PS02.133: THE EFFICACY AND SAFETY OF S-1 MONOTHERAPY FOR RECURRENT OR METASTATIC ESOPHAGEAL SQUAMOUS CELL CARCINOMA REFRACTORY OR INTOLERABLE TO PLATINUM PLUS 5-FU

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 158-159 ◽  
Author(s):  
Takahiko Ito ◽  
Yoshitaka Honma ◽  
Takahiro Miyamoto ◽  
Hidekazu Hirano ◽  
Hirokazu Shoji ◽  
...  

Abstract Background Platinum plus 5-fluorouracil (FP) is recognized as the standard regimen of palliative chemotherapy for recurrent or metastatic esophageal squamous cell carcinoma (ESCC). Although taxane is widely selected for 2nd line regimen, other options are very limited. In Japan, S-1 is available for esophageal cancer. In this retrospective study, we evaluated the efficacy of S-1 monotherapy for recurrent or metastatic (advanced) ESCC refractory or intolerable to FP. Methods The subjects of this study were 11 patients with advanced ESCC who received S-1 after failure of FP. The endpoints evaluating efficacy were overall survival (OS), progression free survival (PFS), and overall response rate (ORR) in patients with target lesions (TLs). Results The characteristics of the subjects were: median age 69 years, PS (0/1) 5/6, number of prior chemotherapy regimens (1/2/3 ≥ ) 4/4/3. 9 patients were refractory and 2 were intolerant to prior FP. 9 patients had good control of the primary lesions. Only 2 patients received post-S-1 therapy. The median OS and PFS were 11.7and 3.0 months. Two of 9 patients with TLs, one refractory and the other intolerant to prior FP, achieved partial response (PR) while the remaining 7 patients showed progressive disease (ORR 22%). The other 2 patients without TLs showed nonCR/nonPD. Common treatment-related adverse events included grade 3 leukopenia for 1 patients (9.1%), but there were no serious cases. Conclusion ORR of 22% suggests modest activity of S-1 for advanced ESCC refractory or intolerable to platinum plus 5-FU (FP). However, more than half of the patients showed progressive disease. Future study exploring optimal patient selection for S-1 is warranted. Disclosure All authors have declared no conflicts of interest.

2021 ◽  
Vol 11 ◽  
Author(s):  
Chi Zhang ◽  
Xiao-Lin Ge ◽  
Chen-Jun Huang ◽  
Shu Zhang ◽  
Xin-Chen Sun

Purpose: Recurrence of esophageal squamous cell carcinoma (ESCC) in regional lymph nodes (LNs) after surgical section can be treated with salvage resection, radiotherapy (RT) or chemoradiotherapy (CRT). RT or CRT is more widely used in clinic. This paper investigates the effects, toxicities and prognostic risk factors of salvage RT or CRT on patients with LN recurrence.Methods: We retrospectively analyzed the clinical outcomes of 103 patients receiving salvage RT or CRT for LN recurrence after ESCC resection. In total, 39 patients received RT alone and 64 received concurrent CRT. All the patients received intensity modulated radiation therapy (IMRT), administered with a median dose of 62 Gy (range, 50–70 Gy).Results: The median follow-up time was 44.5 months, and median survival was 22.5 months (5.5–99.5 months). One-, 3-, and 5-year overall survival (OS) were 80.6, 37.0, and 25.8%, respectively. One- and 2-year progression free survival (PFS) were 57.3 and 34.0%, respectively. Grade 3 or above toxicity was low (16.5%) and no treatment-related deaths occurred. In univariate analysis of OS, pN0 (p = 0.039), smaller LN volume (≤25 cm3, p = 0.019), combined chemotherapy (p = 0.041) and single LN recurrence (p = 0.001) were associated with prolonged OS. And pT1-2 (p = 0.044), pN0 (p = 0.042), irradiation dose (>60 Gy, p = 0.044), combined chemotherapy (p = 0.019) and single LN recurrence (p = 0.002) were associated with prolonged PFS. In multivariate analysis, the patients with only one recurrent node had a significant better OS (HR = 0.556, 95% CI 0.324–0.956, p = 0.034) and PFS (HR = 0.528, 95% CI 0.339–0.847, p = 0.008).Conclusions: Salvage RT or CRT for regional LN recurrence is effective and acceptable. Fewer recurrent nodes may indicate a better long-term survival.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16023-e16023
Author(s):  
Qiwei Yao ◽  
Zhichao Fu ◽  
Qisong Chen ◽  
Jianli Huang ◽  
Jintong Wu ◽  
...  

e16023 Background: Camrelizumab, a programmed death 1 (PD-1) inhibitor, has recently demonstrated efficacy for esophageal squamous cell carcinoma (ESCC) patients in a phase III trial. We report real-world clinical outcomes of camrelizumab therapy for ESCC patients in a multicenter prospective cohort. Methods: Eligible patientswereadvanced esophageal squamous cell carcinoma with stage II-IV confirmed by pathology (including histology or cytology). All patients had received at most one systematic treatment and ECOG performance status of 0 or 1. Camrelizumab monotherapy(200mg) or combined with chemo-radiotherapy, chemotherapy, chemotherapy and antiangiogenic therapy as a first or second line of therapy were included. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and overall survival (OS) and safety data were evaluated. This abstract summarizes the findings of an exploratory interim analysis (cut-off Dec 2020). Results: From Oct 2019-Dec 2020, 63 patients were enrolled (19 centers in China; mean age 62.26 years; 97% ECOG PS 1; 54% first line therapy). Patients received camrelizumab monotherapy (8; 13%), camrelizumab/chemo-radiotherapy combination therapy (22, 35%), camrelizumab/chemotherapy combination therapy (26, 41%), camrelizumab/chemotherapy/antiangiogenic therapy combination therapy (7, 11%). One patient achieved a complete response and 27 patients achieved a partial response, leading to an ORR of 41.26%. The DCR was 95.24%. The median progression-free survival (PFS) was 6.33 months (95% confidence interval [CI] 4.73-NA). Among patients with adequate samples test for LBH level and (lung immune prognostic index) LIPI score, 15.7% (8/51) patients had a high LBH level;63% (29/46), 32.6% (15/46) and 4.3% (2/46) patients had a good, middle and poor LIPI score, respectively. A significantly longer PFS was observed in patients with a normal LBH level (NA vs. 6.33 months, P = 0.049), and also in patients treated with first-line therapy (6.33 months vs. NA, P = 0.0338). Among adverse events, 4 patients (6.35%) reported grade 3-4 AEs, including pneumonia (n=2 [3.17%]), and bone marrow suppression (n=2 [3.17%]). 10 of 63 patients (15.87%) experienced any grade pneumonia, and 21 of 63 patients (33.33%) experienced grade 1-2 RCCEP. Conclusions: This real-world population showed that camrelizumab as the first- or second-line therapy was an effective and safe treatment for patients with ESCC. Clinical trial information: CHICTR2000039499.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 188-189
Author(s):  
Pei Yu ◽  
Su Zhang ◽  
Ming Wang ◽  
He Liang ◽  
Hu Fan ◽  
...  

Abstract Background Several studies have suggested an association between poor oral health and esophageal squamous cell carcinoma (ESCC). We conduct this study to further examine the association between oral hygiene and ESCC risk in Linxian, the high risk area of China. Methods We recruit 29,553 healthy and 3318 esophageal squamous dysplasia participants aged between 40 and 69 in 1985 and then followed up until April, 2015. Basic characteristics were collected and oral related diseases were examined by trained doctors. Cox regression models were used to calculate hazard rations (HRs) and 95% confidence intervals (CIs). Results In general group, 2577 participants’ dead for ESCC and the cumulative rate of ESCC death was 12.9%. Teeth loss more than 20, before age of 40, bleeding of teeth, chapped lips, oral leukoplakia were significantly associated with risk of death from ESCC, and with 1.28 (95% CI: 1.18–1.38), 1.12 (95% CI: 1.03–1.23), 1.28 (95% CI: 1.13–1.45), 1.14 (95% CI: 1.04–1.25), 1.23 (95% CI: 1.12–1.35) fold increased risk of death from ESCC respectively in models adjusted for potential confounders. In dysplasia group, 540 participants’ dead for ESCC and the cumulative rate was 24.7%. Those who loss teeth more than 20, before age of 40, bleeding of teeth, have 1.24 (95% CI: 1.02–1.51), 1.25 (95%CI: 1.02–1.52), 1.35(95%CI: 1.06–1.70) fold increased risk after adjustment. Association between chapped lips and ESCC death was not found. Conclusion Severe teeth loss, early age teeth loss and teeth bleeding were associated with ESCC death and excess risk increased as dysplasia occurred. Chapped lips loss association with ESCC death in dysplasia group, it may reveals that it react before dysplasia change. Further studies are warranted to find the mechanism association and improvements of protecting oral health should be done. Disclosure All authors have declared no conflicts of interest.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 145-145
Author(s):  
Yohei Nagai ◽  
Naoya Yoshida ◽  
Yoshifumi Baba ◽  
Hideo Baba

Abstract Background To investigate the association between endoscopic response evaluation of neoadjuvant chemotherapy (NAC) with pathological response and survival in patients with esophageal squamous cell carcinoma (ESCC). Methods We retrospectively reviewed the medical records of patients with the aid of a prospectively entered database. One hundred and eleven consecutive patients with ESCC who underwent radical esophagectomy after NAC were included. All patients were divided into two groups according to endoscopic response after NAC: endoscopic non-responders in whom NAC was poorly or moderately effective, and endoscopic responders in whom NAC was highly effective or completely effective. The clinical response after NAC was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). Results The pretreatment clinical stage was IB in 5 patients (5%), II in 18 (16%), III in 72 (65%), and IV in 16 (14%). All patients received two courses of chemotherapy. Chemotherapy consisted of docetaxel, cisplatin (CDDP), and 5-fluorouracil (5-FU; the DCF regimen) in 82 patients (74%), and 5-FU and CDDP (FP) in 29 (26%). All patients underwent radical esophagectomy with 2- or 3-field lymph node dissection. The postoperative mortality and morbidity rates were 0.9% and 26%, respectively. Pathological stage (ypStage) was 0 in 1 patient (1%), I in 16 (14%), II in 31 (28%), III in 48 (43%), and IV in 15 (13%). Twenty-two patients (20%) were pathological responders, and this group of patients had better overall survival than pathological non-responders (P = 0.02). Pathological response was significantly correlated with tumor depth (cT) (P < 0.01), protruding type of tumor (P = 0.01) before NAC, and clinical response (P < 0.01) and endoscopic response (P < 0.01) after NAC. Of these clinical factors, clinical response and endoscopic response were significantly correlated with prognosis. Conclusion Endoscopic response after NAC can predict the pathological response and prognosis of patients who received NAC followed by surgery. Endoscopic findings are clinically significant to assess the response of NAC in patients with ESCC. Disclosure All authors have declared no conflicts of interest.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4055-4055
Author(s):  
Dashan Ai ◽  
Yun Chen ◽  
Qi Liu ◽  
Xiangpeng Zheng ◽  
Yunhai Li ◽  
...  

4055 Background: Paclitaxel (PTX) is effective in concurrent chemoradiation (CCR) against esophageal squamous cell carcinoma (ESCC) . Which regimen, among cisplatin (DDP) (TP), carboplatin (CBP) (TC) or 5-Fu (TF) in combination with PTX concurrent with radiotherapy, provides best prognosis with minimum adverse events (AEs) is still unknown. Methods: The study compared two pairs of regimens: TF vs. TP and TF vs. TC concurrent with radiotherapy. Patients with histologically confirmed ESCC (clinical stage II, III or IVa) were randomized into the three groups. Patients in TP group were treated with 2 cycles of CCR followed by 2 cycles of consolidation chemotherapy with TP (DDP 25 mg/m2/d, d1-3, PTX 175 mg/m2, d1, q28d). Patients in TF group were treated with 6 cycles of TF (5-Fu 300 mg/m2, civ 96h, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TF (5-FU 1800 mg/m2, civ 72h, PTX 175 mg/m2, d1, q28d) in consolidation chemotherapy. Patients in TC group were treated with 6 cycles of TC (CBP AUC = 2, d1, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TC (CBP AUC = 5, d1, PTX 175 mg/m2 d1, q28d) in consolidation chemotherapy. The radiotherapy dose in all groups was 61.2 Gy delivered in 34 fractions. The primary endpoint was overall survival and the secondary endpoints were progression-free survival and adverse events. Results: Between July 2015 and January 2018, 321 ESCC patients in 11 centers were enrolled. TP group had a significant higher incidence of acute grade 3/4 neutropenia (59.7% vs. 16.8%(TF) or 32.4%(TC)), thrombocytopenia (12.7% vs. 3.5%(TF) or 6.2%(TC)), anemia (6.4% vs. 4.4%(TF) or 4.4%(TC)), fatigue (10.0% vs. 0.9%(TF) or 0.9%(TC)) and vomiting (5.5% vs. 0%(TF) or 0.9%(TC)) than other two groups ( P < 0.05). TF group had a significant higher incidence of grade 3/4/5 esophagitis (13.1% vs. 1.8%(TP) or 5.3%(TC)) and pneumonitis (4.4% vs. 0%(TP) or 1.8%(TC)) than other two groups ( P < 0.05). One patient in TF group died of acute pneumonitis. One patient in TF group and one in TC group died of acute esophagitis. Conclusions: TP and TF regimen showed different severe AEs in CCR in ESCC patients and TC showed mild AEs. Clinical trial information: NCT02459457.


2021 ◽  
Author(s):  
Ting Yan ◽  
lili liu ◽  
Meilan Peng ◽  
Zhenpeng Yan ◽  
Qingyu Wang ◽  
...  

Abstract Objectives: To construct a prognostic model for preoperative prediction based on computed tomography (CT) images of esophageal squamous cell carcinoma (ESCC). Methods: Radiomics signature was constructed using the least absolute shrinkage and selection operator (LASSO) with high throughput radiomics features that extracted from the CT images of 272 patients (204 in training and 68 in validation cohort), who were pathologically confirmed ESCC. Multivariable logistic regression was adopted to build the radiomics signature and another predictive nomogram model, which was composed with radiomics signature, traditional TNM stage and clinical features. Then its performance was assessed by the calibration and decision curve analysis (DCA). Results: 16 radiomics features were selected from 954 to build a radiomics signature,which were significantly associated with progression-free survival (PFS) (p<0.001). The area under the curve (AUC) of performance was 0.891 (95% CI: 0.845-0.936) for training cohort and 0.706 (95% CI: 0.583-0.829) for validation cohort. The radscore of signatures’ combination showed significant discrimination for survival status in both two cohort. Kaplan-Meier survival curve further confirmed the radscore has a better prognostic performance in training cohort. Radiomics nomogram combined radscore with TNM staging showed significant improvement over TNM staging alone in training cohort (C-index, 0.802 vs 0.628; p<0.05), and it is the same with clinical data (C-index, 0.798 vs 0.660; p<0.05). Findings were confirmed in the validation cohort. DCA showed CT-based radiomics model will receive benefit when the threshold probability was between 0 and 0.9. Heat maps revealed associations between radiomics features and tumor stages.Conclusions: Multiparametric CT-based radiomics nomograms provided improved prognostic ability in ESCC.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 166-166
Author(s):  
Jun Nakamura ◽  
Noriaki Manabe ◽  
Ken Haruma ◽  
Rui Nakato ◽  
Takahisa Murao ◽  
...  

Abstract Background Cancer and other chronic diseases such as cardiovascular disease, diabetes, chronic kidney disease, and respiratory disease share common risk factors, including aging and unhealthy lifestyles (eg, smoking and alcohol misuse). Although the recent prospective cohort large-scale study showed chronic diseases contributed to more than one fifth of the risk for incident cancer and more than one third of the risk for cancer death, the relation between esophageal squamous cell carcinoma (ESCC) and non-cancer chronic diseases (NCCD) still remain unknown. The aim of this study is to assess the independent and joint associations of major NCCD and ESCC. Methods From April 2011 to March 2017, 406 consecutive patients with ESCC diagnosed pathologically were enrolled. Their medical records as to patients’ background, the reason for their consultation, lifestyles, and medical history were investigated retrospectively in detail. Results As to the reason for their consultation, 45 patients (25.3%) were diagnosed at annual medical checkup (no symptoms), 125 (70.2%) consulted a doctor for any symptoms such as dysphagia, and 8 (4.5%) had other reasons. As to lifestyles, 304 (78.1%) were drinkers of alcohol (daily amount of alcohol consumption > 20g) and 302 (77.4%) were smokers (Brinkman index > 200), respectively. As to the medical history related to cancer or gastrointestinal diseases, 25 (6.8%) had a history of laryngopharyngeal cancer, 20 (5.1%) had a history of gastric cancer, 2 (0.5%) had a history of breast cancer, one (0.3%) had a history of sclerodema, and one (0.3%) had a history of esophageal achalasia. Of the 406 ESCC patients, 305 were early ESCC and the remaining 101 were advanced ESCC. As to the medical history in patients with advanced ESCC, 22 (21.8%) had a history of cancer of other organs, and 48 (47.5%) had NCCD including hypertension (35 patients), diabetes (18 patients), and hyperlipidemia (12 patients). Conclusion NCCD is an overlooked risk factor for ESCC, as important as two major lifestyle factors combined (drinkers of alcohol and smokers). General physicians who follow up NCCD patients should pay attention to the coexistence of ESCC. Disclosure All authors have declared no conflicts of interest.


2020 ◽  
Author(s):  
HUAN WANG ◽  
Masayuki Kano ◽  
Yasunori Matsumoto ◽  
Takeshi Toyozumi ◽  
Satoshi Endo ◽  
...  

Abstract Background: Exosomes are nano-sized extracellular vesicles and are detectable in most body fluids. Circulating exosomal microRNAs are an easily obtained, and they could be minimally invasive biomarker for cancer treatment. Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas. Radiotherapy is one of the most important treatment option for ESCC, and it would thus be extremely crucial to predict therapeutic sensitivity and the patient prognosis in advance. Methods: A search for miRNAs with a therapeutic biomarker in ESCC was performed using the miRNA expression signatures obtained from ESCC plasma before radiotherapy. miR-191-5p was selected because it was found to be associated with the prognosis in ESCC based on the findings of previous reports. As a result, we decided to perform more studies to elucidate the significance of miR-191-5p. Gain-of-function analyses were performed to evaluate the functional significance of miR-191-5p in ESCC progression. The effects of miR-191-5p on ESCC radiosensitivity were determined by cell proliferation, a clonogenic survival assay and an apoptosis assay. A gene set enrichment analysis was used to investigate the downstream signaling pathway related to the miR-191-5p functions. The 5-year progression-free survival (PFS) rate was used to directly compare the usefulness of these biomarkers for determining the patient prognosis between the miR-191-5p high expression patients and low expression patients. Results: A subset of seven microRNAs (miR-628, miR-363, miR-191-5p, miR-185, miR-148a, miR-320d, miR-30e) was identified to be candidates of therapeutic biomarker for ESCC patients underwent radiotherapy in a global microRNA expression analysis. A high miR-191-5p expression promoted ESCC cell proliferation, invasion and migration and induced G0/G1 to S/G2M transition. miRNA-191-5p overexpression promoted cell survival and reduced cell apoptosis after irradiation. Mechanistically, miR-191-5p may directly target death-associated protein kinase 1 (DAPK1) to induce radiation resistance via the MAPK-JNK pathway. The 5-year progression-free survival rate for ESCC patients who underwent radiotherapy with high circulating exosomal miR-191-5p expression was significantly lower than in those with a low expression. Conclusion: Tumor-derived exosomal miR-191-5p is a potential non-invasive biomarker for predicting the prognosis in esophageal cancer patients after radiotherapy.


2021 ◽  
Author(s):  
Jian Ming Xu ◽  
Yi Li ◽  
Qingxia Fan ◽  
Yongqian Shu ◽  
Lei Yang ◽  
...  

Abstract This randomized, open-label, multi-center phase 2 study (ClinicalTrials.gov, number NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemo in patients with advanced esophageal squamous cell carcinoma (ESCC) refractory to first-line (1L) chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with treatment efficacy. The median OS in the sintilimab group was significantly prolonged compared with that of the chemotherapy group, (objective response rates 12.6% and 6.3 %, respectively). Incidence of treatment-related adverse events of grade 3–5 was lower with sintilimab than with chemotherapy (20.2 vs. 39.1 %). Patients with high TCR clonality and low mTBI showed the longest median OS (15.0 mo), while patients with low NLR at 6 wk post-treatment had a significantly prolonged median OS compared with those with high NLR. High expression of T-follicular helper cells or activated B-cell signature was significantly associated with longer progression-free survival in the sintilimab group.


2020 ◽  
Author(s):  
Xi-Lei Zhou ◽  
Chang-Hua Yu ◽  
Wan-Wei Wang ◽  
Fu-Zhi Ji ◽  
Yao-Zu Xiong ◽  
...  

Abstract Background: This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients who had locally advanced ESCC and received CCRT with S-1 (70mg/m2 twice daily on days 1-14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25mg/m2) and cisplatin (25mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Treatment-related toxicities, response rate, and survival outcomes were compared between groups. Results: A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3-4 adverse events were significantly lower in the S-1 group than in the DP group (22.2% versus 45.6%, p = 0.002). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% versus 25.0%, p = 0.275). Conclusion: CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.


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