Recent Advances in Combination of Immunotherapy and Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

Wang, Ruixi; Liu, Shiliang; Chen, Baoqing; Xi, Mian

doi:10.3390/cancers14205168

Cited by 16 publications

(11 citation statements)

References 42 publications

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“…32,33 The two most prevalent histologic subtypes of EC are squamous cell carcinoma and adenocarcinoma. 34 The majority of EC occurrences and deaths worldwide occur in China, which also has the highest burden of the disease. 35 Therefore, it is of necessity to focus on the precancerous condition of esophageal epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

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Arecoline promotes Akt‐c‐Myc‐driven aerobic glycolysis in esophageal epithelial cells

Han,

Chen,

Huang

et al. 2024

Environmental Toxicology

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Aerobic glycolysis is a typical metabolic rearrangement for tumorigenesis. Arecoline is of explicit carcinogenicity, numerous works demonstrate its mutagenicity, genotoxicity, and cytotoxicity. However, the effects of arecoline on aerobic glycolysis of esophageal epithelial cells remain unclear. In the present study, 5 μM arecoline efficiently increased HK2 expression to induce aerobic glycolysis in Het‐1A‐Are and NE2‐Are cells. The mechanistic analysis showed that arecoline activated the Akt‐c‐Myc signaling pathway and reduced the GSK3β‐mediated phosphorylation of c‐Myc on Thr58 to prevent its ubiquitination and destruction, subsequently promoting HK2 transcription and expression. Taken together, these results suggest that arecoline can induce aerobic glycolysis of esophageal epithelial cells and further confirm that arecoline is a carcinogen harmful to human health.

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Section: Discussionmentioning

confidence: 99%

“…Worldwide, the five‐year survival rate varies between 15% and 25% 32,33 . The two most prevalent histologic subtypes of EC are squamous cell carcinoma and adenocarcinoma 34 . The majority of EC occurrences and deaths worldwide occur in China, which also has the highest burden of the disease 35 .…”

Section: Discussionmentioning

confidence: 99%

Arecoline promotes Akt‐c‐Myc‐driven aerobic glycolysis in esophageal epithelial cells

Han,

Chen,

Huang

et al. 2024

Environmental Toxicology

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“…ICIs are immunotherapies that target immune cell surface checkpoints and enhance immunity through the use of antibodies to ‘tumor escape’, ultimately leading to an antitumor response by turning off the immune system’s braking mechanisms. 43–47 An increasing number of studies have demonstrated the efficacy and safety of ICIs in patients with ESCC. In a phase III clinical trial of advanced ESCC second-line therapy (RATIONALE-302, NCT03430843), the use of tislelizumab was associated with improved OS and better safety compared to chemotherapy alone.…”

Section: Discussionmentioning

confidence: 99%

Retrospective study of the combination of TP and PF regimens with or without immune checkpoint inhibitors for the first-line treatment of locally advanced or advanced esophageal squamous cell carcinoma

et al. 2023

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Objective: To investigate the efficacy and safety differences between the cisplatin + paclitaxel (TP) and cisplatin + fluorouracil (PF) regimens in combination with or without immune checkpoint inhibitors (ICIs) in advanced esophageal squamous cell carcinoma (ESCC) first-line treatment and prognostic factors. Methods: We selected the medical records of patients with late stage ESCC admitted to the hospital between 2019 and 2021. Based on the first-line treatment regimen, control groups were divided into chemotherapy plus ICIs ( n = 243) and non-ICIs ( n = 171), 119 (49%) in the TP + ICIs group, 124 (51%) in the PF + ICIs group, 83 (48.5%) in the TP group, and 88 (51.5%) in the PF group in the control group. We analyzed and compared factors related to efficacy, safety, or response to toxicity and prognosis across four subgroups. Results: The overall objective response rate (ORR) and disease control rate (DCR) of the TP plus ICIs group were 42.1% (50/119) and 97.5% (116/119), respectively, which were 6.6% and 7.2% higher than those of the PF plus ICIs group. Patients in the TP combined with ICIs group had higher overall survival (OS) and progression-free survival (PFS) than those in the PF combined with ICIs group [hazard ratio (HR) = 1.702, 95% confidence interval (CI): 0.767–1.499, p = 0.0167 and HR = 1.158, 95% CI: 0.828–1.619, p = 0.0055] ORR and DCR were 15.7% (13/83) and 85.5% (71/83) in the TP chemotherapy alone group, significantly higher than the PF group [13.6% (12/88) and 72.2% (64/88)] ( p < 0.05), OS and PFS were also better in patients treated with TP regimen chemotherapy than PF (HR = 1.173, 95% CI: 0.748–1.839, p = 0.0014 and HR = 0.1.245, 95% CI: 0.711–2.183, p = 0.0061). Furthermore, following the combination of TP and PF diets with ICIs, the OS of the patients was higher than that of the group treated with chemotherapy alone (HR = 0.526, 95% CI: 0.348–0.796, p = 0.0023 and HR = 0.781, 95% CI: 0.0.491–1.244, p < 0.001). Regression analysis showed that the neutrophil-to-lymphocyte ratio (NLR), the control nuclear status score (CONUT), and the systematic immune inflammation index (SII) were independent prognostic factors for the efficacy of immunotherapy ( p < 0.05). The overall incidence of treatment-associated adverse events (TRAEs) was 79.4% (193/243) and 60.8% (104/171) in the experimental and control groups, respectively, and there was no statistically significant difference in TRAEs between TP + ICIs (80.6%) and PF + ICIs (78.2%) (61.4%) and PF groups (60.2%) ( p > 0.05). Overall, 21.0% (51/243) of patients in the experimental group experienced immune-related adverse events (irAEs), and all of these adverse effects were tolerated or remitted following drug treatment without affecting follow-up. Conclusion: The TP regimen was associated with better PFS and OS with or without ICIs. Furthermore, high CONUT scores, high NLR ratios, and high SII were found to be associated with poor prognosis in combination immunotherapy.

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“…Despite the improvement in the survival of EC in the past decades, the ve-year survival is still unsatisfactory, only less than 20% [3] . In addition to the as high as 30-50% recurrence rate after radical treatment, some patients with esophageal squamous cell carcinoma are diagnosed at an advanced stage and lose the opportunity to receive radical treatment [4] .…”

Section: Introductionmentioning

confidence: 99%

Anti-PD-1 therapy with or without local intervention for oligometastatic esophageal squamous cell carcinoma (ESO- Shanghai20): a prospective, multicenter, randomized controlled, Phase III clinical trial

Mao,

Xin,

Fan

et al. 2024

Preprint

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Background Anti-PD-1 therapy combined with or without chemotherapy is the standard regimen for metastatic esophageal cancer. Oligometastatic carcinoma is an intermediate state of tumor development between locally advanced and widespread metastasis, with potential long-term survival. The value of the addition of local intervention therapy to standard systemic therapy is still controversial for patients with oligometastasis. The ESO-Shanghai 13 trial demonstrated that systemic therapy combined with local intervention improved progression-free survival and overall survival in patients with oligometastatic esophageal squamous cell carcinoma. However, it is a phase II trial and has two systemic treatment regimens including chemotherapy and chemoimmunotherapy. There were only 43 patients treated with immunotherapy with or without local intervention therapy in ESO-Shanghai 13. To further assess the efficacy of Anti-PD-1 therapy with local intervention therapy in oligometastatic esophageal patients, we initiated a multicenter randomized controlled phase III clinical trial, ESO-Shanghai 20. Methods The ESO-Shanghai20 trial will recruit histology-proven esophageal squamous cell carcinoma patients with genuine oligometastasis (four or fewer metastatic lesions) and the eligible patients will be randomly assigned in a 2:1 ratio to receive either the combined local intervention therapy and systemic therapy (the combined group) or the systemic therapy only (the systemic group). Both groups receive anti-PD-1 with or without chemotherapy for 4 cycles every 21 days, followed by anti-PD-1 maintenance therapy every 21 days for 2 years. The local intervention therapy in this trial includes radiotherapy, surgery, and ablation, and allowed different metastases in the same patient to receive different local intervention treatment modes according to the characteristics of the metastatic site. The expected enrollment time is 36 months, and the follow-up time is 24 months. The combined treatment group and the systemic treatment group required 236 and 118 samples, respectively, and a total of 354 cases needed to be enrolled. The primary endpoint is progression free survival, and the second endpoint is overall survival and the toxicity and safety of the treatment. Discussion If the result of ESO-Shanghai20 shows that the combination of local intervention therapy with anti-PD-1 therapy is safe and promising for patients with oligometastatic esophageal squamous cell carcinoma, this study will provide a basis for the precise stratified treatment of patients with advanced esophageal squamous cell carcinoma. Trial registration NCT06190782.

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Recent Advances in Combination of Immunotherapy and Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

Cited by 16 publications

References 42 publications

Arecoline promotes Akt‐c‐Myc‐driven aerobic glycolysis in esophageal epithelial cells

Arecoline promotes Akt‐c‐Myc‐driven aerobic glycolysis in esophageal epithelial cells

Retrospective study of the combination of TP and PF regimens with or without immune checkpoint inhibitors for the first-line treatment of locally advanced or advanced esophageal squamous cell carcinoma

Anti-PD-1 therapy with or without local intervention for oligometastatic esophageal squamous cell carcinoma (ESO- Shanghai20): a prospective, multicenter, randomized controlled, Phase III clinical trial

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