At the 2023 ASCO Gastrointestinal Cancers Symposium, Laura Dawson, MD, Princess Margaret Cancer Center, Toronto, Ontario, Canada, presented on the Canadian Cancer Trials Group study evaluating the use of radiotherapy in the palliative setting for patients with hepatocellular carcinoma or liver metastases. Dr Dawson explains the results of the study showed that palliative radiotherapy reduced the pain experienced by patients when compared to the best supportive care and analgesics.

Transcript:

Hello, I'm Laura Dawson. I am professor and chair of the Department of Radiation Oncology at the University of Toronto, and I'm a practicing radiation oncologist at the Radiation Medicine Program at the Princess Margaret Cancer Center at UNH in Toronto. My main area of clinical and research interest is in the treatment of patients with liver cancer, both primary liver cancer and metastases.

It's my pleasure to talk to you about the results of the Canadian Clinical Trials Group, abstract HE1. This is a phase 3 randomized study of palliative radiotherapy for patients who have symptomatic hepatocellular carcinoma and liver metastases. The purpose of the study was to determine if more patients treated with a simple palliative radiotherapy had improvement of pain 1 month after the intervention than supportive care and analgesic use alone.

This was a multi-center Canadian phase 3 study where patients had to have a pain score of at least 4 on a scale from 0 to 10. If that pain was reproducible and not responsive to standard analgesia and supportive care measures, they were eligible for the study. Patients could have very locally advanced disease and had to not have disease that was eligible for treatment with standard treatments such as systemic chemotherapy, immunotherapy, or targeted therapy. These patients really were in supportive care transition near the end of their life. Performance status could also be impaired, with up to ECOG performance status 2 patients permitted to be treated and patients who had quite impaired liver function were eligible. They could have Child-Pugh A, B, or even C liver function.

The primary objective was to learn if the patient reported pain at worst was improved one month following treatment. All patients completed their patient-reported outcomes using the Brief Pain Inventory —the question that was the primary end point being “What is your pain at worse in the past 24 hours?” Our hypothesis was that there would be a large difference and a large improvement in the percentage of patients who felt better 1 month after treatment with the use of radiotherapy.

This is a very pragmatic, relatively simple randomized trial looking for a large effect size. 66 patients were randomized. The majority had liver metastases predominantly from colorectal, breast, pancreas, or lung cancer, also some cancers such as renal cell and melanoma. About one-third of patients had hepatocellular carcinoma and 60% of patients had an ECOG performance status of 2 or 3, quite poor performance status, and reported pain needing treatment not responsive to standard analgesia. The median clinical target volume in radio was very high. Approximately 2 liters and that is reflective of patients with a lot of cancer within the liver. And treating the whole liver meant a very large volume of the upper abdomen was treated with radiation.

42 patients completed the baseline in 1 month with patient-reported outcomes and were evaluable for the primary end point and secondary analyses. And as hypothesized, this study did show clinically important and statistically significant improvement in the proportion of patients who reported relief of pain one month following treatment. In patients who are randomized to radiotherapy, 67% of patients had an improvement on their pain score by 2 or more at 1 month following treatment compared to 22% who received best supportive care alone with a significant P-value of 0.004. And furthermore, there were other pain end points such as “pain at worst with no change in analgesia,” “pain at least,” were statistically and clinically significantly improved in those patients who received radiotherapy. At 1 month, those patients who didn't receive radiation upfront could cross over and receive radiation. Then further testing of their pain was done at 3 months following treatment and that was the end of the study.

There was a sensitivity analysis and that assumed anyone who did not complete their 1-month pain scores had worsening of pain. And even with that sensitivity analysis, there was a clinically important and statistically significant improvement in the proportion of patients who had improvement in pain with radiotherapy.

Furthermore, there's a trend to improved quality of life and another interesting observation was that there was a trend to improved 3-month survival in those patients who were treated with radiotherapy with 3-month survival being 51% in those receiving radiation versus 33% in those who were in the best supportive care arm with a P-value of 0.07.

Overall, the study did show what we hypothesized, that there are clinically significant and meaningful improvements in pain in patients who suffer from intractable, challenging-to-treat pain near the end of their life, whether they have metastases or primary liver cancer.

Source:

Dawson L, Fairchild A, Dennis K. Canadian Cancer Trials Group HE.1: A phase III study of palliative radiotherapy for symptomatic hepatocellular carcinoma and liver metastases. Presented at 2023 ASCO Cancers Symposium; January 19 – 21, 2023; San Francisco, California. Abstract LBA492