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Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone. The findings, from a large randomized trial of neoadjuvant chemoradiotherapy for the disease, were published May 31, 2012, in the New England Journal of Medicine.

Patients treated with carboplatin and paclitaxel chemotherapy plus radiation prior to surgery had a median overall survival of nearly 50 months, compared with 24 months for patients treated with surgery alone.

Pieter van Hagen, M.D., of Erasmus University Medical Center and his colleagues enrolled 368 patients who had cancer of the esophagus or of the junction between the stomach and the esophagus that had not spread to other organs. Participants in the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) were mostly men, and the median age was 60. Patients benefited from preoperative therapy regardless of whether they had adenocarcinoma, the most prevalent form of esophageal cancer in the United States, or squamous cell carcinoma, the most prevalent form of the disease worldwide.

Previous trials to test the superiority of preoperative chemotherapy and radiation in esophageal cancer failed to enroll enough patients to reach definitive conclusions. “The successful completion of this trial is an impressive effort, and the results should be considered high-level evidence in favor of this preoperative regimen,” commented Jack Welch, M.D., Ph.D., head of gastrointestinal therapeutics for NCI’s Cancer Therapy Evaluation Program, who was not involved in the study.

Patients randomly assigned to the chemoradiotherapy arm of the study received five courses of chemotherapy with carboplatin and paclitaxel plus concurrent external-beam radiation therapy, followed by surgery, usually within 4 to 6 weeks of completing preoperative treatment. This preoperative regimen has been widely adopted in the United States within the past year and has also been adopted as a standard therapy in some trials being conducted by NCI-supported cooperative groups, Dr. Welch said. For example, a phase III trial is testing a combination of neoadjuvant chemoradiotherapy with the targeted agent trastuzumab in patients whose tumors express the HER2 biomarker, explained Dr. Welch.

In another study, patients initially treated with chemotherapy based either on the Dutch study regimen or an alternative regimen are being assessed with PET scans; those who do not respond are switched to the other therapy, which is then combined with radiation. In both studies, researchers are trying to tailor the chemoradiation regimen used in Dr. van Hagen’s study to obtain the best possible result for individual patients, Dr. Welch said.


Long-term results from the CROSS trial, published August 5, 2015, in Lancet Oncology, confirmed the overall survival benefit of adding neoadjuvant chemoradiotherapy to surgery that was reported in 2012. With a median follow-up of 84.1 months, the median overall survival was 48.6 months for patients who received neoadjuvant chemoradiotherapy plus surgery and 24.0 months for patients who received surgery alone. At the longer follow-up, patients continued to benefit from preoperative therapy, regardless of whether they had adenocarcinoma or squamous cell carcinoma.

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