Clinical value of muscle index changing value during neoadjuvant chemotherapy in predicting the prognosis of gastric cancer after radical gastrectomy / 中华消化外科杂志

ABSTRACT

Objective:To investigate the clinical value of muscle index changing value during neoadjuvant chemotherapy in predicting the prognosis of gastric cancer after radical gastrec-tomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 362 gastric cancer patients undergoing neoadjuvant chemotherapy combined with radical gastrectomy in 3 medical centers, including 163 cases in Fujian Medical University Union Hospital, 141 cases in the Affiliated Hospital of Qinghai University and 58 cases in St. Mary′s Hospital, from January 2010 to December 2017 were collected. There were 270 males and 92 females, aged from 26 to 79 years, with a median age of 61 years. Of 362 patients, 304 cases in Fujian Medical University Union Hospital and the Affiliated Hospital of Qinghai University were allocated into modeling group and 58 cases in St. Mary′s Hospital were allocated into validation group. Observation indicators (1) changes of indicators including body composition parameters, tumor markers and stress status indicators in patients in modeling group during neoadjuvant chemotherapy; (2) follow-up and survival of patients; (3) analysis of risk factor affecting prognosis of patients in modeling group; (4) construc-tion and comparison of prognostic prediction models; (5) evaluation of prognostic prediction models. Follow-up was conducted using outpatient examination, telephone interview and mail communication to detect postoperative survival of patients up to April 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Univariate and multivariate analysis were performed using the COX proportional hazard model. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Results:(1) Changes of indicators including body composition parameters, tumor markers and stress status indicators in patients in modeling group during neoadjuvant chemotherapy the subcutaneous adipose index, visceral adipose index, muscle index, carcinoem-bryonic antigen, CA19-9, body mass index, prognostic nutritional index and modified systemic inflammation score of 304 gastric cancer patients in the modeling group before neoadjuvant chemotherapy were 31.2 cm 2/m 2(range, 0.6?96.0 cm 2/m 2), 25.1 cm 2/m 2(range, 0.1?86.3 cm 2/m 2), 47.1 cm 2/m 2(range, 27.6?76.6 cm 2/m 2), 43.2 μg/L(range, 0.2?1 000.0 μg/L), 108.7(range, 0.6? 1 000.0)U/mL, 21.9 kg/m 2(range, 15.6?29.7 kg/m 2), 46.8(range, 28.6?69.0), 1.0±0.8, respectively. The above indicators of 304 gastric cancer patients in the modeling group before radical gastrec-tomy were 32.5 cm 2/m 2(range, 5.1?112.0 cm 2/m 2), 25.4 cm 2/m 2(range, 0.2?89.0 cm 2/m 2), 47.0 cm 2/m 2(range, 16.8?67.0 cm 2/m 2), 17.0 μg/L(range, 0.2?1 000.0 μg/L), 43.9 U/mL(range, 0.6?1 000.0 U/mL), 21.6 kg/m 2(range, 31.1?29.0 kg/m 2), 47.7(range, 30.0?84.0), 1.0±0.8, respectively. The changing value of above indicators of 304 gastric cancer patients in the modeling group during neoadjuvant chemotherapy were 1.4 cm 2/m 2(range, ?31.0?35.1 cm 2/m 2), 0.2 cm 2/m 2(range, ?23.5?32.6 cm 2/m 2), ?0.1 cm 2/m 2(range, ?18.2?15.9 cm 2/m 2), ?26.2 μg/L(range, ?933.5?89.9 μg/L), ?64.9 U/mL(range, ?992.1?178.6 U/mL), ?0.3 kg/m 2(range, ?9.7?7.1 kg/m 2), 0.9(range, ?27.1?38.2), 0.0±0.8, respec-tively. (2) Follow-up and survival of patients 284 of 304 patients in the modeling group were followed up for 3 to 130 months, with a median follow-up time of 36 months. During follow-up, 130 cases died of tumor recurrence and metastasis and 9 cases died of non-tumor causes. The 5-year overall survival rate was 54.6%. Fifty-two of 58 patients in the validation group were followed up for 2 to 91 months, with a median follow-up time of 29 months. During follow-up, 21 cases died with the 5-year overall survival rate of 63.8%. (3) Analysis of risk factor affecting prognosis of patients in modeling group results of univariate analysis showed that the postoperative pathological type and postoperative pathological staging were related factors affecting 5-year overall survival rate [ hazard ratio=1.685, 2.619, 95% confidence interval(CI) 1.139?2.493, 1.941?3.533, P<0.05] and 5-year progression free rate survival of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio=1.468, 2.577, 95% CI 1.000?2.154, 1.919?3.461, P<0.05). Results of multivariate analysis showed that the postoperative pathological type and postoperative pathological staging were independent influencing factors for 5-year overall survival rate of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio=1.508, 2.287, 95% CI 1.013?2.245, 1.691?3.093, P<0.05) and the postoperative patholo-gical staging was an independent influencing factor for 5-year progression free survival rate of 304 gastric cancer patients in the modeling group after radical gastrectomy ( hazard ratio= 2.317,95% CI 1.719?3.123, P<0.05). (4) Construction and comparison of prognostic prediction models the area under curve (AUC) of prognostic prediction model of subcutaneous adipose index changing value, visceral adipose index changing value, carcinoembryonic antigen changing value, CA19-9 changing value, body mass index changing value, prognostic nutritional index changing value, modified systemic inflammation score changing value for 304 gastric cancer patients in the modeling group were 0.549(95% CI 0.504?0.593), 0.501(95% CI 0.456?0.546), 0.566(95% CI 0.521?0.610), 0.519(95% CI 0.474?0.563), 0.588(95% CI 0.545?0.632), 0.553(95% CI 0.509?0.597), 0.539(95% CI 0.495?0.584). The AUC of prognostic prediction model of muscle index changing value was 0.661(95% CI 0.623?0.705) with significant differences to the AUC of prognostic predic-tion model of subcutaneous adipose index changing value, visceral adipose index changing value, carcinoembryonic antigen changing value, CA19-9 changing value, body mass index changing value, prognostic nutritional index changing value, modified systemic inflammation score changing value, respectively ( Z=3.960, 5.326, 3.353, 4.786, 2.455, 3.448, 3.987, P<0.05). The optimum cut-off value was 0.7 cm 2/m 2 for prognostic prediction model of muscle index changing. Kaplan-Meier survival curve showed there were significant differences of overall survival and progression free survival for gastric cancer patients with subcutaneous adipose index changing value <0.7 cm 2/m 2 and ≥0.7 cm 2/m 2 in the modeling group ( χ2 =27.510, 21.830, P<0.05). The nomogram prognostic prediction model was cons-tructed based on 3 prognostic indicators including muscle index change value combined with postoperative pathological type and postoperative pathological staging and the AUC of nomogram prognostic prediction model were 0.762(95% CI 0.708?0.815) and 0.788(95% CI 0.661?0.885) for the modeling group and the validation group, respectively. The AUC of postoperative pathological staging prognostic prediction model were 0.706(95% CI 0.648?0.765) and 0.727(95% CI 0.594?0.835)for the modeling group and the validation group, respectively. There were significant differences of the AUC between the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging and the postoperative pathological staging prognostic prediction model in the modeling group and the validation group, respectively ( Z=3.522, 1.830, P<0.05). (5) Evaluation of prognostic prediction models the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging showed that patients with score of 0-6 were classified in the low risk group, patients with score of >6 and ≤10 were classified in the moderate-low risk group, patients with score of >10 and ≤13 were classified in the moderate-high risk group and patients with score of >13 were classified in the high risk group. Kaplan-Meier survival curve showed there were significant differences of the overall survival between the low risk group, moderate-low risk group, moderate-high risk group and high risk group patients in the modeling group and the validation group, respectively ( χ2 =75.276, 14.989, P<0.05). Results of decision making curve showed the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging had better clinical utility than the postoperative pathological staging prognostic prediction model in the modeling group and the validation group. Conclusions:The muscle index changing value of gastric cancer patient during neoadjuvant chemotherapy can be used as a prognostic indicator for gastric cancer patient prognosis after radical gastrectomy. The risk score of the nomogram prognostic prediction model of muscle index change value combined with postoperative pathological type and postoperative pathological staging can be used to evaluate the survival and prognosis of gastric cancer patients after radical gastrectomy.