Advanced Esophageal Squamous Carcinoma Research Articles

Analysis of factors affecting complete pathological remission after neoadjuvant immunocombination chemotherapy treatment for locally advanced esophageal squamous carcinoma.

e16061 Background: Chemotherapy combined with immunotherapy for locally advanced esophageal squamous carcinoma has achieved a high rate of complete pathological remission, which is conducive to a better prognosis for patients; however, not all ESCC patients benefit from ICI therapy, so finding validated prognostic markers of efficacy will help us to screen for populations that are superior to neoadjuvant immunotherapy. Methods: Patients with locally advanced esophageal squamous carcinoma treated with neoadjuvant immune-combination chemotherapy followed by radical surgery from January 2019 to June 2023 at our institution were collected. The grouping was based on whether pathologic complete remission (pCR) was achieved after neoadjuvant therapy. Clinical and treatment-related data as well as hematologic, inflammatory, and nutritional indices within 1 week before neoadjuvant therapy and within 1 week after 2 cycles of neoadjuvant immune-combination chemotherapy treatment were collected from all patients, and univariate and multivariate analyses were performed to assess independent predictors of pCR. Results: Patients in both pCR and Non-pCR groups were more likely to obtain pCR if they had pre-treatment BMI > 21Kg/m2 vs BMI ≤21Kg/m2, number of neoadjuvant therapy cycles ≥3 cycles vs number of neoadjuvant therapy cycles = 2 cycles, and CYFRA21-1ng/ml < 3.28 vs ≥3.28 before neoadjuvant therapy (p < 0.05). Patients with albumin ≥40.10g/L vs albumin < 40.10g/L, NLR < 2.50 vs NLR ≥2.50, and NRI ≥98.06 vs NRI < 98.06 were more likely to achieve pCR before treatment in both groups (p < 0.05). SII ≥521.75 VS SII < 521.75 was more likely to achieve pCR after 2 cycles of treatment (p < 0.05). Univariate analysis of the comparison of dynamic changes in nutritional inflammatory indexes during treatment between the two groups of patients showed that pCR was more likely to be achieved in patients with persistently elevated eosinophil counts and NLR after 2 cycles of neoadjuvant immune-combination chemotherapy treatment (p < 0.05). The results of multifactorial analysis showed that pre-treatment BMI, SII after 2 cycles of treatment, and dynamic changes in eosinophils during neoadjuvant therapy were independent influences on complete pathological remission after neoadjuvant immune-combination chemotherapy treatment (p < 0.05). Conclusions: Complete pathological remission after neoadjuvant immune-combination chemotherapy treatment for esophageal squamous carcinoma was significantly correlated with the patient's pre-treatment BMI, Post-treatment SII, and eosinophil dynamics during treatment.

A phase 2 study of fruquintinib in combination with S-1 for second-line treatment of esophageal squamous cell carcinoma after first-line immunotherapy failure.

323 Background: Patients with advanced esophageal squamous carcinoma (ESCC) who experience progression after first-line immunotherapy face a challenging treatment landscape. The potential of anti-vascular therapy combined with chemotherapy in the treatment of esophageal cancer is well-established. Mechanistically, anti-angiogenic agents can promote the normalization of tumor vasculature and facilitate the access of chemotherapeutic agents to tumor targets. Considering the compromised physical condition of advanced ESCC patients, there is a preference for more convenient oral medications. Therefore, we conducted this phase II study to assess the clinical efficacy and safety of combining fruquintinib with S-1 in treating advanced ESCC patients following first-line immunotherapy failure. Methods: This open-label, single-arm, phase II study consists of dose-finding and dose-expansion phases, enrolling advanced or metastatic ESCC patients after first-line immunotherapy failure. The dose-finding phase followed a 3+3 design. Patients received fruquintinib (3mg, 4mg, 5mg, d1-d14, q3w, respectively), in combination with S-1 (40mg, 50mg, 60mg, bid, d1-d14, q3w, based on body surface area (BSA)), until unacceptable toxicities, progressive disease, or death. The initial fruquintinib dose was 4 mg d1-d14, q3w, in combination with an appropriate S-1 dose. Additional patients were enrolled in the dose-expansion phase and received the maximum tolerated dose determined in the dose-finding phase. Results: As of August 1, 2023, seven patients were enrolled in the dose-finding phase. One patient withdrew consent during the DLT assessment period. Among the patients administered a 4mg dose of fruquintinib, one out of three achieved a confirmed partial response (PR) after 7 cycles of treatment. Additionally, two out of three patients at the 5mg dose level achieved PR after 2 cycles of treatment, resulting in an overall response rate (ORR) of 50% (3/6). The disease control rate (DCR) was 100% (6/6). The median progression-free survival (PFS) was observed to be 4.93 months (95% CI: 1.93 – 10.73), with overall survival (OS) at 10.73 months (95% CI: 2.1 – 10.73). In terms of safety, no dose-limiting toxicities (DLTs) were reported at 4mg dose level. While DLTs were observed in two out of the three patients at the 5mg dose level. The most common treatment-related adverse events (TRAE) across all grades were fatigue (5/7) and extremity pain (4/7). Grade 3 TRAE were identified in 5 patients, with hypertension (2/7), mucositis (2/7), and fatigue (2/7) being reported. No grade 4 or higher TRAEs were observed. Conclusions: Potential benefits were demonstrated when using fruquintinib in combination with S-1 for the treatment of ESCC patients after immunotherapy failure. The efficacy and safety of fruquintinib and S-1 will be further investigated in this trial later. Clinical trial information: NCT05636150 .

Camrelizumab in combination with neoadjuvant chemotherapy in resectable locally advanced esophageal squamous carcinoma cancer: Results from a retrospective study.

This study aimed to evaluate the safety and efficacy of camrelizumab combined with chemotherapy during preoperative neoadjuvant therapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) of clinical Stages II and III. The patients received camrelizumab plus chemotherapy regimen on Day 1 for up to three to four cycles (3 weeks per cycle). The probabilities of overall survival (OS) were 55.6% at 12 months and 35.6% at 18 months (45 patients). The disease-free survival (DFS) rates were 70.0% at 12 months and 63.3% at 18 months (30 patients). The median OS and DFS were not reached. The proportion of patients at postneoadjuvant pathological tumor stages ypT0, ypT2, and ypT3 were 10 (33.3%), 14 (46.7%), and 6 (20.0%), respectively, and those at stages ypN0 and ypN1 were 19 (63.3%) and 11 (36.7%), respectively. Additionally, the pathological complete response rate was 33.3% (95% confidence interval [CI]: 0.154-0.512), and the major pathologic response rate was 46.7% (95% CI: 0.277-0.656). Grade ≥3 adverse events (AEs) were reported in five patients (11.1%), with vomiting being the most common AE (three patients; 3.3%). Other common AEs of any grade included decreased lymphocyte count (48.9%), reactive capillary endothelial proliferation (46.7%), decreased white blood cell count (40.0%), anemia (31.1%), and vomiting (31.1%). The combination of camrelizumab and neoadjuvant chemotherapy in patients with locally advanced resectable ESCC demonstrated promising efficacy and acceptable safety.

Positive lymph node ratio is an important index to predict long-term survival for advanced esophageal squamous carcinoma patients (II∼III) with R0 resection--a SEER-based analysis

BackgroundEsophageal squamous carcinoma (ESCC) is one of the most malignant cancers in the world due to nodal metastasis. Therefore, a reasonable nodal staging system is extremely important for further treatment strategies. Recently the positive lymph node ratio (PLNR) is an important prognostic factor in various solid tumors MethodIn this study, we investigated the clinical significance of the PLNR in stage II∼III ESCC patients. We collected the pathological characteristics of 272 stage II∼III ESCC patients from the SEER database from 2004–2016. ROC curves were used to calculate the best cutoff value of the PLNR; Pearson's Chi-square (χ2) and Fisher's exact probability tests were used to compare the clinical baseline and characteristics of patients. For continuous variables, Student's t-test and ANOVA were performed to evaluate statistical significance. Clinical outcomes were estimated by using the Kaplan‒Meier method and log-rank test. Furthermore, univariate and multivariate Cox regression models were utilized to analyze independent prognostic factors of ESCC patients. ResultsConsequently, advanced ESCC patients were effectively stratified into two groups by prognosis using a PLNR cutoff value of 0.15 (P value = 0.04). The median survival time of patients with PLNR <0.15 (n = 145) was much higher than that of patients (n = 127) in the PLNR ≥0.15 group (20.0 vs. 13.0 months, P value < 0.0001). Notably, the PLNR significantly predicted the prognosis of ESCC patients with stage N1 (P value 0.01) and stage III (P value < 0.001) disease. The multivariate Cox proportional hazard model showed that T stage (HR 1.33, 95 % CI 0.97–1.82), tumor size >45 mm (HR 1.32, 95 % CI 1.02–1.70), N stage (HR 1.41, 95 % CI 0.98–2.01) and PLNR ≥0.15 (HR 1.35, 95 % CI 0.87–1.74) were independent risk factors for prognostic prediction in ESCC patients. Meanwhile, 117 II∼III ESCC patients from Shaanxi Provincial People's Hospital shown that the overall survival with a PLNR <0.15 (n = 96) was significantly longer than that with a PLNR ≥0.15 (n = 21) . ConclusionsThe PLNR is useful for accurately predicting clinical outcomes and determining postoperative strategies.

Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.

Moderately hypo-fractionated radiotherapy combined with S-1 in inoperable locally advanced esophageal squamous cell carcinoma: A prospective, single-arm phase II study (GASTO-1045).

We launched this prospective phase II single-arm trial on the combination of moderately hypo-fractionated radiotherapy and S-1, to explore the safety and efficacy of the new potent regimen in inoperable locally advanced esophageal squamous carcinoma (LA-ESCC) patients. Patients with unresectable stage II-IVB LA-ESCC (UICC 2002, IVB only with metastatic celiac or supraclavicular lymph nodes) were included. Moderately hypofractionated radiotherapy (60Gy in 24 fractions) concurrent with S-1 was delivered. Meanwhile, gastrostomy tube placement by percutaneous endoscopic gastrostomy (PEG) was performed to provide nutritional support. Nutritional supplements were prescribed to meet requirements. The study outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), failure pattern, toxicities, nutritional status and treatment compliance. Endoscopy was routinely performed during post-treatment follow-up. Fifty-eight patients were included with a median follow-up of 24.4 months. The median age was 63 years (range 49-83 years) and 42 patients (72.4%) had stage III or IV diseases. The ORR was 91.3% and the CR rate was 60.3%. The estimated 2-year PFS rate and 2-year OS rate was 44.2% (95% confidence interval (CI), 31.3-57.1%) and 71.4% (95% CI, 59.4-83.4%), respectively. Radiation-induced esophagitis was the most common non-hematologic toxicity and 5 patients (8.6%) developed grade≥3 esophagitis. While, with PEG nutrition support, the nutrition-related indicators presented a clear trend toward a gradual improvement. Treatment-related death was not observed. The moderately hypo-fractionated radiotherapy combined with S-1 showed promising loco-regional disease control and survival benefit in inoperable LA-ESCC patients. Meanwhile, favorable nutritional status and low incidence of severe radiation-induced esophagitis were observed with PEG nutritional support. Moreover, endoscopy examination contributed to the early detection of recurrent esophageal lesions and timely salvage treatment. The efficacy and toxicity of the combined regimen deserved further evaluation. Clinicaltrials.gov, identifier NCT03660449.

Predictive nomogram for postoperative atrial fibrillation in locally advanced esophageal squamous carcinoma cell with neoadjuvant treatment.

Neoadjuvant therapy following minimally invasive esophagectomy is recommended as the standard treatment for locally advanced esophageal squamous carcinoma cells (ESCC). Postoperative atrial fibrillation (POAF) after esophagectomy is common. We aimed to determine the risk factors and construct a nomogram model to predict the incidence of POAF among patients receiving neoadjuvant therapy. We retrospectively included patients with ESCC receiving neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), or neoadjuvant immunochemotherapy (nICT) following minimally invasive esophagectomy (MIE) for analysis. Patients without a history of AF who did not have any AF before surgery and who developed new AF after surgery, were defined as having POAF. We applied a LASSO regression analysis to avoid the collinearity of variables and screen the risk factors. We then applied a multivariate regression analysis to select independent risk factors and constructed a nomogram model to predict POAF. We used the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) curve to evaluate the nomogram model. A total of 202 patients were included for analysis, with 35 patients receiving nCRT, 88 patients receiving nCT, and 79 patients receiving nICT. POAF occurred in 34 (16.83%) patients. There was no significant difference in the distribution of neoadjuvant types between the POAF group and the no POAF group. There was a significant increase in postoperative hospital stay (p = 0.04), hospital expenses (p = 0.01), and comprehensive complication index (p < 0.001). The LASSO analysis screened the following as risk factors: blood loss; ejection fraction (EF); forced expiratory volume in 1 s; preoperative albumin (Alb); postoperative hemoglobin (Hb); preoperative Hb; hypertension; time to surgery; age; and left atrial (LA) diameter. Further, preoperative Alb ≤41.2 g/L (p < 0.001), preoperative Hb >149 g/L (p = 0.01), EF >67.61% (p = 0.008), and LA diameter >32.9 mm (p = 0.03) were determined as independent risk factors of POAF in the multivariate logistic analysis. The nomogram had an area under the curve (AUC) of 0.77. The Briser score of the calibration curve was 0.12. The DCA confirmed good clinical value. Preoperative Alb ≤41.2 g/L, LA diameter >32.9 mm, preoperative Hb >149 g/L, and EF >67.61% were determined as the risk factors for POAF among patients with ESCC. A novel and valuable nomogram was constructed and validated to help clinicians evaluate the risk of POAF and take personalized treatment plans.

Abstract 416: Toripalimab plus paclitaxel and carboplatin as neoadjuvant therapy in patients with locally advanced resectable esophageal squamous carcinoma: An open-label, single arm phase 2 trial

Abstract Background: Immune checkpoint inhibitors (ICIs) have shown promising results in patients with advanced esophageal squamous carcinoma (ESCC), while their efficacy for locally advanced patients is unclear. We conducted a neoadjuvant immunotherapy trial, investigating the safety and feasibility of toripalimab, a PD-1 inhibitor, combined with paclitaxel and carboplatin in patients with resectable ESCC (ClinicalTrials.gov identifier: NCT04177797). Methods: Between May 2020 and June 2020, 18 patients with histopathologically diagnosed ESCC, clinically staged as T3N1-3M0, ECOG PS 0, received toripalimab 240 mg IV, D1, Q3W and paclitaxel 135 mg/m2, IV, D1, Q3W and carboplatin AUC 5 mg/mL per min, IV, D1, Q3W for two cycles, followed by McKeown esophagectomy 4-6 weeks later. The primary endpoint were safety and major pathological response (MPR) rate, and the secondary point were pathological complete response (pCR) rate, DFS and OS. Results: Sixteen patients received surgery with no treatment-related surgical delay, and the R0 resection rate was 87.5% (14/16). Two patients refused surgery due to the clinical assessment as complete response. Among 16 patients undergoing surgery, 3 (16.6%) were pCR and 7 (43.8%) were MPR. Treatment-related adverse events occurred in all patients (100%), and 4 patients (22.2%) experienced grade 3 or higher treatment-related adverse events including neutropenia (2, 12.5%), leukopenia (1, 6.2%), diarrhea (1, 6.2%), fatigue (1, 6.2%). No surgery-related adverse events or treatment-related death occurred. Conclusions: The combination of toripalimab, paclitaxel and carboplatin for patients with locally advanced resectable ESCC is well tolerated and shows antitumor activity, which might be a potential neoadjuvant therapy regimen. Citation Format: Wenwu He, Lin Peng, Yu Bao, Wenguang Xiao, Qiang Fang, Xuefeng Leng, Jiaxin Yan, Tianqin Mao, Xudong Shen, Depei Huang, Hushan Zhang, Xueke She, Yongtao Han. Toripalimab plus paclitaxel and carboplatin as neoadjuvant therapy in patients with locally advanced resectable esophageal squamous carcinoma: An open-label, single arm phase 2 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 416.

Abstract 344: Correlative biomarker analyses: Toripalimab plus paclitaxel and carboplatin as neoadjuvant therapy in an open-label, single arm phase 2 trial in locally advanced esophageal squamous carcinoma

Abstract Background: NCT04177797 was an open-label, single arm phase 2 trial in locally advanced esophageal squamous carcinoma (ESCC), which adopted toripalimab, plus paclitaxel and carboplatin as neoadjuvant immunotherapy regimen. Here we report correlative biomarker analyses for all 18 included patients. Methods: After two cycles of neoadjuvant immunotherapy, sixteen patients underwent surgery and seven of them achieved major pathological response (MPR). Two patients did not receive surgery but their imaging evaluation were both clinical complete response (cCR). We defined MPR or cCR as responders, and others as non-responders. Peripheral blood, gastroscopic tumor and adjacent normal tissues were collected before the first dose of drug and so did surgery samples. Whole exome sequencing (WES) and RNA-seq were conducted for the pretreatment tissues, and surgery samples were performed for multiplex immunohistochemistry (mIHC) with 5 markers. Results: In pretreatment tumor tissues, there was no significant difference either in the CD8+ (p=0.19) or CD68+HLA-DR- (p=0.57) density between responders and non-responders. However, CD8+ density increased (p=0.0078) and CD68+HLA-DR- density decreased (p=0.039) significantly in responders after neoadjuvant combined immunotherapy, whereas these two markers did not in non-responders (p=0.13 and p=0.36, respectively). Meanwhile, responders were associated with higher baseline gene expression levels of CXCL 5 (p=0.03) and lower baseline CCL 19 (p=0.017) and UMODL1 (p=0.03). Conclusions: The mechanism of tumor response may be associated reduction of M2 macrophages and CD8 cells recruitment after combined immunotherapy in locally advanced resectable ESCC. Citation Format: Wenwu He, Lin Peng, Yu Bao, Wenguang Xiao, Qiang Fang, Xuefeng Leng, Jiaxin Yan, Tianqin Mao, Xudong Shen, Depei Huang, Hushan Zhang, Xueke She, Yongtao Han. Correlative biomarker analyses: Toripalimab plus paclitaxel and carboplatin as neoadjuvant therapy in an open-label, single arm phase 2 trial in locally advanced esophageal squamous carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 344.

A real-world clinical study of camrelizumab in the treatment of esophageal cancer.

e16008 Background: Camrelizumab, a fully humanized monoclonal antibody against PD-1, has been approved in the treatment of advanced esophageal squamous carcinoma in China. The purpose of this study was to observe the efficacy and safety of Camrelizumab in the treatment of esophageal cancer in the real world. Methods: This is an open-label, prospective, multicenter, observational study. Eligible patients (pts) who received Camrelizumab had esophageal cancer; age≥18, ECOG PS of 0-2; and measurable disease. Results: As of November 30, 2020, a total of 229 patients were enrolled, of which 192 were male (83.8%). The ECOG PS score was 0 in 48 cases (21.0%), 1 in 149 cases (65.0%), and 2 in 32 cases (14.0%). Among the 134 patients of stage IV patients (58.5%), 174 patients had metastases (76.0%), and 99% of patients did not undergo PD-L1 testing. A history of radiotherapy accounted for 57.6%, and a history of surgery on the primary lesion accounted for 42%. Camrelizumab accounted for 26.2% of the first-line treatment, 33.6% of the second-line treatment, and 35.4% of the third-line and above. Camrelizumab combined with chemotherapy accounted for 40%, combined with anti-angiogenesis therapy accounted for 38.0%, combined with anti-angiogenesis + chemotherapy accounted for 9.0%, and combined radiotherapy accounted for 6.2%. Among 145 patients with evaluable efficacy, 5 cases of CR, 14 cases of PR, 97 cases of SD, and 29 cases of PD. The ORR reached 13.1% and the DCR reached 80.0%. The overall adverse event rate was 42.8%, the major adverse event RCCEP rate was 11.7%, pneumonia was 8.3%, and fatigue was 4.1%. Adverse events greater than or equal to grade 3 included 1 case of RCCEP, 3 cases of bleeding, 1 case of diarrhea, and 1 case of fever. Conclusions: In this real-world study of esophageal cancer, most of the patients enrolled were patients with poor PS score and late stage, but the efficacy and safety of Camrelizumab in patients with advanced esophageal cancer were still confirmed. The dominant population and combination therapy are still under study. Clinical trial information: ChiCTR1900027275.

Dynamic contrast-enhanced MRI histogram parameters predict progression-free survival in patients with advanced esophageal squamous carcinoma receiving concurrent chemoradiotherapy.

There is increased interest in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for predicting the outcomes of patients with advanced esophageal cancer. To explore whether DCE-MRI histogram parameters can predict 12-month progression-free survival (PFS) in patients with advanced esophageal squamous carcinoma receiving concurrent chemoradiation therapy (CRT). This retrospective study enrolled 134 patients with advanced esophageal squamous carcinoma who were receiving CRT. The pre-CRT DCE-MRI histogram parameters (median, mean, SD, skewness, kurtosis, and 10th and 90th percentiles) of Ktrans, Kep, and Ve were collected. PFS analyses were performed using the Kaplan-Meier method and log-rank tests to compute the survival curves. The significant prognostic predictors among the data characteristics and DCE-MRI parameters were determined using multivariate Cox proportional hazards regression analyses. There were 65 good responders (PFS ≥ 12 months) and 69 poor responders (PFS < 12 months). The median and mean values of Ktrans were higher, and the kurtosis value of Ktrans was lower in good responders. The median, mean, and 10th and 90th percentile values of Ktrans were higher, and the kurtosis values of Ktrans and Ve were lower in good responders. The PFS of patients aged ≥60 years, a CR effect, or a 10th percentile value of Ktrans ≥0.13 was increased (P < 0.001, <0.001, and 0.014, respectively). DCE-MRI histogram parameters can be used to evaluate the response to CRT in patients with advanced esophageal squamous carcinoma. The 10th percentile value of Ktrans has significant prognostic value for 12-month PFS.

Serum MicroRNAs in Predicting the Efficacy of Chemoradiotherapy for Locally Advanced Esophageal Squamous Carcinoma

Chemoradiotherapy is the main treatment for locally advanced esophageal squamous cell cancer, yet the molecular mechanisms underlying its response and outcomes remain elusive. MicroRNAs (miRNAs) are closely related with tumor genesis, diagnosis and prognosis. Serum miRNAs, steadily expressed and easily to test, are expected to be ideal markers in predicting chemoradiotherapeutic efficacy. Our study is to explore whether serum miRNAs can predict the clinical outcomes for locally advanced esophageal squamous cell carcinoma patients. Patients with primary pathologically diagnosed esophageal squamous cell carcinoma, with disease of stage T3-4/N1, M0-M1a, who received chemoradiotherapy were enrolled. Before starting the treatment, patients received a baseline blood draw for miRNA expression profiling. Tumor assessment and follow up were performed every 3 months. According to overall survival time and local regional relapse free survival time, patients were divided into good and poor outcome groups. We selected 15 patients in each group （Group A with good prognosis, Group B with poor prognosis) and their characteristics were without significant differences from chi-square test. We surveyed the expression of 769 miRNAs of these 30 patients, using ABI TaqMan miRNA chip method. MiRNAs with RQ value≤0.5 or ≥2 and P value ≤0.05 were defined to be associated with therapeutic efficacy. From August 2007 to December 2010, 30 patients were selected for miRNA profiling. The gender(P=0.543), age (P=0.477), location(P=0.519) , and stage(P=0.879) were comparable between the 15 patients from Group A and the 15 patients from Group B. The median survival time of the two group were with significant differences(P<0.001). High level of miR-624, miR-338 and miR-196 were observed in Group A compared with Group B. The RQ values were 3.6269、4.3804 and 3.6661, respectively and P values were 0.0499,0.0191, and 0.0129，respectively. Moreover, log-rank test indicated that patients with high levels of miR-328 (P=0.019) and miR-374a(P=0.044) had more favorable overall survival compared with patients with low levels. Another result from log-rank test is that patients with high levels of miR-323a(P=0.004) and low levels of miR-222(P=0.024) had poor locoregional relapse free survival. We developed a prognostic serum miR-328, miR-374a, miR-323a, miR-222, miR-624, miR-338 and miR-196 signature in an independent dataset of patients with locally advanced esophageal squamous cell carcinoma who received chemoradiotherapy. These preliminary results indicated that miRNAs might serve as promising molecular prognostic markers and new therapeutic targets for esophageal carcinoma.

Involved Field Radiation Therapy (IFRT) with Omission of Prophylactic Nodal Irradiation in Locally Advanced Squamous Carcinoma of the Thoracic Esophagus: A Retrospectively Comparative Analysis of Clinical Outcomes

Involved field radiotherapy (IFRT) omitting prophylactic radiation to clinically uninvolved lymph nodes has raised concerns for increased nodal failures. This retrospective cohort analysis evaluated the failure patterns and survival of locally advanced squamous carcinoma of the thoracic esophagus patients treated with elective nodal irradiation (ENI) or IFRT at a single institution. We assessed all locally advanced esophageal squamous carcinoma (LA-ESCC) patients treated with definitive concurrent chemoradiotherapy from January 2003 to January 2013. Thoracic LA-ESCC patients with well-documented clinical reports available were included whether they underwent ENI or IFRT. Survival time was calculated using Kaplan-Meier methodology. The cumulative incidence of failure patterns was determined according to the first sites of failure including local, regional, distant failure patterns. Regional recurrences were classified as “PTVifi,” “Out-PTVifi in-PTVeni failure,” “Out-PTVeni failure” through comparing the three-dimensional localization images with tumor recurrence images. A total of 313 thoracic LA-ESCC patients met the inclusion criteria. Similar response rates were observed in two groups (P = 0.204). No significant difference existed in 1-, 2-, and 3-year survival rates (P = 0.101) while patients of IFRT group exhibited better 5-year survival rate (P= 0.042). Local failure rate ranked the first in both groups. Either isolated out-PTVifi in-PTVeni failure rates (7% IFRT vs. 5% ENI) or Out-PTVifi in-PTVeni failure simultaneously with other failures rates (11% IFRT vs. 14% ENI) showed no significant difference in two groups. IFRT patients demonstrated a significantly lower risk of high-grade (Grade ≥3) esophagitis (P = 0.03), lung injury (P = 0.011), and bone marrow suppression (P = 0.041). Omission of prophylactic nodal irradiation could significantly alleviate acute toxicities without impairing the eventual treatment outcome, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients especially in thoracic LA-ESCC cases.

Effect of three dimensional conformal radiotherapy combined with chemotherapy for advanced esophageal carcinoma

Objective To evaluate the clinical efficacy and toxicities of three dimensional conformal radiotherapy combined with chemotherapy for advanced esophageal carcinoma. Methods We retrospectively reviewed 127 patients with advanced esophageal squamous carcinoma in our department from January 2008 to January 2011, who were divided into two groups: conformal radiotherapy combined with chemotherapy (RCT) group, 69 patients and radiotherapy(RT) group, 58 patients. The side effects, quality of life and effective rates of them were compared. Results The severe rate of the marrow toxic effect and the incidences of radiation-induced esophagitis were higher in the RCT group (29.0%vs 12.1%, χ2=5.387, P=0.020; 24.6%vs10.3%, χ2=4.341, P=0.037). Patients in the RT group had better quality of life than those in the RCT group in gastrointestinal side effects (nausea, vomiting, diarrhea) and food intake (73.9%vs 12.1%, χ2=48.574, P=0.000; 43.5%vs 25.9%, χ2=4.274, P=0.039). In the RCT group, the effective rate was 91.30% (63/69) and 72.41 % (42/58) in the RT group, with a statistical significance (χ2=7.852, P=0.005). Conclusion Three dimensional conformal radiotherapy combined with chemotherapy for advanced esophageal carcinoma can improve the short-term curative effects, but it also increase the acute toxic effect. Further follow-up studies are needed for its long-term effect. Key words: Esophageal neoplasms; Radiotherapy; Drug therapy

Clinical Prognostic Factors for Locally Advanced Esophageal Squamous Carcinoma Treated after Definitive Chemoradiotherapy

PurposeLocally advanced esophageal cancers are generally treated with neoadjuvant chemoradiotherapy, followed by surgery in operable candidates. However, even if the patients were diagnosed as operable disease, surgery could not be performed on patients with poor condition or other comorbidity. In this case, definitive chemoradiotherapy (dCRT) is the other option for localized esophageal cancer. Therefore, the purpose of this study was to evaluate the efficacy and clinical prognostic factors for dCRT in locally advanced esophageal cancer.Materials and MethodsWe conducted a review of patients who received dCRT for locally advanced squamous esophageal cancer from 2004 to 2010, focusing on stages III and IVa. All patients received at least two cycles of platinum-based chemotherapy during radiation, and all tumor burdens were included in the radiation field. The treatment results were analyzed for patterns of failure and prognostic factors associated with survival.ResultsIn total, 63 patients were enrolled in this study. The overall response rate was 84.1%. Relief from dysphagia after dCRT was achieved in 48 patients. The most frequent failure was local recurrence. The median overall survival (OS) was 23.0 months, and the 2-year survival rate was 45.4%. Similar results were observed for elderly study patients. Significant prognostic factors for OS were duration of smoking, high grade of dysphagia (score of 3 or 4), and shorter duration of progression-free and dysphagia-free survival. Maintenance chemotherapy after dCRT did not influence OS. However, "good risk" patients receiving maintenance chemotherapy showed better OS than those who did not receive maintenance chemotherapy (30.4 months vs. 12.0 months, p=0.002).ConclusiondCRT has a major role in improving survival and palliation of dysphagia in inoperable advanced esophageal cancer, even in elderly patients. Maintenance chemotherapy after dCRT may be effective in prolonging survival in "good risk" patients.

Operation combined with preoperative radiochemotherapy on esophageal squamous carcinoma

Objective To evaluate the effects of preoperative radiochemotherapy on pathological staging and prognosis in the patients with advanced esophageal squamous carcinoma(ESCC). Methods 1997-2007,477 patients with advanced ESCC were randomized into four groups:neoadjuvant chemothera-py, neoadjuvant radiotherapy, neoadjuvant radiochemotherapy, and surgery alone (control group). The tumor resection rate, pathological stage, treatment-related complication, and survival among groups were compared. Results The radical resection rate for the patients in radiotherapy and radiochemotherapy groups was increased in comparison with the control group (P ＜ 0.05). Their pathological stage after esophagectomy was regressed significandy than that of the control group (50.8% ,54.2% vs 0% ,P ＜0.05). The chemotherapy group showed significant improvement on resection rate and pathological staging compared with the control group. The treatment related complication in three neoadjuvant groups had no significant difference from that of the control group (P ＞ 0. 05). The 3-year survival rate of radiotherapy and radiochemotherapy groups were significantly higher than that of the control group(69.5% ,72.9% vs 53.4%, P ＜ 0.05). The 5-year survival rate of radiochemotherapy and radiotherapy groups were was high-er than that of the control group(P ＜ 0.05), meanwhile the 5-year survival rate of radiochemotherapy was higher than that of radiotherapy group, but no statistical difference (P ＞ 0. 05). Conclusion Preoperative radiochemotherapy seems to provide an efficient therapy in radical resection and survival of patients with advanced ESCC. Key words: Esophageal carcinoma; Radiochemotherapy; Pathological stage