Downstaging strategies for unresectable hepatocellular carcinoma.

A significant number of patients with hepatocellular carcinoma (HCC) are usually diagnosed in advanced stages, that leads to inability to achieve cure. Palliative options are focusing on downstaging a locally advanced disease. It is well-supported in the literature that patients with HCC who undergo successful conversion therapy followed by curative-intent surgery may achieve a significant survival benefit compared to those who receive chemotherapy alone or those who are successfully downstaged with conversion therapy but not treated with surgery. Hepatic artery infusion chemotherapy can be a potential downstaging strategy, since recent studies have demonstrated excellent outcomes in patients with colorectal liver metastatic disease as well as primary liver malignancies.

First-line hepatic arterial infusion chemotherapy plus lenvatinib and PD-(L)1 inhibitors versus systemic chemotherapy alone or with PD-(L)1 inhibitors in unresectable intrahepatic cholangiocarcinoma.

PURPOSE: Limited treatment options exist for unresectable intrahepatic cholangiocarcinoma (ICC), with systemic chemotherapy (SC) serving as the primary approach. This study aimed to assess the effectiveness of first-line hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib and PD-(L)1 inhibitors (HLP) compared to SC combined with PD-(L)1 inhibitors (SCP) or SC alone in treating unresectable ICC. METHODS: Patient with unresectable ICC who underwent first-line treatment with HLP, SCP or SC from January 2016 to December 2022 were retrospectively analyzed. The study evaluated and compared efficacy and safety outcomes across the three treatment groups. RESULTS: The study comprised 42, 49, and 50 patients in the HLP, SCP, and SC groups, respectively. Median progression-free survival (PFS) times were 30.0, 10.2, and 6.5 months for HLP, SCP, and SC groups. While the SC group had a median overall survival (OS) time of 21.8 months, the HLP and SCP groups hadn't reached median OS. The HLP group demonstrated significantly superior PFS (p < 0.001) and OS (p = 0.014) compared to the others. Moreover, the HLP group exhibited the highest objective response rate (ORR) at 50.0% and the highest disease control rate (DCR) at 88.1%, surpassing the SC group (ORR, 6.0%; DCR, 52.0%) and SCP group (ORR, 18.4%; DCR, 73.5%) (p < 0.05). Generally, the HLP group reported fewer grades 3-4 adverse events (AEs) compared with others. CONCLUSION: In contrast to systemic chemotherapy with or without PD-(L)1 inhibitors, the triple combination therapy incorporating HAIC, lenvatinib, and PD-(L)1 inhibitors showcased favorable survival benefits and manageable adverse events for unresectable ICC.

Similar Efficacy Between Atezolizumab Plus Bevacizumab Versus Hepatic Arterial Infusion Chemotherapy For Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Retrospective Cohort Study.

BACKGROUND/AIM: The landscape of treatments for hepatocellular carcinoma (HCC), including immune checkpoint inhibitors, has expanded significantly. However, unresectable HCC patients with portal vein tumor thrombus (PVTT) continue to face a poor prognosis. This investigation examined the survival outcomes and determinants influencing survival rates in advanced HCC patients with PVTT undergoing treatment with atezolizumab plus bevacizumab (ATZ+BEV) or hepatic arterial infusion chemotherapy (HAIC). PATIENTS AND METHODS: Between December 2003 and June 2023, 48 advanced HCC with PVTT underwent treatment with either ATZ+BEV (16 patients) or HAIC (32 patients). RESULTS: The analysis revealed no significant disparities in overall survival (OS) or treatment efficacy between the ATZ+BEV and HAIC groups (ATZ+BEV: 10.0 months, HAIC: 15.3 months). Treatment with either ATZ+BEV or HAIC resulted in minimal alterations in the ALBI score and preserved hepatic function. Independent prognostic factors for OS, identified via multivariate logistic regression, included serum α-fetoprotein levels >400 ng/ml [hazard ratio (HR)=1.94; p=0.001], the existence of more than five tumors (HR=1.55; p=0.043), and the Child-Pugh score (HR=2.53; p=0.002). CONCLUSION: This investigation revealed no significant variance in OS and response rates between patients receiving ATZ+BEV and those treated with HAIC. The survival of advanced HCC patients with PVTT is intricately linked to the preservation of liver function, emphasizing the necessity for additional research to enhance treatment approaches for this patient population.

Association of serum AFP trajectories and hepatocellular carcinoma outcomes after hepatic arterial infusion chemotherapy: A longitudinal, multicenter study.

AIM: This study aims to investigate α-fetoprotein (AFP) trajectories for prediction of survival outcomes after hepatic arterial infusion chemotherapy (HAIC) treatment in large hepatocellular carcinoma (HCC). METHODS: From May 2014 to June 2020, 889 eligible patients with large HCC underwent HAIC were retrospectively enrolled from five hospitals. A latent class growth mixed (LCGM) model was applied to distinguish potential AFP level dynamic changing trajectories. Inverse-probability-of-treatment weighted (IPTW) analyses were performed to eliminate unmeasured confounders through marginal structural models. Multivariate Cox proportional hazard regression analyses were used to determine the overall survival (OS) in patients with large HCC. Performance of these serum markers for survival prediction was compared by areas under receiver operating characteristic analysis with the Delong test. RESULTS: The median follow-up time was 23.7 (interquartile range, 3.8-115.3). A total of 1009 patients with large HCC, who underwent HAIC with AFP repeatedly measured 3-10 times, were enrolled in the study. Three distinct trajectories of these serum AFP were identified using the LCGM model: high stable (37.0%; n = 373), low stable (15.7%; n = 159), and sharp-falling (47.3%; n = 477). Multivariate Cox proportional hazard regression analyses found that ALBI stage 2-3, BCLC-C stage and high-stable AFP trajectories were associated with OS. AFP trajectories yield the optimal predictive performance in all risk factors. CONCLUSIONS: The AFP trajectories based on longitudinal AFP change showed outstanding performance for predicting survival outcomes after HAIC treatment in large HCC, which provide a potential monitoring tool for improving clinical decision-making.

Efficacy and safety of lenvatinib plus durvalumab combined with hepatic arterial infusion chemotherapy for unresectable intrahepatic cholangiocarcinoma.

Background: The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor and the efficacy of traditional chemotherapy remains unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) is effective in patients with unresectable ICC. In this study, we determined the preliminary clinical efficacy and safety of lenvatinib plus durvalumab combined with FOLFOX-HAIC in patients with untreated, unresectable ICC. Materials and methods: Between July 2021 and July 2023, patients with unresectable ICC who initially received lenvatinib plus durvalumab combined with FOLFOX-HAIC at the Sun Yat-Sen University Cancer Center (SYSUCC) were reviewed for eligibility. Efficacy was evaluated by tumor response rate and survival, and safety was assessed by the frequency of key adverse events (AEs). Results: A total of 28 eligible patients were enrolled. The objective response rates (ORRs) based on mRECIST and RECIST 1.1 criteria were 65.2% and 39.1%, respectively. The median OS was 17.9 months (95% CI, 5.7-30.1) and the median PFS was 11.9 months (95% CI, 6.7-17.1). Most patients (92.9%) experienced adverse events (AEs), whereas 46.5% (13/28) experienced grade 3 or 4 AEs. Conclusion: Lenvatinib plus durvalumab combined with FOLFOX-HAIC showed promising antitumor activity and manageable AEs in patients with treatment-naive unresectable ICC. This regimen may be suitable as a novel first-line treatment option for this patient population.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma.

BACKGROUND: The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated. AIM: To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC. METHODS: We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen. RESULTS: The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs). CONCLUSION: The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.

A rat-based preclinical platform facilitating transcatheter hepatic arterial infusion in immunodeficient rats with liver xenografts of patient-derived pancreatic ductal adenocarcinoma.

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens underwent histopathological examination. A liver-implanted PDAC PDX rat model was established in all 63 rats, with first CT identifying all tumors. Four weeks post-treatment, arterial infusion groups exhibited significantly smaller tumor volumes than controls for all three tumors on second CT. Xenograft tumors histologically maintained adenocarcinoma features compared to original patient tumors. Ki67 expression was significantly lower in arterial infusion groups than in the other two for the three tumors, indicating reduced tumor growth in PDX rats. A liver-implanted PDAC PDX rat model was established as a rat-based preclinical platform. Arterial cisplatin infusion chemotherapy represents a potential therapy for PDAC liver metastasis.

Beneficial effects of maintaining liver function during hepatic arterial infusion chemotherapy combined with tyrosine kinase and programmed cell death protein-1 inhibitors on the outcomes of patients with unresectable hepatocellular carcinoma.

BACKGROUND AND AIM: Combination therapy is the primary treatment for unresectable hepatocellular carcinoma (u-HCC). The hepatic functional reserve is also critical in the treatment of HCC. In this study, u-HCC was treated with combined hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKIs), and programmed cell death protein-1 (PD-1) inhibitors to analyze the therapeutic response, progression-free survival (PFS), and safety. METHODS: One hundred sixty-two (162) patients with u-HCC were treated by combination therapy of HAIC, TKIs, and PD-1 inhibitors. PFS was assessed by Child-Pugh (CP) classification subgroups and the change in the CP score during treatment. RESULTS: The median PFS was 11.7 and 5.1 months for patients with CP class A (CPA) and CP class B (CPB), respectively (p = 0.013), with respective objective response rates of 61.1 and 27.8% (p = 0.002) and conversion rates of 16 and 0% (p = 0.078). During treatment, the CP scores in patients with CPA worsened less in those with complete and partial response than in those with stable and progressive disease. In the CP score 5, patients with an unchanged CP score had longer PFS than those with a worsened score (Not reached vs. 7.9 months, p = 0.018). CPB was an independent factor negatively affecting treatment response and PFS. Patients with CPA responded better to the combination therapy and had fewer adverse events (AEs) than those with CPB. CONCLUSIONS: Thus, triple therapy is more beneficial in patients with good liver function, and it is crucial to maintain liver function during treatment.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma with macrovascular invasion.

BACKGROUND AND AIMS: The prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion(MaVI)is poor, and the treatment is limited. This study aims to explore the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC), combined with lenvatinib and programmed cell death-1(PD-1) inhibitor in the first-line treatment of HCC with MaVI. METHODS: From July 2020 to February 2022, we retrospectively analyzed consecutive patients with HCC with MaVI who received hepatic arterial infusion FOLFOX(oxaliplatin, 5-fluorouracil, and leucovorin)combined with lenvatinib and PD-1 inhibitor. The efficacy was evaluated by RECIST 1.1. Kaplan-Meier was used to explore the overall survival and progression-free survival (PFS), and the COX regression model was used to analyze the risk factors of PFS. Adverse events (AEs) were evaluated according to CTCAE5.0. RESULTS: Thirty-two patients with HCC complicated with MaVI were recruited from the Second Affiliated Hospital of Nanchang University. Among the patients treated with HAIC combined with lenvatinib and PD-1 inhibitor, ten patients (31.25%) got partial response, eighteen patients (56.25%) maintained stable disease and four patients (12.50%) suffered progressive disease during follow-up; and objective response rate was 31.25%, and disease control rate was 87.5%. The median PFS was 179 days. Univariate and multivariate Cox analysis showed that the extrahepatic metastases and Child-Pugh score were independent prognostic factors of PFS. Twenty-two (68.75%) patients suffered adverse reactions. The main AEs were elevated transaminase (46.87%), thrombocytopenia (40.63%), hypoalbuminemia (28.13%), nausea and vomiting (21.88%), leukopenia (18.76%), abdominal pain (15.63%), hypertension (15.63%) and fever (15.63%). There were seven cases (21.88%) that had grade 3 or above AEs; Among them, two cases with elevated transaminase (6.25%), leukopenia, thrombocytopenia, nausea and vomiting, abdominal pain, and diarrhea occurred in one case respectively. Moreover, no treatment-related death was observed. CONCLUSIONS: Hepatic arterial infusion of FOLFOX combined with lenvatinib and PD-1 inhibitor as the first-line treatment for HCC complicated with MaVI is effective, and adverse reactions are tolerable.

Robotic Biliary Stricturoplasty and Roux-en-Y Hepaticojejunostomy After Hepatic Artery Infusion Pump Injury.

BACKGROUND: Hepatic artery infusion pump (HAIP) with floxuridine/dexamethasone and systemic chemotherapy is an established treatment regimen, which had been reported about converting 47% of patients with stage 4 colorectal liver metastasis from unresectable to resectable.1,2 To this effect, HAIP chemotherapy contributes to prolonged survival of many patients, which otherwise may not have other treatment options. Biliary sclerosis, however, is a known complication of the HAIP treatment, which occurs in approximately 5.5% of patients receiving this modality as an adjuvant therapy after hepatectomy and in 2% of patients receiving HAIP treatment for unresectable disease.3 While biliary sclerosis diffusely affects the perihilar and intrahepatic biliary tree, a dominant stricture maybe found in select cases, which gives an opportunity for a local surgical treatment after failure of endoscopic stenting/dilations. While the use of minimally invasive approach to biliary surgery is gradually increasing,4 there have been no descriptions of its application in this scenario. In this video, we demonstrate the use of minimally invasive robotic technique for biliary stricturoplasty and Roux-en-Y (RY) hepaticojejunostomy to treat persistent right hepatic duct stricture after HAIP chemotherapy. PATIENT: A 68-year-old woman with history of multifocal bilobar stage 4 colorectal liver metastasis presented to our office with obstructive jaundice and recurrent cholangitis that required nine endoscopic retrograde cholangiopancreatographies (ERCPs) and a placement of internal-external percutaneous transhepatic biliary drain (PTBD) by interventional radiology within the past 2 years. Her past surgical history was consistent with laparoscopic right hemicolectomy 3 years prior, followed by a left lateral sectorectomy with placement of an HAIP for adjuvant treatment. The patient had more than ten metastatic liver lesions within the right and left lobe, ranging from 2 to 3 cm in size at the time of HAIP placement. The patient had a histologically normal background liver parenchyma before the HAIP chemotherapy treatment. The patient did not have any history of alcohol use, diabetes mellitus, metabolic syndrome, nonalcoholic steatohepatitis, or other underlying intrinsic liver disorders, which are known to contribute to the development of hepatic fibrosis. Despite a radiologically disease-free status, the patient started to have episodes of acute cholangitis 1 year after the placement of HAIP that required multiple admissions to a local hospital. The HAIP was subsequently removed once the diagnosis of biliary sclerosis was made despite dose reductions and treatment with intrahepatic dexamethasone for almost 1 year. In addition to this finding, the known liver metastases have shown complete radiological resolution. Therefore further treatment with HAIP was deemed unnecessary, and pump removal was undertaken. Magnetic resonance imaging showed a dominant stricture at the junction of the right anterior and right posterior sectoral hepatic duct. The location of the dominant stricture was confirmed by an ERCP and cholangioscopy. Absence of neoplasia was confirmed with multiple cholangioscopic biopsies. Multiple endoscopic and percutaneous attempts with stent placement failed to dilate the area of stricture. Postprocedural cholangiographies showed a persistent significant narrowing, which led to multiple recurrent obstructive jaundice and severe cholangitis. While the use of surgical approach is rarely needed in the treatment of biliary sclerosis, a decision was made after extensive multidisciplinary discussions to perform a robotic stricturoplasty and RY hepaticojejunostomy with preservation of the native common bile duct. TECHNIQUE: The operation began with a laparoscopic adhesiolysis to allow for identification of HAIP tubing (which was later removed) and placement of robotic ports. A peripheral liver biopsy was obtained to evaluate the degree of hepatic parenchymal fibrosis. Porta hepatic area was carefully exposed without causing an inadvertent injury to the surrounding hollow organs. Biopsy of perihepatic soft tissues was taken as appropriate to rule out any extrahepatic disease. The common bile duct and common hepatic duct with ERCP stents within it were identified with the use of ultrasonography. Anterior wall of the common hepatic duct was then opened, exposing the two plastic stents. Cephalad extension of the choledochotomy was made toward the biliary bifurcation and the right hepatic duct. The distal common bile duct was preserved for future endoscopic access to the biliary tree. After lowering the right-sided hilar plate, dense fibrosis around the right hepatic duct was divided sharply with robotic scissors, achieving a mechanical release of the dominant stricture. An intraoperative cholangioscopy was performed to confirm adequate openings of the right hepatic duct secondary and tertiary radicles, as well as patency of the left hepatic duct. A 4-Fr Fogarty catheter was used to sweep the potential biliary debris from within the right and left hepatic lobe. Finally, a confirmatory choledochoscopy was performed to ensure patency and clearance of the right-sided intrahepatic biliary ducts and the left hepatic duct before fashioning the hepaticojejunostomy. A 40-cm antecolic roux limb was next prepared for the RY hepaticojejunostomy. A side-to-side double staple technique was utilized to create the jejunojejunostomy. The common enterotomy was closed in a running watertight fashion. Once the roux limb was transposed to the porta hepatic in a tension-free manner, a side-to-side hepaticojejunostomy was constructed in a running fashion by using absorbable barbed sutures. The index suture was placed at 9 o'clock location, and the posterior wall of the anastomosis was run toward 3 o'clock location. This stabilized the roux limb to the bile duct. The anterior wall of the anastomosis was next fashioned by using a running technique from both corners of the anastomosis toward the middle (12 o'clock), where both sutures were tied together. This completed a wide side-to-side hepaticojejunostomy anastomosis encompassing the upper common hepatic duct, biliary bifurcation, and the right hepatic duct. A closed suction drain was placed before closing.5 RESULTS: The operative time was approximately 4 hr with 60 ml of blood loss. The postoperative course was uneventful. The patient was discharged home on postoperative Day 5 after removal of the closed suction drain, confirming the absence of bile leak. The patient had developed periportal/periductal fibrosis, cholestasis, and moderate-severe parenchymal fibrosis (F3-F4) based on liver biopsy, often seen in patients treated with a long course of floxuridine HAIP chemotherapy. The patient is clinically doing well at 1 year outpatient follow-up without any evidence of recurrent cholangitis at the time of this manuscript preparation. CONCLUSIONS: Robotic biliary stricturoplasty with RY hepaticojejunostomy for treatment of biliary sclerosis after HAIP chemotherapy is safe and feasible. Appropriate experience in minimally invasive hepatobiliary surgery is necessary to achieve this goal.

Hepatic arterial infusion chemotherapy, lenvatinib plus programmed cell death protein-1 inhibitors: A promising treatment approach for high-burden hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has demonstrated remarkable local therapeutic efficacy in treating patients with large unresectable hepatocellular carcinoma (HCC). Additionally, the combination of lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has demonstrated promising antitumor effects in unresectable HCC. Therefore, we conducted a retrospective analysis to evaluate the efficacy and safety of combining HAIC with lenvatinib and PD-1 inhibitors as a first-line therapeutic approach in high-burden HCC patients. METHODS: We conducted a retrospective analysis on patients diagnosed with high-burden HCC who had major portal vein tumor thrombosis (Vp3 and Vp4) or tumor occupancy exceeding 50% of the liver. These patients received a first-line treatment consisting of HAIC with a combination of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), along with lenvatinib and PD-1 inhibitors between November 2020 and June 2023. The primary endpoints of this study included progression-free survival (PFS) and overall survival (OS), while the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: Ninety-one patients were enrolled in this study, with a median PFS of 8.8 months (95% confidence interval [CI]: 5.75-11.78) and a median OS of 14.3 months (95% CI: 11.23-17.31). According to RECIST 1.1 criteria, the ORR was 52.7%, and DCR was 95.6%. According to the mRECIST criteria, the ORR was 72.5%, and the DCR was 96.5%. Among all patients, 86 (94.5%) experienced TRAEs, and there were no instances of treatment-related deaths. CONCLUSION: The combination of HAIC-FOLFOX with lenvatinib and PD-1 inhibitors as a first-line therapy has exhibited notable therapeutic efficacy and well-tolerated adverse events among patients with high-burden HCC.

A preliminary study of optimal treatment response rates in patients undergoing hepatic arterial infusion chemotherapy combined with molecular targeting and immunotherapy.

Objectives: This study aimed to examine the effectiveness of the best response rate (BRR) as a surrogate for overall survival (OS), using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), in patients with unresectable hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) combined with molecular targeting and immunotherapy. Methods: This study enrolled 111 consecutive patients who had complete imaging data. The median age of patients was 58 years (IQR 50.5-65.0). Among the patients, those with Barcelona Clinic Liver Cancer (BCLC) stage A, BCLC stage B, and BCLC stage C comprised 6.4%, 19.1%, and 73.6%, respectively. The optimal threshold of BRR can be determined using restricted cubic splines (RCS) and the rank sum statistics of maximum selection. Survival curves of patients in the high rating and low rating groups were plotted. We then used the change-in-estimate (CIE) method to filter out confounders and the inverse probability of treatment weighting (IPTW) to balance confounders between the two groups to assess the robustness of the results. Results: The median frequency of the combination treatment regimens administered in the overall population was 3 times (IQR 2.0-3.0). The optimal BRR truncation value calculated was -0.2. Based on this value, 77 patients were categorized as the low rating group and 34 as the high rating group. The differences in the OS between the high and low rating groups were statistically significant (7 months [95%CI 6.0-14.0] vs. 30 months [95%CI 30.0-]; p< 0.001). Using the absolute 10% cut-off value, the CIE method was used to screen out the following confounding factors affecting prognosis: successful conversion surgery, baseline tumor size, BCLC stage, serum total bilirubin level, number of interventional treatments, alpha-fetoprotein level, presence of inferior vena cava tumor thrombus, and partial thrombin activation time. The survival curve was then plotted again using IPTW for confounding factors, and it was found that the low rating group continued to have better OS than the high rating group. Finally, the relationship between BRR and baseline factors was analyzed, and inferior vena cava tumor thrombus and baseline tumor size correlated significantly with BRR. Conclusions: BRR can be used as a surrogate endpoint for OS in unresectable HCC patients undergoing FOLFOX-HAIC in combination with molecular targeting and immunotherapy. Thus, by calculating the BRR, the prognosis of HCC patients after combination therapy can be predicted. Inferior vena cava tumor thrombus and baseline tumor size were closely associated with the BRR.

Hepatic artery infusion chemotherapy combined with the FOLFOX regimen for the treatment of hepatocellular carcinoma: recent advances and literature review.

INTRODUCTION: The incidence of primary liver cancer (PLC) has experienced a significant global increase, primarily attributed to the rise in hepatocellular carcinoma (HCC). Unfortunately, HCC is often diagnosed in advanced stages, leaving patients with limited treatment options. Therefore, transformation therapy is a crucial approach for long-term survival and radical resection in patients with advanced HCC. Conversion therapy has demonstrated promise in the treatment of advanced HCC. When integrated with the FOLFOX regimen, hepatic artery infusion chemotherapy (HAIC) can significantly improve tumor response efficiency, leading to high conversion and resection rates. AREAS COVERED: We reviewed landmark trials of HAIC in combination with different drugs or means for the treatment of HCC to determine the clinical value of HAIC-centric translational therapies in HCC treatment. Furthermore, we specifically emphasize the advantages associated with employing FOLFOX-HAIC in the treatment of advanced HCC. EXPERT OPINION: The combination of HAIC with the FOLFOX regimen can help prevent the low intratumoral accumulation and high adverse reaction rate caused by the FOLFOX alone, holding significant potential in the comprehensive treatment of future HCC patients.

Hepatic artery infusion chemotherapy with systemic capecitabine and camrelizumab for treating unresectable hilar cholangiocarcinoma: An initial investigation of efficacy and safety.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of sequential treatment of continuous transcatheter hepatic artery infusion chemotherapy (HAIC) with systemic capecitabine monotherapy and camrelizumab for treating unresectable hilar cholangiocarcinoma (HCCA). METHODS: This study retrospectively analyzed patients with unresectable HCCA admitted to Linyi Cancer Hospital in Shandong Province from October 2019 to December 2021. All enrolled patients were treated with HAIC (mFOLFOX7) + camrelizumab for 2-6 cycles and administered systemic therapy with capecitabine and camrelizumab. The objective response rate (ORR), disease control rate (DCR), and adverse reactions of patients were assessed. The Kaplan-Meier method was used to describe overall survival (OS), and univariate and multivariate Cox regression models were utilized to analyze the influencing factors of OS. RESULTS: This study included 34 patients, ORR was 61.76% (21/34), and DCR was 97.06% (33/34) after two HAIC cycles. The median follow-up time was 17.5 months, with an average of 18.32 ± 8.06 months, and the median OS was 20.0 months. HAIC-related adverse reactions included mainly gastrointestinal symptoms and hematological toxicity caused by chemotherapy drugs, all of which were grades 1-2. Further, adverse events for camrelizumab treatment included fatigue, skin rash, and hypothyroidism, all of which were grade <3. Cox regression analysis revealed that the periductal infiltrating type of growth pattern indicated a worse OS, whereas more HAIC cycles (5 ~ 6) were a protective factor for OS. CONCLUSION: HAIC sequentially combined with systemic capecitabine chemotherapy and a programmed death-1 inhibitor displayed favorable effects for unresectable HCCA, with controllable adverse reactions.

Advanced Interventional Treatments in Retinoblastoma Management: A Comprehensive Review.

Retinoblastoma is the most common eye malignancy in children that if left untreated can invade intraocular structures, metastasize, and rarely lead to death. Traditionally treated with systemic chemotherapy, Intra-arterial chemotherapy is gaining popularity as it allows for the direct administration of chemotherapy through the ophthalmic artery, thus reducing systemic side effects. Intra-arterial chemotherapy procedures have evolved, with refinements to reduce risks and radiation exposure. Intra-arterial chemotherapy boasts an impressive technical success rate and one year ocular survival even amongst advanced cases. This review offers a thorough examination of the technique, indications, contraindications, outcomes, and alternative options for Intra-arterial chemotherapy.

Robotic Versus Open Hepatic Arterial Infusion Pump Placement for Unresectable Intrahepatic Cholangiocarcinoma.

BACKGROUND: Hepatic arterial infusion pump (HAIP) chemotherapy is an effective treatment for patients with unresectable intrahepatic cholangiocarcinoma (iCCA). HAIP chemotherapy requires a catheter inserted in the gastroduodenal artery and a subcutaneous pump. The catheter can be placed using an open or robotic approach. OBJECTIVE: This study aimed to compare perioperative outcomes of robotic versus open HAIP placement in patients with unresectable iCCA. METHODS: We analyzed patients with unresectable iCCA included in the PUMP-II trial from January 2020 to September 2022 undergoing robotic or open HAIP placement at Amsterdam UMC, Erasmus MC, and UMC Utrecht. The primary outcome was time to functional recovery (TTFR). RESULTS: In total, 22 robotic and 28 open HAIP placements were performed. The median TTFR was 2 days after robotic placement versus 5 days after open HAIP placement (p < 0.001). One patient (4.5%) in the robotic group underwent a conversion to open because of a large bulky tumor leaning on the hilum immobilizing the liver. Postoperative complications were similar-36% (8/22) after robotic placement versus 39% (11/28) after open placement (p = 1.000). The median length of hospital stay was shorter in the robotic group-3 versus 5 days (p < 0.001). All 22 robotic patients initiated HAIP chemotherapy post-surgery, i.e. 93% (26/28) in the open group (p = 0.497). The median time to start HAIP chemotherapy was 14 versus 18 days (p = 0.153). CONCLUSION: Robotic HAIP placement in patients with unresectable iCCA is a safe and effective procedure and is associated with a significantly shorter TTFR and hospital stay than open HAIP placement.

Outcomes of Hepatic Artery-Based Therapies and Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

BACKGROUND: Treatment of unresectable colorectal liver metastases (UCRLM) includes locoregional and systemic therapy. A comprehensive analysis capturing long-term outcomes of these treatment options has not been performed. OBJECTIVE: A systematic review and meta-analysis was performed to calculate pooled outcomes of hepatic artery infusion with systemic chemotherapy (HAI-S), transarterial chemoembolization with systemic chemotherapy (TACE-S), transarterial radioembolization with systemic chemotherapy (TARE-S), doublet (FOLFOX, FOLFIRI), and triplet chemotherapy (FOLFOXIRI). METHODS: Outcomes included overall survival (OS), progression-free survival (PFS), rate of conversion to resection (CTR), and response rate (RR). RESULTS: A total of 32, 7, 9, and 14 publications were included in the HAI-S, TACE-S, and TARE-S chemotherapy arms. The 6/12/24/36-month OS estimates for HAI-S, TACE-S, TARE-S, FOLFOX, FOLFIRI, and FOLFOXIRI were 97%/80%/54%/35%, 100%/83%/40%/14%, 82%/61%/34%/21%, 96%/83%/53%/36%, and 96%/93%/72%/55%. Similarly, the 6/12/24/36-month PFS estimates were 74%/44%/19%/14%, 66%/20%/9%/3%, 57%/23%/10%/3%, 69%/30%/12%/7%, and 88%/55%/18%/11%. The corresponding CTR and RR rates were 31, 20%, unmeasurable (TARE-S), 35, 53; and 49, 45, 45, 50, 80%, respectively. The majority of chemotherapy studies included first-line therapy and liver-only metastases, whereas most HAI-S studies were pretreated. On subgroup analysis in first-line setting with liver-only metastases, the HAI-S arm had comparable outcomes to FOLFOXIRI and outperformed doublet chemotherapy regimens. Although triplet chemotherapy appeared to outperform other arms, high toxicity and inclusion of potentially resectable patients must be considered while interpreting results. CONCLUSIONS: HAI-S and multiagent chemotherapy are effective therapies for UCRLM. To make definitive conclusions, a randomized trial with comparable patient characteristics and line of therapy will be required. The upcoming EA2222 PUMP trial may help to address this question.