Prognostic Prediction and Risk Stratification of Transarterial Chemoembolization Combined with Targeted Therapy and Immunotherapy for Unresectable Hepatocellular Carcinoma: A Dual-Center Study.
Journal of hepatocellular carcinoma
Purpose:The combination of transarterial chemoembolization, molecular targeted therapy, and immunotherapy (triple therapy) has shown promising outcomes in the treatment of unresectable hepatocellular carcinoma (HCC). This study aimed to build a prognostic model to identify patients who could benefit from triple therapy. Patients and Methods:This retrospective study encompassed 242 patients with HCC who underwent triple therapy from two centers (Training cohort: 158 patients from the Center 1; External validation cohort: 84 patients from the Center 2). Independent predictors of overall survival (OS) and progression-free survival (PFS) were identified through Cox regression analyses, and prognostic models based on Cox proportional hazards models were developed. Prognosis was assessed using Kaplan - Meier curves. Results:In the training cohort, independent predictors of PFS included vascular invasion and the C-reactive protein and alpha-fetoprotein in immunotherapy (CRAFITY) score. Independent predictors of OS were the CRAFITY score, extrahepatic metastasis, and the neutrophil-to-lymphocyte ratio. Prognostic prediction models were constructed based on these variables. The prognostic model for OS demonstrated a C-index of 0.715 (95% confidence interval (CI), 0.662-0.768) in the training cohort and 0.701 (95% CI, 0.628-0.774) in the validation cohort. Patients were divided into low- and high-risk categories using the predictive model (P<0.001). These findings were corroborated by the external validation cohort. Conclusion:The developed prognostic model serves as a reliable and convenient tool to predict outcomes in patients with unresectable HCC undergoing triple therapy. It aids clinicians in making informed treatment decisions.
10.2147/JHC.S487080
Combined Stereotactic Body Radiotherapy and Immunotherapy (SBRT-IO) vs. TACE in Locally Advanced Hepatocellular Carcinoma (HCC): Propensity Score Matching Analysis.
Chiang C L,Chan A C Y,Chiu W H K,Kong F M
International journal of radiation oncology, biology, physics
PURPOSE/OBJECTIVE(S):We reported the first study of combined stereotactic body radiotherapy and immunotherapy (SBRT-IO) in unresectable hepatocellular carcinoma (uHCC) and found this combination was synergistic and safe. Based on these results, we conducted a propensity score matching analysis to compare the clinical outcome of this combination versus TACE alone. MATERIALS/METHODS:This was a retrospective study conducted in a tertiary center of Hong Kong. Eligible patients were HCC patients, who were unsuitable or refractory to curative surgical interventions. Patients with extra-hepatic vascular invasion or metastasis were excluded. 16 and 202 patients received SBRT-IO and TACE alone respectively. Propensity score matching was used to adjust for the differences in patients' demographics and tumor characteristics. The primary outcome was progression-free survival (PFS); the secondary outcomes included overall survival (OS), objective response rate (ORR) per modified response evaluation criteria in solid tumors (mRECIST version 1.1) and toxicities. RESULTS:After matching, 16 patients were in the SBRT-IO group and 48 patients in the TACE group with similar baseline characteristics. Median 2 sessions of TACE (range: 1-16) were given in TACE group; for SBRT-IO arm, median dose of 35Gy in 5 fractions (range: 27.5-37.5Gy) was prescribed and median 10 cycles of nivolumab (range: 1-20 doses) were given. The median size of tumor was 10cm (range: 3.4-19.6cm) and 20.3% had portal vein invasion. The 12-month and 24-month PFS were better in SBRT-IO group (93.3% vs. 41.7% and 77.8% vs. 2.1%, P < 0.001); the 12-month and 24-month OS were also better in combination arm (93.8% vs. 54.2% and 80.4% vs. 8.3%, P < 0.001). The ORR was 87.5% (CR: 50%, PR: 37.5%) in patients receiving SBRT-IO compared to 11.9% (CR: 2.4%, PR: 9.5%) in those receiving TACE alone (P < 0.001). There were fewer ≥ grade 3 adverse events (AE) and treatment discontinuation due to AE in SBRT-IO arm (60.4% vs. 18.8%, P = 0.004; 25% vs. 12.5%, P = 0.295). No classical RILD and treatment-related death was reported in SBRT-IO arm. In multivariate analysis, SBRT-IO was an independent good prognostic factor for OS and PFS (HR of OS = 0.14 [0.30-0.96], P = 0.036; HR of PFS = 0.1 [range 0.03-0.33], P < 0.001) CONCLUSION: SBRT-IO resulted in better survival than TACE alone in unresectable HCC. Our results provided strong rationale for studying this combination in prospective trial.
10.1016/j.ijrobp.2021.07.352
Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study.
Frontiers in immunology
Background and aims:The efficacy and safety of systemic atezolizumab and bevacizumab (atezo/bev) in treatment of patients with unresectable hepatocellular carcinoma (HCC) have been demonstrated. However, the efficacy of this treatment in patients with HCC and extrahepatic portal vein tumor thrombus (ePVTT) is not satisfactory. This study aimed to study the efficacy and safety of combining intensity-modulated radiotherapy (IMRT) with systemic atezo/bev in treatment of these patients. Methods:This multicenter prospective study included patients with ePVTT treated with IMRT combined with atezo/bev from March to September 2021 in three centers in China. The outcomes of this study included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and association between response and tumor mutational burden (TMB). Treatment-related adverse events (TRAEs) were analyzed to assess safety. Results:Of 30 patients in this study, the median follow-up was 7.4 months. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, the ORR was 76.6%, the median OS for the entire cohort was 9.8 months, the median PFS was 8.0 months, and the median TTP was not reached. This study failed to establish a significant correlation between TMB with any of the following outcomes, including ORR, OS, PFS or TTP. The most common TRAEs at all levels were neutropenia (46.7%), and the most common grade 3/4 TRAE was hypertension (16.7%). There was no treatment-related deaths. Conclusions:IMRT combined with atezo/bev showed encouraging treatment efficacy with an acceptable safety profile, making this treatment to be a promising option for HCC patients with ePVTT. Further studies are required to support the findings of this preliminary study. Clinical trial registration:http://www.chictr.org.cn, Identifier ChiCTR2200061793.
10.3389/fimmu.2023.1107542
Radiation Therapy With Combination Therapy of Immune Checkpoint Inhibitors and Antiangiogenic Therapy for Hepatocellular Carcinoma.
International journal of radiation oncology, biology, physics
PURPOSE:Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have limited efficacy in treating advanced hepatocellular carcinoma (HCC). The synergistic effect of systemic therapy and radiation therapy (RT) might resolve this problem. We aimed to investigate the effect of RT on the treatment outcomes of ICIs and antiangiogenic combination therapy in patients with advanced-stage HCC. METHODS AND MATERIALS:This retrospective observational study analyzed the medical records of 194 patients with Barcelona Clinic Liver Cancer stage C HCC who were admitted to our center from August 2018 to June 2022 and received ICIs combined with antiangiogenic therapy as the first-line treatment. Patients who were administered RT for tumor thrombus or symptomatic metastases within 8 weeks of the commencement of combination therapy were allocated to the RT group, whereas those who did not receive RT were assigned to the non-radiation therapy (NRT) group. Propensity score matching was used to mitigate selection bias. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints included objective response rate, disease control rate (DCR), local PFS, out-of-field PFS, and treatment-related adverse events. RESULTS:A total of 76 patients diagnosed with advanced-stage HCC and treated with ICIs and antiangiogenic therapy were included in the study, with 33 patients in the RT group and 43 patients in the non-RT group. After propensity score matching, 29 matched patient pairs were generated. The median follow-up was 15.5 months, and the RT sites were mainly located on the tumor thrombus (55.2%) and extrahepatic metastatic lesions (48.3%). The median PFS was 8.3 months (95% CI, 5.4-11.3) in the RT group and 4.2 months (95% CI, 3.4-5.0) in the NRT group (P < .001). The median OS was not reached in the RT group and was 9.7 months (95% CI, 4.1-15.3) in the NRT group (P = .002). The objective response rate was 75.9% (95% CI, 56.5-89.7) in the RT group and 24.1% (95% CI, 10.3-43.5) in the NRT group (P < .001). The DCR was 100% in the RT group and 75.9% (95% CI, 56.5-89.7) in the NRT group (P = .005). The median local PFS and out-of-field PFS were 13.2 months (95% CI, 6.3-20.1) and 10.8 months (95% CI, 7.0-14.7), respectively. RT was an independent prognostic factor for PFS (hazard ratio = 0.33; 95% CI, 0.17-0.64; P < .001) and OS (hazard ratio = 0.28; 95% CI, 0.11-0.68; P = .005), respectively. The rates of any grade treatment-related adverse events were similar between the 2 groups. CONCLUSIONS:In comparison to the combination of ICIs and antiangiogenic therapy, the inclusion of RT has been observed to improve the DCR and survival outcomes in patients with advanced-stage HCC. The safety profile of this triple therapy was satisfactory.
10.1016/j.ijrobp.2023.07.001
Advances in radiotherapy and immunity in hepatocellular carcinoma.
Journal of translational medicine
Primary liver cancer is one of the most common malignant tumours worldwide; it caused approximately 830,000 deaths in 2020. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for over 80% of all cases. Various methods, including surgery, chemotherapy, radiotherapy, and radiofrequency ablation, have been widely used in the treatment of HCC. With the advancement of technology, radiotherapy has become increasingly important in the comprehensive treatment of HCC. However, due to the insufficient sensitivity of tumour cells to radiation, there are still multiple limitation in clinical application of radiotherapy. In recent years, the role of immunotherapy in cancer has been increasingly revealed, and more researchers have turned their attention to the combined application of immunotherapy and radiotherapy in the hope of achieving better treatment outcomes. This article reviews the progress on radiation therapy in HCC and the current status of its combined application with immunotherapy, and discusses the prospects and value of radioimmunotherapy in HCC.
10.1186/s12967-023-04386-y
Radiotherapy for Hepatocellular Carcinoma.
Yu Yao,Feng Mary
Seminars in radiation oncology
For patients with unresectable or medically inoperable hepatocellular carcinoma, there are many local and regional therapies available, including stereotactic body radiotherapy, radiofrequency ablation, and transcatheter embolic approaches. This article will describe these treatment options and review the current comparative literature, suggesting that stereotactic body radiotherapy provides similar or better tumor control and a favorable side effect profile.
10.1016/j.semradonc.2018.06.005
Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.
International journal of radiation oncology, biology, physics
This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined hepatocellular carcinoma (HCC) and presents consensus guidelines regarding appropriate patient management. Using the Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published before October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases with the following search terms: ("stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "stereotactic ablative radiotherapy") AND ("hepatocellular carcinoma" OR "HCC"). An aggregated data meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, individual patient data analyses incorporating data from 6 institutions were conducted as their own subgroup analyses. Seventeen observational studies, comprising 1889 patients with HCC treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the aggregated data meta-analysis. The 3- and 5-year OS rates after SBRT were 57% (95% confidence interval [CI], 47%-66%) and 40% (95% CI, 29%-51%), respectively. The 3- and 5-year LC rates after SBRT were 84% (95% CI, 77%-90%) and 82% (95% CI, 74%-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the individual patient data analyses. Factors prognostic for improved OS were tumor size <3 cm, Eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. SBRT is an effective treatment modality for patients with HCC with mature follow-up. Clinical practice guidelines were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).
10.1016/j.ijrobp.2023.08.015
Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma.
Nature reviews. Gastroenterology & hepatology
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality and has an increasing incidence worldwide. Locoregional therapies, defined as imaging-guided liver tumour-directed procedures, play a leading part in the management of 50-60% of HCCs. Radiofrequency is the mainstay for local ablation at early stages and transarterial chemoembolization (TACE) remains the standard treatment for intermediate-stage HCC. Other local ablative techniques (microwave ablation, cryoablation and irreversible electroporation) or locoregional therapies (for example, radioembolization and sterotactic body radiation therapy) have been explored, but have not yet modified the standard therapies established decades ago. This understanding is currently changing, and several drugs have been approved for the management of advanced HCC. Molecular therapies dominate the adjuvant trials after curative therapies and combination strategies with TACE for intermediate stages. The rationale for these combinations is sound. Local therapies induce antigen and proinflammatory cytokine release, whereas VEGF inhibitors and tyrosine kinase inhibitors boost immunity and prime tumours for checkpoint inhibition. In this Review, we analyse data from randomized and uncontrolled studies reported with ablative and locoregional techniques and examine the expected effects of combinations with systemic treatments. We also discuss trial design and benchmarks to be used as a reference for future investigations in the dawn of a promising new era for HCC treatment.
10.1038/s41575-020-00395-0
Portal vein tumour thrombosis radiotherapy improves the treatment outcomes of immunotherapy plus bevacizumab in hepatocellular carcinoma: a multicentre real-world analysis with propensity score matching.
Frontiers in immunology
Background:This study aimed to evaluate the efficacy and safety of sequential immune checkpoint inhibitors (ICIs) plus bevacizumab therapy after radiotherapy for portal vein tumour thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC). Methods:Retrospective data were collected from 113 patients with HCC with PVTT. Patients in the PVTT radiotherapy (radiotherapy + ICIs + bevacizumab) and control groups (ICIs + bevacizumab) were enrolled according to propensity score matching (PSM) analysis (1:1). The differences in progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and potential factors affecting PFS between the groups were analysed. The adverse events (AEs) were compared between the two groups. Results:There were 47 patients in the two groups after PSM (1:1). The differences in neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), CRP, and CD4, CD8, and CD4-to-CD8 ratio before and after radiotherapy for PVTT ( < 0.05) in the PVTT radiotherapy group were significant. The patients in the PVTT radiotherapy group had a longer PFS (median, 9.6 5.4 months, < 0.001), and the PFS rates of 3, 6, 9, and 12 months were 97.87% 94.19%, 80.85% 44.68%, 53.19% 6.38%, and 23.40% 0.00%, respectively ( < 0.001). There were also significant differences in the ORR (48.94% 27.66%, = 0.0339) and DCR (97.87% 82.98%, = 0.0141) between the two groups, and no serious AEs were observed. Multivariate Cox analysis showed that AFP expression, gross classification of HCC, PVTT type, extrahepatic metastasis, PVTT radiotherapy, and reduction in PVTT were independent factors influencing PFS ( < 0.05). Conclusions:Sequential ICIs plus bevacizumab therapy after radiotherapy for PVTT in patients with HCC is safe and feasible and may further prolong the PFS of patients.
10.3389/fimmu.2023.1254158
Radiation and Immune Checkpoint Inhibitors: Combination Therapy for Treatment of Hepatocellular Carcinoma.
International journal of molecular sciences
The liver tumor immune microenvironment has been thought to possess a critical role in the development and progression of hepatocellular carcinoma (HCC). Despite the approval of immune checkpoint inhibitors (ICIs), such as programmed cell death receptor 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors, for several types of cancers, including HCC, liver metastases have shown evidence of resistance or poor response to immunotherapies. Radiation therapy (RT) has displayed evidence of immunosuppressive effects through the upregulation of immune checkpoint molecules post-treatment. However, it was revealed that the limitations of ICIs can be overcome through the use of RT, as it can reshape the liver immune microenvironment. Moreover, ICIs are able to overcome the RT-induced inhibitory signals, effectively restoring anti-tumor activity. Owing to the synergetic effect believed to arise from the combination of ICIs with RT, several clinical trials are currently ongoing to assess the efficacy and safety of this treatment for patients with HCC.
10.3390/ijms242316773
Hepatocellular carcinoma: signaling pathways, targeted therapy, and immunotherapy.
MedComm
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a high mortality rate. It is regarded as a significant public health issue because of its complicated pathophysiology, high metastasis, and recurrence rates. There are no obvious symptoms in the early stage of HCC, which often leads to delays in diagnosis. Traditional treatment methods such as surgical resection, radiotherapy, chemotherapy, and interventional therapies have limited therapeutic effects for HCC patients with recurrence or metastasis. With the development of molecular biology and immunology, molecular signaling pathways and immune checkpoint were identified as the main mechanism of HCC progression. Targeting these molecules has become a new direction for the treatment of HCC. At present, the combination of targeted drugs and immune checkpoint inhibitors is the first choice for advanced HCC patients. In this review, we mainly focus on the cutting-edge research of signaling pathways and corresponding targeted therapy and immunotherapy in HCC. It is of great significance to comprehensively understand the pathogenesis of HCC, search for potential therapeutic targets, and optimize the treatment strategies of HCC.
10.1002/mco2.474
Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study.
JHEP reports : innovation in hepatology
Background and Aims:Nivolumab was the first immune checkpoint inhibitor approved for hepatocellular carcinoma (HCC). External beam radiation therapy (EBRT) is locally effective and may enhance the effectiveness of immunotherapy. This study investigated the efficacy and safety of concurrent nivolumab and EBRT in HCC with macrovascular invasion. Methods:In this phase II multicenter trial, patients with HCC and macrovascular invasion were concurrently treated with intravenous nivolumab (3 mg/kg every 2 weeks) and EBRT, followed by maintenance nivolumab until progression or unacceptable toxicity. Primary endpoints were progression-free survival (PFS) and safety, and secondary endpoints were overall survival, time-to-progression, objective response rate, and disease control rate. Results:Between January 2020 and June 2021, 50 patients (male 84%, median age 62.5) were enrolled; 47 (94.0%) and 13 (26.0%) with portal (Vp1/2, n = 21; Vp3, n = 23; Vp4, n = 3) and hepatic vein invasion, respectively. Patients received EBRT (median dose: 50 [IQR 43-50] Gy) after the first nivolumab dose. The median number of nivolumab doses was 8.5. Median PFS was 5.6 (90% CI 3.6-9.9) months. Median overall survival and time-to-progression were 15.2 (90% CI 10.8-19.6) and 5.6 (90% CI 3.6-9.9) months, respectively. The objective response rate and disease control rate were 36.0% and 74.0%, respectively. The median duration of response was 9.9 months. Of 35 patients with follow-up data, 23 received subsequent systemic treatment, including atezolizumab-bevacizumab, sorafenib, lenvatinib, and regorafenib. Treatment-related any grade adverse events (AEs) and grade 3/4 AEs occurred in 40 (80.0%) and 6 (12.0%) patients, respectively. Common treatment-related AEs included pruritus (38.0%) and rash (16.0%), with no treatment-related deaths. Conclusion:Concurrent nivolumab therapy and EBRT showed encouraging PFS with acceptable safety in patients with advanced HCC and macrovascular invasion. Impact and implications:Immune checkpoint inhibitors, the standard care for advanced hepatocellular carcinoma (HCC), show relatively poor therapeutic effects in patients with advanced HCC and macrovascular invasion. In this investigator-initiated phase II study, we, for the first time, show that concurrent external beam radiation therapy with nivolumab, an immune checkpoint inhibitor, led to encouraging progression-free survival in patients with HCC and macrovascular invasion. The concurrent treatment was tolerable without significant safety concerns. Further randomized studies investigating the combination of immunotherapy and external beam radiation therapy are required. ClinicalTrialsgov identifier:NCT04611165.
10.1016/j.jhepr.2023.100991
Survival Outcome Analysis of Stereotactic Body Radiotherapy and Immunotherapy (SBRT-IO) versus SBRT-Alone in Unresectable Hepatocellular Carcinoma.
Liver cancer
Introduction:While combination of stereotactic body radiotherapy (SBRT) and immunotherapy are promising, their efficacy and safety have not been compared with SBRT-alone in patients with unresectable hepatocellular carcinoma (HCC). Methods:This retrospective study included 100 patients with nonmetastatic, unresectable HCC in two hospitals. Eligible patients had tumor nodules ≤3 and Child-Pugh liver function score of A5 to B7. Seventy patients received SBRT-alone, and 30 patients underwent combined SBRT and immunotherapy (SBRT-IO). Overall survival (OS), time to progression (TTP), overall response rate (ORR), and toxicity were analyzed. We adjusted for the potential confounding factors using propensity score matching. Results:The median tumor size was 7.3 cm (range, 2.6-18 cm). Twenty-five (25%) of patients had vascular invasion. Before propensity score matching, the 1-year and 3-year OS rate was 89.9% and 59.8% in the SBRT-IO group and 75.7% and 42.3% in SBRT-alone group ( = 0.039). After propensity score matching (1:2), 25 and 50 patients were selected from the SBRT-IO and SBRT-alone group. The 1-year and 3-year OS was 92.0% and 63.9% in the SBRT-IO group versus 74.0% and 43.3% in the SBRT-alone group ( = 0.034). The 1-year and 3-year TTP was better in SBRT-IO group (1-year: 68.9% vs. 58.9% and 3-year: 61.3% vs. 32.5%, = 0.057). The ORR of 88% (complete response [CR]: 56%, partial response [PR]: 22%) in SBRT-IO arm was significantly better than 50% (CR: 20%, PR: 30%) in the SBRT-alone arm ( = 0.006). Three patients (12%) developed ≥grade 3 immune-related treatment adverse events ( = 2 hepatitis, = 1 dermatitis) leading to permanent treatment discontinuation. Conclusion:Adding immunotherapy to SBRT resulted in better survival with manageable toxicities. Prospective randomized trial is warranted.
10.1159/000533425
Complete Response to Locoregional Therapy Plus Immunotherapy for Hepatocellular Carcinoma.
JAMA oncology
Importance:Previous studies showed that 42% to 50% of patients with locally advanced hepatocellular carcinoma (HCC) achieved complete remission (CR) after combined locoregional therapy (LRT) plus immunotherapy (IO). However, data on predictors of CR and long-term clinical outcomes without surgery and after discontinuation of IO are lacking. Objective:To assess the long-term clinical outcomes among patients with unresectable HCC who achieved CR after LRT-IO and were placed on a watch-and-wait protocol. Design, Setting, and Participants:This cohort study included patients with unresectable HCC who achieved CR after LRT-IO in 2 prospective studies between January 2018 and December 2022. The time of data cutoff was June 2023. Radiologic CR was defined per modified Response Evaluation Criteria in Solid Tumors. All patients underwent close surveillance after CR without surgical interventions, and IO was discontinued. Exposure:All patients had received stereotactic body radiotherapy followed by anti-programmed cell death protein 1 or anti-programmed death ligand 1 therapy. Forty-nine patients had received a dose of transarterial chemoembolization before stereotactic body radiotherapy. Main Outcomes and Measures:The primary outcome was the 3-year overall survival (OS) rate. Secondary outcomes included the 3-year time-to-progression rate, 3-year local control rate, and relapse pattern. Factors associated with CR were analyzed using multivariate analyses. Results:A total of 63 patients were enrolled (58 male [92.1%]; median age, 69 years [range, 18-90 years]); 38 patients (60.3%) had macrovascular invasion, and the median tumor diameter was 10 cm (range, 3.8-31.1 cm). The median follow-up time was 34.7 months (95% CI, 6.5-64.6 months). Twenty-nine patients (46.0%) achieved CR. The patients achieving CR had a significantly better 3-year OS rate than patients not achieving CR (75.5% [95% CI, 58.2%-98.3%] vs 28.1% [95% CI, 7.4%-29.4%]; P < .001). Among the 29 patients with CR, the 3-year time-to-progression rate was 58.7% (95% CI, 38.7%-79.1%) and the 3-year local control rate was 90.5% (95% CI, 78.2%-100%). Ten patients (34.5%) developed recurrence; among them, 6 (60.0%) with solitary intrahepatic disease relapse underwent curative surgical treatment. The absence of tumor vascular invasion (odds ratio, 0.30; 95% CI, 0.10-0.89) and the sum of the largest lesion diameters of 8 cm or less (odds ratio, 0.26; 95% CI, 0.07-0.98) were associated with CR. Conclusions and Relevance:This cohort study of LRT-IO with long-term follow-up data found a durable response in patients with locally advanced unresectable HCC. Long-term survival was attainable in patients with radiologic CR. Further randomized clinical trials are warranted.
10.1001/jamaoncol.2024.4085
The Immunology of Hepatocellular Carcinoma.
Lawal Gbemisola,Xiao Yao,Rahnemai-Azar Amir A,Tsilimigras Diamantis I,Kuang Ming,Bakopoulos Anargyros,Pawlik Timothy M
Vaccines
Liver cancer is the third leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Liver resection or transplantation offer the only potentially curative options for HCC; however, many patients are not candidates for surgical resection, either due to presentation at advanced stages or poor liver function and portal hypertension. Liver transplantation is also limited to patients with certain characteristics, such as those that meet the Milan criteria (one tumor ≤ 5 cm, or up to three tumors no larger than 3 cm, along with the absence of gross vascular invasion or extrahepatic spread). Locoregional therapies, such as ablation (radiofrequency, ethanol, cryoablation, microwave), trans-arterial therapies like chemoembolization (TACE) or radioembolization (TARE), and external beam radiation therapy, have been used mainly as palliative measures with poor prognosis. Therefore, emerging novel systemic treatments, such as immunotherapy, have increasingly become popular. HCC is immunogenic, containing infiltrating tumor-specific T-cell lymphocytes and other immune cells. Immunotherapy may provide a more effective and discriminatory targeting of tumor cells through induction of a tumor-specific immune response in cancer cells and can improve post-surgical recurrence-free survival in HCC. We herein review evidence supporting different immunomodulating cell-based technology relative to cancer therapy in vaccines and targeted therapies, such as immune checkpoint inhibitors, in the management of hepatocellular carcinoma among patients with advanced disease.
10.3390/vaccines9101184