After a median follow-up of 47.1 months, 25.2% of the chemoradiation group and 34.4% of the chemotherapy group had experienced disease recurrence or death.
Adjuvant chemoradiation may bolster survival outcomes in patients with high-risk locally advanced gastric cancer following D2 resection vs chemotherapy alone, according to results from a randomized phase 3 trial (NCT02648841) published in the International Journal of Radiation Oncology, Biology, and Physics.
After a median follow-up of 47.1 months (IQR, 20.8-64.6), 25.2% of the chemoradiation group and 34.4% of the chemotherapy group had experienced disease recurrence or death. Additionally, the 3-year disease-free survival (DFS) rates in each respective group were 70.7% vs 66.7%, and the 5-year rates were 69.4% vs 63.8% (HR, 0.82; 95% CI, 0.54-1.25; P = .35).
In postoperative treatment, DFS outcomes did not significantly improve with the addition of chemoradiation. Overall survival (OS; HR, 1.17; 95% CI, 0.74-1.87; P = .50), local recurrence-free survival (LRFS; HR, 0.59; 95% CI, 0.26-1.33; P = .20), or distant metastasis-free survival (DMFS; HR, 0.81; 95% CI, 0.51-1.28; P = .36) outcomes also did not significantly improve with chemoradiation.
In high-risk patients, defined as those with pN stage N2 disease or greater and with extraperigastric lymph node metastases, the 3-year DFS rates in the chemoradiation and chemotherapy groups were 71.0%% vs 53.0%, respectively (HR, 0.53; 95% CI, 0.29-0.97; P < .05). Significant differences were also observed between the 2 groups in this high-risk subgroup in LFRS (HR, 0.21; 95% CI, 0.05-0.94; P < .05) and DMFS (HR, 0.52; 95% CI, 0.27-1.00; P < .05).
“Our findings suggest that for patients with resectable [gastric cancer] after D2 radical gastrectomy, the addition of concurrent [chemoradiation] to adjuvant therapy did not result in further survival benefit, despite being well tolerated overall,” Xia-Xi Qiao, MD, of the Department of Radiation Oncology in the National Cancer Center and Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China, wrote in the publication with study coinvestigators. “However, after further selection of patients, we…concluded that for high-risk patients, the DFS of the treatment regimen with adjuvant [chemoradiation] was significantly better than that of adjuvant chemotherapy alone. In addition, the LRFS and DMFS of high-risk patients after [chemoradiation] were also significantly improved. This finding provides evidence for better identification of patient populations that can benefit from [radiation] and personalized treatment in clinical practice.”
Investigators in the phase 3 study enrolled 315 patients with locally advanced disease following D2 resection and randomly assigned them 1:1 to receive chemotherapy (n = 157) or chemoradiation (n = 155). Patients in both groups underwent 8 cycles of S-1 (Teysuno) plus oxaliplatin in the adjuvant setting. S-1 was given orally at 40 mg to 60 mg twice daily on days 1 to 14, and oxaliplatin was given at 130 mg/m2 intravenously on day 1 of each 21-day cycle.
Patients in the chemoradiation group received 4 to 6 cycles of chemotherapy as well as intensity modulated radiation therapy, comprised of 45 Gy in 25 fractions of 1.8 Gy from Monday to Friday over 5 weeks. Additionally, concurrent chemotherapy consisted of S-1 at 40 mg to 60 mg twice daily.
Patients in the chemotherapy and chemoradiation groups were primarily male (70.7% vs 72.9%) and the median age in each group was 59 years (range, 29-74) vs 57 years (range, 23-73). The primary tumor site in the respective arms was in the lower gastrointestinal tract (84.7% vs 84.1%), the most common histology subtype was diffuse (45.2% vs 51.0%), and the most common pN stage was N3 (42.7% vs 38.1%). In each arm, 99.4% vs 98.7% had 16 lymph nodes examined on study, and the median number of metastatic lymph nodes was 6 (IQR, 3-14) vs 7 (IQR, 3-12).
The primary end point of the trial was DFS. Secondary end points included OS, LRFS, DMFS, and adverse effects (AEs).
In the chemoradiation and chemotherapy groups, respectively, 69.5% and 65.6% of patients experienced acute toxicities, with events grade 3 or 4 in severity occurring in 18.5% and 26.1%. No significant differences between the groups were observed in any-grade or grade 3/4 toxicities.
The most common AEs in the investigational and control arms included leukopenia (52.3% vs 38.2%), anorexia (43.7% vs 47.1%), nausea and vomiting (41.7% vs 47.1%), thrombocytopenia (34.4% vs 31.2%), and body weight loss (15.2% vs 47.8%). The most common grade 3 or 4 AEs included leukopenia (7.9% vs 9.6%), thrombocytopenia (7.3% vs 9.3%), and nausea and vomiting (5.3% vs 7.0%).
Reference
Qiao X-X, Jiang H-G, Tang Y, et al. Long-term prognostic analysis of chemoradiation therapy versus chemotherapy after D2 Resection for high-risk gastric cancer: results from a prospective randomized control study. Int J Radiat Oncol Biol Phys. 2025;123(1):238-248. doi:10.1016/j.ijrobp.2025.03.044