations of two prominent large language models (LLMs), enhanced representation through knowledge integration (ERNIE Bot) and chat generative pre-trained transformer (ChatGPT), in answering questions about liver cancer interventional radiology. Through a comparative analysis, the performance of these models will be evaluated based on their responses to questions about transarterial chemoembolization and hepatic arterial infusion chemotherapy in both English and Chinese contexts. A total of 38 questions were developed to cover a range of topics related to transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC), including foundational knowledge, patient education, and treatment and care. The responses generated by ERNIE Bot and ChatGPT were rigorously evaluated by 10 professionals in liver cancer interventional radiology. The final score was determined by one seasoned clinical expert. Each response was rated on a five-point Likert scale, facilitating a quantitative analysis of the accuracy and comprehensiveness of the information provided by each language model. ERNIE Bot is superior to ChatGPT in the Chinese context (ERNIE Bot: 5, 89.47%; 4, 10.53%; 3, 0%; 2, 0%; 1, 0% vs ChatGPT: 5, 57.89%; 4, 5.27%; 3, 34.21%; 2, 2.63%; 1, 0%; P = 0.001). However, ChatGPT outperformed ERNIE Bot in the English context (ERNIE Bot: 5, 73.68%; 4, 2.63%; 3, 13.16; 2, 10.53%；1, 0% vs ChatGPT: 5, 92.11%; 4, 2.63%; 3, 5.26%; 2, 0%; 1, 0%; P = 0.026). This study preliminarily demonstrated that ERNIE Bot and ChatGPT effectively address questions related to liver cancer interventional radiology. However, their performance varied by language: ChatGPT excelled in English contexts, while ERNIE Bot performed better in Chinese. We found that choosing the appropriate LLMs is beneficial for patients in obtaining more accurate treatment information. Both models require manual review to ensure accuracy and reliability in practical use.

Nomogram for prognosis prediction in metastatic pancreatic cancer patients undergoing intra-arterial infusion chemotherapy: incorporating immune-inflammation scores and coagulation indicators

BackgroundPancreatic cancer is one of the most malignant tumors with an inferior prognosis. This study aims to determine the prognostic significance of immune-inflammatory scores and coagulation indices in patients with metastatic pancreatic cancer(MPC) and develop a predictive nomogram.MethodsThis study retrospectively analyzed the clinical data of 384 patients with MPC who underwent intra-arterial infusion chemotherapy (IAIC). Patients were randomly divided into training and validation cohorts. Firstly, the optimal cutoff values for continuous variables were obtained in the training cohort. Then, survival analysis was performed to evaluate the impact of immune-inflammatory scores neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and coagulation indicators prothrombin time (PT), fibrinogen (FIB), and D-dimer on the overall survival (OS) of patients. Next, univariate analysis was utilized to identify prognostic factors, and a stepwise regression method was employed for variable selection to construct a nomogram based on the Cox proportional hazards model. Additionally, the predictive performance of the nomogram was assessed by the concordance index (C-index), the area under the ROC curve (AUC), and calibration curves. Finally, patients were stratified into risk groups based on the total score of the nomogram.ResultsThe Kaplan–Meier survival curves indicated that immune-inflammatory scores NLR, PLR, SII, and coagulation indicators PT, FIB, and D-dimer were associated with OS. Through Cox regression analysis, a nomogram was ultimately constructed incorporating NLR, PLR, PT, alkaline phosphatase (ALP), carbohydrate antigen 125 (CA125), age, and ablation. The model demonstrated good discriminative ability, with a C-index of 0.722, and the AUC values at 6- and 12-month OS predictions were 0.828 and 0.851 in the training cohort, while in the validation cohort, the corresponding AUC values were 0.754 and 0.791, respectively. The calibration curves showed a good fit, confirming the stability of the model. A cutoff value of 353.3 was identified as optimal for risk stratification, with a statistically significant difference in OS between the high- and low-risk groups.ConclusionThe nomogram based on immune-inflammatory scores, coagulation indicators, and other clinicopathological factors can effectively predict the OS of patients with MPC.

Deep learning-based CT radiomics predicts prognosis of unresectable hepatocellular carcinoma treated with TACE-HAIC combined with PD-1 inhibitors and tyrosine kinase inhibitors

ObjectiveTo develop and validate a computed tomography (CT)-based deep learning radiomics model to predict treatment response and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (uHCC) treated with transarterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC) combined with PD-1 inhibitors and tyrosine kinase inhibitors (TKIs).MethodsThis retrospective study included 172 patients with uHCC who underwent combination therapy of TACE-HAIC with TKIs and PD-1 inhibitors. Among them, 122 were from the Interventional Department of the Harbin Medical University Cancer Hospital, with 92 randomly assigned to the training cohort and 30 cases randomly assigned to the testing cohort. The remaining 50 cases were from the Interventional Department of the Affiliated Fourth Hospital of Harbin Medical University and were used for external validation. All patients underwent liver enhanced CT examination before treatment. Residual convolutional neural network (ResNet) technology was used to extract image features. A predictive model for treatment response of combination therapy and PFS was established based on image features and clinical features. Model effectiveness was evaluated using metrics such as the area under the receiver operating characteristic (ROC) curve (AUC), concordance index (C-index), accuracy, precision, and F1-score.ResultsAll patients had a median follow-up of 25.2 months (95% CI 24.4–26.0), with a median PFS of 14.0 months (95% CI 8.5–19.4) and a median overall survival (OS) of 26.2 months (95% CI 15.9–36.4) achieved. Objective response rate (ORR) and disease control rate (DCR) was 41.0% and 55.7%, respectively. In the treatment response prediction model, the AUC for the training cohort reached 0.96, with an accuracy of 89.5%, precision of 85.6%, and F1-score of 0.896; the AUC for the testing cohort was 0.87, with an accuracy of 80.4%, precision of 74.5%, and F1-score of 0.802. The AUC of the external validation cohort was 0.85, with accuracy of 79.1%, precision of 73.6%, and f1-score of 0.784. In the PFS prediction model, the predicted AUC for 12 months, 18 months, and 24 months-PFS in the training cohort were 0.874, 0.809, 0.801, respectively. The AUC of testing cohort were 0.762, 0.804, 0.792. The AUC of external validation cohort were 0.764, 0.796, 0.773. The C-index of the combination model, radiomics model, and clinical model were 0.75, 0.591, and 0.655, respectively. The calibration curve demonstrated that the combination model was significantly superior to both the radiomics and clinical models.ConclusionsThe study provides a CT-based radiomics model that can predict PFS for patients with uHCC treated with TACE-HAIC combined with PD-1 and TKIs.

A new prognostic model for predicting overall survival and progression-free survival in unresectable hepatocellular carcinoma treated with the FOLFOX-HAIC regimen based on patient clinical characteristics and blood biomarkers

BackgroundWe developed a prognostic model to evaluate the overall survival (OS) and progression-free survival (PFS) of patients with unresectable hepatocellular carcinoma (u-HCC) treated with Hepatic arterial infusion chemotherapy of infusion oxaliplatin, fluorouracil and leucovorin (FOLFOX-HAIC).MethodsThis model was based on a retrospective study of u-HCC patients treated with the FOLFOX-HAIC (oxaliplatin 130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2,400 mg/m2 for 23–46 h, once every 3–4 weeks). We divided the patients into a training cohort and a validation cohort, used LASSO regression construct prognostic models, predict patient’s OS and PFS based on nomograms of models. Patients were divided into high-risk, medium-risk, and low-risk groups according to their respective model risk scores. Kaplan-Meier survival analysis was used to assess the survival time between the three patient cohorts.ResultsA total of 333 patients were enrolled in the study and divided into a training cohort and a verification cohort at a ratio of 7:3 (233 in the training cohort and 100 in the validation cohort). The prognostic model we established contained nine prognostic variables. The results of concordance index (C-index) of the OS and PFS prognostic model was 0.75 and 0.71, respectively, higher than that of the TNM staging (0.57 and 0.55, p < 0.001), time-dependent ROC (td-ROC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) also showed that the model was better than the TNM staging for u-HCC predicting OS and PFS. Subsequently, the model was used to develop a nomogram to predict the individualized prognosis of patients with u-HCC treated with the FOLFOX-HAIC, with a higher net benefit than the TMN staging. According to the risk score, patients were divided into a low-risk group (risk score ≤ 0.458), the medium-risk group (risk score: 0.458–0.799) and the high-risk group (risk score > 0.799). There were significant differences in the OS and PFS between the three groups.ConclusionsThe model developed by our team enables risk stratification and personalized prognosis assessment for u-HCC patients undergoing FOLFOX-HAIC treatment, exhibiting superior predictive accuracy and discriminative capability compared to TNM staging.

Phase I study of CD19 CAR T-cell therapy harboring a fully human scFv in CAR-naïve adult B-ALL patients.

CD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971). Twenty-three patients received lymphodepletion chemotherapy and JCAR021 infusion. Nineteen patients developed CRS (any grade, 83%; grade 2, 61%) and 12 developed neurotoxicity (52%; grade ≥3, 35%). The overall response and CR/CRi rates were 82% and 64%, respectively. We observed MRD-negative marrow responses in 82% of those with marrow disease and extramedullary responses by PET-CT in 79% (CR, 50%) of those with measurable FDG-avid disease. The median duration of remission (DOR) was 10 months with a 4-year DOR probability of 29%. Four patients underwent allo-HCT while in CR/CRi after JCAR021. Durable remissions were observed in patients with low marrow disease burden. In contrast, the DOR was limited in those with high marrow burden, highlighting a remaining critical need to identify new strategies to prolong remissions. We observed similar outcomes in CAR-naïve adult B-ALL patients receiving CD19 CAR T-cells expressing a fully human or murine scFv-containing CAR.

Advancing treatment strategies: Insights from network meta-analysis of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma.

This study examines the pivotal findings of the network meta-analysis of Zhou et al, which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma (HCC). This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments. The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC. Additionally, this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.

HAIC plus lenvatinib and tislelizumab for advanced hepatocellular carcinoma with Vp4 portal vein invasion.

The treatment strategy for hepatocellular carcinoma (HCC) with Vp4 (main trunk) portal vein tumor thrombosis (PVTT) remains controversial due to the dismal prognosis. We aimed to investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC)plus lenvatinib and tislelizumab in these patients. This multicenter retrospective study included treatment-naive HCC patients with Vp4 PVTT from 2017 to 2022. They were treated with HAIC plus lenvatinib and tislelizumab (HLP group) or HAIC alone (HAIC group). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) were assessed. Propensity score matching (PSM) was performed to reduce bias. In this study, 155 HCC patients with Vp4 PVTT were included, with 38 in the HLP group and 117 in the HAIC group, with 35 per group matched by PSM. The HLP group showed longer median OS (23.2 vs. 6.9months; HR 0.333, p < 0.001) and PFS (6.6 vs. 2.4months; HR 0.403, p = 0.002) than the HAIC group. Higher ORR for tumor (77.1% vs. 42.9%, p = 0.003) and PVTT (51.4% vs. 22.9%, p = 0.025) was observed in the HLP group. More patients underwent hepatectomy post-conversion therapy (15.8% vs. 0.9%). Grade 3/4 AEs were higher in the HLP group (47.4% vs. 35.0%), but there was no significant difference, and no grade 5 AEs occurred in either group. HAIC combined with lenvatinib and tislelizumab may be a promising treatment in patients with HCC and Vp4 PVTT because of the improved prognosis and acceptable safety profile.

Efficiency and safety of HAIC combined with lenvatinib and tislelizumab for advanced hepatocellular carcinoma with high tumor burden: a multicenter propensity score matching analysis.

The present work focused on assessing whether hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and tislelizumab was safe and effective on advanced hepatocellular carcinoma (HCC) showing high tumor burden. In the present multicenter retrospective study, treatment-naive advanced HCC patients (BCLC stage C) showing high tumor burden (maximum diameter of intrahepatic lesion beyond 7cm) treated with lenvatinib and tislelizumab with or without HAIC were reviewed for eligibility from June 2020 to June 2023. Baseline differences between groups were mitigated by propensity score matching (PSM). Our primary endpoint was overall survival (OS); and secondary endpoints included adverse events (AEs), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR) according to RECIST 1.1 criteria, respectively. After eligibility reviewed, total 162 patients treated with lenvatinib and tislelizumab were enrolled: 63 patients with HAIC (HTP group), and the remaining 99 patients without HAIC (TP group). After PSM 1:1, 47 cases were evenly divided into each group. Of them, HTP group showed significant prolonged median OS compared with TP group (16.6 versus 21.0 months; hazard ratio [HR]: 0.26, 95% confidence interval [CI]: 0.35-0.98; p = 0.039), and median PFS of HTP group was also prolonged (8.9 versus 11.6months; HR: 0.55, 95% CI: 0.34-0.87; p = 0.010). Higher DCR and ORR could be observed in HTP relative to TP groups (ORR: 53.2% versus 17.0%, p < 0.001; DCR: 87.2% versus 61.7%, p = 0.004). The severe AEs (grade 3/4) and all grades were comparable between the groups, while all of these AEs could be controlled, and AEs of grade 5 were not reported. HAIC combined with lenvatinib and tislelizumab is the candidate treatment for advanced HCC patients because of its improved prognosis and acceptable safety.

PD(L)1 Inhibitors Plus Lenvatinib Vs Atezolizumab Plus Bevacizumab Combined With HAIC for Unresectable HCC: A Propensity Score Matching Study.

To compare the clinical outcomes of different systemic therapies, specifically PD(L)1 inhibitors plus Lenvatinib versus Atezolizumab plus Bevacizumab, when combined with hepatic arterial infusion chemotherapy (HAIC) based on the FOLFOX regimen (oxaliplatin, fluorouracil, and leucovorin) as first line treatment for unresectable hepatocellular carcinoma. This real-world retrospective study enrolled 294 patients with unresectable HCC. All patients received HAIC in combination with either PD(L)1 inhibitors plus Lenvatinib (PLEN-HAIC) or Atezolizumab plus Bevacizumab (AT-HAIC). Propensity score matching (PSM) was performed to balance patient characteristics. The overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared. After PSM, 80 and 130 patients received AT-HAIC and PLEN-HAIC, respectively. No significant differences were found in ORR between the AT-HAIC and PLEN-HAIC groups (50.0% vs 40.0% per RECIST, p = 0.202; 60.0% vs 57.7% per mRECIST, p = 0.853). Both groups showed similar disease control rates. Median PFS was 14.3 months for PLEN-HAIC versus 8.8 months for AT-HAIC (p = 0.018). Median OS was significantly better in the PLEN-HAIC group (p = 0.045, both not reached). Subgroup analysis revealed that Lenvatinib showed a better OS compared to Bevacizumab when combined with HAIC and PDL1 inhibitors (p = 0.023). PLEN-HAIC offers significant survival benefits over AT-HAIC in advanced HCC. Given its remarkable efficacy, PLEN-HAIC could be a promising first-line option for unresectable HCC.

Clinical Outcomes of Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib and Tislelizumab for Treating Hepatocellular Carcinoma and Type IV Portal Vein Tumor Thrombus.

To assess the activity and toxicity of hepatic arterial infusion chemotherapy (HAIC)+tislelizumab+lenvatinib (HAIC+tisle+len) in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) type IV (Vp4hCC) in a real-world context. Fifty-five patients, with Vp4hCC receiving HAIC+tisle+len therapy from April 2021 to December 2022, were analyzed retrospectively. Data on patient characteristics, adverse events (AEs), treatment, and survival were collected. Outcomes were disease control rate (DCR), overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and treatment-related AEs (TRAEs). As of December 20, 2023, the median follow-up was 17.5 months (95% confidence interval [CI]: 14.7-22.5). The ORR was 52.7% (3 complete response [CR], 26 partial response [PR]) as per RECIST v1.1 and 65.5% (12 CR, 24 PR) as per mRECIST. The DCR was 94.5% using both RECIST v1.1 and mRECIST. The median PFS and the median OS were 8.0 months (95% CI: 6.2-12.3) and 16.7 months (95% CI: 12.0-not reached), respectively. Additionally, PFS was independently predicted only by the best tumor response. In patients with the best tumor response (PR or CR), the median PFS was 11.7 months (95% CI: 8.02-not reached) by mRECIST and 15.4 months (95% CI: 7.39-not reached) by RECIST v1.1. Hypertension (14.5%), decreased albumin levels (10.9%) and anorexia (9.1%) were the most frequently observed grade 3-4 TRAEs. HAIC+tisle+len regimen demonstrated a promising efficacy and favorable safety for patients with HCC and Vp4, providing valuable real-world evidence to complement the trial data for Vp4hCC.

Hepatic arterial infusion chemotherapy enhances the efficacy of lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma: A meta-analysis and trial sequential analysis.

Hepatic arterial infusion chemotherapy (HAIC) was an effective treatment for advanced hepatocellular carcinoma (HCC), and its effectiveness in combination with targeted immunotherapy regimens was controversial. This meta-analysis was performed to evaluate the efficacy of adding HAIC to lenvatinib in combination with programmed death-1 (PD-1) inhibitors. Literature related to the efficacy of HAIC in combination with lenvatinib plus PD-1 inhibitors in the treatment of advanced HCC was searched through PubMed, Cochrane Library, Embase, and Web of Science databases. TSA was used to control for the risk of random error and assess whether the meta-analysis evidence was conclusive. Eight relevant papers with a total of 1244 patients. Compared with the L-P treatment group, the H-L-P treatment group significantly prolonged OS (hazard ratio [HR] 2.11 [95% confidence interval (CI) 1.82-2.44]; p<0.001) and PFS (HR 1.91 [95% CI 1.67-2.17]; p<0.001) and improved ORR (risk ratio [RR] 2.20 [95% CI 1.74-2.78]; p<0.001) and DCR (RR 1.28 [95% CI 1.15-1.42]; p<0.001) in patients with advanced HCC. TSA analysis indicated that further trials were unnecessary, preliminary positive results were promptly obtained. Prognostic factor analysis demonstrated that extrahepatic metastasis were common independent risk factor for OS and PFS. The rate of adverse events (AEs) was higher in the H-L-P treatment group than in the L-P treatment group. HAIC combined with lenvatinib plus PD-1 inhibitors markedly extended OS and PFS, particularly in patients without extrahepatic metastases. Furthermore, it markedly enhanced ORR and DCR in patients with HCC.

Efficacy and Safety of Short Intravenous Hydration for Preventing Nephrotoxicity From High-Dose Cisplatin: A Randomized, Open-Label, Phase II Trial.

The use of short hydration (SH) to prevent cisplatin-induced nephrotoxicity lacks substantive prospective evaluation. The aim of this study was to evaluate the safety and efficacy of SH, including those with head and neck cancer (HNC) who are at higher risks of mucositis that causes diminished oral intake. This phase II randomized noncomparative trial included patients with cancer who were scheduled to receive high-dose cisplatin (≥60 mg/m2) in combination with another chemotherapy or concurrently with radiotherapy. Patients were randomly assigned to receive either the SH or conventional hydration (CH) protocol. The primary end point was the proportion of patients with increased serum creatinine (SCr) after undergoing SH. Secondary end points included the severity of SCr elevation, adverse events, cisplatin modification as a result of nephrotoxicity, duration of hospital stay, quality of life (QoL), and cost. Among 100 enrolled patients, 64 and 36 patients underwent the SH and CH protocols, respectively. The median duration of chemotherapy infusion and intravenous hydration were 5.79 and 27.58 hours with SH and CH, respectively. A total of 32.8% and 33.3% of the SH and CH groups, respectively, experienced SCr elevation. Grade 2 SCr elevations were rarely observed in both groups (1.6% in SH, 2.8% in CH). Rate of cisplatin modification was similar between the two groups. Out of 82 patients with HNC, the rate of SCr elevation was comparable for both hydration protocols. The QoL scores were meaningfully higher in the SH group during the second cycle of cisplatin, although the overall direct medical costs were similar. The SH protocol is feasible and safe, with a remarkably reduced duration of administration. Thus, SH can be an alternative to CH in the prevention of cisplatin-related nephrotoxicity.

Landscape of transarterial chemoembolization represented interventional therapy for hepatocellular carcinoma.

This article discusses the article written by Tan et al. Transarterial chemoembolization (TACE) is one of the main treatment methods for advanced hepatocellular carcinoma (HCC). There are other vascular interventional therapies, including drug-eluting bead TACE, transarterial radioembolization, and hepatic arterial infusion chemotherapy. TACE combined with anti-angiogenesis therapy may improve tumor control and prolong progression free survival. The combination therapy of TACE and immunotherapy may improve the clinical efficacy of HCC. In future research, more basic and clinical studies are needed to explore the immunogenic intervention therapy.

Hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors versus lenvatinib and PD-1 inhibitors for unresectable HCC: a meta-analysis.

This study aimed to evaluate the effectiveness of combining hepatic arterial infusion chemotherapy (HAIC) with lenvatinib and programmed cell death protein 1 (PD-1) inhibitors in the treatment of advanced, unresectable hepatocellular carcinoma (HCC). A comprehensive search across multiple databases was conducted to identify relevant studies published up to May 2024. This search focused on clinical trials investigating the combination of HAIC with lenvatinib and PD-1 inhibitors for the treatment of advanced HCC. Data from these trials were analyzed using either fixed-effects or random-effects models, with results reported as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). To evaluate the robustness of the findings, trial sequential analysis was employed. A total of 8 cohort studies encompassing 1073 patients with unresectable HCC were included. Compared with other treatment regimens, the combined use of HAIC, lenvatinib, and PD-1 inhibitors significantly improved overall survival (OS) (HR=0.53 [95% CI 0.45, 0.63], P<0.00001), progression-free survival (PFS) (HR 0.56 [95% CI 0.46, 0.61], P<0.0001), the objective response rate (ORR) (RR=1.82 [95% CI 1.52, 2.18], P<0.00001), and the disease control rate (DCR) (RR=1.24 [95% CI 1.16, 1.33], P<0.00001). Trial sequential analysis (TSA) results indicated that the existing data were sufficient for making quantitative conclusions about the ORR and DCR. Combining HAIC with lenvatinib and PD-1 inhibitors enhances the effectiveness of treatment for unresectable HCC. This approach is particularly beneficial for patients who have a high tumor burden or those who are refractory to transarterial chemoembolization (TACE), providing a more effective solution for these challenging cases. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024575853, identifier CRD42024575853.

Single-Nucleus and Spatial Transcriptome Profiling Delineates the Multicellular Ecosystem in Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy.

Hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment strategy for hepatocellular carcinoma (HCC), but a detailed understanding of the multicellular ecosystem after HAIC treatment is lacking. Here, we collected tumor samples from treatment-naïve primary and post-HAIC HCC, and integrated single-nucleus RNA sequencing with spatial transcriptomics to characterize the tumor ecosystem in the post-HAIC HCC. Increased fractions and enhanced cellular communication of CD4+ T, CD20+ B, and dendritic cell subtypes were identified in post-HAIC tumors. Moreover, it is substantiated that HAIC promoted tertiary lymphoid structures (TLS) formation, and addressed the roles of TLSs as spatial niches of cellular communication. Specifically, intermediate exhausted CD8+ T cells expressing Granzyme-K and PD-1 (PD-1+CD8+ Tex-int) expanded following HAIC and exhibited a functionally antitumor phenotype. PD-1+CD8+ Tex-int accumulated in the TLS vicinity and disseminated throughout the tumor microenvironment, demonstrating potential as an effective biomarker for HAIC-based treatment in HCC. This study provides valuable resources and biological insights in the cellular underpinnings of HAIC treatment.