scholarly journals Brain Metastases from Esophageal Squamous Cell Carcinoma: Clinical Characteristics and Prognosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Linlin Xiao ◽  
Yvonne M. Mowery ◽  
Brian G. Czito ◽  
Yajing Wu ◽  
Guangbin Gao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Brain Metastases ◽  
Supportive Care ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Clinical Characteristics ◽  
Survival Rates ◽  
Locoregional Treatment

PurposeDue to the low incidence of intracranial disease among patients with esophageal cancer (EC), optimal management for these patients has not been established. The aim of this real-world study is to describe the clinical characteristics, treatment approaches, and outcomes for esophageal squamous cell carcinoma (ESCC) patients with brain metastases in order to provide a reference for treatment and associated outcomes of these patients.MethodsPatients with ESCC treated at the Fourth Hospital of Hebei Medical University between January 1, 2009 and May 31,2020 were identified in an institutional tumor registry. Patients with brain metastases were included for further analysis and categorized by treatment received. Survival was evaluated by the Kaplan-Meier method and Cox proportional hazards models.ResultsAmong 19,225 patients with ESCC, 66 (0.34%) were diagnosed with brain metastases. Five patients were treated with surgery, 40 patients were treated with radiotherapy, 10 with systemic therapy alone, and 15 with supportive care alone. The median follow-up time was 7.3 months (95% CI 7.4-11.4). At last follow-up, 59 patients are deceased and 7 patients are alive. Median overall survival (OS) from time of brain metastases diagnosis was 7.6 months (95% CI 5.3-9.9) for all cases. For patients who received locoregional treatment, median OS was 10.9 months (95% CI 7.4-14.3), and survival rates at 6 and 12 months were 75.6% and 37.2%, respectively. For patients without locoregional treatment, median OS was 3.0 months (95% CI 2.5-3.5), and survival rates at 6 and 12 months were 32% and 24%, respectively. OS was significantly improved for patients who received locoregional treatment compared to those treated with systematic treatment alone or supportive care (HR: 2.761, 95% CI 1.509-5.053, P=0.001). The median OS of patients with diagnosis-specific graded prognostic assessment (DS-GPA) score 0-2 was 6.4 months, compared to median OS of 12.3 months for patients with DS-GPA >2 (HR: 0.507, 95% CI 0.283-0.911).ConclusionBrain metastases are rare in patients with ESCC. DS-GPA score maybe a useful prognostic tool for ESCC patients with brain metastases. Receipt of locoregional treatment including brain surgery and radiotherapy was associated with improved survival.

Nivolumab in advanced esophageal squamous cell carcinoma (ATTRACTION-1/ONO-4538-07): Minimum of five-year follow-up.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 207-207
Author(s):  
Ken Kato ◽  
Yuichiro Doki ◽  
Takashi Ura ◽  
Yasuo Hamamoto ◽  
Takashi Kojima ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Squamous Cell ◽  
Group Performance ◽  
Objective Response

207 Background:ATTRACTION-1/ONO-4538-07 (AT-1), an open-label, single-arm, multicenter phase 2 clinical trial conducted in Japan, evaluated the clinical activity and safety of nivolumab in patients with advanced esophageal squamous cell carcinoma (ESCC) refractory/intolerant to fluoropyrimidine-, platinum-, and taxane-based chemotherapy. We previously reported the 2-year follow-up findings of AT-1, in which nivolumab demonstrated antitumor activity with a manageable safety profile for these patients. Here we report the final findings from AT-1 at a minimum follow-up of 5 years. Methods:Patients aged ≥20 years with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 received 3 mg/kg nivolumab intravenously every 2 weeks in 6-week cycles until disease progression or unacceptable toxicity. The primary endpoint was centrally-assessed objective response rate (ORR), defined as the proportion of patients whose best overall response was either a complete or partial response. Secondary endpoints included overall survival (OS), investigator-assessed ORR, progression-free survival (PFS), change in tumor burden, time to response, time to disease progression, and duration of response. Results:Between February 25 and November 14, 2014, a total of 65 patients were enrolled. Sixty-four patients were evaluated for the efficacy, and all patients were evaluated for the safety. At the final database lock on August 6, 2020, 11 (17.2%, 95% confidence interval [CI] 9.9-28.2) of 64 patients had an objective response by central assessment. The median OS was 10.8 months (95% CI, 7.4-13.9), and the estimated 5-year OS rate was 6.3% (95% CI, 2.0-14.0). The median PFS was 1.5 months (95% CI, 1.4-2.8), and the estimated 5-year PFS rate was 6.8% (95% CI, 2.2-15.1). Treatment-related adverse events that occurred with a frequency of > 10% were diarrhea and rash. The presentation will include characteristics of long-term survivors as well as detailed efficacy and safety data of nivolumab. Conclusions:This final assessment represents the longest follow-up of patients with advanced ESCC treated with nivolumab. Nivolumab demonstrated continued long-term efficacy in these patients based on a minimum of 5-year long-term survival update of AT-1. Furthermore, no new safety signals with nivolumab were identified during long-term follow-up. These findings are consistent with those of nivolumab monotherapy for various types of cancer. Clinical trial information: No.142422.

Tumor progression and chemoradiosensitivity in relation to the expression of apoptosis related proteins in esophageal squamous cell carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4588-4588
Author(s):  
S. Tsujitani ◽  
H. Saito ◽  
S. Tatebe ◽  
M. Ikeguchi
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Rates ◽  
Mutant P53 ◽  
Survivin Mrna ◽  
P53 Expression ◽  
Significant Difference ◽  
Related Proteins

4588 To study apoptosis related protein expression and their impact on patient’s survival time and sensitivity to postoperative chemoradiotherapy (CRT), we examined the expression of RB, mutant p53, MDM2 and Bax proteins using immunohistochemistry in 115 (CRT; 42) surgically resected esophageal squamous cell carcinoma (ESCC). We also investigated the survivin mRNA expression with quantitative analysis by real-time RT-PCR in 57 (CRT; 30) patients with ESCC. CRT contained 40–60 Gy radiation and continuous infusion of 5-FU (300mg/sqm, day1–5qw). Expression of RB, mutant p53, MDM2, Bax proteins and survivin mRNA were detected in 65%, 46%, 33%, 37% and 32% of patients, respectively. Patients with RB(+), MDM2(-), Bax(+) or survivin(-) tumor had significantly better survival rates than those with RB(-), MDM2(+), Bax(-) or survivin(+) tumor, respectively. However, there was no significant difference in survival between patients with and without mutant p53 expression. In patients not treated with CRT, those with RB(+) or survivin(-) tumor survived significantly longer than those with RB(-) or survivin(+) tumor, respectively. In patients treated with CRT, the expression of Bax protein and survivin mRNA was prognostic indicator. The 5-year survival rates of patients with Bax(+) and survivin(-) tumors were 65% and 39%, significantly superior to 21% and 0% of those with Bax(-) and survivin(+) tumors (P<0.05 and P<0.01, respectively). These results indicate that the expression levels of apoptosis related proteins are important for predicting the prognosis of ESCC patients. Furthermore, CRT may be effective in patients with Bax(+) or survivin(-) tumors. Further investigations are required for clarifying the relationship between the efficacy of postoperative CRT and apoptosis promoting status of ESCC. No significant financial relationships to disclose.

scholarly journals Nuplazid suppresses esophageal squamous cell carcinoma growth in vitro and in vivo by targeting PAK4

2021 ◽  
Author(s):  
Yaxing Wei ◽  
Wenjie Wu ◽  
Yanan Jiang ◽  
Hao Zhou ◽  
Yin Yu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Rates ◽  
Kinase Assay ◽  
Anticancer Effects ◽  
P21 Activated Kinase

Abstract Background Due to the high recurrence and low 5-year survival rates of esophageal squamous cell carcinoma (ESCC) after treatment, the discovery of novel drugs for recurrence chemoprevention is of particular importance. Methods We screened the FDA-approved drug library and found that Nuplazid, an atypical antipsychotic that acts as an effective 5-HT 2 A receptor inverse agonist, could potentially exert anticancer effects in vitro and in vivo on ESCC. Results Pull-down results indicated that Nuplazid binds with p21-activated kinase 4 (PAK4), and a kinase assay showed that Nuplazid strongly suppressed PAK4 kinase activity. Moreover, Nuplazid exhibited inhibitory effects on ESCC in vivo. Conclusions Our findings indicate that Nuplazid can suppress ESCC progression through targeting PAK4.

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