E. Strong (ed.). Gastric cancer. Principles and practice. Springer (2015)
An attempt to answer the question of whether there is a benefit for postoperative radiation in patients who have undergone a D2 gastrectomy was made by investigators of the Korean Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) trial. This study randomized 458 patients with stage IB-IV gastric cancer who had undergone D2 resections to either six cycles of adjuvant chemotherapy with the oral 5-FU pro-drug capecitabine and cisplatin or to two cycles of capecitabine/cisplatin before and after chemoradiation with capecitabine (Table 21.2; ). This study must of course be interpreted cautiously in a Western context but it does potentially offer insight into the benefit of radiation under these circumstances.
Table 21.2. Results of phase III postoperative chemoradiation trials in gastric and GE junction cancer
In the overall population, patients in the chemoradiation arm had a nonstatistically significant trend toward improved 3-year DFS (78.2 vs. 74.2%, p = 0.09). In a subgroup analysis of 396 patients with lymph node-positive disease, there was a statistically significant improvement in 3-year DFS in the chemoradiation arm (77.5 vs. 72.3%, p = 0.04). There was no difference in the rate of locoregional or metastatic recurrence in either arm. Based on these results, a follow-up study (ARTIST-II, NCT01761461) is ongoing for patients with lymph node-positive disease; in addition to being randomized to receive chemoradiation or chemotherapy alone, the systemic chemotherapy will consist of another 5-FU pro-drug S-1 alone or with the platinum compound, oxaliplatin.
Unfortunately, the results of the ARTIST trial do not provide definitive evidence for incorporating radiation into adjuvant therapy for optimally resected patients, although there may be a small absolute benefit of about 5% in 3-year DFS for radiation. The finding that radiation appears to benefit patients with lymph node-positive disease is somewhat counterintuitive since these patients are presumed to be at greater risk for developing distant metastases than patients with lymph nodenegative disease and might therefore be expected to derive less benefit from an approach designed to improve locoregional control. Finally, even if one were to adopt a strategy of adjuvant chemoradiation for this population, it is entirely unclear that the systemic chemotherapy should consist of a fluoropyrimidine/platinum doublet since the negative CALGB 80101 study has already shown no benefit to adding cisplatin (and an anthracycline) to a fluoropyrimidine.
In addition to the ARTIST-II study, the Dutch CRITICS study (NCT00407186) and the Australian TOPGEAR trial (NCT01924819) are also trying to definitively address the benefit of adding chemoradiation to postand preoperative chemotherapy, respectively.
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