New developments in ablation therapy for hepatocellular carcinoma: combination with systemic therapy and radiotherapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Numata K
PROVIDER: S-EPMC9577998 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Publications
New developments in ablation therapy for hepatocellular carcinoma: combination with systemic therapy and radiotherapy.
Numata Kauzshi K Wang Feiqian F
Hepatobiliary surgery and nutrition 20221001 5
Similar Datasets
Project description:Many potential systemic therapies are being investigated for the treatment of hepatocellular carcinoma (HCC). The incidence of this malignancy is rising sharply and the vast majority of patients present at advanced stages. Although the earlier dismal results with cytotoxic chemotherapies made way for the development of locoregional therapies that provided improved overall survival, truly personalized therapy will require the selection of phenotypically similar stages of disease and populations, an understanding of the complex molecular and genetic pathways leading to HCC, and a keen understanding of the pathobiology of cirrhosis. Only then will we understand how to offer a particular patient at a specific stage of disease the appropriate therapy to truly prolong survival.
| S-EPMC3758582 | biostudies-other
Project description:Optimal treatment of hepatocellular carcinoma (HCC) is clinically challenging. Systemic treatment for advanced HCC was limited until the approval of sorafenib. This discovery resulted in the advent of many clinical trials. An ongoing Phase III trial is examining the benefit of adjuvant sorafenib. Utilization of doxorubicin-eluting bead embolization may offer safer treatment in eligible HCC patients. The use of systemic treatment peritransarterial chemoembolization is also being investigated. Many targeted therapies are being explored as first-/second-line treatment options in advanced HCC. The potential benefit of c-MET inhibitors, particularly in those with advanced, MET high expression HCC, may result in new systemic patient-directed targeted medicinal approaches. Remaining dilemmas query the appropriate management of patients with advanced Child-Pugh B, HCC and those recurring post-transplant.
| S-EPMC6114012 | biostudies-literature
Project description: Not available
| S-EPMC10121316 | biostudies-literature
Project description:Surgical resection and liver transplant remain the only curative therapies for most patients with hepatocellular carcinoma (HCC). Systemic therapy options have typically been ineffective, but recent advances, such as the combination of immune checkpoint inhibitors and targeted therapies, have shown great promise. Neoadjuvant systemic therapy in resectable or locally advanced HCC is under active investigation with encouraging results in small, early-phase trials. Many of these completed and ongoing trials include combinations of systemic therapy (e.g. immune checkpoint inhibitors, tyrosine kinase inhibitors), transarterial therapies, and radiation. Despite early successes, larger trials with evaluation of long-term oncologic outcomes are needed to determine the role of neoadjuvant systemic therapy in patients with HCC who may be eligible for curative intent surgery or transplant.
| S-EPMC10940409 | biostudies-literature
Project description:Despite being a common therapy for hepatocellular carcinoma (HCC), insufficient thermal ablation can leave behind tumor residues that can cause recurrence. This is believed to augment M2 inflammatory macrophages that usually play a pro-tumorigenic role. To address this problem, we designed d-mannose-chelated iron oxide nanoparticles (man-IONPs) to polarize M2-like macrophages into the antitumor M1 phenotype. In vitro and in vivo experiments demonstrated that man-IONPs specifically targeted M2-like macrophages and accumulated in peri-ablation zones after macrophage infiltration was augmented under insufficient microwave ablation (MWA). The nanoparticles simultaneously induced polarization of pro-tumorigenic M2 macrophages into antitumor M1 phenotypes, enabling the transformation of the immunosuppressive microenvironment into an immunoactivating one. Post-MWA macrophage polarization exerted robust inhibitory effects on HCC progression in a well-established orthotopic liver cancer mouse model. Thus, combining thermal ablation with man-IONPs can salvage residual tumors after insufficient MWA. These results have strong potential for clinical translation.
| S-EPMC9513490 | biostudies-literature
Project description:Stereotactic body radiotherapy (SBRT) has shown promising results in the control of macroscopic vascular invasion in patients with hepatocellular carcinoma (HCC); however, its efficacy in comparison to sorafenib when combined with transarterial chemoembolization (TACE) remains to be determined. Between 2009 and 2017, 77 HCC patients with macroscopic vascular invasion receiving TACE⁻SBRT or TACE⁻sorafenib combination therapies were enrolled. The best treatment responses, overall survival (OS), and progression-free survival (PFS) of the two treatment arms were compared. Of the patients enrolled, 26 patients (33.8%) received TACE⁻SBRT treatment, and 51 (66.2%) received TACE⁻sorafenib treatment. The patients in the TACE⁻SBRT group were more frequently classified as elder in age (p = 0.012), having recurrent disease (p = 0.026), and showing lower rates of multiple hepatic lesions (p = 0.005) than patients in TACE⁻sorafenib group. After propensity score matching (PSM), 26 pairs of well-matched HCC patients were selected; patients in the TACE⁻SBRT group showed better overall response rates in trend compared to those in the TACE⁻sorafenib group. The hazard ratio (HR) of OS to PFS for the TACE⁻SBRT approach and the TACE⁻sorafenib approach was 0.36 (95% CI, 0.17⁻0.75; p = 0.007) and 0.35 (95% CI, 0.20⁻0.62; p < 0.001), respectively. For HCC patients with macrovascular invasion, TACE plus SBRT could provide improved OS and PFS compared to TACE⁻sorafenib therapy.
| S-EPMC6315557 | biostudies-literature
Project description:The pathophysiologic complexity of hepatocellular carcinoma (HCC) and underlying hepatic cirrhosis, make optimal treatment choice a clinical challenge. The radical change in the treatment algorithm of patients with advanced unresectable HCC over the past 7 years, with the introduction of anti-angiogenic agents in patients with only preserved liver function reflect this challenge. Even though data from studies on the combination of transcatheter arterial chemoembolization and anti-angiogenic agents demonstrate a survival advantage in selected patients, this combination is not straightforward. In this review, we'll examine current data of administering anti-angiogenic therapy in combination with transcatheter arterial chemoembolization and critically evaluate the progress and gaps in current knowledge.
| S-EPMC3760461 | biostudies-literature
Project description: Not available
| S-EPMC6291538 | biostudies-literature
Project description:Background & aimsTremelimumab is a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of activated T lymphocytes. Ablative therapies induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment in patients with advanced hepatocellular carcinoma (HCC). This study aimed to demonstrate whether tremelimumab could be combined safely and feasibly with ablation.MethodsThirty-two patients with HCC were enrolled: male:female: 28:4; median age: 62 (range 36-76). Patients were given tremelimumab at two dose levels (3.5 and 10mg/kg i.v.) every 4weeks for 6 doses, followed by 3-monthly infusions until off-treatment criteria were met. On day 36, patients underwent subtotal radiofrequency ablation or chemoablation. Staging was performed by contrast-enhanced CT or MRI scan every 8weeks.ResultsNo dose-limiting toxicities were encountered. The most common toxicity was pruritus. Of the 19 evaluable patients, five (26.3%; 95% CI: 9.1-51.2%) achieved a confirmed partial response. Twelve of 14 patients with quantifiable HCV experienced a marked reduction in viral load. Six-week tumor biopsies showed a clear increase in CD8+ T cells in patients showing a clinical benefit only. Six and 12-month probabilities of tumor progression free survival for this refractory HCC population were 57.1% and 33.1% respectively, with median time to tumor progression of 7.4months (95% CI 4.7 to 19.4months). Median overall survival was 12.3months (95% CI 9.3 to 15.4months).ConclusionsTremelimumab in combination with tumor ablation is a potential new treatment for patients with advanced HCC, and leads to the accumulation of intratumoral CD8+ T cells. Positive clinical activity was seen, with a possible surrogate reduction in HCV viral load.Lay summaryStudies have shown that the killing of tumors by direct methods (known as ablation) can result in the immune system being activated or switched on. The immune system could potentially also recognize and kill the cancer that is left behind. There are new drugs available known as immune checkpoint inhibitors which could enhance this effect. Here, we test one of these drugs (tremelimumab) together with ablation.Clinical trial numberClinicalTrials.gov: NCT01853618.
| S-EPMC5316490 | biostudies-literature
Project description:BackgroundThe purpose of this study is to assess the role of locoregional radiotherapy (RT) when used in combination with systemic chemotherapy, for patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC), in a non-endemic region of northern China.MethodsIn total, 611 patients with NPCs were newly diagnosed between June 2011 and June 2016 following visits to our hospital; of these, 32 patients presented with metastasis at initial diagnosis. Among these 32 patients, 29 had single-organ metastasis and 3 had multiple-organ metastasis. All patients were treated with RT for local and regional disease.ResultsThe median follow-up for all patients was 20 months (range 9-59 months), and median survival was not achieved (some patients had succumbed) at the time of the last follow-up. The 2-year overall survival (OS) rate was 75.2%, and 3-year OS rate was 50.1%. There was a significant difference between patients with single- and multiple-organ metastasis: 2-year OS was 67.5% for single- vs 0% for multiple-organ metastasis (p=0.039). Patients treated with intensity-modulated RT had a better prognosis than patients treated by conventional RT: 2-year OS was 76.6% for single- vs 44.4% for multiple-organ metastasis (no significant difference was found between the 2 groups, p=0.297). For patients with progression (all were with distant disease progression), the median progression time was 8 months (6-22 months), and the median survival after disease progression was 6 months (2-14 months).ConclusionFor patients with newly diagnosed metastatic NPCs, especially with single-organ metastasis, the addition of RT to systemic chemotherapy improved survival and disease control compared with historical cohort.
| S-EPMC5709994 | biostudies-literature