Trimodality Tx May Be Best for Esophageal Ca

SAN FRANCISCO — Trimodality therapy outperformed surgery alone in the treatment of stage I-III esophageal cancer in a prospective, randomized study presented at a symposium sponsored by the American Society of Clinical Oncology.

Patients who received chemoradiation followed by surgery had a median survival of 4.5 years, compared with 1.8 years for those who received surgery alone in the multi-institution Cancer and Leukemia Group B (CALGB)-9781 study.

Five years after diagnosis, 39% of 30 patients in the trimodality group were alive, compared with 16% of 26 patients in the surgery-alone group.

However, the study conducted by 12 institutions in the U.S. Gastrointestinal Intergroup accrued just 56 patients, hundreds short of the original planned cohort, leaving some experts still unsure of the best therapeutic strategy to recommend.

Because so few patients could be found who would agree to be randomized to surgery alone, CALGB-9781 was “very underpowered” to make sweeping conclusions or to clarify ambiguity left in the wake of a host of small studies with conflicting results, said Dr. Bruce D. Minsky of Memorial Sloan-Kettering Cancer Center in New York City.

He said he thinks trimodality therapy probably confers about a 5%–10% survival advantage over other alternatives, “but we would need a large trial to show that.”

Dr. Mark Krasna, head of the division of thoracic surgery at the University of Maryland, Baltimore, countered that, despite its small numbers, the CALGB-9781 study was powered to show small differences between the trimodality and surgery-alone arms.

After 6 years of follow-up, the differences were not small. “The results are so stark that I think the conclusions will be vindicated,” he said during a press conference preceding the presentation of the study findings.

“What's extremely exciting is that in a study that included surgery after combination therapy, we were actually able to assess … pathological response, no visible viable tumors or significant response,” Dr. Krasna said at the meeting, which was also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiation and Oncology, and the Society of Surgical Oncology.

Complete or partial pathological response to chemoradiation was seen in 24 of 30 trimodality patients. No viable tumor cells were seen at surgery in 12.

The study population reflected the demographic population associated with adenocarcinoma of the esophagus. There were 42 patients with that diagnosis, compared with just 14 with squamous cell carcinoma. Males predominated, with 51 enrolled, compared with 5 females. There were 48 whites and 8 blacks.

The trial randomized trimodality patients to receive 5-fluorouracil and cisplatin and 50.4 Gy of radiation over 5 weeks. They underwent surgery 3–8 weeks later.

Patients in the surgery arm underwent surgery shortly after their diagnosis.

Complications were frequent in both study arms, including grade 3 hematologic toxicities in more than half of all patients and GI toxicity in 40%. Surgical complications also occurred, as expected. “This is a very big surgery, considered one of the largest operations we do,” said Dr. Krasna.

In the surgery-alone arm, 14 patients suffered complications and 2 died post surgery. There were no surgery-related deaths in the trimodality arm, but 17 patients suffered complications, including 2 who developed leaks between the esophagus and stomach.

Esophagectomy with lymph node dissection is associated with a 3%–10% mortality rate, so the surgical results were not surprising, Dr. Krasna said.

The mean postoperative stay was 10–12 days, “which is actually quite reasonable,” he added.

“The important message we can take from this trial is that there is actually a curative possibility for esophageal cancer patients,” said Dr. Krasna. “Hopefully, chemotherapy and radiation followed by surgery will make a difference.”

Esophageal cancer results in 12,000 deaths a year in the United States, and adenocarcinoma of the esophagus is rising for reasons that are not fully understood.

SAN FRANCISCO — Trimodality therapy outperformed surgery alone in the treatment of stage I-III esophageal cancer in a prospective, randomized study presented at a symposium sponsored by the American Society of Clinical Oncology.

Patients who received chemoradiation followed by surgery had a median survival of 4.5 years, compared with 1.8 years for those who received surgery alone in the multi-institution Cancer and Leukemia Group B (CALGB)-9781 study.

Five years after diagnosis, 39% of 30 patients in the trimodality group were alive, compared with 16% of 26 patients in the surgery-alone group.

However, the study conducted by 12 institutions in the U.S. Gastrointestinal Intergroup accrued just 56 patients, hundreds short of the original planned cohort, leaving some experts still unsure of the best therapeutic strategy to recommend.

Because so few patients could be found who would agree to be randomized to surgery alone, CALGB-9781 was “very underpowered” to make sweeping conclusions or to clarify ambiguity left in the wake of a host of small studies with conflicting results, said Dr. Bruce D. Minsky of Memorial Sloan-Kettering Cancer Center in New York City.

He said he thinks trimodality therapy probably confers about a 5%–10% survival advantage over other alternatives, “but we would need a large trial to show that.”

Dr. Mark Krasna, head of the division of thoracic surgery at the University of Maryland, Baltimore, countered that, despite its small numbers, the CALGB-9781 study was powered to show small differences between the trimodality and surgery-alone arms.

After 6 years of follow-up, the differences were not small. “The results are so stark that I think the conclusions will be vindicated,” he said during a press conference preceding the presentation of the study findings.

“What's extremely exciting is that in a study that included surgery after combination therapy, we were actually able to assess … pathological response, no visible viable tumors or significant response,” Dr. Krasna said at the meeting, which was also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiation and Oncology, and the Society of Surgical Oncology.

Complete or partial pathological response to chemoradiation was seen in 24 of 30 trimodality patients. No viable tumor cells were seen at surgery in 12.

The study population reflected the demographic population associated with adenocarcinoma of the esophagus. There were 42 patients with that diagnosis, compared with just 14 with squamous cell carcinoma. Males predominated, with 51 enrolled, compared with 5 females. There were 48 whites and 8 blacks.

The trial randomized trimodality patients to receive 5-fluorouracil and cisplatin and 50.4 Gy of radiation over 5 weeks. They underwent surgery 3–8 weeks later.

Patients in the surgery arm underwent surgery shortly after their diagnosis.

Complications were frequent in both study arms, including grade 3 hematologic toxicities in more than half of all patients and GI toxicity in 40%. Surgical complications also occurred, as expected. “This is a very big surgery, considered one of the largest operations we do,” said Dr. Krasna.

In the surgery-alone arm, 14 patients suffered complications and 2 died post surgery. There were no surgery-related deaths in the trimodality arm, but 17 patients suffered complications, including 2 who developed leaks between the esophagus and stomach.

Esophagectomy with lymph node dissection is associated with a 3%–10% mortality rate, so the surgical results were not surprising, Dr. Krasna said.

The mean postoperative stay was 10–12 days, “which is actually quite reasonable,” he added.

“The important message we can take from this trial is that there is actually a curative possibility for esophageal cancer patients,” said Dr. Krasna. “Hopefully, chemotherapy and radiation followed by surgery will make a difference.”

Esophageal cancer results in 12,000 deaths a year in the United States, and adenocarcinoma of the esophagus is rising for reasons that are not fully understood.

SAN FRANCISCO — Trimodality therapy outperformed surgery alone in the treatment of stage I-III esophageal cancer in a prospective, randomized study presented at a symposium sponsored by the American Society of Clinical Oncology.

Patients who received chemoradiation followed by surgery had a median survival of 4.5 years, compared with 1.8 years for those who received surgery alone in the multi-institution Cancer and Leukemia Group B (CALGB)-9781 study.

Five years after diagnosis, 39% of 30 patients in the trimodality group were alive, compared with 16% of 26 patients in the surgery-alone group.

However, the study conducted by 12 institutions in the U.S. Gastrointestinal Intergroup accrued just 56 patients, hundreds short of the original planned cohort, leaving some experts still unsure of the best therapeutic strategy to recommend.

Because so few patients could be found who would agree to be randomized to surgery alone, CALGB-9781 was “very underpowered” to make sweeping conclusions or to clarify ambiguity left in the wake of a host of small studies with conflicting results, said Dr. Bruce D. Minsky of Memorial Sloan-Kettering Cancer Center in New York City.

He said he thinks trimodality therapy probably confers about a 5%–10% survival advantage over other alternatives, “but we would need a large trial to show that.”

Dr. Mark Krasna, head of the division of thoracic surgery at the University of Maryland, Baltimore, countered that, despite its small numbers, the CALGB-9781 study was powered to show small differences between the trimodality and surgery-alone arms.

After 6 years of follow-up, the differences were not small. “The results are so stark that I think the conclusions will be vindicated,” he said during a press conference preceding the presentation of the study findings.

“What's extremely exciting is that in a study that included surgery after combination therapy, we were actually able to assess … pathological response, no visible viable tumors or significant response,” Dr. Krasna said at the meeting, which was also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiation and Oncology, and the Society of Surgical Oncology.

Complete or partial pathological response to chemoradiation was seen in 24 of 30 trimodality patients. No viable tumor cells were seen at surgery in 12.

The study population reflected the demographic population associated with adenocarcinoma of the esophagus. There were 42 patients with that diagnosis, compared with just 14 with squamous cell carcinoma. Males predominated, with 51 enrolled, compared with 5 females. There were 48 whites and 8 blacks.

The trial randomized trimodality patients to receive 5-fluorouracil and cisplatin and 50.4 Gy of radiation over 5 weeks. They underwent surgery 3–8 weeks later.

Patients in the surgery arm underwent surgery shortly after their diagnosis.

Complications were frequent in both study arms, including grade 3 hematologic toxicities in more than half of all patients and GI toxicity in 40%. Surgical complications also occurred, as expected. “This is a very big surgery, considered one of the largest operations we do,” said Dr. Krasna.

In the surgery-alone arm, 14 patients suffered complications and 2 died post surgery. There were no surgery-related deaths in the trimodality arm, but 17 patients suffered complications, including 2 who developed leaks between the esophagus and stomach.

Esophagectomy with lymph node dissection is associated with a 3%–10% mortality rate, so the surgical results were not surprising, Dr. Krasna said.

The mean postoperative stay was 10–12 days, “which is actually quite reasonable,” he added.

“The important message we can take from this trial is that there is actually a curative possibility for esophageal cancer patients,” said Dr. Krasna. “Hopefully, chemotherapy and radiation followed by surgery will make a difference.”

Esophageal cancer results in 12,000 deaths a year in the United States, and adenocarcinoma of the esophagus is rising for reasons that are not fully understood.