scholarly journals Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report

2021 ◽  
Vol 11 ◽  
Author(s):  
Tian Zeng ◽  
Lei Zhang ◽  
Can Chen ◽  
Xiang Zhao ◽  
Xiaoqing Liu ◽  
...  

Microsatellite instability-high (MSI-H) is widely believed to be a biomarker for immune checkpoint inhibitors (ICIs) such as pembrolizumab in solid tumors. However, due to the low prevalence of MSI-H in most cancers, it tends to be insufficient to identify whether patients should receive ICIs according to this biomarker alone. Here, we report a Chinese esophageal squamous cell carcinoma (ESCC) patient with unusual divergent MSI status between the primary lesion (MSS) and metastatic lesion (MSI-H) which developed after platinum-based therapy and radiotherapy. Both his primary and metastatic tumors responded well to pembrolizumab-containing therapies or pembrolizumab monotherapy and maintained a complete response for over 24 months. Whole-exome sequencing and multiplex immunohistochemistry were used to examine his tissue specimens. Notably, there were multiple high-frequency mutations of DDR (DNA damage repair) genes shared in the primary lesion and metastatic lesion, especially in the latter. Besides, we observed considerable degrees of infiltrating CD3+/CD8+ lymphocytes in both of his primary tumor and metastatic tumor without obvious difference, suggesting that the conversion of microsatellite status had little effect on the infiltration of lymphocytes. Collectively, given the predictive role of DDR alterations for ICIs in other malignancies, the alterations of DDR genes might also be promising biomarkers in ESCC individuals receiving ICIs.

2006 ◽  
Vol 41 (5) ◽  
pp. 425-432 ◽  
Author(s):  
Yosuke Kumekawa ◽  
Kazuhiro Kaneko ◽  
Hiroaki Ito ◽  
Toshinori Kurahashi ◽  
Kazuo Konishi ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3147
Author(s):  
Shau-Hsuan Li ◽  
Yen-Hao Chen ◽  
Hung-I Lu ◽  
Chien-Ming Lo ◽  
Chao-Cheng Huang ◽  
...  

The galectin-1 has been found to be involved in poor outcomes after treatment of a variety of cancers. To the best of our knowledge, however, the significance of galectin-1 expression in the sensitivity to chemoradiotherapy (CCRT) of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear. Expression levels of galectin-1 were evaluated by immunohistochemistry and correlated with the treatment outcome in 93 patients with locally advanced ESCC who received preoperative CCRT between 1999 and 2012. Galectin-1 expression was significantly associated with the pathological complete response (pCR). The pCR rates were 36.1% and 13.0% (p = 0.01) in patients with low and high galectin-1 expression, respectively. Univariate analyses revealed that galectin-1 overexpression, clinical 7th American Joint Committee on Cancer (AJCC) stage III and a positive surgical margin were significant factors of worse overall survival and disease-free survival. In multivariate analyses, galectin-1 overexpression and a positive surgical margin represented the independent adverse prognosticators. Therefore, galectin-1 expression both affects the pCR and survival in patients with locally advanced ESCC receiving preoperative CCRT. Our results suggest that galectin-1 may be a potentially therapeutic target for patients with ESCC treated with preoperative CCRT.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 79-79
Author(s):  
C. Lin ◽  
C. Hsu ◽  
J. C. Cheng ◽  
C. Yen ◽  
H. Shiah ◽  
...  

79 Background: We investigated the efficacy and safety of adding cetuximab into twice-weekly paclitaxel/cisplatin-based concurrent chemoradiotherapy (CCRT), followed by surgery, for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients with operable ESCC (T3N0-1M0 or T1-3N1M0 or M1a) were treated with paclitaxel (35 mg/m2 1 h on days 1 and 4/week), cisplatin (15 mg/m2 1 h on days 2 and 5/week), cetuximab (400 mg/m2 2 h on day -5, then 250 mg/m2 2 h on day 3/week) and radiotherapy (2 Gy on days 1-5/week). When the accumulated radiation dose reached 40 Gy, the feasibility of esophagectomy was evaluated for all patients. In patients for whom esophagectomy was not feasible, CCRT was continued to a radiation dose of 60-66 Gy. Results: Sixty-two patients with ESCC were enrolled, and the majority had T3N1M0 or M1a tumors by endoscopic ultrasonographic staging (94%). All patients received CCRT to 40 Gy. Forty-three patients underwent surgery, and 17 patients continued definitive CCRT to 60-66 Gy. Of the scheduled doses of paclitaxel, cisplatin, and cetuximab, 80%, 79%, and 99% were given, respectively. The intent-to-treat pathological complete response rate was 24% (15/62) (95% confidence interval: 13-35%). At the median follow-up of 13.3 months, the one-year progression-free and overall survivals were 76% and 63%, respectively. The most common grade 3/4 toxic effects were leukopenia (51%), neutropenia (15%), esophagitis (19%), and infection (12%). Grade 1, 2, and 3 skin rash occurred in 59%, 36%, and 2% of patients, respectively. Grade 1, 2, 3, and 4 hypomagnesemia occurred in 14%, 5%, 0%, and 5% of patients, respectively. Conclusions: Adding cetuximab to twice-weekly paclitaxel/cisplatin-based CCRT prior to esophagectomy is an active and tolerable treatment for locally advanced ESCC. No significant financial relationships to disclose.


Author(s):  
Tatcha Rerkrak ◽  
Somkiat Sunpaweravong

The treatment of locally advanced esophageal squamous cell carcinoma is still controversial. Although, preoperative chemoradiation, followed by esophagectomy is the standard treatment, morbidity and patients’ quality of life problems after an esophagectomy are still considerable. Since a good pathologic complete response rate in patients after preoperative chemoradiation, a wait and see policy (with active surveillance) has been introduced as a new alternative approach after chemoradiation. Active surveillance involves imaging and biopsy evaluations in patients after chemoradiation to detect residual or recurrent tumors. If there are no residual tumors, observation is considered. Surgery is reserved for patients who present with residual tumors or locoregional recurrence after surveillance to achieve complete resection (salvage esophagectomy). Based on evidence from recent studies, surveillance with salvage esophagectomy is a treatment option for locally advanced esophageal squamous cell carcinoma patients achieving a clinical complete response after chemoradiation.


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