September 09, 2011

Much controversy exists in determining the appropriate treatment for patients with localized gastroesophageal cancers. Contributing factors include differences in epidemiology of these cancers in different areas of the world, which lead to differences in behavior of these cancers and potentially in responses to therapy; inconsistent control for the type of surgical resection that is performed on the patients in trials; inclusion in some trials of cancers ranging from the distal esophagus to distal stomach, which may or may not be different diseases; and a number of trials that closed early due to lack of accrual and whose data may not be able to provide definitive answers.

Dr. Johanna C. Bendell

Multiple trials have tried to address the use of adjuvant chemotherapy for patients with gastric cancer, some showing benefit and others showing no benefit. Meta-analyses of these trials have also produced inconsistent results. We do know through the MAGIC trial (N. Engl. J. Med. 2006;355:11-20) that perioperative chemotherapy provides benefit to gastric cancer patients and through the INT-0116 study (N. Engl. J. Med 2001;345:725-30) that adjuvant chemoradiation therapy benefits patients.

There has been discussion that the radiation therapy in the INT-0116 trial may have improved local control, as only 10% of patients this trial had a D2 lymph node dissection, while 54% had a D0 lymph node dissection. The CLASSIC trial is a well-designed trial that controlled for surgery with all patients undergoing D2 resections. This trial showed a significant improvement in outcomes using adjuvant chemotherapy compared to observation.

The question now is - how does chemotherapy compare with chemoradiation? The POET study (J. Clin. Oncol. 2009;27:851-6) attempted to compare preoperative chemotherapy with chemoradiation therapy for patients with distal esophageal adenocarcinomas, GE junctional tumors, and proximal gastric tumors. This study closed early secondary to low accrual. However, there was a distinct trend to improved outcomes with chemoradiation, though with more toxicity. Surgery was relatively well-balanced between the two arms, suggesting that for this study there was no influence of the extent of lymph node dissection on the trial results.

Currently in the United States adjuvant chemoradiation therapy remains standard of care for gastric cancer patients. However, the CLASSIC trial teaches us several lessons and leaves us with several questions:

-- Should D2 resection be standard of care in the United States? National Comprehensive Cancer Center guidelines recommend this.

-- Are the results of the CLASSIC trial applicable to a U.S. population where the gastric cancers tend to be more proximal and more aggressive (rather than distal as in Asia) and in older patients?

<- Back to: What Matters