1. Susman, Ed

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SAN FRANCISCO-Palliative treatment for patients with advanced esophageal cancer can be accomplished with radiation alone, sparing patients the adverse side effects of chemotherapy without sacrificing survival, according to data reported here at the American Society for Radiation Oncology Annual Meeting (Abstract CT-03).

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The median survival for patients receiving chemotherapy plus radiation was 210 days, compared with 203 days for patients who received just radiation, a non-significant difference, reported Michael Penniment, MBBS, Director of Radiation Oncology at Royal Adelaide Hospital in South Australia. "There was no significant difference between the two treatment arms for either dysphagia, progression-free survival, or overall survival."


Overall, by the end of nine weeks, a reduction in dysphagia was achieved by about 68 percent of patients undergoing radiation alone, compared with about 74 percent of patients receiving both radiation and platinum-based chemotherapy. A total of 42 percent of the patients on radiation therapy alone maintained the improvement through week 13, compared with 47 percent of those receiving both radiation and chemotherapy.


After six months, 33 patients receiving radiation plus chemotherapy had a dysphagia-free status compared with 31 patients who received just radiation.


The primary endpoint of the study was defined as at least a one-point improvement on the five-point Mellow scale at nine weeks and that improvement in swallowing was to be maintained until at least week 13.


Penniment noted that while the higher percentages were not significantly different for patients receiving both therapies, the impact of adverse side effects was significant. Nausea occurred in more patients with combination therapy, as was vomiting.


In terms of quality of life, there were no significant differences between the two groups of patients, although about one half of the patients in the chemoradiation group reported an improvement in dysphasia compared with 64 percent of those patients who were treated with radiation alone.


'Potential to Change Clinical Practice in U.S.'

Asked her opinion of the study, Kimberly Johung, MD, PhD, Assistant Professor of Therapeutic Radiology at Yale University, was quite positive: "The results from this trial have the potential to change clinical practice in the United States. It is not often that we have a clinical trial that looks at practices in the palliative care setting. That small amount of difference in survival was not significant, but there was an increase in gastrointestinal side effects that was significant.


"This study shows that radiation treatment alone can shrink the tumors causing dysphagia without further gastrointestinal toxicity."


Penniment said that although it is common for chemotherapy to be prescribed for patients with advanced esophageal cancer, that is based on the standard use of chemoradiation therapy in patients with less advanced disease. "Some clinicians, however, believe that no treatment should be offered, assuming treatment is futile and potentially toxic.


"These results will allow us to simplify the treatment for patients who cannot be cured but who can expect an improvement in swallowing and quality of life, and these patients can be spared the extra toxicity and cost of chemotherapy."


About 10 percent of patients in the trial appeared to have long-term survival, he continued: 21 of the 220 patients in the trial were still alive more than two years after the palliative treatment was provided.


"Radiation therapy alone remains an excellent tool for palliation of patients with advanced esophageal cancer and should remain the standard of care," he said. "Patients with advanced esophageal cancer should receive advice on active treatment from a radiation oncologist."


Dose Differed by Region

In the study, the researchers enrolled 220 patients, assigning 109 to receive radiation alone and 111 to radiation and chemotherapy. The dose differed by region: The 115 patients enrolled in sites in Australia and New Zealand received a total dose of 35 Gy, delivered in 15 fractions; in Canada and the U.K., patients had a total dose of 30 Gy delivered in 10 fractions.


Those patients assigned to concomitant chemotherapy received intravenous cisplatin at 80 mg/m2 on day 1, or 20 mg/m2 on days 1-4, and fluorouracil at 800 mg/m2 a day for days 1-4; 203 of the 220 patients received the allocated treatments.


Of the 184 men and 36 women in the study, 151 had adenocarcinoma and 58 had squamous cell carcinoma of the esophagus.

MICHAEL PENNIMENT, M... - Click to enlarge in new windowMICHAEL PENNIMENT, MBBS. MICHAEL PENNIMENT, MBBS: "These results will allow us to simplify the treatment for patients who cannot be cured but who can expect an improvement in swallowing and quality of life, sparing them from the extra toxicity and cost of chemotherapy."

The degree of dysphagia reported was based on patient-reported questionnaires that measuring swallowing ability and quality of life, and via clinician-based questionnaires that measured side effects and adverse events.


The trial was initiated, Penniment explained, because only a small number of clinical studies in this group of patients have focused on the palliative setting, especially looking at relief of dysphagia, the commonest presenting symptom of advanced esophageal cancer, which is the highest priority for treatment.


The research was particularly aimed at establishing an evidence base for patient decision-making regarding the optimal management for esophageal cancer considered to be incurable he said. Seventy five percent of the patients in the radiation-only arm had metastatic disease, as did 72 percent of the patients treated with chemoradiation therapy. About 17 percent of the patients receiving radiation therapy alone were in Eastern Cooperative Oncology Group performance status 2 compared with 13 percent of the patients receiving both chemotherapy and radiation.