Radiation therapy reduces pain in advanced hepatocellular carcinoma

January 25, 2023

4 minutes of reading

Source/Disclosures

Source:

Dawson LA, and others. Summary LBA492. Presented at: ASCO Gastrointestinal Cancers Symposium; January 19 to 21, 2023; San Francisco.

Disclosures:
The Canadian Cancer Society Research Institute funded this study. Dawson reports research funding from Merck, as well as patents, royalties or other intellectual property from RaySearch Laboratories. Please see the summary for all relevant financial disclosures from other researchers.


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Single-fraction radiotherapy reduced liver pain in most patients with end-stage hepatocellular carcinoma or liver metastases, according to randomized phase 3 trial results presented at the ASCO Gastrointestinal Cancers Symposium.

The researchers also observed a trend towards longer survival among those who received radiation.

Infographic showing improvement in pain

Dawson LA, and others. Summary LBA492. Presented at: ASCO Gastrointestinal Cancers Symposium; January 19 to 21, 2023; San Francisco.

“I absolutely believe this is a practice change,” researcher Laura A. Dawson, MD, FRCPC, FASTRO, chairman of the department of radiation oncology at the University of Toronto and a practicing radiation oncologist at the Princess Margaret Cancer Center, Healio said. “We routinely treat patients with bone metastases or bleeding from lung metastases or with primary metastatic brain cancer. We do not routinely treat patients with liver pain or discomfort. This study shows that a very simple one-dose intervention can help patients.”

Background and methods

Patients with pain from end-stage HCC or liver metastases who are not eligible for systemic therapies – such as immunotherapy, targeted therapy or chemotherapy – receive the best supportive care. This usually consists of pain relievers. However, as these patients often have cirrhosis or liver failure, high-dose pain relievers are often less effective, leading to a poorer quality of life.

Laura Dawson
Laura A. Dawson

“These patients with primary or end-stage metastatic cancer are underserved. Most are treated by palliative care physicians or in hospices, so many medical oncologists, radiation therapists and surgeons don’t see patients at the end of life when they are suffering,” said Dawson. “A substantial part are troubled by pain or discomfort due to the burden of disease on the liver.”

Previous single-arm studies have shown that single-dose radiotherapy reduced pain within 1 month.

The Canadian Cancer Trials Group supported the HE.1 trial to definitively determine whether adding radiotherapy to best supportive care reduced pain in patients with primary liver cancer or liver metastases.

The multicenter study included patients with end-stage painful HCC or liver metastases who were not candidates for local, regional, or systemic therapies.

At least 4 weeks have passed since the last chemotherapy or transarterial chemoembolization and at least 2 weeks have passed since the last targeted therapy or immunotherapy.

The researchers randomly assigned study participants to the best supportive care alone or with single-fraction (8 Gy) radiotherapy, with the clinical target volume irradiated being the entire liver or nearly the entire liver.

Improvement in “worst intensity” of liver cancer pain – as measured by an improvement of at least two points on the Brief Pain Inventory from baseline to 1 month – served as the primary outcome measure.

Secondary outcomes included proportion of patients alive at 3 months; proportion of those with at least two-point improvement on the Brief Pain Inventory at 1 month and 3 months; proportion of those with a 25% reduction in opioids at 1 month; and proportion who reported improvement in quality of life as determined by a change of at least five points in the Hepatobiliary Functional Assessment of Hepatobiliary Cancer Therapy (FACT-Hep) subscale and a change of at least seven points in the FACT-Hep Trial Outcome Index score in 1 month.

The researchers enrolled 66 patients. Twenty-three had HCC and 43 had liver metastases (colorectal, n = 12; breast, n = 5; pancreas, n = 4; lung, n = 3; other, n = 19).

More than half (59%) of the patients had an ECOG performance status of 2 or 3. Two-thirds (64%) had a Child-Pugh A score and one-third (36%) had a Child-Pugh B or C score.

All had stable pain rated at least 4 on a 10-point Likert scale.

Results

The final analysis included 42 patients who completed baseline and 1-month assessments; 24 received radiotherapy and 18 received best supportive care alone.

The researchers reported an average “pain at worst” score of 7 out of 10.

Several outcomes at 1 month favored the radiotherapy group, including the percentage of those who exhibited significant improvement in the “worst” pain score as assessed by the Brief Pain Inventory (67% vs. 22%; P = 0.004); percentage who reported improvement in “worst” pain without increasing opioid use (21% vs. 0%); proportion reporting significant improvement on the Brief Pain Inventory “at least pain” (63% vs. 28%; P = 0.03); Brief pain inventory “percent pain relief per treatment” (59% vs. 25%; P = 0.04).

A sensitivity analysis of all patients – which classified those who did not complete the 1-month assessments as no improvement – showed 49% of those who received radiotherapy plus best supportive care and 12% of those who received only best supportive care exhibited improvements in Brief Pain Inventory “worst” pain (P = 0.002).

“The fact that we still saw statistically significant and clinically important improvements in the sensitivity analysis was quite reassuring,” said Dawson.

Eleven patients designated best supportive care alone went on to receive radiotherapy within 1 month.

Despite the crossover, the results showed 3-month survival rates of 51% with radiotherapy and 33% with only the best supportive care.

“That was a little surprising, but I was certainly pleased to see this result,” said Dawson. “This was close to statistical significance with a P-value of 0.07. It suggests that there was no serious toxicity increase that we couldn’t see. I suggest that for some patients there may be little more than a pain benefit, or perhaps helping patients not need as much painkillers, which has led to them having fewer side effects of analgesia. I’m not sure the pathophysiology of this and the numbers are low, but it deserves validation in future studies.”

The researchers observed a trend toward improvement on the FACT-Hep hepatobiliary subscale at 1 month among those who received radiotherapy.

A greater percentage of those who received radiotherapy experienced grade 2 or greater adverse events at day 30 (58% vs. 33%; P = 0.05). The most common ones included nausea, vomiting, diarrhea and other gastrointestinal events; however, most were short-lived, Dawson said. The researchers also observed transient fatigue among patients who received radiotherapy.

Grade 3 or higher adverse events were uncommon, according to the investigators.

Investigators plan correlative studies of blood samples in hopes of providing insight into why some patients benefited and others did not.

“I think this study also raises the question of whether we can help more patients,” Dawson told Healio. “There may be patients who still tolerate targeted therapy or immunotherapy who may benefit from radiation. … There are also patients with a lower disease burden than those included in this study, and perhaps these patients could benefit from this type of treatment or even from a treatment with higher doses”.

Radiation therapy reduces pain in advanced hepatocellular carcinoma

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