Preop Chemoradiation Benefits Confirmed in Esophageal Cancer

Megan Brooks

January 16, 2014

For patients with cancer of the esophagus or gastroesophageal junction, preoperative chemoradiotherapy (CRT) is better than surgery alone for local, regional, and distant disease control, new research shows.

In particular, it has a favorable effect on both hematogenous metastasis and peritoneal carcinomatosis, report Maarten Hulshof, MD, from the Academic Medical Center of Amsterdam, and colleagues.

The results of their study were published online January 13 in Journal of Clinical Oncology.

"Patterns of recurrence of esophageal cancer after surgery compared with CRT plus surgery are infrequently reported in the literature," the investigators note. "Understanding relapse patterns provides insight into the effectiveness of the combined treatment and may lead to improvements."

Dr. Hulshof's team analyzed patterns of recurrence after surgery alone and after preoperative CRT plus surgery in patients with esophageal or junctional cancer enrolled in the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) I and II.

Previous CROSS data have shown a significant overall survival advantage with CRT plus surgery (N Engl J Med. 2012;366:2074-2084).

For their analysis of recurrence patterns, Dr. Hulshof and colleagues used data on 418 of the 422 patients involved in the CROSS trials from 2001 to 2008. Histology indicated most disease was adenocarcinoma (75%).

CRT consisted of 5 weekly courses of paclitaxel and carboplatin (50 mg/m²) plus concurrent radiation (41.4 Gy delivered in 23 fractions of 1.8 Gy, 5 fractions per week, to the primary tumor and all pathologic lymph nodes). The target volume provided a proximal and distal margin of 4.0 cm and a radial margin of 1.5 cm around the gross tumor volume.

After a minimum follow-up of 24 months (median, 45 months), the overall recurrence rate was lower in the group treated with CRT plus surgery than in the group treated with surgery alone (35% vs 58%).

Preoperative CRT reduced locoregional recurrence from 34% to 14% (P < .001) and peritoneal carcinomatosis from 14% to 4% (P < .001).

There was also a "small but significant" effect on hematogenous dissemination in the CRT group (35% vs 29%; P < .025).

A pathological complete response was a favorable prognostic factor for both locoregional and systemic recurrence, the investigators report.

Most of the locoregional recurrences occurred with synchronous distant metastases, 5% were within the radiation field, 2% were in the margins, and 6% were outside the field. In 1% of recurrences, the exact site in relation to the target volume was unclear. Only 1% had an isolated infield recurrence after CRT plus surgery.

Partial findings were presented at the 2013 European Society for Radiotherapy & Oncology Forum, as reported at that time by Medscape Medical News.

"Important" Study

The investigators are to be "congratulated for this meticulous analysis," write Harvey J. Mamon, MD, PhD, from the Dana-Farber Cancer Institute in Boston, and Joel E. Tepper, MD, PhD, from the Lineberger Comprehensive Cancer Center at the University of North Carolina School of Medicine in Chapel Hill, in an accompanying editorial.

"The previous data from the CROSS trial demonstrated a survival advantage for combined preoperative radiation therapy and chemotherapy. This study strengthens the findings in terms of tumor control, which is important," Dr. Tepper explained in an email to Medscape Medical News.

"It also provides information that gives the practicing oncologist a better understanding of the reason for the improvement," he added.

"This study provides strong evidence that improving local control is critically important in improving survival in this disease, and that the combined use of neoadjuvant radiation therapy and chemotherapy is important for this benefit. Control of the primary tumor is essential for tumor cure, and it is likely that persistence of local disease will subsequently lead to disseminated tumor," Dr. Tepper noted.

The study was supported by the Dutch Cancer Foundation. The authors, Dr. Mamon, and Dr. Tepper have disclosed no relevant financial relationships.

J Clin Oncol. Published online January 13, 2014. Abstract, Editorial

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