Immunotherapy for Squamous Esophageal Cancer: A Review

Petrillo, Angelica; Smyth, Elizabeth

doi:10.3390/jpm12060862

Cited by 17 publications

(7 citation statements)

References 32 publications

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“…In curative patients, ctDNA could stratify patient recurrence risk after neoadjuvant treatment and detect early disease recurrence. For palliative patients, ctDNA can guide targeted therapy by detecting druggable gene alterations and early switch from criterion-standard CT to immunotherapy or combined immunotherapy and CT to improve survival . Previous ctDNA studies focused on pretreatment and/or posttreatment ctDNA.…”

Section: Discussionmentioning

confidence: 99%

Circulating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma

Ng,

Ko,

Lam

et al. 2023

JAMA Surg

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ImportanceEsophageal squamous cell carcinoma (ESCC) is a deadly disease with frequent recurrence. There are unmet needs for prognostic biomarkers for dynamically monitoring disease progression and detecting minimal residual disease.ObjectiveTo examine whether circulating tumor DNA is clinically useful as a prognostic biomarker for ESCC recurrence and patient survival.Design, Setting, and ParticipantsThis single-center, population-based cohort study consecutively enrolled 147 patients receiving curative (n = 74) or palliative (n = 73) treatment at the surgery and clinical oncology departments of Queen Mary Hospital in Hong Kong from August 1, 2016, to September 31, 2021. Patients were followed up for 2 years. Plasma samples were collected at different longitudinal time points for a prospective circulating tumor DNA (ctDNA) next-generation sequencing profiling study of 77 actionable genes.InterventionPatients were treated with up-front surgery, neoadjuvant chemoradiotherapy plus surgery with or without adjuvant therapy, or palliative chemotherapy (CT).Main Outcomes and MeasuresDetection of circulating tumor DNA (ctDNA), progression-free survival (PFS), and overall survival (OS).ResultsA total of 478 serial plasma samples from 147 patients with locoregional or metastatic ESCC were prospectively analyzed. Among the 74 patients in the curative group (median [range] age, 66 [46-85] years; 56 [76.0%] male), 44 (59.5%) relapsed and 36 (48.6%) died. For patients receiving curative surgical treatment, a high ctDNA level (hazard ratio [HR], 7.84; 95% CI, 1.87-32.97; P = .005) and ctDNA alterations (HR, 5.71; 95% CI, 1.81-17.97; P = .003) at 6 months postoperation were independently associated with poor OS. Among patients receiving neoadjuvant chemoradiotherapy, postneoadjuvant ctDNA alterations were associated with poor PFS (HR, 3.16; 95% CI, 1.17-8.52; P = .02). In the 73 patients in the palliative group (median [range] age, 63 [45-82] years; 63 [86.0%] male), 71 (97.3%) had disease relapse and 68 (93.2%) died. Detectable pre-CT NFE2L2 alterations were independently associated with PFS (HR, 2.99; 95% CI, 1.35-6.61; P = .007) and OS (HR, 28.39; 95% CI, 7.26-111.03; P = 1.52 × 10−6), whereas high ctDNA levels (HR, 2.41; 95% CI, 1.18-4.95; P = .02) and alterations in pre–cycle III ctDNA (HR, 1.99; 95% CI, 1.03-3.85; P = .04) showed weaker associations with PFS. Alterations in pre-CT ctDNA were independently associated with OS (HR, 4.46; 95% CI, 1.86-10.69; P = 7.97 × 10−4).Conclusions and RelevanceThe findings of this cohort study indicate that prognostic models incorporating ctDNA features are useful in ESCC. Both ctDNA level and NFE2L2 alterations pre-CT and before cycle III were found to be important prognostic factors in palliative groups, and ctDNA alterations after treatment and at 6 months after surgery may define high-risk groups for recurrence in the curative group. High-risk patients can benefit by a timely switch to the next therapeutic options.

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Section: Discussionmentioning

confidence: 99%

Circulating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma

Ng,

Ko,

Lam

et al. 2023

JAMA Surg

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“…Further evaluation of this combination therapy in a randomized phase III trial with a larger sample size and longer follow-up period is warranted in the near future. The combination of chemotherapy and immunotherapy is changing the paradigm in the field of advanced ESCC [13]. Interestingly, anti-angiogenesis, immunotherapy, and chemotherapy have shown encouraging efficacy in patients with ESCC based on recent studies [35].…”

Section: Discussionmentioning

confidence: 99%

“…As reported in the CheckMate 648 trial, a longer overall survival (OS; 13.2 months vs. 10.7 months, P = 0.002) was observed from nivolumab plus chemotherapy in ESCC compared to chemotherapy alone [11]. Despite the efficacy of the combined regimens being impressive, they may support modest response rates [11,13,14]. Furthermore, the combination may increase the incidence and severity of irAEs, which underlies significant morbidity for patients and considerable cost for healthcare systems [15].…”

Section: Introductionmentioning

confidence: 89%

A multi-center, single-arm, phase II study of anlotinib plus paclitaxel and cisplatin as the first-line therapy of recurrent/advanced esophageal squamous cell carcinoma

Hong

et al. 2022

BMC Med

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Background Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study was designed to assess the efficacy and safety of anlotinib plus paclitaxel and cisplatin (TP) as first-line therapy for advanced ESCC. Methods In a multi-center, single-arm, phase II clinical trial, patients (aged > 18 years) with ESCC, which was judged to be locally advanced, recurrent, or metastatic, received 10 mg oral anlotinib once daily on days 1–14, 135 mg/m2 intravenous paclitaxel on day 1, and 60–75 mg/m2 intravenous cisplatin on days 1–3 every 3 weeks for a maximum of 4–6 cycles as the initial therapy in five centers in China. Subsequently, patients received anlotinib monotherapy (10 mg) as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Results Forty-seven patients were enrolled in this study between October 2019 and March 2021. The median follow-up was 14.04 months (IQR, 9.30–19.38). Of 46 with assessable efficacy, the median PFS and median overall survival were 8.38 months (95% CI, 6.59–10.17) and 18.53 months (95% CI, 13.11–23.95), respectively. The objective response rate was 76.1% (95% CI, 61.2–87.4%), with 4 (8.7%) complete responses and 31 (67.4%) partial responses. The disease control rate was 91.3% (95% CI, 79.2–97.6%). The median duration of response was 6.80 months (95% CI, 4.52–9.08), and 1 patient had an ongoing response for 23 months. Subgroup analysis revealed no association between clinical factors and survival or response. Of the 47 patients with assessable safety, the main grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (17.0%), bone marrow suppression (12.8%), and vomiting (10.6%). No treatment-related deaths or serious TEAEs were observed. Notably, higher c-Kit levels were an independent factor for superior PFS (HR = 0.032; 95% CI, 0.002–0.606; P = 0.022). Conclusions The study demonstrated a manageable safety profile and durable clinical response of anlotinib plus TP as first-line therapy in advanced ESCC, which suggested a potential therapeutic option for this population. Trial registration ClinicalTrials.gov NCT04063683. Registered 21 August 2019.

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“…The burgeoning interest in immunotherapy for ESCC is aimed at enhancing patient survival outcomes, further emphasizing its significance in comprehensive treatment. Recently, the treatment of nivolumab exhibited a good survival in patients with ESCC [ 16 ]. Therefore, it is an urgency to find novel biomarkers to accurately predict the outcome of ESCC patients receiving immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

A demonstration based on multi-omics transcriptome sequencing data revealed disulfidptosis heterogeneity within the tumor microenvironment of esophageal squamous cell carcinoma

Liu¹,

Yuan²,

Liu³

et al. 2023

Discov Onc

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Background It is of great concern to identify prognostic signatures for the prediction and prediction of esophageal squamous cell carcinoma (ESCC), which is the lethal pathological type of malignancy. Method Bulk RNA sequencing and scRNA-seq data were retrieved from GSE53624, GSE53622, and GSE188900. Disulfidptosis-related differentially expressed genes (DEGs) were identified between disulfidptosis-high score and disulfidptosis-low score groups. Functional annotation of DEGs were analyzed by Gene Ontology (GO). Consistent clustering and co-expression modules were analyzed, and then constructed a risk score model via multivariate Cox regression analysis. Immune infiltration and immunotherapy response analyses were conducted based on risk score. qRT-PCR, colony formation assay, and flow cytometry analysis were conducted in KYSE-150 and TE-1 cell lines. Results Seven genes (CD96, CXCL13, IL2RG, LY96, TPK1, ACAP1, and SOX17) were selected as marker genes. CD96 and SOX17 are independent prognostic signatures for ESCC patients, with a significant correlation with infiltrated immune cells. ESCC patients had worse response to nivolumab in the high-risk group. Through cellular experiments, we found that CD96 expression was associated with apoptosis and cell cycle ESCC cells. Conclusion In a word, the risk score based on disulfidptosis is associated with prognosis and the immune microenvironment, which may direct immunotherapy of ESCC. The key gene of risk score, namely CD96, plays a role in proliferation and apoptosis in ESCC. We offer an insight into the exploration of the genomic etiology of ESCC for its clinical management.

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Immunotherapy for Squamous Esophageal Cancer: A Review

Cited by 17 publications

References 32 publications

Circulating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma

Circulating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma

A multi-center, single-arm, phase II study of anlotinib plus paclitaxel and cisplatin as the first-line therapy of recurrent/advanced esophageal squamous cell carcinoma

A demonstration based on multi-omics transcriptome sequencing data revealed disulfidptosis heterogeneity within the tumor microenvironment of esophageal squamous cell carcinoma

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