Radiotherapy underused in liver cancer

As case numbers rise in Australia, this treatment offers hope for patients with few other options.

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More Australians are being diagnosed with hepatocellular carcinoma, but outcomes are poor and most patients don’t get curative therapies. Now experts are calling for greater use of radiation therapy.

“Hepatocellular carcinoma is an underserved cancer, and we need to expand options,” Associate Professor David Pryor told delegates at the 2022 RANZCR Annual Scientific Meeting in Queenstown last month.

“We need something that can provide good local control with organ preservation, and that’s where we come in,” the Brisbane radiation oncologist said.

“We need to do better.”

Associate Professor David Pryor

Liver cancer is the third leading cause of death globally. In Australia, it’s the seventh most common cause of cancer death and while other cancer numbers are improving, liver cancer numbers are going the other way, jumping from 8 to almost 9 cases per 100,000 between 2018 and 2022.

“This is largely driven by hepatitis viruses and alcohol, but increasingly, there’s a large proportion from the so-called metabolic syndrome associated liver disease.” he said.

There is currently no national screening program for liver cancer in Australia.

“High risk populations do need screening. And if we see them early, we can potentially cure them. But at the moment, we’re not curing many, and we’re seeing many too late,” he said.

Treatment options are limited

Survival rates had not improved much over the last 15 years, Professor Pryor told delegates, and most patients don’t get curative treatments.

“More than 80% are not suitable for resection, either because of underlying liver disease, comorbidities, extent or location of the tumour,” he said. And while thermal ablation was a good treatment, only around half of Australian patients were eligible, either because of the size or location of the tumour or because of comorbidities, he said.

Transplantation resources were also scarce, and few were suitable, he added.

“After that, is a big line where people go down what we call the ‘treatment stage migration pathway’, where they receive palliative therapies for early-stage disease,” said Professor Pryor.

These include transarterial therapies like chemoembolisation (TACE) and radioembolisation (RE), but TACE in particular had low durable control, he said.

Even systemic therapies did not have stellar results.

“Unlike cancers like melanoma, where immunotherapy has revolutionised management, there are very few inroads in liver cancer. The median progression-free survival period is still only in the order of four –to-six months,” he said.

Even combination therapy atezolizumab and bevacizumab, which has recently become the new standard of care in patients that can tolerate it, only had a median survival of six months.

“We need to do better,” Professor Pryor said.

Why radiation is the way to go

Hepatocellular carcinoma is a radiosensitive tumour, and it was possible to get “remarkable” responses, said Professor Pryor.

Yet he noted that radiation played no role in the guidelines.

In a systematic review of radiation for local control, survival and toxicity, researchers found that local control rates at around three years after treatment were greater than 90%.

Stereotactic ablative radiotherapy (SABR) had benefits for early-stage hepatocellular carcinoma; as a bridge to transplant to keep the disease under control while the patient waited; to improve local control for liver-confined or liver-dominant advanced disease, particularly bulky tumours or those with vascular invasion; oligometastatic relapse; and for palliative treatment of bone pain and liver capsular pain, explained Professor Pryor.

Research has shown that SABR is not inferior to ablation, and can provide better local control with the same overall survival rates than TACE. But there were few randomised trials, fewer still of high quality, and none in a first-line setting, he said, resulting in minimal uptake of the treatment globally.

“For example, at our centre, the predominant treatment for early-stage HCC is stereotactic radiotherapy. At other centres, it’s not available or not practiced,” he said.

Professor Pryor and his colleagues are working to define the role of SABR in the first line setting at the first point of diagnosis in early-stage hepatocellular carcinoma. “The hypothesis is that SABR will provide superior local control,” he said.

Some small studies looking at SABR as a bridging therapy to transplant showed it was feasible, had low toxicity and resulted in good local control, he said, but many randomised control trials were in the pipeline.

Korean and Chinese results showed significant benefit in the use of radiation therapy for larger tumours, but those results had not made their way into western guidelines, said Professor Pryor.

“The key thing at the moment is just making sure that cohort of patients who don’t get any curative treatment have that option,” he said.