Abstract: Objective:To investigate the clinical efficacy of surgical treatment for stage Ⅳ gastric cancer after conversion therapy.
Methods:The retrospective cohort study was conducted. The clinicopathological data of 50 stage Ⅳ gastric cancer patients who were admitted to the First Affiliated Hospital of Dalian Medical University between January 2012 and June 2016 were collected. All the 50 patients who were diagnosed with single distal metastasis underwent chemotherapy. After chemotherapy, 21 patients with operation indication receiving gastrectomy (R₀ or R₁ resection) were allocated into the conversion surgery group and 29 without operation indication continuing to chemotherapy were allocated into the chemotherapy group. Patients received S1+oxaliplatin or S1 + docetaxel regimen. Patients underwent open distal or total gastrectomy. Observation indicators: (1) response assessment of chemotherapy (complete remission, partial remission, stable disease and progressive disease), grading of of adverse reactions; (2) intra and postoperative situations of conversion surgery group: operation procedures, intraoperative situations (operation time, volume of blood loss, number of lymph node dissected and surgical margin) and postoperative situations (complications and duration of hospital stay); (3) comparison of followup and survival between the 2 groups; (4) prognostic factors analysis affecting stage Ⅳ gastric cancer patients. Followup using outpatient examination, correspondence and telephone interview was performed to detect postoperative survival of patients up to September 2016. Survival time was from operation to the last followup or death. Measurement data with normal distribution were represented as ±s. Comparison of count data and univariate analysis were done using the chisquare test. Ordinal data were analyzed by the nonparametric test. The survival rate was calculated by the KaplanMeier method, and the Logrank test was used for survival analysis. Multivariate analysis was done using the COX regression model.
Results:(1) Response assessment of chemotherapy: of 50 patients, 24 received S1 + oxaliplatin regimen and 26 received S1 + docetaxel regimen. Twentyone patients in the conversion surgery group underwent chemotherapy, with negative peritoneal metastasis, N2 and below of lymph node metastasis (No.16 lymph node disappeared or reduced), invasive depth <T4b and narrowing or disappeared hepatic metastasis. A median preoperative chemotherapy cycle was 4.2 cycles (range, 2.0-9.0 cycles). Chemotherapy reaction of 21 patients: 15 had partial remission and 6 had stable disease. Twentynine patients without operation indication in the chemotherapy group didn′t receive surgery. The median cycle of firstline chemotherapy was 5.5 cycles (range, 2.0-10.0 cycles). Chemotherapy reaction of 29 patients: 13 had partial remission, 11 had stable disease and 5 patient had progressive disease. Chemotherapy adverse reactions of 50 patients: 26 had reduced white blood cells (WBCs), including 6 with grade Ⅲ-Ⅳ of adverse reactions; 29 had reduced neutrophils, including 12 with grade Ⅲ-Ⅳ of adverse reactions; 18 had anemia, including 6 with grade Ⅲ-Ⅳ of adverse reactions; 12 had reduced platelets, including 2 with grade Ⅲ-Ⅳ of adverse reactions; 27 had apositia, including 5 with grade Ⅲ-Ⅳ of adverse reactions; 7 had stomatitis; 9 had diarrhea; 3 had elevated serum creatinin; 4 had handfoot syndrome; 3 had abnormal sensory nerve. There was no chemotherapyrelated death. (2) Intra and postoperative situations of conversion surgery group: of 21 patients in the conversion surgery group, 8 underwent radical total gastrectomy + D3 lymph node dissection, 6 underwent radical distal gastrectomy + D3 lymph node dissection and 7 underwent radical distal gastrectomy + D2 lymph node dissection (including 4 combined with resection of hepatic metastatic tumors and 1 combined with radiofrequency ablation of hepatic metastatic tumor). Operation time, volume of blood loss, number of lymph node dissected and recovery time of gastrointestinal function of 21 patients were (216±31)minutes, (128±52)mL, 31±8 and (3.0±0.7)days, respectively. There were 17 patients receiving R₀ resection and 4 receiving R₁ resection (3 with positive gastric margin and 1 with positive hepatic margin). There was no death. Seven of 21 patients with complications were cured by conservative treatment, including 2 with pancreatic fistula, 1 with intraabdominal hemorrhage, 1 with intestinal obstruction, 1 with pneumonia, 1 with intraabdominal infection and 1 with wound infection. Duration of hospital stay of 21 patients was (13.0±3.0)days. (3) Comparison of followup and survival between the 2 groups: 50 patients were followed up for 6-46 months, with a median time of 24 months. The 3year cumulative survival rates in the conversion surgery and chemotherapy groups were respectively 33.3% and 6.9%, with a statistically significant difference between the 2 groups (x²=7.678, P<0.05). Results of further analysis showed that R₀ resection of 17 patients and R₁ resection of 4 patients in the conversion surgery group were respecgtively (25.3±2.8)months and (8.3±0.9)months, with a statistically significant difference between the 2 groups (x²=16.242, P<0.05). (4) Prognostic factors analysis affecting stage Ⅳ gastric cancer patients: results of univariate analysis showed that T stage, N stage, response assessment of chemotherapy, surgery after chemotherapy and degree of tumor radical resection were related factors affecting prognosis of stage Ⅳ gastric cancer patients (x²=5.288, 12.645, 25.581, 8.372, 12.001, P<0.05). Results of multivariate analysis showed that R₁ resection after conversion therapy was an independent risk factor affecting prognosis of stage Ⅳ gastric cancer patients (HR=14.021, 95% confidence interval: 1.928-10.938, P<0.05).
Conclusion:Radical resection after conversion therapy can increase survival rate of stage Ⅳ gastric cancer patients, and R₁ resection after conversion therapy is an independent risk factor affecting poor prognosis of stage Ⅳ gastric cancer patients.