Esophageal cancer in China: Practice and research in the new era

International Journal of Cancer, Год журнала: 2022, Номер 152(9), С. 1741 - 1751

Опубликована: Сен. 24, 2022

Abstract China, as the one of largest developing countries in world and with about one‐fifth global population, is bearing an increasing burden on health from cancer. In area esophageal cancer (EC), China accounts for more than 50% cases, this disease being a particularly worse those disadvantaged populations. Along China's socioeconomic condition, epidemiology, diagnosis, therapeutics research EC have developed throughout 21st century. current review, existing control measures are outlined, including incidence, mortality, screening, clinical multidisciplinary treatment landscape. very different some other parts world, especially Western countries. Core that could contribute to prevention improve outcomes patients less beyond recommended. International cooperation among academia, government industry warranted control.

Язык: Английский

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Evaluation of Clinical and Safety Outcomes of Neoadjuvant Immunotherapy Combined With Chemotherapy for Patients With Resectable Esophageal Cancer

JAMA Network Open, Год журнала: 2022, Номер 5(11), С. e2239778 - e2239778

Опубликована: Ноя. 2, 2022

Importance A considerable number of clinical trials neoadjuvant immunotherapy for patients with resectable esophageal cancer are emerging. However, systematic evaluations these studies lacking. Objective To provide state-of-the-art evidence and normative theoretical support locally advanced cancer. Data Sources PubMed, Embase, Cochrane Library, ClinicalTrials.gov databases were searched relevant original articles conference proceedings that published in English through April 1, 2022. Study Selection Published phase 2 or 3 included stage I to IV who received immune checkpoint inhibitors (ICIs) before surgery as monotherapy combination other therapies. Extraction Synthesis The Preferred Reporting Items Systematic Reviews Meta-analyses the Meta-analysis Observational Studies Epidemiology guidelines meta-analysis followed extract data. random-effects model was adopted if heterogeneity significant ( statistic >50%); otherwise, common-effects used. analyses conducted from 8, Main Outcomes Measures Pathological complete response (pCR) rate major pathological (MPR) considered be primary outcomes calculated immunotherapy. Incidence treatment-related severe adverse events set measure safety outcome. R0 surgical resection summarized. Subgroup according histologic subtype ICI types. Results total 27 815 included. Pooled rates 31.4% (95% CI, 27.6%-35.3%) pCR 48.9% 42.0-55.9%) MCR In terms safety, pooled incidence 26.9% 16.7%-38.3%). Most achieved (98.6%; 95% 97.1%-99.6%). Regarding subtypes, 32.4% 28.2%-36.8%) squamous cell carcinoma 25.2% 16.3%-35.1%) adenocarcinoma. MPR 49.4% 42.1%-56.7%) carcinoma. Conclusions Relevance This study found chemotherapy had promising Randomized long-term follow-up warranted validate findings benefits ICIs.

Язык: Английский

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Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma

Cancer Cell, Год журнала: 2023, Номер 41(11), С. 1852 - 1870.e9

Опубликована: Окт. 12, 2023

Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset exhausted CD8+ T cells expressing SPRY1 (CD8+ Tex-SPRY1) that displays progenitor (Tpex) phenotype and correlates complete response to ICB. We validate Tex-SPRY1 as an ICB-specific predictor improved survival using independent ICB-/non-ICB cohorts demonstrate expression enforces Tpex enhances ICB efficacy. Additionally, contribute proinflammatory macrophages functional state B cells, which thereby promotes antitumor immunity by enhancing effector functions. Overall, our findings unravel progenitor-like cells' role effective responses for inform mechanistic biomarkers future individualized immunotherapy.

Язык: Английский

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Neoadjuvant sintilimab and chemotherapy in patients with potentially resectable esophageal squamous cell carcinoma (KEEP-G 03): an open-label, single-arm, phase 2 trial

Journal for ImmunoTherapy of Cancer, Год журнала: 2023, Номер 11(2), С. e005830 - e005830

Опубликована: Фев. 1, 2023

Background The standard neoadjuvant treatments in patients with esophageal squamous cell carcinoma (ESCC) still have either poor safety or efficacy. Better therapies are needed China. Methods This was an open-label, single-arm, phase 2 trial. Patients potentially resectable ESCC (cT1b-3, Nany, M0 T4a, N0-1, M0) received preoperative intravenous sintilimab plus triplet chemotherapy (liposomal paclitaxel, cisplatin, and S-1) every 3 weeks for two cycles. primary endpoints were surgical feasibility; the secondary endpoint major pathological response (MPR) rate. Genomic biomarkers (genetic mutations, tumor mutational burden (TMB), circulating DNA status immune microenvironment) baseline samples investigated. Results All 30 completed cycles of treatment underwent resection. Grade 3–4 treatment-related adverse events (TRAEs) occurred 36.7% (11/30) patients. most frequent TRAEs decreased white count (76.7%), anemia neutrophil (73.3%). hematological toxicities; none caused ≥30 days delay. MPR complete (pCR) rates 50.0% (15/30; 95% CI 33.2 to 66.9) 20.0% (6/30; 9.5 37.3), respectively. higher TMB more clonal mutations likely respond. ERBB2 alterations ctDNA high-releaser a negative correlation ICI response. No significant difference observed between therapeutic microenvironment. Conclusions Neoadjuvant platinum-based appeared safe feasible, did not delay surgery induced pCR rate ESCC. Trial registration number NCT03946969 .

Язык: Английский

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Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial

Nature Medicine, Год журнала: 2024, Номер 30(9), С. 2549 - 2557

Опубликована: Июль 2, 2024

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of camrelizumab followed by adjuvant compared alone. A total 391 patients with thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified clinical stage (I/II, III IVA) randomized in 1:1:1 ratio undergo two cycles therapy. Treatments included albumin-bound paclitaxel cisplatin (Cam+nab-TP group; n = 132); (Cam+TP 130); (TP 129), surgical resection. Both Cam+nab-TP Cam+TP groups also received camrelizumab. The dual primary endpoints rate pathological complete response (pCR), as evaluated blind independent review committee, event-free survival (EFS), assessed investigators. study reports final analysis pCR rates. In intention-to-treat population, exhibited significantly higher rates 28.0% 15.4%, respectively, 4.7% TP group versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; 10.9%, CI 3.7-18.1, 0.0034). met its endpoint pCR; however, EFS is not yet mature. incidence grade ≥3 treatment-related adverse events during treatment was 34.1% group, 29.2% 28.8% postoperative complication 34.2%, 38.8% 32.0%, respectively. Neoadjuvant demonstrated superior alone LA-ESCC, tolerable profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .

Язык: Английский

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Neoadjuvant chemotherapy combined with immunotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma

Journal of Thoracic and Cardiovascular Surgery, Год журнала: 2024, Номер 168(2), С. 417 - 428.e3

Опубликована: Янв. 19, 2024

Язык: Английский

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The Neo-PLANET phase II trial of neoadjuvant camrelizumab plus concurrent chemoradiotherapy in locally advanced adenocarcinoma of stomach or gastroesophageal junction

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Ноя. 10, 2022

Abstract The synergistic effect of neoadjuvant immunotherapy and chemoradiotherapy in gastric adenocarcinoma is unclear. This phase II trial (NCT03631615) investigated this combination locally advanced stomach or gastroesophageal junction. Thirty-six patients received capecitabine 850 mg/m 2 twice daily simultaneous radiotherapy for 5 weeks, sandwiched by a 21-day cycle oxaliplatin 130 (day 1) plus 1000 (days 1–14), respectively, followed surgery. Camrelizumab 200 mg was given cycles since initiating chemotherapy. Primary endpoint pathological complete response (pCR, ypT0) rate. Secondary endpoints included total pCR (tpCR, ypT0N0) rate, major (MPR, < 10% residual tumor cells) margin-free (R0) resection downstaging, progression-free survival (PFS), overall (OS), safety. rate 33.3% (95% CI, 18.6–51.0), meeting pre-specified endpoint. TpCR, MPR, R0 rates were 33.3%, 44.4%, 91.7%, respectively. Twenty-eight (77.8%) reached ypN0. Two-year PFS OS 66.9% 76.1%, most common grade 3–4 adverse event decreased lymphocyte count (27 [75.0%]). Neoadjuvant camrelizumab concurrent exhibits promising with adenocarcinoma, an acceptable safety profile.

Язык: Английский

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Efficacy and safety of neoadjuvant immunotherapy in surgically resectable esophageal cancer: A systematic review and meta-analysis

International Journal of Surgery, Год журнала: 2022, Номер 104, С. 106767 - 106767

Опубликована: Июль 14, 2022

Язык: Английский

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Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction

Clinical Cancer Research, Год журнала: 2022, Номер 28(14), С. 3021 - 3031

Опубликована: Май 12, 2022

Abstract Purpose: This phase Ib/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma. Patients and Methods: GEJ adenocarcinoma (cT1–3NanyM0) received neoadjuvant chemoradiation (CROSS regimen) followed by surgical resection adjuvant pembrolizumab. The primary endpoints were tolerability the first 16 pathologic complete response [pCR (ypT0N0)]. Secondary included progression-free survival (PFS) overall (OS). An independent propensity-score-matched cohort (treated CROSS without immunotherapy) was used for comparison. Exploratory analyses immune biomarkers tumor microenvironment (TME) plasma. Results: We enrolled 31 eligible patients, of whom 29 all expected doses pembrolizumab 28 underwent R0 resection. Safety met. efficacy endpoint not met [7/31 (22.6%) achieved pCR]. high [i.e., combined positive score (CPS) ≥ 10] baseline expression programmed death (PD)-L1 TME had a significantly higher pCR rate than those low [50.0% (4/8) vs. 13.6% (3/22); P = 0.046]. PD-L1 also experienced longer PFS OS patients. Among CPS &lt; 10, unprespecified analysis explored whether extracellular vesicles (EV) could identify further responders: an elevated plasma level PD-L1–expressing EVs associated pCR. Conclusions: Adding to showed acceptable but did meet pre-specified endpoint. suggested that and/or on may most likely achieve response.

Язык: Английский

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Multi-omics analysis uncovers tumor ecosystem dynamics during neoadjuvant toripalimab plus nab-paclitaxel and S-1 for esophageal squamous cell carcinoma: a single-center, open-label, single-arm phase 2 trial

EBioMedicine, Год журнала: 2023, Номер 90, С. 104515 - 104515

Опубликована: Март 13, 2023

Immune checkpoint inhibitors combined with chemotherapy as a neoadjuvant therapy have been applied to the treatment of esophageal squamous cell carcinoma (ESCC). However, optimal regimen needs be further explored, particularly for older patients, and mechanisms by which immune inhibitor modulates evolution ESCC are unknown.In this single-arm phase 2 trial, patients resectable (stage II/III/IV without metastasis) were enrolled received nanoparticle albumin-bound (nab) paclitaxel two cycles oral S-1 weeks, intravenous toripalimab before surgery. Combination postoperative adjuvant was administered. The primary outcome major pathological response (MPR). Secondary outcomes included complete (pCR), overall rate (ORR), disease control (DCR), disease-free survival (DFS), (OS), improvement in Stooler's dysphagia score degree daily living ability (dADL). Biopsies plasma pre- post-neoadjuvant performed using whole-exome sequencing, transcriptome immunohistochemistry (IHC) PD-L1, multiplex immunofluorescence (mIF) proximity extension assay technology (PEA) 92 proteins.From November 2019 July 2021, 60 enrolled. After therapy, R0 resection achieved 55 (98.21%) patients. MPR identified 27 (49.09%), 16 (29.09%) pCR. Patients PR, SD PD 37 (61.67%), 21 (35.00%) (3.33%), respectively. staging, Stooler scores dADL significantly decreased after treatment. 11 (18.3%) experienced grade ≥3 AEs. Compared PD-L1-Low PD-L1-High had higher ratio PR. During tumor mutation burden (TMB) neoantigen (TNB) Differential clonal within tumors demonstrated analysis intratumoral heterogeneity. Transcriptome analyses revealed that infiltration CD4+ T lymphocytes at baseline associated clinical outcome. CD8+ cells increased all patients; however, exhausted cells, nTregs iTregs non-MPR. Protein levels IFN-γ, Gal.1 LAMP3 can predict benefit. In addition, expression CD83, TNFRSF4, TNFSF14, VEGFR2, ADA, ARG1, HO-1 serious More importantly, integration protein or could distinguish responders from non-responders.In study, toripalimab, nab-paclitaxel less toxic showed promising antitumor activity ESCC. Changes genome, transcriptome, PD-L1 serum proteins comprehensively analyzed correlated outcomes, provides insight into mechanism action ESCC.This study funded Major projects ministry science 13th five-year plan China [grant number: 2018ZX09201013].

Язык: Английский

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