Dataset Information

GASC1-Adapted Neoadjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma: A Prospective Clinical Biomarker Trial.

ABSTRACT: Neoadjuvant chemotherapy (NCT) is a standard care for esophageal squamous cell carcinoma (ESCC), but the efficacy is unsatisfactory. Cancer stem cells (CSCs) play key roles in chemotherapy resistance. Gene amplified in squamous cell carcinoma 1 (GASC1) is a neoteric gene in stemness maintaining of ESCC. We aimed to reveal whether GASC1 could be a predictive biomarker for NCT in ESCC. ESCC patients (T2-4N0-2M0) were evaluated for GASC1 expression using immunohistochemical staining and classified as GASC1-low group (GLG) and GASC1-high group (GHG). NCT was delivered in two cycles and then the surgery was completed. Primary endpoints were tumor regression grade (TRG) and objective response rate (ORR); secondary endpoints were radical surgical resection (R0) rate and three-year overall survival (OS). 60 patients were eligible with evaluable outcomes: 24 in GHG and 36 in GLG. Between GHG and GLG, TRG1, TRG2, TRG3, and TRG4 were 0?:?16.7%, 20.8%?:?41.7%, 58.3%?:?36.1%, and 20.8%?:?5.6%, respectively (P=0.006); ORR and R0 rate were 33.3%?:?69.4% (P=0.006) and 75%?:?94.4% (P=0.046), respectively; the median OS was 20?:?32 (months) (P=0.0356). No significant difference in the three-year OS was observed between GHG and GLG: 29.2%?:?41.7% (P=0.24). Furthermore, the GASC1 expression level was associated with poor OS independent of other factors by univariate and multivariate analyses. Therefore, GASC1 might be a potential biomarker to predict NCT efficacy for ESCC.

SUBMITTER: Jia R

PROVIDER: S-EPMC7204099 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

GASC1-Adapted Neoadjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma: A Prospective Clinical Biomarker Trial.

Jia Ruinuo R Mi Youjia Y Yuan Xiang X Kong Dejiu D Li Wanying W Li Ruonan R Wang Bingbing B Zhu Yafei Y Kong Jinyu J Ma Zhikun Z Li Na N Mi Qiangjian Q Gao Shegan S

Journal of oncology 20200130

Neoadjuvant chemotherapy (NCT) is a standard care for esophageal squamous cell carcinoma (ESCC), but the efficacy is unsatisfactory. Cancer stem cells (CSCs) play key roles in chemotherapy resistance. Gene amplified in squamous cell carcinoma 1 (GASC1) is a neoteric gene in stemness maintaining of ESCC. We aimed to reveal whether GASC1 could be a predictive biomarker for NCT in ESCC. ESCC patients (T2-4N0-2M0) were evaluated for GASC1 expression using immunohistochemical staining and classified ...[more]

PMID: 32411232

Similar Datasets

Project description:BackgroundWe have previously shown that podocalyxin-like protein (PODXL) is a prognostic biomarker for poor survival in gastric and esophageal adenocarcinoma treated with surgery up-front. The aim of the present study was to assess PODXL expression in tumors from patients treated with neoadjuvant ± adjuvant (i.e. preoperative with or without postoperative) chemotherapy, with regard to histopathologic response, time to recurrence (TTR) and overall survival (OS).MethodsThe neoadjuvant cohort encompasses 148 consecutive patients who received neoadjuvant ± adjuvant chemotherapy for resectable gastric or esophageal adenocarcinoma between 2008 and 2014. Immunohistochemical expression of PODXL was assessed in pre-neoadjuvant biopsies, resected primary tumors and lymph node metastases. Histopathologic response was evaluated using the Chirieac grading. TTR and OS were estimated using Kaplan-Meier and Cox regression analyses. To investigate a potential predictive role for PODXL, the neoadjuvant cohort was pooled with the previously reported surgery up-front cohort.ResultsThe majority (> 95%) of the patients were treated with fluoropyrimidine- and oxaliplatin-based chemotherapy. Patients with high PODXL expression in their pre-neoadjuvant biopsies had a superior histopathologic response (notably 36% with no residual cancer cells) compared to those with negative or low PODXL expression, and were all recurrence-free at last follow-up. In the pooled cohort, no benefit of chemotherapy could be shown for PODXL negative cases, whereas PODXL positive (low or high) cases had a prolonged TTR and OS when treated with neoadjuvant ± adjuvant chemotherapy compared to surgery alone. The potential predictive role of PODXL was further strengthened for TTR in Cox regression analyses, especially for patients treated with neoadjuvant fluoropyrimidine and oxaliplatin for a minimum of 8 weeks, with a significant interaction term in both unadjusted (p = 0.006) and adjusted (p = 0.024) analyses. The interaction term was not statistically significant for overall survival.ConclusionsPatients with resectable gastric or esophageal adenocarcinoma with high PODXL expression in their diagnostic biopsies have an excellent prognosis when treated with neoadjuvant ± adjuvant fluoropyrimidine- and oxaliplatin-based chemotherapy. If the suggested predictive role of PODXL for benefit of chemotherapy can be confirmed, patients with PODXL negative tumors could be spared chemotherapy and treated with surgery alone.

Project description:Background Definitive chemoradiation is the preferred treatment for cervical esophageal carcinoma (CEC), per the National Comprehensive Cancer Network (NCCN) guidelines. However, in treatment failures, salvage surgery poses significant technical challenges. If non-responders could be identified, prior to chemoradiation, these patients may benefit from primary esophagectomy. Programmed cell death protein 1 (PD-1) inhibitor is widely used and recognized as an effective treatment method in various cancers including esophageal cancer. Therefore, we propose to screen for treatment response to neoadjuvant immunotherapy plus chemotherapy to select patients who are radiosensitive and potential candidates for laryngeal preservation. While non-responders are likely to be insensitive to chemoradiation would be offered radical esophagectomy. Methods A total of 36 patients with histopathologically-confirmed locally advanced CEC have been enrolled in our study. All participants will receive 2 cycles of induction therapy, which was tislelizumab combined with paclitaxel and carboplatin. Patients will be classified into 3 groups according to their response to induction therapy: a remarkable response (RR) group, limited partial response (LPR) group, and poor response (POR) group. Stratified patients will receive the following follow-up treatments: those in the RR group will receive dCRT, and those in the LPR and POR groups will undergo radical surgery. Then, participants in the RR group will be administrated with tislelizumab alone for 1 year. The choice of postoperative treatment for patients in the LPR and POR groups will depend on the patient’s condition, including chemotherapy, radiotherapy, immunotherapy, or follow-up. The primary endpoint of the study is the 2-year event-free survival (EFS). The secondary endpoints are disease-free survival (DFS), regression-free survival (RFS), objective response rate (ORR), and 5-year overall survival (OS). At the same time, we will assess the patient’s quality of life (QoL). Conclusions Screening CEC patients after immune-induction therapy combined with chemotherapy using different treatment strategies might lead to improvements in their QoL and OS time. No relevant double-endpoint studies have been reported until now. Our study is the first multicenter, prospective, exploratory study to seek the optimal treatment for locally advanced CEC patients. The results may offer high-level evidence for future CEC treatment. Trial Registration Chictr.Org identifier: ChiCTR2200057732.

Dataset Information

GASC1-Adapted Neoadjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma: A Prospective Clinical Biomarker Trial.

Publications

GASC1-Adapted Neoadjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma: A Prospective Clinical Biomarker Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets