Study On Treatment Models And Survival In Patients(≥70 Years Old)with Esophageal Squamous Cell Carcinoma

Objective:Through analyzing clinical data and prognostic factors of esophageal squamous cell carcinoma in elderly,and taking related adverse reactions into account to further explore its treatment modality,the study was performed to provide theoretical basis for evaluation of prognosis and choice of reasonable treatment modality.Methods:A total of 693 patients with esophageal squamous cell carcinoma confirmed by esophagoscopy/gastroscopy or operation pathologically in the fourth hospital of Hebei medical university from January 1 st 2014 to December 31th 2018 had been selected to make a retrospective study. Among those,the median age was 74 years（70-95）;416 cases（60.0%）were male;277 cases（40.0%）were female.25 cases were located in the cervical part of esophagus;136 cases in the upper thoracic segment;368 cases in the middle thoracic segment;189 cases in the lower thoracic segment.There were 43 cases（6.2%）in stageⅠ;233 cases（33.6%）in stageⅡ;417cases（60.2%）in stageⅢ.There were 247 cases who had received surgery,including 83 cases of postoperative chemotherapy and 164 cases of resection alone;There were 446 cases received radiotherapy,including 124 cases of radiochemotherapy and 322 cases of radiotherapy alone.Using a propensity score matching method,the covariates were 1:1 paired between the operation group and the radiotherapy group.The median age was 73 years（70-95）in the matching cohort.228 cases（65.1%）were males and 122（34.9%）were females.30 cases were located in the upper thoracic segment;205 cases in the middle thoracic segment;115 cases in the lower thoracic segment.There were 17cases（4.9%）in stageⅠ;165 cases（47.1%）in stageⅡ;168 cases（48.0%）in stageⅢ.There were 175 cases in each group after matching,including 111cases of resection alone;64 cases of postoperative chemotherapy;105 cases with radiotherapy alone;70 cases of radiochemotherapy.Survival conditions were analyzed,and the effects of different pathological characteristics and treatment modality on survival condition were explored.Besides,prognostic factors were analyzed.Results:1. Pre-matching equilibrium tests showed that the composition ratios of the distribution of case characteristics between groups was not well-balanced. The unbalanced baseline data were lesion length,lesion location,T staging,N staging and TNM staging.350 patients were matched by using propensity score matching method,with 175 cases in each group.2. Clinicopathological characteristics: （1）100 cases in operation group had lymph node metastasis of which the rate was 40.5%（100/247）.A total of4046 lymph nodes were dissected.Among them,267 nodes had lymph node metastasis of which the ratio was 6.6%（267/4046）.（2）Lymphatic metastasis ratio and positive lymph nodes ratio at stage T1,T2,T3 were of great metastasis rate and rate of positive lymph nodes in patients with tumor≤3cm, 3 to 5cm,and>5 cm were significantly different（χ²=16. 343,P=0.000;χ²=26.024,P=0.000）.3. Short-term efficacy:Among the patients in radiotherapy group,37cases（8.3%）reached CR;293 cases（65.7%）reached PR;110 cases（24.7%）reached SD;6 patients（1.3%）reached PD.The objective response rate（CR+PR）was 74.0%and the disease control rate（CR+PR+SD）was 98.7%.There was no significant difference in objective response rate and disease control rate between the radiotherapy group and the radiochemotherapy group4. Survival condition1)overall survival（OS）:the 1-,2-,3-and 5-year survival rates were 78.3%,60.4%,49.9%and 40.1%respectively.2)The survival rates of patients at stage T_1-2 were dramatically higher than those of patients at stage T₃（76.3%,57.1%,46.4%and 37.3%）（χ²=8.980,P=0.003）.3)The survival rates of patients at stage N0 were dramatically higher than those of patients at stage N+（χ²=9.648,P=0.002）.4)The survival rates of patients at stageⅠandⅠwere dramatically higher than those of patients at stageⅢ（χ²=5.731,P=0.017）.5)The survival rate of the operation group was much more promising than that of the radiotherapy group（χ²=5.415,P=0.020）.6)The survival rate of postoperative chemotherapy was much more promising than that of the radiochemotherapy（χ²=7.553,P=0.006）.7)The survival rate of postoperative chemotherapy was much more promising than that of the surgery alone（χ²=3.831,P=0.049）.8)No significant differences were found in the survival rate between the simple radiotherapy group and the radiochemotherapy group（χ²=0.114,P=0.735）.The survival rate of the group with irradiation dose between60.0～66.0Gy was significantly higher than that of the 50.4～59.4Gy group（χ²=5.940,P=0.015）.The survival rate of the IFI group and the ENI group had no significant difference（χ²=0.259,P=0.611）.9)The survival rate of the group with and without chemotherapy,had no significant difference（χ²=2.340,P=0.126）.5. Prognostic factors analysisMultivariate analysis showed that T staging,N staging and surgery/radiotherapy were independent influencing factors of OS（χ²=8.311,P=0.004;χ²=7.866,P=0.005;χ²=6.202,P=0.013）.6. Security analysis1)Complications and perioperative mortality in surgery group:There were 17 cases（9.7%）of postoperative complications,including 10 cases of anastomotic fistula,3 cases of lung infection,1 case of cardiac arrest,1 case of lower extremity venous thrombosis,1 case of intestinal obstruction and 1 case of wound rupture.There were 7 cases（4.0%）of perioperative death（within 30days after operation）among which 6 cases had multiple organ failure due to secondary thoracic infection of anastomotic fistula and there was 1 case of postoperative cardiac arrest.2)There were 68 cases（38.8%）with acute hematological toxicity in the radiotherapy group,including 28 cases（16.0%）graded 2 and 14 cases（8.0%）graded 3 or more.There were 96 cases（54.9%）with acute radiation esophagitis,including 67 cases（38.3%）graded 2 and 3 cases（1.7%）graded 3or more.There were 47 cases（26.9%）with acute radiation pneumonia,including 32 cases（18.3%）graded 2 and 8 cases（2.2%）graded 3 or more.The incidence of bone marrow suppression in the radiochemotherapy group was significantly higher than that in the radiotherapy alone group（χ²=18.769,P=0.000）.There was no significant difference in the incidence of radiation esophagitis and radiation pneumonitis between the two groups.And there were no significant differences in the incidence of bone marrow suppression,radiation esophagitis,and radiation pneumonia between the IFI group and the ENI group.Conclusions:1.The invasion depth and tumor length were the main factors for lymph node metastasis.With deeper invasive depth and longer of lesion,lymph node metastasis was easier to happen.2.If the elderly patients with esophageal cancer have good fitness,the first choice of surgery-based treatment model is recommended.A surgery in combination with adjuvant therapy regimen may be considered.3.Elderly patients with esophageal cancer who are not operable or refuse to operate,considering the efficacy and tolerability of elderly patients with esophageal cancer,radiation therapy alone is recommended,with a radiation dose of 60.0 to 66.0 Gy,and the irradiation field should be involved field radiation.4.T stage、N stage and surgery/radiotherapy are independent factors for survival of elderly patients with esophageal squamous cell carcinoma.