Transarterial Radioembolization for Hepatocellular Carcinoma with Major Vascular Invasion: A Nationwide Propensity Score–Matched Analysis with Target Trial Emulation

Kwee, Sandi A.; Sato, Miles M.; Acoba, Jared D.; Rho, Young Soo; Srivastava, Avantika; Landsittel, Douglas

doi:10.1016/j.jvir.2021.07.001

Cited by 9 publications

(9 citation statements)

References 37 publications

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“…Apart from the main findings for efficacy, we also found some interesting discoveries for efficacy from the subgroup analysis and multivariate Cox’s regression analysis, which disclosed that the presence of vascular invasion was not associated with the ORR, DCR, or PFS, while correlated with unfavorable OS; a longer interval between camrelizumab administration and TACE was related to the unsatisfying OS; more cycles of camrelizumab were correlated with satisfactory PFS and OS; and the timing of camrelizumab administration (before and after TACE) was not associated with the PFS and OS. Possible explanations might be that: 1) Although vascular invasion in HCC patients is known to be related to pejorative survival in a wide range of studies, the occurrence of vascular invasion was not associated with the ORR, DCR, or PFS in our study, which is possible due to the relatively few HCC patients being concurrent with vascular invasion (only 42 patients) ( 33 ); 2) Previous studies have exhibited that the long-term interval between TACE and other treatment modalities might yield a worse survival compared to the short-term interval between these two treatment modalities such as radiotherapy ( 34 ). In our study, we also found that the longer interval between camrelizumab administration and TACE was related to the unsatisfactory OS, which might be due to a decrease in intratumoral density of Tregs by TACE, further leading to an immune tolerance microenvironment.…”

Section: Discussionmentioning

confidence: 57%

Efficacy and safety of camrelizumab plus transarterial chemoembolization in intermediate to advanced hepatocellular carcinoma patients: A prospective, multi-center, real-world study

You

Wang

et al. 2022

Front. Oncol.

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ObjectiveCamrelizumab is a newly developed program-death receptor one inhibitor; the real-world evidence about its application in hepatocellular carcinoma (HCC) treatment is lacking. Therefore, this prospective, multi-center, real-world study evaluated the efficacy and safety of camrelizumab plus transarterial chemoembolization (TACE) in treating intermediate-to-advanced HCC patients.MethodsThis study consecutively enrolled 101 intermediate to advanced HCC patients. All patients received camrelizumab-based treatment within 30 days of the perioperative period of the TACE operation. The primary outcome was progression-free survival (PFS), and the secondary effects were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and AEs.ResultsSpecifically, the median PFS was 9.7 (95% confidence interval: 7.4–12.0) months, with a 1-year PFS rate of 30.6%. Meanwhile, the median OS was not reached (NR) yet, with a 1-year OS rate of 61.9%. Besides, the CR, PR, SD, and PD rates were 12.8%, 44.9%, 29.5%, and 12.8%, respectively. The ORR and DCR were 57.7% and 87.2%, respectively. More cycles of camrelizumab were independently correlated with prolonged PFS (hazard ratio (HR): 0.415, P = 0.002), whereas longer intervals between camrelizumab administration and TACE were independently associated with unfavorable PFS (HR: 1.873, P = 0.032). The incidence of total AEs was 90.1%; most AEs were grade 1 (20.8%), grade 2 (28.7%) and grade 3 (37.6%), while only 3 (3.0%) patients had grade 4 AEs.ConclusionThe camrelizumab plus TACE regimen is effective and safe, indicating its potential to serve as a promising treatment choice for intermediate to advanced HCC patients.

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Section: Discussionmentioning

confidence: 57%

Efficacy and safety of camrelizumab plus transarterial chemoembolization in intermediate to advanced hepatocellular carcinoma patients: A prospective, multi-center, real-world study

You

Wang

et al. 2022

Front. Oncol.

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“…18,22 Although previously completed randomized trials have failed to demonstrate the superiority of TARE over systemic therapy, these trials notably exhibited significant imbalances in time to treatment after random assignment and a disproportionate rate of canceled treatments in the TARE arm. 23 As these trials were analyzed on the basis of intention to treat, it has been hypothesized that their outcomes might have been negatively affected by such factors. 24 Inadequate patient accrual and follow-up also led to the stoppage of one important clinical trial to compare TARE against systemic therapy in patients with advanced HCC with portal vein tumor involvement (NCT01887717).…”

Section: Rationale For Emulating the Target Trialmentioning

confidence: 99%

“…clinical trials of TARE because of their underlying liver disease or comorbidities although nationwide registries such as the National Cancer Database (NCDB) reveal that such patients are increasingly undergoing this treatment clinically. 23 Recognizing the difficulties encountered by these prospective trials, we previously conducted an observational study involving target trial emulation of NCT01887717, finding improved overall survival in TARE-treated patients who were matched by treatment propensity scores to systemic therapy-treated patients. 23 The current study further applies target trial emulation to examine how suitable the eligibility criteria were for this trial.…”

Section: Knowledge Generatedmentioning

confidence: 99%

Target Trial Emulation: A Design Tool for Cancer Clinical Trials

Kwee

Ludema

Deng

et al. 2023

JCO Clinical Cancer Informatics

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PURPOSE To apply target trial emulation to explore the potential impact of eligibility criteria on the primary outcome of a randomized controlled trial. METHODS Simulations of a real-world explanatory trial of transarterial radioembolization for advanced unresectable hepatocellular carcinoma with portal vein invasion were performed to examine the effects of cohort specification on survival outcomes and patient sample size. Simulations comprised 24 different permutations of the trial varied on three disease nonspecific eligibility parameters. Treatment and control arms for these emulated trials were drawn from the National Cancer Database and matched by treatment propensity. Target trial emulation served as the causal framework for this analysis, allowing the architecture of a true controlled experiment to address forms of bias routinely encountered in comparative effectiveness studies involving real-world observational data. RESULTS Twenty-four propensity score–matched cohorts comprising a wider clinical spectrum of patients than specified by the original target trial were successfully generated using the National Cancer Database. The arms for each of the emulated trials demonstrated exchangeability across all eligibility criteria and other clinical covariates. Significant treatment benefits were associated with only a narrow range of eligibility criteria, indicating that the original target trial was well specified. CONCLUSION The impact of patient selection on treatment outcomes can be studied using target trial emulation. This analytical framework can furthermore serve to leverage existing real-world data to inform the task of cohort specification for a randomized controlled trial, facilitating a more data-driven approach for this important step in clinical trial design.

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“…Despite these negative findings, these three trials were combined in a meta-analysis that was adequately powered to demonstrate that TARE is non-inferior to sorafenib and offers a better safety profile [15]. This analysis and others suggest there may be a subset of patients with PVTT, specifically non-cirrhotic patients, patients with hepatitis B-associated HCC, and patients with preserved functional status, who would benefit from TARE over systemic therapy [47]. This is reflected in the most recent NCCN guidelines, which state that TARE may be appropriate in the treatment of segmental or lobar PVTT [8].…”

Section: Transarterial Radioembolizationmentioning

confidence: 99%

“…The use of TARE for HCC doubled from 2010 to 2015 [47]. With increased operator familiarity, the advent of personalized dosimetry, and patient data from randomized controlled trials to date, it may be possible to demonstrate a survival advantage for TARE over systemic therapy for patients with PVTT in the near future.…”

Section: Transarterial Radioembolizationmentioning

confidence: 99%

Locoregional Therapies for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

Zane

Makary

2021

Cancers

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Hepatocellular carcinoma is the fourth leading cause of cancer worldwide, and the fastest increasing cause of cancer mortality in the United States. Its propensity for vascular invasion leads to the presence of portal vein tumor thrombus in up to half of patients. PVTT results in a classification of advanced disease, given the risk recurrence secondary to intravascular spread, and formal guidelines recommend systemic therapy in these patients. However, recent advances in locoregional therapies including TACE, TARE, and ablation have demonstrated the potential to drastically improve overall survival in patients with HCC complicated by PVTT.

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Transarterial Radioembolization for Hepatocellular Carcinoma with Major Vascular Invasion: A Nationwide Propensity Score–Matched Analysis with Target Trial Emulation

Cited by 9 publications

References 37 publications

Efficacy and safety of camrelizumab plus transarterial chemoembolization in intermediate to advanced hepatocellular carcinoma patients: A prospective, multi-center, real-world study

Efficacy and safety of camrelizumab plus transarterial chemoembolization in intermediate to advanced hepatocellular carcinoma patients: A prospective, multi-center, real-world study

Target Trial Emulation: A Design Tool for Cancer Clinical Trials

Locoregional Therapies for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

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