The sequence of chemotherapy and anti-PD-1 antibody influence the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell cancer: A phase II study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4051-4051
Author(s):  
Lingdi Zhao ◽  
Wenqun Xing ◽  
Yonghao Yang ◽  
Yong Zhang ◽  
Baozhen Ma ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Esophageal Squamous Cell Cancer ◽  
Control Group ◽  
Chemotherapy Drugs ◽  
Grade 3 ◽  
And Control ◽  
Experimental Group

4051 Background: PD-1 blockade may result in expansion of tumor-specific T cells. However, traditional immunochemotherapy regimens usually designed to use chemotherapy drugs and anti-PD-1 antibody on the same day, which may make chemotherapy drugs kill activated T cells. The purpose of this study was to investigate the rate of pCR of chemotherapy plus anti-PD-1 therapy and the influence of sequence of chemotherapy and anti-PD-1 therapy on pCR in patients with locally advanced esophageal squamous cell cancer. Methods: Thirty esophageal squamous cell cancer patients with T3, T4, or lymph node positive were assigned into experiment group (anti-PD-1 antibody was administrated two days after chemotherapy) and control group ( anti-PD-1 antibody and chemotherapy were administrated on the same day) according to the order of enrollment. There were fifteen patients in each group. The chemotherapeutic regimen was paclitaxel and cisplatin, paclitaxel was given at the dose of 150-175mg/m2 on day 1 and cisplatin was given at the dose of 70-75mg/m2 on day 1. The anti-PD-1 antibody was toripalimab at the fixed dose of 240mg on day 3 or day 1. Operation was performed four to six weeks after the second cycle of chemotherapy combined with toripalimab. Results: From July 2019 to September 2020, a total of 30 patients completed at least one cycle of immunochemotherapy. 11 in the experimental group received operation after two cycles of neoadjuvant chemotherapy plus toripalimab. Thirteen in control groupreceived operation aftertwo cycles of neoadjuvant chemotherapy plus toripalimab. Four patients in experimental group and one in control group got pCR, the rates of pCR in experimental group and control group were 36.4% and 7.7% individually. Although the difference was not significant in statistics, the experimental group had the trend of higher pCR rate(c2= 3.092, p = 0.079). PD-L1 CPS examination before treatment was performed in fourteen patients, it was found that except one patient with PD-L1 CPS was 10, the left thirteen with PD-L1 CPS were all below one. The patient with PD-L1 CPS 10 was in control group and pCR was got in this patient. Except one patient in the experimental group had grade 3 immune-related enteritis, one patient in the control group died from immune-related myocarditis after operation, there were no more immune-related events more than grade 3. Conclusions: Toripalimab was delayed on day 3 when toripalimab plus chemotherapy was taken as neoadjuvant therapy regimen in locally advanced esophageal squamous cell carcinoma might achieve a higher pathological complete response than toripalimab and chemotherapy used on the same day. Clinical trial information: NCT 03985670.

Cetuximab, paclitaxel, carboplatin and radiation for esophageal and gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4029-4029 ◽  
Author(s):  
M. Suntharalingam ◽  
T. Dipetrillo ◽  
P. Akerman ◽  
H. Wanebo ◽  
B. Daly ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Esophageal Cancer ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Complete Response ◽  
Grade 3

4029 Background: Cetuximab is an IgG1, chimerized, monoclonal antibody that binds specifically to the epidermal growth factor receptor. Cetuximab improves survival when combined with radiation for patients with locally advanced head and neck cancer. We evaluated the safety and efficacy of the addition of cetuximab to concurrent chemoradiation for patients with esophageal and gastric cancer. Methods: Patients with adenocarcinoma or squamous cell cancer of the esophagus or stomach without distant organ metastases were eligible. Patients with locally advanced disease from mediastinal, celiac, portal and gastric lymphadenopathy were eligible. Surgical resection was not required. Clinical complete response was defined as no tumor on postreatment endoscopic biopsy. Patients received cetuximab, 400mg/m2 week #1 then 250 mg/m2/week for 5 weeks, paclitaxel, 50 mg/m2/week, and carboplatin, AUC =2 weekly for 6 weeks, with concurrent 50.4 Gy radiation. Results: Thirty-seven patients have been entered. The median age was 61 (range of 30–87). Thirty-four have esophageal cancer and 3 have gastric cancer. Of the patients with esophageal cancer, twenty-five have adenocarcinoma and nine have squamous cell cancer. Thus far, 30 patients have completed treatment and are evaluable for toxicity. There have been no grade 4 non-hematologic toxicities and 1 pt had grade 4 neutropenia (3%). Six patients (20%) had grade 3 esophagitis. Other grade 3 toxicities included dehydration (n=5), rash (n=9), and paclitaxel/cetuximab hypersensitivity reactions (n=2). Eighteen of 27 patients (67%) have had clinical complete response. Seven pts out of 16 (43%) who have gone to surgery have had a pathologic CR. Conclusions: Cetuximab can be safely administered with chemoradiation for patients with esophageal cancer. Consistent with the data in head and neck cancer, cetuximab increases cutaneous toxicity but does not increase mucositis/esophagitis when combined with chemoradiation. Further evaluation is ongoing. [Table: see text]

scholarly journals Radiomics Signature Facilitates Organ-Saving Strategy in Patients With Esophageal Squamous Cell Cancer Receiving Neoadjuvant Chemoradiotherapy

2021 ◽  
Vol 10 ◽  
Author(s):  
Yue Li ◽  
Jun Liu ◽  
Hong-xuan Li ◽  
Xu-wei Cai ◽  
Zhi-gang Li ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Esophageal Squamous Cell Cancer ◽  
Clinical Model ◽  
Clinical Variables ◽  
Treatment Plans ◽  
Radiomics Signature

After neoadjuvant chemoradiotherapy (NCRT) in locally advanced esophageal squamous cell cancer (ESCC), roughly 40% of the patients may achieve pathologic complete response (pCR). Those patients may benefit from organ-saving strategy if the probability of pCR could be correctly identified before esophagectomy. A reliable approach to predict pathological response allows future studies to investigate individualized treatment plans.MethodAll eligible patients treated in our center from June 2012 to June 2019 were retrospectively collected. Radiomics features extracted from pre-/post-NCRT CT images were selected by univariate logistic and LASSO regression. A radiomics signature (RS) developed with selected features was combined with clinical variables to construct RS+clinical model with multivariate logistic regression, which was internally validated by bootstrapping. Performance and clinical usefulness of RS+clinical model were assessed by receiver operating characteristic (ROC) curves and decision curve analysis, respectively.ResultsAmong the 121 eligible patients, 51 achieved pCR (42.1%) after NCRT. Eighteen radiomics features were selected and incorporated into RS. The RS+clinical model has improved prediction performance for pCR compared with the clinical model (corrected area under the ROC curve, 0.84 vs. 0.70). At the 60% probability threshold cutoff (i.e., the patient would opt for observation if his probability of pCR was >60%), net 13% surgeries could be avoided by RS+clinical model, equivalent to implementing organ-saving strategy in 31.37% of the 51 true-pCR cases.ConclusionThe model built with CT radiomics features and clinical variables shows the potential of predicting pCR after NCRT; it provides significant clinical benefit in identifying qualified patients to receive individualized organ-saving treatment plans.

608 RADIOMICS MODEL FACILITATES ORGAN-SAVING STRATEGY IN PATIENTS WITH ESOPHAGEAL SQUAMOUS CELL CANCER RECEIVING NEOADJUVANT CHEMORADIOTHERAPY

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Yue Li
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Esophageal Squamous Cell Cancer ◽  
Minimum Diameter ◽  
Clinical Model ◽  
Clinical Variables ◽  
Treatment Plans

Abstract   After neoadjuvant chemoradiotherapy(NCRT) in locally advanced esophageal squamous cell cancer(ESCC), roughly 40% of the patients may achieve pathologic complete response (pCR) of the primary tumor. Those patients may benefit from organ-saving strategy if the probability of pCR could be correctly identified before esophagectomy. A reliable approach to predict pathological response allows future studies to investigate individualized treatment plans. We aim to establish a CT-based radiomics model to predict tumor response to NCRT. Methods 121 patients with ESCC who underwent NCRT followed by esophagectomy were retrospectively collected. Radiomics features extracted from pre−/post-NCRT CT images were selected by univariate logistic (p < 0.157) and LASSO regression. A radiomics signature(RS) developed with selected features was combined with 4 clinical variables, including percentage of tumor thickness reduction, tumor adventitia type, tumor minimum diameter on post-NCRT esophagogram and age, to construct RS + clinical model with multivariate logistic regression which was internally validated by bootstrapping. Performance and clinical usefulness of RS + clinical model were assessed by receiver operating characteristic(ROC) curves and decision curve analysis, respectively, comparing with the model of clinical variables alone. Results Among the 121 patients, 51 achieved pCR(42%) after NCRT. 16 radiomics features were selected and incorporated into RS. The RS + clinical model has improved prediction performance for pCR compared with the clinical model(corrected area under the ROC curve,0.843 vs. 0.700). At the 60% probability threshold cutoff(i.e., the patient would opt for observation if his probability of pCR was >60%), net 12% surgeries could be avoided by RS + clinical model without an increase in the number of missed residual diseases, equivalent to implementing organ-saving strategy in 29.4% of the 51 true-pCR cases. Conclusion The model built with CT radiomics features and clinical variables shows the potential of predicting pCR after NCRT; it provides significant clinical benefit in identifying qualified patients to receive individualized organ-saving treatment plans.

scholarly journals Comprehensive Study of Germline Mutations and Double-Hit Events in Esophageal Squamous Cell Cancer

2021 ◽  
Author(s):  
Bing Zeng ◽  
Peide Huang ◽  
Peina Du ◽  
Xiaohui Sun ◽  
Xuanlin Huang ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cancer Susceptibility ◽  
Cell Cancer ◽  
Germline Mutations ◽  
Esophageal Squamous Cell Cancer ◽  
Cancer Susceptibility Genes ◽  
Double Hit ◽  
And Control ◽  
Comprehensive Study

AbstractEsophageal squamous cell cancer (ESCC) is the eighth most common cancer around the world. Several reports have focused on somatic mutations and common germline mutations in ESCC. However, the contributions of pathogenic germline alterations in cancer susceptibility genes (CSGs), highly frequently mutated CSGs, and pathogenically mutated CSG-related pathways in ESCC remain unclear. We obtained data on 571 ESCC cases from public databases and East Asian from the 1000 Genomes Project database and the China Metabolic Analytics Project database to characterize pathogenic mutations. We detected 157 mutations in 75 CSGs, accounting for 25.0% (143/571) of ESCC cases. Six genes had more than five mutations: TP53 (n = 15 mutations), GJB2 (n = 8), BRCA2 (n = 6), RECQL4 (n = 6), MUTYH (n = 6), and PMS2 (n = 5). Our results identified significant differences in pathogenic germline mutations of TP53, BRCA2, and RECQL4 between the ESCC and control cohorts. Moreover, we identified 84 double-hit events (16 germline/somatic double-hit events and 68 somatic/somatic double-hit events) occurring in 18 tumor suppressor genes from 83 patients. Patients who had ESCC with germline/somatic double-hit events were diagnosed at younger ages than patients with the somatic/somatic double-hit events, although the correlation was not significant. Fanconi anemia was the most enriched pathway of pathogenically mutated CSGs, and it appeared to be a primary pathway for ESCC predisposition. The results of this study identified the underlying roles that pathogenic germline mutations in CSGs play in ESCC pathogenesis; increased our awareness about the genetic basis of ESCC; and provided suggestions for using highly mutated CSGs and double-hit features in the early discovery, prevention, and genetic counseling of ESCC.

Clinical efficacy of irinotecan plus raltitrexed chemotherapy in refractory esophageal squamous cell cancer: a retrospective study

2019 ◽  
Author(s):  
Min Liu ◽  
Qingqing Jia ◽  
Xiaolin Wang ◽  
Changjiang Sun ◽  
Jianqi Yang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Cancer Patients ◽  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Optimal Dose ◽  
Esophageal Squamous Cell Cancer ◽  
Grade 3

Abstract Background: The optimal chemotherapy regimen for refractory esophageal squamous cell cancer patients is uncertain. Our retrospective study assessed the efficacy and safety of irinotecan plus raltitrexed in esophageal squamous cell cancer patients who were previously treated with multiple systemic therapies. Methods: Between January 2016 and December 2018, records of 38 esophageal squamous cell cancer patients who underwent irinotecan plus raltitrexed chemotherapy after at least one line of chemotherapy were reviewed. Efficacy assessment was performed every two cycles according to the RECIST version 1.1. Results: A total of 95 cycles of chemotherapy were administered, and the median course was 3 (range 2–6). There was no treatment-related death. Nine patients had partial response, 21 had stable disease and 8 had progressive disease. The overall objective response rate was 23.68% (9/38) and the disease control rate was78.94% (30/38). After a median follow-up of 18.5 months, the median progression-free survival and overall survival were 105 days and 221 days respectively. There were 5 patients (13.15%) with grade 3/4 leukopenia, 3 patients (7.89%) with grade 3/4 neutropenia and 1 patient (2.63%) with grade 3/4 diarrhea. Conclusions: The combination of irinotecan plus raltitrexed was effective for pretreated esophageal squamous cell cancer patients. Further studies are needed to determine the optimal dose of the two drugs.

scholarly journals Comprehensive Study of Germline Mutations and Double-Hit Events in Esophageal Squamous Cell Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Bing Zeng ◽  
Peide Huang ◽  
Peina Du ◽  
Xiaohui Sun ◽  
Xuanlin Huang ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cancer Susceptibility ◽  
Cell Cancer ◽  
Germline Mutations ◽  
Esophageal Squamous Cell Cancer ◽  
Cancer Susceptibility Genes ◽  
Double Hit ◽  
And Control ◽  
Comprehensive Study

Esophageal squamous cell cancer (ESCC) is the eighth most common cancer around the world. Several reports have focused on somatic mutations and common germline mutations in ESCC. However, the contributions of pathogenic germline alterations in cancer susceptibility genes (CSGs), highly frequently mutated CSGs, and pathogenically mutated CSG-related pathways in ESCC remain unclear. We obtained data on 571 ESCC cases from public databases and East Asian from the 1000 Genomes Project database and the China Metabolic Analytics Project database to characterize pathogenic mutations. We detected 157 mutations in 75 CSGs, accounting for 25.0% (143/571) of ESCC cases. Six genes had more than five mutations: TP53 (n = 15 mutations), GJB2 (n = 8), BRCA2 (n = 6), RECQL4 (n = 6), MUTYH (n = 6), and PMS2 (n = 5). Our results identified significant differences in pathogenic germline mutations of TP53, BRCA2, and RECQL4 between the ESCC and control cohorts. Moreover, we identified 84 double-hit events (16 germline/somatic double-hit events and 68 somatic/somatic double-hit events) occurring in 18 tumor suppressor genes from 83 patients. Patients who had ESCC with germline/somatic double-hit events were diagnosed at younger ages than patients with the somatic/somatic double-hit events, though the correlation was not significant. Fanconi anemia was the most enriched pathway of pathogenically mutated CSGs, and it appeared to be a primary pathway for ESCC predisposition. The results of this study identified the underlying roles that pathogenic germline mutations in CSGs play in ESCC pathogenesis, increased our awareness about the genetic basis of ESCC, and provided suggestions for using highly mutated CSGs and double-hit features in the early discovery, prevention, and genetic counseling of ESCC.

Sign in / Sign up

Export Citation Format

Share Document