SIRT vs. Sorafenib: A visual representation of liver cancer treatment options.

Targeting Liver Cancer: Is SIRT a Better Bet Than Sorafenib?

Kai Mendoza in Health & Wellness November 2025 • 4 min read.

"A groundbreaking study, SARAH, sheds light on the effectiveness and quality-of-life impact of SIRT versus Sorafenib in treating advanced liver cancer."

Liver cancer, or hepatocellular carcinoma (HCC), is a formidable health challenge worldwide. When HCC reaches an advanced stage, treatment options become limited, and the focus shifts to managing the disease and extending life expectancy. For years, sorafenib has been a standard systemic treatment, but its impact on quality of life due to significant side effects has been a concern.

Selective Internal Radiation Therapy (SIRT) has emerged as a potential alternative. SIRT involves delivering targeted radiation directly to liver tumors using yttrium-90 (Y-90) microspheres. The SARAH trial directly compared SIRT to sorafenib, evaluating not only survival rates but also the patients' quality of life. These study results could shift how advanced HCC is managed.

This article breaks down the critical findings of the SARAH trial, interpreting the data to provide clear insights into the efficacy, tolerability, and impact on quality of life for patients undergoing SIRT versus sorafenib treatment. Understanding these nuances is crucial for patients, their families, and healthcare professionals in making informed decisions about liver cancer care.

SARAH Trial: A Detailed Look

SIRT vs. Sorafenib: A visual representation of liver cancer treatment options.

The SARAH trial was a Phase III, randomized, controlled study conducted across multiple centers. It aimed to compare SIRT using Y-90 resin microspheres to sorafenib in patients with locally advanced or recurrent HCC who were not eligible for other treatments or had experienced treatment failure after chemoembolization. The trial randomized 459 patients, with 237 receiving SIRT and 222 receiving sorafenib.

Key inclusion criteria were adult patients diagnosed with locally advanced or recurrent HCC. The primary endpoint was overall survival (OS), assessed using the Kaplan-Meier method. Secondary endpoints included progression-free survival (PFS), time to radiological progression, objective tumor response, adverse event rates, and quality of life (QoL) as measured by the QLQ-C30 questionnaire.

Study Design: Randomized, controlled, open-label, multicenter.
Participants: Patients with locally advanced or recurrent HCC.
Interventions: SIRT with Y-90 resin microspheres vs. oral sorafenib.
Primary Outcome: Overall survival (OS).

The trial revealed that overall survival was not statistically different between the two treatment groups. Median OS was 8.0 months in the SIRT group and 9.9 months in the sorafenib group (HR, 1.15; 95% CI, 0.94-1.41; p = 0.18). However, when considering the population that completed the treatment per protocol (PP), median OS was 9.9 months in both groups (HR, 0.99; 95% CI 0.79-1.24; p = 0.92).

Making Informed Decisions

The SARAH trial provides crucial insights for patients and healthcare providers in managing advanced HCC. While overall survival was similar between SIRT and sorafenib, the differences in tumor response, adverse events, and quality of life highlight the importance of individualized treatment decisions. Liver-directed SIRT offers a valuable alternative, particularly for patients seeking to maintain a higher quality of life during treatment.

About this Article -

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Everything You Need To Know

What was the design and purpose of the SARAH trial in the context of advanced liver cancer?

The SARAH trial was a Phase III randomized controlled study that compared Selective Internal Radiation Therapy (SIRT) using Y-90 resin microspheres to sorafenib in patients with locally advanced or recurrent hepatocellular carcinoma (HCC). It aimed to evaluate overall survival, progression-free survival, time to radiological progression, objective tumor response, adverse event rates, and quality of life.

What were the main findings of the SARAH trial when comparing Selective Internal Radiation Therapy (SIRT) and sorafenib for treating advanced hepatocellular carcinoma (HCC)?

The SARAH trial revealed that overall survival was not statistically different between Selective Internal Radiation Therapy (SIRT) and sorafenib treatment groups when considering the intention-to-treat population. However, there were differences in tumor response, adverse events, and quality of life, suggesting that Selective Internal Radiation Therapy (SIRT) may offer benefits in terms of tolerability and quality of life for some patients.

How does Selective Internal Radiation Therapy (SIRT) differ from sorafenib in their mechanisms of action and what are the implications for treating liver cancer?

Selective Internal Radiation Therapy (SIRT) involves delivering targeted radiation directly to liver tumors using yttrium-90 (Y-90) microspheres. This allows for a focused approach to treating the cancer while potentially minimizing damage to surrounding healthy tissue. Sorafenib is a systemic treatment that works by inhibiting certain kinases, which can help slow cancer growth but also has more widespread effects throughout the body. Understanding these different mechanisms of action is crucial for selecting the most appropriate treatment based on individual patient needs and circumstances.

Given the results of the SARAH trial, what future research directions could help improve outcomes for patients with advanced hepatocellular carcinoma (HCC) treated with Selective Internal Radiation Therapy (SIRT)?

While the SARAH trial did not demonstrate a statistically significant difference in overall survival between Selective Internal Radiation Therapy (SIRT) and sorafenib, future research could explore combination therapies involving Selective Internal Radiation Therapy (SIRT) with other systemic treatments or immunotherapies. Additionally, further investigation into predictive biomarkers could help identify which patients are most likely to benefit from Selective Internal Radiation Therapy (SIRT) versus sorafenib, leading to more personalized treatment strategies.

Beyond overall survival, what other key outcomes were evaluated in the SARAH trial when comparing Selective Internal Radiation Therapy (SIRT) and sorafenib for treating advanced hepatocellular carcinoma (HCC), and why are they important?

The primary endpoint of the SARAH trial was overall survival (OS), assessed using the Kaplan-Meier method. Secondary endpoints included progression-free survival (PFS), time to radiological progression, objective tumor response, adverse event rates, and quality of life (QoL) as measured by the QLQ-C30 questionnaire. These secondary endpoints provide a more comprehensive understanding of the treatment effects beyond just survival, considering factors that impact patients' well-being and disease progression.