Kate Johnson

May 01, 2013

GENEVA, Switzerland — Preoperative chemoradiation for esophageal cancer reduces locoregional recurrence and peritoneal seeding, according to a new study.

Although expanding the radiation field might further reduce locoregional recurrence rates, the effect on survival would likely be minimal, said Maarten Hulshof, MD, from the Academic Medical Center of Amsterdam in the Netherlands.

"The majority of patients [in our study] had both locoregional recurrence and distant metastasis," Dr. Hulshof told Medscape Medical News. Therefore, "further intensification of locoregional treatment is not expected to have a large impact on overall survival."

Dr. Hulshof presented the study findings here at the 2nd European Society for Radiotherapy & Oncology Forum.

Retrospective Analysis of Data

He and his colleagues conducted a retrospective analysis of data from 373 patients with esophageal cancer from 2 previous trials: the phase 2 nonrandomized CROSS I trial of preoperative chemoradiation; and the randomized CROSS II trial comparing preoperative chemoradiation with surgery alone (N Engl J Med. 2012;366:2074-2084). A total of 213 subjects received chemoradiation followed by surgery and 160 underwent surgery alone.

The mean age of the patients was 60 years; 75% presented with adenocarcinoma and the remainder presented with squamous cell carcinoma, said Dr. Hulshof.

All patients were treated with a 4-field conformal radiation technique (total dose, 41.4 Gy) delivered in 23 fractions of 1.8 Gy to the primary tumor and to all pathologic lymph nodes, and an elective lymph node area of 4 cm in the craniocaudal direction from the primary tumor, Dr. Hulshof reported.

Patients also received 5 weekly concurrent courses of carboplatin and paclitaxel 50 mg/m².

Esophageal-cardia resection was performed at 8 weeks.

After a minimum follow-up of 24 months (median, 45 months), the overall recurrence rate was significantly lower in patients who received preoperative chemoradiation than in those who underwent surgery alone (35% vs 58%).

Locoregional recurrences accounted for most of the difference between the groups (13% vs 36%; P <.0001), with a much smaller difference in the rate of distant metastases (29% vs 36%).

An analysis of the location of locoregional recurrences showed that chemoradiation patients had a significantly lower rate of recurrence at the anastomosis (5% vs 9%) and the mediastinum (7% vs 21%).

Peritoneal carcinomatosis was significantly lower in the chemoradiation group (4% vs 14%; P < .0001), which is "a very remarkable finding," said Dr. Hulshof. There was also a small but significant effect on the rate of hematogenous dissemination (29% vs 36%; P = .025).

Of the 28 chemoradiation patients with a recurrence, 23 had both locoregional and distant metastases, and 5 had solitary locoregional recurrence.

A total of 11 (5%) recurrences occurred within the radiation field, 13 (6%) occurred outside the field, and 6 (3%) were classified as borderline or unclear.

"Therefore, extending the fields could prevent, at the most, 9% of locoregional failure," Dr. Hulshof told Medscape Medical News. "Given the expected low toxicity of the preop treatment and the burden of a locoregional recurrence, we have suggested a small extension of the field, to include the supraclavicular region for proximal tumors and the upper abdominal lymph node area (truncus coeliacus) for distal and gastroesophageal junction tumors."

Decrease in Peritoneal Seeding

Ravi Shridhar MD, PhD, a radiation oncologist from the Moffitt Cancer Center in Tampa, Florida, said he is not surprised that preoperative chemoradiation is associated with a reduction in locoregional recurrence and a nonsignificant difference in hematogenous spread, compared with surgery alone.

"The really interesting finding is the decrease in peritoneal seeding, which is considered metastatic," he told Medscape Medical News. "If a surgeon laparoscopically inspects the abdomen prior to resection and sees peritoneal carcinomatosis, the surgery is aborted; this is now stage IV disease. So in reality, this trial is showing not only a decrease in local recurrence, but also decrease in distant recurrence, which is a first for all the randomized trials conducted to date."

Dr. Shridhar noted that this study resulted in similar outcomes despite a lower radiation dose than that used in most studies.

"In the United States, the standard preoperative dose is 50.4 Gy, but in the CROSS trial, the dose was 41.4 Gy," he explained. "Pathologic complete response rates were reported as 29%, which is similar to that reported in many of the other trials conducted in esophageal cancer. Despite the lower dose used in the CROSS trial, response and local recurrence rates were just as good as, if not better than, previous reported trials."

Dr. Hulshof and Dr. Shridhar have disclosed no relevant financial relationships.

2nd European Society for Radiotherapy & Oncology (ESTRO) Forum. Abstract OC-0417. Presented April 22, 2013.


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