Comparison of Response Between Combination of Transarterial Chemoembolization and Lenvatinib Therapy Versus Lenvatinib Monotherapy in Patients With Unresectable Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality, particularly in low- and middle-income countries where access to advanced interventional oncology services is often limited. Transarterial chemoembolization (TACE) is an established treatment option for patients with unresectable HCC; however, in real-world clinical practice, TACE cannot be offered to all indicated patients due to multiple constraints, including limited interventional radiology facilities, availability of trained personnel, procedure-related costs, and patient-related factors.

In many resource-limited settings, systemic therapy with tyrosine kinase inhibitors such as lenvatinib is frequently used as an alternative or as initial therapy when TACE is not feasible or must be deferred. Lenvatinib has demonstrated efficacy as monotherapy in unresectable HCC and is widely accessible compared to locoregional therapies. As a result, a significant proportion of patients who would otherwise be candidates for TACE are treated with lenvatinib alone in routine clinical practice.

This study is designed to reflect this real-world scenario and aims to compare treatment response between patients receiving a combination of transarterial chemoembolization plus lenvatinib therapy and those receiving lenvatinib monotherapy. By evaluating radiological response using modified RECIST (mRECIST) criteria, the study seeks to evaluate whether the addition of TACE to lenvatinib improves tumor response compared to systemic therapy alone in patients with unresectable hepatocellular carcinoma.

The findings of this study are expected to provide clinically relevant evidence to guide treatment decision-making in settings where access to TACE is limited, and to help identify whether lenvatinib monotherapy offers a reasonable alternative when locoregional therapy cannot be performed. This pragmatic comparison may assist clinicians in optimizing treatment strategies for unresectable HCC within the constraints of available healthcare resources.

Patients will be primarily selected from the inpatient and outpatient departments of Hepatology of Bangladesh Medical University. Based on inclusion and exclusion criteria patients will be included in the study after taking informed written consent. TACE will be done according to institutional protocol. Lenvatinib will be started after 7 days following TACE to this arm. In another arm, Lenvatinib will started to the patients with an ALBI score 2b , patients who have any contraindication to TACE like history of hepatic encephalopathy, inaccessible site lesion etc. , patients who don't want to undergo TACE after being thoroughly counseled all about the procedure. After 1.5 months biochemical tests will be done to compare the ALBI score and AFP in both groups. In TACE plus lenvatinib arm dynamic CT scan or MRI will be done to assess necessity of second time TACE. After 3 months , dynamic CT scan or MRI will done to assess the tumor response on the basis of mRECIST criteria and biochemical tests will be done to compare the ALBI score and AFP in both groups.

Data will be analyzed using appropriate descriptive and inferential statistical methods. Continuous variables will be summarized using measures of central tendency and dispersion, and categorical variables will be summarized as frequencies and percentages. Comparisons between treatment groups will be performed using appropriate statistical tests. A p value \<0.05 will be considered statistically significant.

• To compare tumor size on dynamic CT scan or MRI according to mRECIST criteria between the TACE plus Lenvatinib group and the Lenvatinib group after 3 months of treatment. [Time frame: at baseline and after 3 months of initiation of treatment]
• To compare new intrahepatic lesions and/ or extrahepatic metastatic lesions ( portal vein, intra-abdominal lymph node, lungs ) with dynamic CT scan or MRI according to mRECIST criteria between the TACE plus Lenvatinib group and the Lenvatinib group [Time frame: at baseline and after 3 month of initiation of treatment]
• To compare the Albumin-Bilirubin score (ALBI score) of patients between the TACE plus lenvatinib group and the Lenvatinib group [Time frame: at Baseline , 1.5 months and at 3 months after initiation of therapy]
• To compare the alpha-fetoprotein level of patients between the TACE plus lenvatinib group and the Lenvatinib group [Time frame: at baseline and after 1.5 months and 3 months after initiation of treatment]