BACKGROUND: Palliative treatment options for painful hepatic cancer can be restricted due to patients eventually becoming refractory to standard treatment. The aim of this study was to determine whether radiotherapy improves hepatic pain from cancer.
METHODS: In this open-label, randomised, controlled, phase 3 trial (CCTG HE1) done in nine cancer centres across Canada, we included patients aged 18 years or older with hepatocellular carcinoma or liver metastases, who were refractory to standard treatment, with an Eastern Cooperative Oncology Group performance status of 0-3, with life expectancy of more than 3 months, and pain or discomfort at its worst in the past 24 hours on the Brief Pain Inventory (BPI) of at least 4 out of 10, which was stable for up to 7 days before randomisation. Patients were randomly assigned (1:1), via a minimisation method after stratification by centre and type of cancer (hepatocellular carcinoma vs liver metastases), to single-fraction radiotherapy (8 Gy) to the liver with 8 mg ondansetron (or equivalent) orally and 4 mg dexamethasone orally given 1-2 h before radiotherapy plus best supportive care (including non-opioid or opioid analgesia, or dexamethasone, or a combination of these) or best supportive care alone. The primary endpoint was improvement in patient-reported liver cancer pain or discomfort of at least 2 points on worst pain intensity on the BPI at 1 month after randomisation. All patients with both baseline and 1-month assessments were included in the primary endpoint analysis. Safety was assessed in all patients randomly assigned to treatment. This trial is registered with ClinicalTrials.gov, NCT02511522, and is complete.
FINDINGS: Between July 25, 2015, and June 2, 2022, 66 patients were screened and randomly assigned to radiotherapy plus best supportive care (n=33) or best supportive care (n=33). Median age was 65 years (IQR 57-72), 37 (56%) of 66 patients were male, 29 (44%) were female, 43 (65%) had liver metastases, and 23 (35%) had hepatocellular carcinoma (data on race and ethnicity were not collected). As of data cutoff (Sept 8, 2022), median follow-up was 3·2 months (95% CI 3·0-3·4). 24 (73%) of 33 in the radiotherapy plus best supportive care group and 18 (55%) of 33 in the best supportive care only group completed baseline and 1-month assessments. An improvement in hepatic pain of at least 2 points in worst pain intensity on the BPI at 1 month was seen in 16 (67%) of 24 patients in the radiotherapy plus best supportive care group versus four (22%) of 18 patients in the best supportive care group (p=0·0042). The most common grade 3-4 adverse events within 1 month after randomisation were abdominal pain (three [9%] of 33 in the radiotherapy group vs one [3%] of 33 in best supportive care group) and ascites (two [6%] vs one [3%]). No serious adverse events or treatment-related deaths were observed.
INTERPRETATION: Single-fraction radiotherapy plus best supportive care improved pain compared with best supportive care alone in patients with liver cancer, and could be considered a standard palliative treatment.
FUNDING: Canadian Cancer Society.
| Discipline Area | Score |
|---|---|
| Physician |  |
Physician rater
As a palliative care physician, I often do not think of radiation therapy for solid organs. This is a nice study that shows that it can help with HCC. Pain improvement was within one month, which is important given the poor prognosis.
Physician rater
Interesting study suggesting single # rads for refractory pain from large volume liver mets/HCC is safe and potentially effective. I am not sure the 2 groups were equivalent at baseline (from the demographics, supportive care appeared to be sicker, no p values provided, perhaps explaining their higher death rate). A useful option though for refractory pain now with reasonable evidence to lean on.
Physician rater
Interesting RCT suggesting that in select patients with end-stage HCC or liver metastasis, palliative radiotherapy (RT) may improve pain over and above standard of care (SOC). However, the results should be interpreted with caution as only ~70% patients in the intervention arm & 55% in the SOC arm completed both the pre- and post-BPI questionnaire. Also, although the primary end point was logical and clinically relevant (2 point difference at 1 month post-RT), the longer-term efficacy of pain relief by SFRT is not known/tested. Follow-up was only ~3 months, which is especially relevant as the trial was designed to enroll patients with an expected survival of at least 3 months.
Physician rater
It is interesting that severe pain improved more with radiation than without. It is important to note the risks and benefits of intervening vs best supportive care only.
, McMaster University