scholarly journals Long-term outcome of percutaneous radiofrequency ablation for periportal hepatocellular carcinoma: tumor recurrence or progression, survival and clinical significance

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Shoujin Cao ◽  
Tianshi Lyu ◽  
Zeyang Fan ◽  
Haitao Guan ◽  
Li Song ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Tumor Recurrence ◽  
Percutaneous Radiofrequency Ablation ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Therapeutic Outcomes

Abstract Background/aim Recent studies have suggested that periportal location of percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is considered as one of the independent risk factors for local tumor progression (LTP). However, the long-term therapeutic outcomes of percutaneous RFA as the first-line therapy for single periportal HCCand corresponding impacts on tumor recurrence or progression are still unclear. Materials and methods From February 2011 to October 2020, a total of 233 patients with single nodular HCC ≤ 5 cm who underwent RFA ± transarterial chemoembolization (TACE) as first-line therapy was enrolled and analyzed, including 56 patients in the periportal group and 177 patients in the nonperiportal group. The long-term therapeutic outcomes between the two groups were compared, risk factors of tumor recurrence or progression were evaluated. Results The LTP rates at 1, 3, and 5 years were significantly higher in the periportal group than those in the nonperiportal group (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year overall survival (OS) rates in the periportal group were significantly worse than those in the nonperiportal group (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P<0.0001). In the subgroup of single HCC ≤ 3 cm, patients with periportal HCC showed significantly worse LTP P = 0.0006) and OS (P<0.0001) after RFA than patients with single nonperiportal HCC; The univariate and multivariate analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. Furthermore, patients with single periportal HCC had significantly higher risk for IDR(P = 0.0012), PVTT(P<0.0001) and extrahepatic recurrence(P = 0.0010) after RFA than those patients with single nonperiportal HCC. . Conclusion The long-term therapeutic outcomes of RFA as the first-line therapy for single periportal HCC were worse than those for single nonperiportal HCC, an increased higher risk of tumor recurrence or progression after RFA was significantly associated with periportal HCC.

scholarly journals Outcomes of radiofrequency ablation as first-line therapy for hepatocellular carcinoma less than 3 cm in potentially transplantable patients

2019 ◽  
Vol 70 (5) ◽  
pp. 866-873 ◽  
Author(s):  
Adam Doyle ◽  
Andre Gorgen ◽  
Hala Muaddi ◽  
Aloysious D. Aravinthan ◽  
Assaf Issachar ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Weiwei Tang ◽  
Ziyi Chen ◽  
Wenling Zhang ◽  
Ye Cheng ◽  
Betty Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Theoretical Basis ◽  
Transport Processes ◽  
Tumor Cell Proliferation ◽  
First Line ◽  
Multikinase Inhibitor ◽  
First Line Therapy ◽  
Line Therapy ◽  
Regulated Cell Death ◽  
Therapeutic Outcomes

Abstract Sorafenib is a multikinase inhibitor capable of facilitating apoptosis, mitigating angiogenesis and suppressing tumor cell proliferation. In late-stage hepatocellular carcinoma (HCC), sorafenib is currently an effective first-line therapy. Unfortunately, the development of drug resistance to sorafenib is becoming increasingly common. This study aims to identify factors contributing to resistance and ways to mitigate resistance. Recent studies have shown that epigenetics, transport processes, regulated cell death, and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression. This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.

scholarly journals First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 931
Author(s):  
Chi-Leung Chiang ◽  
Sik-Kwan Chan ◽  
Shing-Fung Lee ◽  
Horace Cheuk-Wai Choi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cost Effectiveness ◽  
Lifetime Cost ◽  
Cost Effective ◽  
First Line ◽  
First Line Therapy ◽  
Payer Perspective ◽  
Life Years ◽  
Using Data

Background: The IMbrave 150 trial revealed that atezolizumab plus bevacizumab (atezo–bev) improves survival in patients with unresectable hepatocellular carcinoma (HCC) (1 year survival rate: 67.2% vs. 54.6%). We assessed the cost-effectiveness of atezo–bev vs. sorafenib as first-line therapy in patients with unresectable HCC from the US payer perspective. Methods: Using data from the IMbrave 150, we developed a Markov model to compare the lifetime cost and efficacy of atezo–bev as first-line systemic therapy in HCC with those of sorafenib. The main outcomes were life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results: Atezo–bev demonstrated a gain of 0.44 QALYs, with an additional cost of USD 79,074. The ICER of atezo–bev was USD 179,729 per QALY when compared with sorafenib. The model was most sensitive to the overall survival hazard ratio and body weight. If we assumed that all patients at the end of the IMbrave 150 trial were cured of HCC, atezo–bev was cost-effective (ICER USD 53,854 per QALY). However, if all patients followed the Surveillance, Epidemiology, and End Results data, the ICER of atezo–bev was USD 385,857 per QALY. Reducing the price of atezo–bev by 20% and 29% would satisfy the USD 150,000/QALY and 100,000/QALY willingness-to-pay threshold. Moreover, capping the duration of therapy to ≤12 months or reducing the dosage of bev to ≤10 mg/kg would render atezo–bev cost-effective. Conclusions: The long-term effectiveness of atezo–bev is a critical but uncertain determinant of its cost-effectiveness. Price reduction would favorably influence cost-effectiveness, even if long-term clinical outcomes were modest. Further studies to optimize the duration and dosage of therapy are warranted.

scholarly journals Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Xiang Zhang ◽  
Jiejing Qian ◽  
Huafeng Wang ◽  
Yungui Wang ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Underlying Mechanism ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Dominant Mutation ◽  
First Line Therapy ◽  
Line Therapy ◽  
Acute Myeloid

AbstractVenetoclax (VEN) plus azacitidine has become the first-line therapy for elderly patients with acute myeloid leukemia (AML), and has a complete remission (CR) plus CR with incomplete recovery of hemogram rate of ≥70%. However, the 3-year survival rate of these patients is < 40% due to relapse caused by acquired VEN resistance, and this remains the greatest obstacle for the maintenance of long-term remission in VEN-sensitive patients. The underlying mechanism of acquired VEN resistance in AML remains largely unknown. Therefore, in the current study, nine AML patients with acquired VEN resistance were retrospectively analyzed. Our results showed that the known VEN resistance-associated BCL2 mutation was not present in our cohort, indicating that, in contrast to chronic lymphocytic leukemia, this BCL2 mutation is dispensable for acquired VEN resistance in AML. Instead, we found that reconstructed existing mutations, especially dominant mutation conversion (e.g., expanded FLT3-ITD), rather than newly emerged mutations (e.g., TP53 mutation), mainly contributed to VEN resistance in AML. According to our results, the combination of precise mutational monitoring and advanced interventions with targeted therapy or chemotherapy are potential strategies to prevent and even overcome acquired VEN resistance in AML.

Modeling sequential systemic therapy for unresectable hepatocellular carcinoma in the era of immunotherapy: What comes next?

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 324-324
Author(s):  
Ciro Celsa ◽  
Giuseppe Cabibbo ◽  
Marco Enea ◽  
Salvatore Battaglia ◽  
Giacomo Emanuele Maria Rizzo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Data ◽  
Survival Curve ◽  
Second Line ◽  
First Line ◽  
Lifetime Horizon ◽  
First Line Therapy ◽  
Line Therapy ◽  
Unresectable Hepatocellular Carcinoma ◽  
Sequential Strategy

324 Background: Atezolizumab plus Bevacizumab represents the new best performing first-line approach for unresectable hepatocellular carcinoma (u-HCC). However, the best sequential strategy after every first-line failure (for progression or intolerance) remains elusive, and options for retreating patients failing Atezolizumab plus Bevacizumab with multi-kinase inhibitors (MKI) or immune checkpoint inhibitor (ICI) are yet undefined. Methods: We developed a Markov model to analyze simulated-Overall Survival (s-OS) of second-line ICIs or MKIs after first-line Atezolizumab plus Bevacizumab over a lifetime horizon. For first-line therapy, PFS of Atezolizumab plus Bevacizumab was extracted from Imbrave 150 trial and it was used as endpoint since it is not influenced by post-progression survival. For second-line retreatment, pooled OS of MKIs (Regorafenib and Cabozantinib), or ICIs (Nivolumab and Pembrolizumab) were adopted. Survival estimates for sequential settings considered the proportion of patients who did not receive second-line therapy due to death during first-line therapy. Individual patient survival data were extracted from PFS and OS Kaplan-Meier curves of RESORCE trial for Regorafenib, CELESTIAL trial for Cabozantinib, CheckMate-040 for Nivolumab and Keynote-240 for Pembrolizumab. Each reconstructed survival curve was inspected for accuracy and was compared with originally published curves. Results: First-line Atezolizumab plus Bevacizumab followed by second-line ICIs turned on from the model as the best sequential strategy (median s-OS 24 months; 95% Confidence Interval (CI) 23-26 months) and extends survival when compared Atezolizumab plus Bevacizumab followed by MKIs (median s-OS 20 months; 95% CI 19-21 months). Conclusions: To our knowledge and given the absence of adequately designed sequential RCTs, this is the first model to date which suggests, with a proper methodological approach, an accurate estimate of outcome of patients with u-HCC treated by sequential systemic therapies. In patients with u-HCC failing first-line treatment, modelling estimates of s-OS for each retreatment strategies may assist in choosing the most promising sequences in order to plan appropriate RCTs.

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