Since the INT-0116 trial reported a survival advantage, postoperative chemoradiotherapy (CRT) has been a care standard for US patients in whom gastric adenocarcinoma has been diagnosed. We sought to estimate the association between treatment and survival among the older US Medicare population.

This is a retrospective cohort study of Medicare beneficiaries aged 65-79 years with stage IB-III gastric adenocarcinoma diagnosed between 2002 and 2009 in a Surveillance, Epidemiology, and End Results region. Patients were categorized on the basis of treatment: (1) gastrectomy only and (2) gastrectomy plus adjuvant CRT. We examined factors associated with receipt of adjuvant CRT, including stage at diagnosis, comorbidity, and tumor subtype. Overall survival was measured from 90 days after gastrectomy until death or the censoring date of December 31, 2010.

Of the 1519 patients who underwent gastrectomy, 41.7% received adjuvant CRT. Factors associated with adjuvant CRT included age younger than 75 years at cancer diagnosis and stage II or stage III cancer. The median overall survival from the time of gastrectomy was 25.1 months (interquartile range 43.7 months) for gastrectomy only and 26.9 months (interquartile range 40.9 months) for adjuvant CRT. Multivariable and propensity-score-stratified models demonstrated a survival benefit associated with adjuvant CRT [hazard ratio (HR) 0.58; 95% confidence interval (CI) 0.50-0.67], although the magnitude was greater for stage II tumors (HR 0.50; 95% CI 0.39-0.61) and stage III tumors (HR 0.58; 95% CI 0.45-0.73) than for stage IB tumors (HR 1.02; 95% CI 0.71-1.45).

Adjuvant CRT, in conjunction with gastrectomy, was associated with a survival benefit among older patients with stage II or stage III tumors.

While the curative approach to gastric cancer includes perioperative regimens in several countries, a substantial proportion of patients may not receive treatment prior to surgery. This study examines the adjuvant provision of chemoradiotherapy (CRT) for non-pretreated patients with cancer of the stomach including the gastric cardia.

All surgically treated patients with primary adenocarcinoma of the stomach and gastric cardia diagnosed between January 2004-December 2013 were selected from the Netherlands Cancer Registry. Patients who did not receive neoadjuvant treatment were included. Early gastric cancers (cT1), postoperative deaths within 90 days, patients with metastatic disease (M1), patients who received adjuvant chemotherapy and patients with macroscopic tumor after surgery (R2) were excluded.

Some 3277 patients underwent surgery, and 99 patients (3%) received adjuvant CRT. Treatment was more often administered in patients with a younger age (<65 years) and a high socioeconomic status (SES), in case of non-cardia cancer, positive lymph nodes, and positive resection margins (R1). Median survival time was 28 months (95% CI 17-39), compared to 35 months (95% CI 33-38) in CRT-naïve patients. After adjustment for confounders, a small net benefit for adjuvant CRT was found (hazard ratio, HR: 0.75, 95% CI 0.58-0.96). In subgroup analyses, benefit was most pronounced for patients with seven or more lymph metastases.

Marginal survival benefit was observed for adjuvant CRT in gastric cancer patients who did not receive neoadjuvant treatment. Treatment could be considered for patients with disease involving nodal invasion and those left with microscopic residual disease after surgery.

Despite results of the Intergroup 0116 (INT-0116) study showing an overall survival benefit of adjuvant chemoradiotherapy in gastric adenocarcinoma, its use in the United States remains controversial. The Surveillance Epidemiology of End Results (SEER) database was used to compare cause-specific survival outcomes in resected gastric adenocarcinoma with various adjuvant therapies and patterns of care.

Individual data from 1988 to 2008 were selected for patients with resected, nonmetastatic gastric adenocarcinoma. These patients were stratified by stage (American Joint Committee on Cancer [AJCC], 6th edition), as well as treatment modalities (surgery alone, S; surgery followed by radiotherapy, SR; surgery with chemotherapy, SC; surgery followed by radiotherapy with chemotherapy, SRC; and radiotherapy followed by surgery with chemotherapy, RSC). Overall 21,472 patients (8335 stages IA and 1B; 5944 stage II, 4594 stage III, and 2599 stage IV) were included in this study.

The median age of the cohort was 66 years, with 63.0% male and 66.4% white. The median number of lymph nodes examined was 17.6. Median survival by stage was 96 months for stage I, 30 months for stage II, 20 months for stage III, and 14 months for stage IV. Using the SRC group as the reference group, for stage I patients, S had the most favorable cause-specific survival (hazard ratio [HR], 0.67; confidence interval, [CI] 0.60-0.76). For patients with stage II, III, or IV, those treated with SRC had the best outcome compared with the other treatment modalities. After 1999, the number of patients treated with surgery alone decreased by at least 14%, whereas the number treated with SRC increased by approximately 12%.

This large SEER database analysis showed that stage I patients benefited most from surgery alone, whereas those at more advanced stages benefited most from adjuvant radiotherapy with chemotherapy. This result is consistent with INT-0116 for gastric adenocarcinoma in support of trimodality therapy and is reflected by the increased fraction of patients receiving chemotherapy and adjuvant radiation.

Randomized trials have shown an increase in survival with perioperative chemotherapy as well as with postoperative chemoradiation. It was hypothesized that combining induction chemotherapy with postoperative chemoradiation would be well tolerated and improve pathologic complete response.

Patients with resectable cancers of the stomach/gastroesophageal junction were eligible. Neoadjuvant chemotherapy consisted of 3 cycles of paclitaxel and cisplatin. Adjuvant therapy consisted of 1 cycle of 5-fluorouracil (FU) and leucovorin (LV) followed by chemoradiation (45 Gy with concurrent 5-FU/LV). Chemoradiation was followed by 2 additional cycles of 5-FU/LV. Response to neoadjuvant therapy was based on pathology.

From 1999 to 2002, 38 eligible patients were enrolled; 35 completed induction chemotherapy, and 29 went on to surgery. Sixteen patients did not develop metastatic progression, 10 developed metastatic disease, and 12 were unevaluable. There were no pathologic complete responses after induction therapy. Twenty-five of 38 patients suffered grade 3-4 toxicities during induction paclitaxel/cisplatin. Six of the 7 patients who received postoperative therapy suffered grade 3-4 toxicities. Only 3 of 38 (7.9%) eligible patients completed all assigned treatment. The median overall survival was 1.6 years, and the 2-year survival was 40%.

This regimen of neoadjuvant paclitaxel/cisplatin followed by postoperative 5-FU/LV-based chemoradiation did not have a high enough response rate and proved to be too toxic for further development.