SAN FRANCISCO – Chemoradiotherapy is not superior to radiotherapy alone for alleviating dysphagia in patients with advanced esophageal cancer. And it causes more nausea and vomiting.
These were among key findings of a randomized phase III trial reported in a session and a related press briefing at the annual meeting of the American Society for Radiation Oncology.
“This trial was powered to see if there was an improvement with chemotherapy, and it wasn’t powered to show equivalence, so it was a truly negative trial. However, we do know that chemotherapy added some toxicity and didn’t improve the quality of life parameters that we were looking at,” commented lead researcher Dr. Michael G. Penniment, director of Radiation Oncology at both the Royal Adelaide Hospital in Adelaide, Australia, and the Alan Walker Cancer Care Centre in Darwin, Australia.
ASTRO/Adam Donohue
Dr. Michael Penniment
“So I think that we can clearly say that radiotherapy alone remains an excellent tool for palliation of these patients with advanced esophageal cancer and should remain the standard of care,” he maintained. “And if you combine that with the fact that we have a proven role [for radiation] in patients who have curable esophageal cancer, I would say that all patients with esophageal cancer should have the opinion of a radiation oncologist, though I’m a little biased.”
There is no gold standard when it comes to palliative care for patients with advanced esophageal cancer, according to Dr. Penniment. “We can’t even explain to these patients facing a very difficult phase of their life what exactly the results of fairly basic treatments are. We need to give them better information about the chances the treatments we offer will actually help them and perhaps some more evidence about which patients fit into this group,” he said, giving some background to the research.
In the trial, 220 patients from Australia, New Zealand, Canada, and the United Kingdom with advanced esophageal cancer were randomized evenly to receive palliative radiation therapy — 30 Gy in 10 fractions or 35 Gy in 15 fractions, depending on the country — either alone or with concomitant chemotherapy. Three-fourths of the patients had metastases, and the rest had locally advanced tumors.
At 9 weeks after the start of radiation therapy, the proportion of patients whose dysphagia responded to treatment, which was defined as an improvement of at least 1 point on the 5-point Mellow Scale, was 68% with radiation alone and 74% with chemoradiation, a nonsignificant difference.
The respective proportions with a sustained response at 13 weeks, the trial’s primary endpoint, were 42% and 47%, also a nonsignificant difference.
But some patients did not live even this long, Dr. Penniment noted. “So there is a group of people we hope to be able to identify who really do exceedingly badly and it might be that simple radiotherapy, such as a single fraction, might be enough for those patients. Or indeed, unfortunately, there might be some people with such poor prognostic signs that a tube might do them if it’s only a week or something like that,” he said.
The 3-year rates of dysphagia, progression-free survival, and overall survival were statistically indistinguishable between groups. Median overall survival was 203 days with radiation and 210 days with chemoradiation.
On a bright note, however, there was a tail to the survival curve, with about 10% of patients in each group still alive at 2 years. “I think there is a message here,” Dr. Penniment said. “You don’t want to give people false hope, but there is certainly a group of patients who have advanced esophageal cancer with or without lymph node involvement for whom potential active cancer treatment may actually cause a reasonably long-term survival and local control. I suspect that this tail to the survival curve would probably not be seen in patients who are offered certainly no treatment, but people who are offered bypass with a stent or bypass tubes. And these are clearly patients that we would not go on to see.”
In quality of life assessments, 64% of patients treated with radiation alone and 50% of patients treated with chemoradiation had an improvement in the dysphagia domain on the esophageal module of the European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ-OES18), a nonsignificant difference.
However, relative to the radiation group, the chemoradiation group had higher rates of both nausea and vomiting (P less than .01 for each).
Some patients who received radiotherapy alone went on to receive chemotherapy, according to Dr. Penniment, who reported having no financial disclosures. “The majority of those patients had no dysphagia but still got chemotherapy after radiotherapy alone. We will do more analysis on this, but I think there is a fixed belief, which hopefully this trial starts to break, that these people need to have chemotherapy,” he said.