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Prognosis impact of clinical characteristics in patients with inoperable esophageal squamous cell carcinoma.

ABSTRACT: Patients with inoperable esophageal squamous cell carcinoma (ESCC) were not homogeneous and their outcomes were widely divergent. There was a lack of identified clinical factors related to prognosis; and there were no previous studies constructing prognosis score to predict survival and guide treatment.In this retrospective cohort study, twelve clinical characteristics of one hundred and twenty inoperable ESCC patients were collected at diagnosis and analyzed by Cox regression model. Various methods including univariate analysis, confounding adjusted multivariate analysis and model selection were applied to determine factors associated with poor prognosis; and prognosis score was built on established factors.Four characters were identified as poor prognosis factors, including mid- and low-thoracic tumor (aHR = 2.20, 95% CI = 1.03, 4.72), abdominal and retroperitoneal lymph node metastasis (aHR = 1.62, 95% CI = 1.00, 2.64), albumin no more than 39g/L (aHR = 2.81, 95% CI = 1.24, 6.41) and hematogenous metastasis (aHR = 1.61, 95% CI = 0.97, 2.69). Patients were stratified into three groups by prognosis score, that was, good survival with none of four identified factors (score zero), poor survival with three to four factors (score three to four) and median with one to two factors (score one to two), survival of three groups were statistically different (ptrend = 0.020).Prognosis score based on selected clinical characteristics could predict survival among inoperable ESCC patients, which was critical for individualized treatment and central of precise medicine.

SUBMITTER: Yang Y

PROVIDER: S-EPMC5546576 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:Despite a series of attempts during the last decades, the prognosis of esophageal squamous cell carcinoma (ESCC) remains poor. Different responses of individual tumors encouraged us to look for valuable prognostic markers. As a key regulator controlling the anabolic ketogenic pathway, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) has been reported to play a crucial role in colorectal cancer and prostate cancer. However, its importance to ESCC has not been verified. Therefore, a large cohort retrospective study was planned, to investigate the relationship between HMGCS2 expression and ESCC prognosis. By adopting real-time polymerase chain reaction (PCR) and immunohistochemical (IHC) staining, HMGCS2 expression was examined in tissues of 300 ESCC patients with complete resection. Besides, the association between HMGCS2 protein expression and survival time was evaluated through chi-square test and Kaplan-Meier analysis. With the use of Cox-proportional hazards model, the prognostic impact of clinicopathologic variables and biomarker expression was evaluated. Compared with their non-tumor counterparts, HMGCS2 downregulation occurred in 65.5% and 37.6% of primary ESCCs on the mRNA and protein levels (P<0.001), respectively. On the protein level, HMGCS2 expression was associated with tumor cell differentiation (P=0.003), pT status (P=0.006), and TNM stage (P=0.010). In the down-HMGCS2 expression group, the 5-year overall survival (OS) and relapse-free survival (RFS) are poorer than those in the normal expression group (19 months vs 24 months, P=0.002; 13 months vs 17 months, P=0.007, respectively). According to the TNM stage, stratified analysis revealed that its discernibility on RFS was only pronounced in patients with advanced clinical stage (P=0.001). In addition, multivariate Cox regression analysis showed that HMGCS2 expression was an independent risk factor for RFS (P=0.032) instead of OS (P=0.099). The findings of this study provided the evidence that HMGSC2 represented a potential novel prognostic biomarker for ESCC patients.

Project description:Lessons learnedDefinitive concurrent chemoradiotherapy based on oxaliplatin and endostatin was effective with the objective response rate exceeding 80%, and the treatment-related toxicities were acceptable.The treatment compliance of the current combination was much higher, without significant reduction in survival outcomes, than historical reports.BackgroundThis phase II trial aimed at assessing the efficiency and safety of definitive concurrent chemoradiotherapy (dCRT) using oxaliplatin (OHP) and endostatin in patients with inoperable esophageal squamous cell carcinoma (ESCC).MethodsRadiotherapy was delivered with a daily fraction of 2.0 Gy to a total dose of 60.0 Gy over 6 weeks. Endostatin and OHP were both intravenously administered at doses of 7.5 mg/m2 daily for 2 weeks and 135 mg/m2 on day 1, respectively, every 3 weeks. The primary endpoint was the objective response rate (ORR).ResultsThe analysis included 37 patients. The median age was 63 years (range: 49-71 years), and all patients were stage III-IVA. Of these patients, 97.3% (36/37) completed the dCRT course with an ORR of 83.8%, including 10 (27.0%) patients with complete response and 21 (56.8%) patients with partial response. The median overall survival (OS) time was 18.5 months (95% confidence interval [CI]: 10.6-26.4) with a 2-year OS rate of 39.6% (95% CI: 0.202-0.590). The median progression-free survival (PFS) time was 11.5 months (95% CI: 7.6-15.4) with a 2-year PFS rate of 20.2% (95% CI: 0.049-0.355). Grade 3 toxicities included esophagitis (five patients) and leukocytopenia (three patients). Grade 4 leukopenia was observed in one patient. Late toxicity was infrequent, and no treatment-related death occurred. Posttreatment dysphagia scores were significantly improved when compared with baseline (p < .001).ConclusiondCRT based on OHP and endostatin resulted in high treatment compliance with manageable toxicities. This combination resulted in encouraging ORR without compromising survival outcomes. It should be validated in future clinical studies.

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Prognosis impact of clinical characteristics in patients with inoperable esophageal squamous cell carcinoma.

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