A Canadian phase III trial (CCRG HE1) has demonstrated that the addition of a single fraction of palliative radiotherapy to best supportive care significantly reduces pain in patients suffering from painful hepatic cancer. The open-label, multicenter trial, led by Laura A. Dawson, MD, of the University Health Network–Princess Margaret Cancer Centre, University of Toronto, offers a potential new standard for palliative treatment.
The study, published in The Lancet Oncology, involved 66 patients randomized between July 2015 and June 2022. Participants received either radiotherapy plus best supportive care (n = 33) or best supportive care alone (n = 33). The radiotherapy regimen consisted of a single 8 Gy fraction to the liver, accompanied by 8 mg of ondansetron (or equivalent) and 4 mg of dexamethasone administered 1 to 2 hours before radiotherapy. Best supportive care included nonopioid or opioid analgesia, dexamethasone, or a combination thereof.
Patients included in the trial experienced pain or discomfort rated at ≥ 4 out of 10 points on the Brief Pain Inventory (BPI), which remained stable after analgesia optimization for up to 7 days before randomization. The primary outcome measured was an improvement of ≥ 2 points on the worst pain intensity scale of the BPI at 1 month post-randomization.
Significant Pain Reduction Observed
At the data cutoff in September 2022, the median follow-up was 3.2 months (95% CI = 3.0–3.4 months). Among patients with both baseline and 1-month pain assessments, 16 of 24 (67%) in the radiotherapy/best supportive care group reported an improvement in hepatic pain of ≥ 2 points on the BPI, compared to only 4 of 18 patients (22%) in the best supportive care-alone group (P = .0042).
Reduced Opioid Use
An additional benefit observed was a reduction in opioid use among patients receiving radiotherapy. At 1 month, the radiotherapy/best supportive care group experienced a median reduction of 6.25 morphine mg equivalents per day, while the best supportive care-alone group saw a median increase of 34.00 morphine mg equivalents per day.
Adverse Events
Grade ≥ 2 adverse events within 1 month post-randomization were more frequent in the radiotherapy/best supportive care group (58%) compared to the best supportive care-alone group (33%; P = .08). Grade 3 or 4 adverse events were reported in 18% and 12% of the respective groups. The most common adverse events in the radiotherapy/best supportive care group were abdominal pain (9% vs 3% in the best supportive care-alone group) and ascites (6% vs 3%). Notably, no serious adverse events or treatment-related deaths occurred.
Implications for Palliative Care
The investigators concluded that single-fraction radiotherapy plus best supportive care improves pain compared to best supportive care alone in patients with liver cancer. This approach could be considered a standard palliative treatment option for this patient population.
