| Objective:To analyze the pathological reaction,survival and safety of neoadjuvant chemoradiotherapy(nCRT)or neoadjuvant chemotherapy(nCT)in patients with locally advanced adenocarcinoma of esophagogastric junction(AEG)and to explore the difference in efficacy between the two neoadjuvant treatment models.Methods:Prospective analysis of 156 patients with AEG received non-randomized neoadjuvant treatment in the Fourth Hospital of Hebei Medical University from January 2011 to January 2017.Among them,there were 133 males(85.3%)and 23 females(17.3%),the ratio of male to female was approximately 5.8:1.The median age was 62(26-79),and the average age was 61.5.There were 86 Siewert II and 70 Siewert III,of which 33 patients were in stage II and 123 patients were in stage III according to the clinical stage.There were 119 patients with adenocarcinoma alone and 37 patients with other types of adenocarcinoma.There were 66 patients in nCRT group and 90 patinets in nCT group.Patients in nCT group received XELOX regimen(capecitabine 1000 mg/m~2,oral,2/day d1~14;oxaliplatin 130 mg/m~2,intravenous infusion,d1,per 21 days)for chemotherapy;patients in nCRT group received XELOX regimen combined with radiotherapy which was performed in the involved field with an irradiation dose of 45 Gy/25 times.Six to eight weeks after the end of neoadjuvant treatment,patients who had no surgical contraindications received operation.The surgical approach consisted of transabdominal approach to the lower esophagus and proximal/total gastrectomy+D2 lymph node dissection.After radical resection,the original protocol was continued for 6 cycles.Using a propensity score matching method,the covariates were 1:1 paired between the nCRT group and the nCT group.109 cases(89.3%)were males and 13(10.7%)were females in the matching cohort.The ratio of male to female was approximately 8.4:1;the median age was 63 years(26-79),the average age was 62.1 years;Siewert type II was 76 cases,type III 46 cases;there were 92 cases of adenocarcinoma alone and 30 cases of other types of adenocarcinoma.According to the clinical stage,there were 35 cases in stage II and 87 cases in stage III.The short-term efficacy,pathological features,prognosis and safety of the two groups after matching were compared.Results:1.Pre-matching equilibrium tests showed that the composition ratios of the distribution of case characteristics between groups did not get balanced.The unbalanced baseline data were gender,Siewert classification,biopsy pathology,clinical T staging,and clinical N staging.122 patients were matched using propensity score matching method,with 61 cases in each group.2.Recist:There were 13 cases(21.3%)with stable disease(SD)and 48cases(78.7%)with partial remission(PR)in the nCRT group.As a comparison,there were 17 cases(27.9%)with stable disease(SD),34 cases(55.7%)with partial remission(PR),and 10 cases(16.4%)with disease progression(PD)in the nCT group.In the nCRT group,the disease control rate and objective effective rate were 100%and 78.7%,respectively.The disease control rate and objective effective rate in the nCT group were 83.6%and 55.7%,respectively,with statistically significant difference(?~2=10.839,P=0.001;?~2=7.290,P=0.007),which suggested that the disease control rate and objective efficiency in the nCRT group were obviously higher than those in the nCT group.3.Pathological features1)R0 resection rate:The R0 resection rates of nCRT group and nCT group were 91.8%and 86.9%,respectively,with no statistically significant difference.2)Tumor regression grade(TRG):In n CRT group,TRG 0,1,2,3 were10(16.7%),19(31.1%),27(45.0%),and 5 cases(8.3%),respectively.In nCT group,TRG 0,1,2,3 were 1(1.6%),4(6.6%),26(42.6%),and 30 cases(49.2%),respectively.The incidence rate of TRG 0 in the nCRT group was significantly higher than nCT group(?~2=8.093,P=0.004).3)Pathologic Complete Remission(pCR):p CR was defined as a postoperative pathologically confirmed tumor bed without cancerous cells or lymph node metastasis(ypT0N0).There were 11 patients(18.0%)with pCR in nCRT group and 1 patient(1.6%)with pCR in nCT group.The statistical difference was significant(?~2=9.242,P=0.002).4)Status of lymph node metastasis:In nCRT group,lymph node metastasis occurred in 27 cases,and the lymph node metastasis rate was 44.3%(27/61).A total of 1,574 lymph nodes were cleared and averagely 26 lymph nodes(4 to 59)were removed.53(86.9%)patients had more than 15 lymph node dissections,of which 76 lymph nodes were metastasized resulting the degree of lymph node metastasis was4.8%(76/1574).In nCT group,lymph node metastasis occurred in 36 cases,and the lymph node metastasis rate was 59.0%(36/61).A total of 2100 lymph nodes were cleared and averagely 34 lymph nodes(8 to 78)were removed.56(91.8%)patients had more than 15 lymph node dissections,of which 293lymph nodes were metastasized resulting the degree of lymph node metastasis was 14.0%(293/2100).The degree of lymph node metastasis in nCRT group was significantly lower than that in nCT group(?~2=82.895,P=0.000).There was no significant difference in the rate of lymph node metastasis between the two groups(?~2=2.659,P=0.103).5)Vessel tumor thrombus:The incidence rate of vascular tumor embolus in n CRT group and nCT group was 8.2%(5/61)and 14.8%(9/61),respectively,with no statistically significant difference(?~2=1.291,P=0.256).6)Nerve invasion:The incidence of nerve invasion in nCRT group and nCT group was 11.5%(7/61)and 19.7%(12/61),respectively,with no statistically significant difference(?~2=1.559,P=0.212).7)Postoperative declination of tumor's stage:Comparing preoperative with postoperative staging,the proportion of T staging declined in n CRT group was 44.3%(27/61),which was significantly higher than that in nCT group(21.3%)(?~2=7.290,P=0.007).The proportion of N staging declined in nCRT group was 50.8%(31/61),and it was 36.1%(22/61)in nCT group,indicating the proportion of N stage declined had a downward trend(?~2=2.702,P=0.100).4.Prognosis analysisTo the end of the last follow-up,68 patients survived in the whole group,41 patients died of tumor-related deaths,7 patients died of treatment-related deaths,and 6 patients were lost to follow-up.1)Distant metastasis and local recurrence:The incidence rate of distant metastasis in nCRT group and in nCT group was 26.2%(16/61)and 16.4%(10/61),respectively,with no statistically significant difference(?~2=1.760,P=0.185).The local recurrence rate in the nCRT group was 14.8%(9/61),which was significantly lower than that in the n CT group(34.4%)(?~2=6.365,P=0.012).2)Distant metassease-free survival rates in the 1 and 3 years were 82.9%and 55.1%,respectively.In the nCT group,the average DFS was 49.7±4.3months(95%CI:41.11 to 58.24).The 1-and 3-year DFS rates were 83.5%and 58.6%,respectively.There was no significant difference between the two groups(?~2=0.014,P=0.905).Univariate analysis showed that vascular tumor thrombosis and the status of postoperative lymph node metastasis were the influencial factors of DFS.The DFS rates of patients with pathologically confirmed vascular tumor embolism were 72.3%and 53.3%in the 1 and 3years,respectively,which were significantly lower than those of 84.9%and61.9%(?~2=4.427,P=0.035).The 1-and 3-year DFS rates in the patients with positive postoperative lymph node metastasis were 80.5%and 44.3%,which were significantly lower than those in the patients with negative lymph node metastasis group(87.8%and 70.9%).Multivariate analysis showed that the status of postoperative lymph node metastasis was an independent factor for DFS(Wald=8.923,P=0.003).3)Overall survival(OS):The mean OS of the nCRT group was 52.5±3.8months(95%CI:45.85 to 63.02).The 1-and 3-year survival rates were 89.4%and 63.8%,respectively.The mean OS of the nCT group was 54.4±4.3 months(95%CI:45.85 to 63.02).The 1-and 3-year survival rates were 86.9%and60.1%,respectively.There was no statistical difference between the two groups(?~2=0.237,P=0.627).Univariate analysis showed that the status of postoperative lymph node metastasis was an influencial factor for OS.The1-year and 3-year survival rates of patiens with positive postoperative lymph node metastasis group were 85.2%and 49.9%,respectively,which were significantly lower than those of patients with negative lymph node metastasis group(89.5%and 64.3%)(?~2=6.989,P=0.008).Multivariate analysis demonstrated that the status of postoperative lymph node metastasis was an independent influencial factor for OS(Wald=6.573,P=0.010).4)Subgroup survival analysis:Divide the entire patient group into subgroups such as sex(male/female),age(?60 years and 60 years),pathological type(adenocarcinoma alone/other types),lymph node metastasis(N0/N+),T stage(T3/T4),performing prognostic analysis of OS and DFS,respectively.The results showed that there was no significant difference in survival between the two treatment groups among subgroups above.5.Security analysis1)Gastrointestinal reactions were most common in non-hematological toxic reactions.The incidence rate of it in the nCRT group and nCT group were 73.7%(45/61)and 60.7%(37/61),respectively,with no statistically significant difference(?~2=2.380,P=0.123).The incidence rate of acute radiation esophagitis/gastritis in the nCRT group was 31.1%(19/61),including 13 cases(21.3%)in grade 1,4 cases(6.6%)in grade 2,2 cases(3.2%)in grade 3,and 0 cases in grade 4-5.The incidence rate of radiation pneumonitis was 9.8%(6/61),including 4 cases(6.6%)in grade 1,and 2 cases(3.2%)in grade 2.2)Hematologic toxicities:The incidence rate of grade 1 to 2 leukopenia in nCRT group was significantly higher than that in the nCT group(49.2%vs.24.6%,?~2=7.922,P=0.005).There was no significant difference between groups with higer level response.3)Perioperative mortality and hospital stay:There were 2 cases of perioperative death in nCRT group,1 died of respiratory failure,1 died of multiple organ dysfunction syndrome(respiratory,renal)and the rate of perioperative mortality was 3.3%.In nCT group,1 died of MODS(respiration,circulation,kidney)combined with septic shock,and the rate of perioperative mortality was 1.6%,with no statistically significant difference(?~2=0.342,P=0.559).The median hospital stay was 16d(11 to 37)in nCRT group and16d(12 to 40)in nCT group.with no statistically significant difference(P=0.215).Conclusion:The R0 resection rates of patients with locally advanced AEG in Siewert's type II and III were both high in the two treatments.Compared to nCT,nCRT could achieve tumor downstaging more easily,reach a higher pCR rate,reduce the degree of lymph node metastasis and get a lower risk of locoregional disease progression,but it did not significantly prolong OS.Patients in nCRT group could tolerate involved-fieid radiotherapy.The perioperative mortality was not significantly increased and the hospital stay was not significantly prolonged.The status of postoperative lymph node metastasis was an independent factor for PFS and OS. |
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