Laura Dawson, MD, FRCPC, clinician scientist, Princess Margaret Cancer Centre in Toronto, Ontario, Canada, discusses the investigation of palliative radiotherapy for patients with symptomatic hepatocellular carcinoma (HCC) or liver metastases.

Patients who may be nearing the end of their life suffer from burdens of cancer in the liver, whether either in the form of metastases from any solid tumors or from primary HCC, Dawson begins. Medications and palliative care can be utilized to assist patients throughout the process, but some patients still do not experience relief of symptoms, Dawson says. Additionally, underlying liver disease or impaired liver function can also make it more difficult for patients to tolerate best supportive care, Dawson adds.

A randomized trial (NCT02511522) evaluated the use of palliative radiotherapy vs best supportive care in patients with HCC or live metastases. Findings presented at the 2023 Gastrointestinal Cancers Symposium showed that single-fraction radiotherapy at 8 Gy improved hepatic pain, and investigators noted a trend toward an improvement in overall survival (OS). In an assessment using the Brief Pain Inventory, 67% of patients in the radiotherapy arm reported an improvement in worst pain, compared with 22% in the best supportive care arm (

 = .004). Additionally, improvements were reported in a higher proportion of patients in the radiotherapy arm vs best supportive care for pain at its least (63% vs 28%; 

 = .03) and percentage relief in pain by treatment (59% vs 25%; 

The 3-month OS rate was 51% in the radiotherapy arm vs 33% in the best supportive care arm (

Palliative radiation had previously been studied in this setting, and although is routinely used to treat bone, lung, or brain metastases, it has not yet been routinely used to treat liver metastases or HCC, Dawson says. Previously, investigators launched a single-arm study utilizing simple radiation to treat these patients, and data showed that that patient-reported pain was improved in nearly half of patients, Dawson notes. However, this study did not change practice, adding to the rationale to complete a randomized trial with this approach, Dawson notes.

The Canadian Clinical Trials group launched the randomized study, with investigators hypothesizing that most patients who received radiation would have a clinically important improvement in pain, Dawson says. Patients were randomly assigned in a 1:1 fashion to receive radiotherapy or best supportive care.

Videos

Laura Dawson, MD, FRCPC, discusses the investigation of palliative radiotherapy for patients with symptomatic hepatocellular carcinoma or liver metastases.

Dr Dawson on Palliative Radiotherapy in Symptomatic HCC or Liver Metastases

Laura Dawson, MD, FRCPC, clinician scientist, Princess Margaret Cancer Centre in Toronto, Ontario, Canada, discusses results from the phase 3 NRG/RTOG 1112 trial (NCT01730937) of stereotactic body radiation therapy (SBRT) plus sorafenib (Nexavar) compared with sorafenib alone in patients with locally advanced hepatocellular carcinoma (HCC).

Findings presented at the 2023 Gastrointestinal Cancers Symposium

 showed that patients treated with SBRT/sorafenib experienced a median overall survival 15.8 months (90% CI, 11.4-19.2) vs 12.3 months (90% CI, 10.6-14.3) with sorafenib alone (HR, 0.77; 90% CI, 0.59-1.01; 1-sided 

Patients in the SBRT/sorafenib arm also achieved an improvement in progression-free survival (PFS). Those treated with SBRT plus sorafenib had a median PFS of 9.2 months (95% CI, 7.5-11.9), compared with from 5.5 months (95% CI, 3.4-6.3) for those given sorafenib alone (HR, 0.55; 95% CI, 0.40-0.75; 

 = .0001). Moreover, patients in the SBRT/sorafenib arm experienced a median time to progression of 18.5 months, vs 9.5 months for patients in the sorafenib monotherapy arm.

The study enrolled patients with aggressive locally advanced HCC with a sum of tumor mass of up to 20 cm. Dawson notes that patients were also permitted to have any degree of vascular invasion and up to 3 cm of extrahepatic spread. Excluding vascular invasion, patients had a median baseline tumor size of 7.8 cm (range, 1-19.1).

Additionally, 74% of patients had vascular invasion, which was higher than any randomized phase 3 study to date, according to Dawson. The majority of patients with vascular invasion had invasion into the main right or left portal vein, which is associated with worse prognosis, making this a difficult-to-treat subgroup of patients.

Patients were randomly assigned to receive 400 mg of oral sorafenib twice daily, or between 27.5 and 50 Gy of SBRT in 5 fractions, followed by 200 mg of oral sorafenib twice daily for 4 weeks.

Laura Dawson, MD, FRCPC, discusses results from the phase 3 NRG/RTOG 1112 trial of stereotactic body radiation therapy plus sorafenib compared with sorafenib alone in patients with locally advanced hepatocellular carcinoma.

Dr. Dawson on the Addition of SBRT to Sorafenib in Locally Advanced HCC

Laura Dawson, MD, Princess Margaret Hospital, University of Toronto, discusses increasing causes of hepatocellular carcinoma (HCC) and unmet needs related to the disease.

A growing cause of liver cancer is nonalcoholic steatohepatitis (NASH), which can lead to cirrhosis. Dawson says there is a time lapse from when patients with metabolic syndrome can possibly develop NASH, which may lead to cirrhosis. This cause is rapidly increasing, and Dawson says HCC mortality rates are likely to increase in the next few decades.

These predicted increases should lead researchers to make HCC a priority cancer for treatment, screening, and researching treatment outcomes, Dawson says. As more patients will be affected by this disease, she adds that more researchers should work on clinical trials to help move the treatment paradigm forward.

Laura Dawson, MD, Princess Margaret Hospital, University of Toronto, discusses increasing cause of hepatocellular carcinoma (HCC) and unmet needs related to the disease. 

Dr. Dawson on Increasing Causes and Unmet Needs in HCC

Laura Dawson, MD, Princess Margaret Hospital, University of Toronto, talks about the challenges in treating hepatocellular carcinoma (HCC).

Large portions of patients with HCC present with locally advanced disease and don’t get any chance for treatment because disease is too far progressed. This is mainly due to a lack of screening for the disease, says Dawson.

Research focus should be on detection methods for early stage HCC. Those at high risk, including those with hepatitis B or C or cirrhosis, should be screened regularly for the disease.

Laura Dawson, MD

Articles

Dr Dawson on Palliative Radiotherapy in Symptomatic HCC or Liver Metastases

Dr. Dawson on the Addition of SBRT to Sorafenib in Locally Advanced HCC

Dr. Dawson on Increasing Causes and Unmet Needs in HCC

Dr. Laura Dawson on HCC Challenges