Florid Foreign Body-type Giant Cell Response to Keratin Is Associated With Improved Overall Survival in Patients Receiving Preoperative Therapy for Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Wei Chen ◽  
Lei Zhao ◽  
Agoston Agoston ◽  
Abby White ◽  
Emanuele Mazzola ◽  
...  
2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Qingxia Fan ◽  
Junsheng Wang ◽  
Tao Wu ◽  
Yonggui Hong ◽  
...  

Abstract   Esophageal squamous cell carcinoma (ESCC) as a common malignancy is prevalent in East Asia and in eastern and southern Africa. Although pembrolizumab, nivolumab and camrelizumab are respectively recommended as second-line treatment for advanced ESCC due to improved overall survival (OS), objective response rate (ORR) was modest. New effective treatments are needed. Hence, the study of camrelizumab plus apatinib (VEGFR2 inhibitor) as second-line treatment for advanced ESCC was performed. Methods This ongoing phase II trial (NCT03736863) in six sites in China enrolled pts aged 18-75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line chemotherapy, and an ECOG performance status of 0-1. Pts received 200 mg camrelizumab intravenously every 2 weeks and apatinib 250 mg orally once per day in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and OS. Results At data cutoff (Feb 28, 2021), 52 pts were enrolled, including 42 males and 50 with distant metastases, with the median age of 62 years. In the evaluable population of 39 pts, ORR without confirmation was 43.59% and DCR was 94.87%. The median duration of response was 6.9 months (95% CI 4.57–9.23). The median PFS was 6.8 month (95% CI 2.66–10.94). The 12-month overall survival was 52.2%. A total of 80.8% of pts had treatment-related AEs (TRAEs) with 46.2% of grade ≥ 3 TRAEs. The safety profile of camrelizumab and apatinib was consistent with other anti–PD-1 antibodies and angiogenesis inhibitors. Conclusion This is the first study that evaluates the combination anti–PD-1 antibody and anti-angiogenesis inhibitor as a second-line therapy for advanced ESCC. Camrelizumab plus apatinib showed encouraging clinical efficacy and acceptable safety. Further phase III randomized trials are warranted.


PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e63581 ◽  
Author(s):  
Yang Wang ◽  
Shijie Sheng ◽  
Jianzhi Zhang ◽  
Sijana Dzinic ◽  
Shaolei Li ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Ge Zhang ◽  
Wan-Li Liu ◽  
Lin Zhang ◽  
Jun-Ye Wang ◽  
Miao-Huan Kuang ◽  
...  

The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an important role in tumor immune escape. However, the inhibitory effects of IDO on the CD8+tumour-infiltrating lymphocytes (CD8+TILs) in esophageal squamous cell carcinoma (ESCC) have not been clarified yet. Here, we found that the level of IDO expression in ESCC tumor specimens correlated with a reduction in the number of CD8+TILs. Patients with high IDO expression and a low number of CD8+TILs had significantly impaired overall survival time. IDO expression and functional enzyme activity in ESCC cell lines could be induced by IFNγ. When exposed to the milieu generated by IDO-expressing Eca109 cells, the CD8+TILs were suppressed in proliferation, and their cytolytic functions against target tumor cells were lost. These results suggested that impairing CD8+TIL functions by IDO expressed in ESCC possibly contributed to the finding that patients with higher IDO expression have more aggressive disease progression and shorter overall survival time.


2019 ◽  
Vol 60 (4) ◽  
pp. 517-526 ◽  
Author(s):  
Yuichi Ishida ◽  
Katsuyuki Sakanaka ◽  
Kota Fujii ◽  
Satoshi Itasaka ◽  
Takashi Mizowaki

AbstractHypopharyngeal invasion would be a key finding in determining the extent of the irradiation fields in patients with cervical esophageal squamous cell carcinoma (CESCC). This study aimed to investigate the clinical outcomes of chemoradiotherapy using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) omitting upper cervical lymph nodal irradiation in CESCC without hypopharyngeal invasion, and the dosimetric superiority of SIB-IMRT to 3D conformal radiotherapy (3DCRT). We retrospectively identified 21 CESCC patients without hypopharyngeal invasion [clinical Stage I/II/III/IV (M1LYM); 3/6/5/7] (UICC-TNM 7th edition) who underwent chemoradiotherapy using SIB-IMRT between 2009 and 2015. SIB-IMRT delivered 60 Gy to each primary tumor and the metastatic lymph nodes, and 48 Gy to elective lymph nodal regions, including Levels III and IV of the neck, supraclavicular, and upper mediastinal lymphatic regions, in 30 fractions. The overall survival rate, locoregional control rate, and initial recurrence site were evaluated. 3DCRT plans were created to perform dosimetric comparisons with SIB-IMRT. At a median follow-up of 64.5 months, the 5-year locoregional control and overall survival rates were 66.7% and 53.4%, respectively. Disease progressed in eight patients: all were locoregional progressions and no patients developed distant progression including upper cervical lymph nodal regions as initial recurrence sites. The planning study showed SIB-IMRT improved target coverage without compromising the dose to the organs at risk, compared with 3DCRT. In conclusion, omitting the elective nodal irradiation of the upper cervical lymph nodes was probably reasonable for CESCC patients without hypopharyngeal invasion. Locoregional progression remained the major progression site in this population.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Jie Chen ◽  
Wenming Yin ◽  
Hui Yao ◽  
Wendong Gu

Abstract Background Patients with regional lymph node recurrence after radical resection of esophageal cancer have poor therapeutic outcomes. Currently, there is no standard treatment for regional lymph node recurrence, and its prognostic risk factors are not well-understood. This study retrospectively analyzed 83 patients with postoperative regional lymph node recurrence after radical resection of esophageal squamous cell carcinoma. The aim was to evaluate the clinical efficacy and prognostic factors of salvage radiotherapy with or without chemotherapy in these patients. Methods The survival and prognostic factors of 83 patients with esophageal squamous cell carcinoma with regional lymph node recurrence after radical surgery were retrospectively analyzed. All patients underwent radiotherapy, of which 74 patients received volumetric modulated arc therapy (VMAT), 9 patients received three-dimensional conformal radiation therapy (3DCRT), administered using a conventional segmentation protocol with a dose distribution range of 50.4–66.2Gy (median dose of 60Gy). In total, 41 patients received radiotherapy alone, 42 received radiotherapy combined with chemotherapy, and the concurrent chemotherapy regimen was mainly composed of either platinum or fluorouracil monotherapy, except for 4 patients who were given 5-fluorouracil plus platinum (FP) or paclitaxel plus platinum (TP). Results The median follow-up time was 24 (range, 9–75) months. The overall survival (OS) rates at 1 year, 2 years, 3 years, and 5 years were 83.0, 57.1, 40.1, and 35.1%, respectively. The median overall survival (OS) time was 18 (range, 5–75) months. The 3-year survival rate was 47.5% in patients with radiation alone and 41.9% in patients receiving concurrent chemoradiotherapy(p = 0.570), while the response rate (CR + PR) in those two groups was 73.2 and 91.4%, respectively. By multivariate analysis of OS, age (worse in younger patients, p = 0.034) was found to be significantly associated with disease prognosis. The commonly toxicities were esophagitis, neutropenia and anemia. 18% patients experienced grade 3 toxicity and no treatment-related death occurred. Conclusions These results of this retrospective analysis suggest that radiotherapy with or without chemotherapy is an effective and feasible salvage treatment for lymph node recurrence after radical resection of esophageal squamous cell carcinoma.


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