Most patients with end-stage hepatocellular carcinoma experience pain, but when it’s severe, how best to control the pain is debatable. A number of studies, including one recently presented at the ASCO Gastrointestinal Cancers Symposium 2023, shows that low-dose radiotherapy can improve pain, and in this case, even improve survival.
The study, conducted by Laura Dawson, MD, a radiation oncologist with the Princess Margaret Cancer Center, Toronto, was conducted in 66 patients with painful hepatocellular carcinoma or liver metastases. They were randomized to receive either palliative radiotherapy (single fraction 8 gray) or standard pain control. Sixty-three percent of patients treated with radiotherapy reported significant improvements in mild pain compared with 28% of patients who received standard pain control (P = .03).
Currently, palliative radiotherapy to control pain in late stage cancer may be an option for some patients with other types of advanced cancer, but in liver cancer, there is little data to support its routine use in patients with terminal hepatocellular carcinoma. “Several prior studies have shown radiation therapy may be delivered safely and that it may help patients with hepatic cancer pain,” Dr. Dawson said. But the previous studies have mostly been single-arm, she said, and many lacked patient-reported outcomes.
In liver cancer, existing therapies are largely inadequate for pain relief, especially for moderate to severe pain. Systemic therapy isn’t effective for rapid pain relief. And, for a subset of patients with end-stage liver cancer, standard pain control with acetaminophen, steroids, and narcotics either is not effective or cannot be tolerated because of underlying cirrhosis or poor liver function due to the cancer.
Although not clinically significant, palliative radiotherapy improved 3-month survival (51%) compared with patients who received best supportive care (33%, P = .07). “Interestingly, there was a trend for improved survival in those patients who received radiation with a 3-month survival of 51% versus 33% of those who received best supportive care. Clearly, the study was not powered for this, but it is very intriguing and hopefully sets the stage for future clinical trials.”
In this study, “simple radiotherapy was used and could consist of two beams, opposed or oblique parallel pair, or simple intensity modulated radiation. This is available with any medical linear accelerator or any cancer center,” Dr. Dawson said. “.”
New data reported at ASCO GI
The Dawson et al. study included 66 patients with liver cancer who had pain scores of at least 4. They had pain that was specific to the liver and they were unsuitable for or refractory to other therapies with no other planned therapies, such as immunotherapy. Their pain was refractory to standard treatments. Of the patients, 43 had liver metastasis from cancers that originated in the colon (12), breast (5), pancreas (4), lung (3), hepatocellular carcinoma (23), or other sites (19).
At 59%, more than half of patients had ECOG performance status of 2 or 3, suggesting the cancer had progressed to the extent that they were confined to a bed or chair for more than half of their waking hours (level 3) or they were capable of self-care but unable to work (level 2). Of the 66 patients, 42 patients completed 1-month assessments and of these, 67% of 24 patients receiving palliative radiotherapy (21% had no increase in opioids) and 22% of 18 patients receiving best supportive care (with no increase in opioids) reported improvements in their worst pain levels.
The primary endpoint – the proportion of patients with a clinically important improvement in pain 1 month after therapy – was met. “There was a significant improvement in all pain endpoints from baseline to one month, with more patients who received radiotherapy reporting clinically important reduction of pain (a reduction by 2 or more on the 0 to 10 scale). The primary endpoint was pain – worst pain, and 67% of those patients who had radiation reported an improvement in their pain at worst in the past 24 hours versus 22% treated with best supportive care, with a P value .004,” Dr. Dawson said.
Adverse events of at least grade 2 or higher occurred 30 days after radiotherapy, affecting 58% of patients compared with 33% of patients who did not receive the treatment. Adverse events at grade 3 or higher were uncommon.
Dr. Dawson reports institutional research funding from Merck.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.