Advancing Esophageal Cancer Treatment: Immunotherapy in Neoadjuvant and Adjuvant Settings

Cancers, Год журнала: 2024, Номер 16(2), С. 318 - 318

Опубликована: Янв. 11, 2024

Locally advanced esophageal cancer (LAEC) poses a significant and persistent challenge in terms of effective treatment. Traditionally, the primary strategy for managing LAEC has involved concurrent neoadjuvant chemoradiation followed by surgery. However, achieving pathologic complete response (pCR) proven to be inconsistent, despite treatment, roughly half patients experience locoregional recurrence or metastasis. Consequently, there been paradigm shift towards exploring potential immunotherapy reshaping landscape management. Recent research particularly focused on immune checkpoint inhibitors, investigating their application both adjuvant settings. These designed block specific proteins cells, are meant enhance system's ability target combat cells. Emerging evidence from these studies suggests possibility mortality benefit, indicating that may contribute improved overall survival rates individuals grappling with cancer. This manuscript aims meticulously review existing literature surrounding context The intention is thoroughly examine methodologies findings relevant studies, providing comprehensive synthesis current understanding impact

Язык: Английский

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Neoadjuvant Chemoradiotherapy vs Chemoimmunotherapy for Esophageal Squamous Cell Carcinoma

JAMA Surgery, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

Importance The association of neoadjuvant chemoimmunotherapy (NCIT) vs chemoradiotherapy (NCRT) with tumor downstaging and survival in locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear because limited evidence. Objective To compare the associations NCIT NCRT regression long-term patients ESCC. Design, Setting, Participants In this comparative effectiveness research study, from January 2016 to March 2023, ESCC who underwent esophagectomy following or were identified a prospective database 8 high-volume surgery centers China. Follow-up began on date continued until last recorded contact 2024, whichever occurred first. Data analyzed between April September 2024. Main Outcomes Measures primary end points 2-year overall (OS) disease-free (DFS). Secondary included major pathologic response (MPR) complete (pCR). Cox proportional hazard analysis was used investigate risk factors for OS DFS. Results study 1428 (median [IQR] age, 63 [57-68] years; 1184 men [82.9%]), 704 group 724 group. After propensity score matching, there 532 each (81.3% 71.3%; ratio, 1.57; 95% CI, 1.26-1.96; P < .001) DFS (73.9% 63.4%; 1.37; 1.11-1.69; rates significantly higher than had MPR rate that (71.8% 61.5%), whereas pCR similar (25.9% 22.9%). Multivariable demonstrated independently associated both exhibited lower recurrence (126 [23.7%] 190 [35.7%]) distant metastasis (72 [13.5%] 133 [25.0%]), although locoregional (98 [18.4%] 111 [20.9%]). Better obtained group, regardless whether adjuvant immunotherapy given. Conclusions Relevance Compared NCRT, receiving better decrease may be main reason, but further randomized clinical trials are needed verify finding.

Язык: Английский

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Neoadjuvant chemoimmunotherapy for locally advanced squamous cell carcinoma of the head and neck: Systematic review and meta-analysis

Pharmacological Research, Год журнала: 2025, Номер 212, С. 107598 - 107598

Опубликована: Янв. 11, 2025

Neoadjuvant chemoimmunotherapy emerged as a promising treatment for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, comparison clinical outcomes with neoadjuvant chemotherapy was lacking. To provide evidence supporting decision-making in LA-SCCHN treatment. Literature retrieved from PubMed, Web Science, Embase, Cochrane Library studies on efficacy safety published before August 10, 2024. The study registered PROSPERO (CRD42024573816). A total 28 trials 2021 patients were included. group had significantly higher pathologic complete response (pCR) (33 % vs. 18 %, P = 0.04) partial (PR) (65 38 < 0.01). No significant differences found overall survival (OS) (hazard ratio: 0.85, 95 CI: 0.77-0.93) progression-free (PFS) 0.72, 0.61-0.86). Regarding outcomes, single-arm trials, grade 3-4 treatment-related adverse events (TRAEs) occurred 14 13 group, 5 TRAEs at 0 4 respectively, showing no difference (P 0.80; 0.08). In both RCTs non-RCT, Risk Ratio (RR) (RR: 1.42, 0.87-2.31). has shown LA-SCCHN, but further randomized are needed to confirm long-term benefits.

Язык: Английский

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Neoadjuvant immunotherapy for resectable esophageal cancer: A review

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Дек. 8, 2022

Esophageal cancer (EC) is one of the most common cancers worldwide, especially in China. Despite therapeutic advances, 5-year survival rate EC still dismal. For patients with resectable disease, neoadjuvant chemoradiotherapy (nCRT) combination esophagectomy mainstay treatment. However, pathological complete response (pCR) to nCRT 29.2% 43.2% not satisfactory, and approximately half will develop either a locoregional recurrence or distant metastasis. It is, therefore, necessary explore novel effective treatment strategies improve clinical efficacy Immunotherapy utilizing immune checkpoint inhibitors (ICIs) has significantly changed paradigm for wide variety advanced cancers, including EC. More recently, increasing evidence demonstrated that immunotherapy can potentially cancers. Furthermore, accumulating findings support idea chemotherapy and/or radiotherapy activate system through mechanisms, so have synergistic antitumor effect. Therefore, it reasonable evaluate role surgically In this review, we discuss rationale EC, summarize current results strategy, review planned ongoing studies, highlight challenges future research needs.

Язык: Английский

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Pretreatment absolute lymphocyte count is an independent predictor for survival outcomes for esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy and pembrolizumab: An analysis from a prospective cohort

Thoracic Cancer, Год журнала: 2023, Номер 14(17), С. 1556 - 1566

Опубликована: Апрель 24, 2023

Abstract Background The aim of the study was to analyze relationship between pretreatment inflammatory biomarkers (IBs) and survival outcomes for patients with esophageal squamous cell carcinoma (ESCC) treated neoadjuvant chemoradiotherapy (neo‐CRT) pembrolizumab. Methods Clinical variables IBs (absolute monocyte count [AMC], absolute lymphocyte [ALC], platelet [PLT], neutrophil‐to‐lymphocyte ratio [NLR], platelet‐to‐lymphocyte [PLR], lymphocyte‐to‐monocyte [LMR], pan‐immune inflammation value [PIV], systemic immunoinflammatory index [SII], immunoreactivity [SIRI] prognostic nutritional [PNI]) were collected. Univariate multivariate analysis performed identify independent factors ESCC. Results A total 51 included. Of these, 35 achieved pathological complete response (pCR) after neo‐CRT pembrolizumab (pCR: 68.6%). With a median follow‐up 20 months, two‐year PFS OS cohort 64% 91%, respectively. Multivariate logistic regression indicated that ALC (overall [OR] 4.4, p = 0.051) PLT (OR 6.7, 0.023) two predictors achieving pCR among ESCC Cox showed (HR 0.27, 0.028) SIRI 3.13, 0.048) associated PFS. Kaplan Meier demonstrated high baseline significantly better than those low (2‐year PFS: 77% vs. 47%, 0.027), but not overall OS: 96% 87%, 0.46). Conclusions This retrospective based on prospective first time demonstrates is an predictor favorable

Язык: Английский

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Advances in targeted therapy and immunotherapy for esophageal cancer

Chinese Medical Journal, Год журнала: 2023, Номер 136(16), С. 1910 - 1922

Опубликована: Июль 5, 2023

Esophageal cancer (EC) is one of the most common aggressive malignant tumors in digestive system with a severe epidemiological situation and poor prognosis. The early diagnostic rate EC low, patients are diagnosed at an advanced stage. Multiple multimodality treatments have gradually evolved into main treatment for EC, including surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy. And emergence therapy immunotherapy has greatly improved survival patients. This review highlights latest advances discusses efficacy safety relevant drugs, summarizes related important clinical trials, tries to provide references therapeutic strategy EC.

Язык: Английский

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PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with BRPC/LAPC: A biomolecular exploratory, phase II trial

Cell Reports Medicine, Год журнала: 2023, Номер 4(3), С. 100972 - 100972

Опубликована: Март 1, 2023

This is a phase II study of PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with locally advanced or borderline resectable pancreatic cancer (LAPC BRPC, respectively). Twenty-nine are enrolled in the study. The objective response rate (ORR) 60%, and R0 resection 90% (9/10). 12-month progression-free survival (PFS) overall (OS) 64% 72%, respectively. Grade 3 higher adverse events anemia (8%), thrombocytopenia jaundice (8%). Circulating tumor DNA analysis reveals that >50% decline maximal somatic variant allelic frequency (maxVAF) between first clinical evaluation baseline have longer outcome surgical than those who not. displays promising antitumor activity, multiomics potential predictive biomarkers identified warrant further verification.

Язык: Английский

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Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer: an interim analysis of a phase III randomized clinical trial

Cancer Communications, Год журнала: 2024, Номер unknown

Опубликована: Сен. 2, 2024

Abstract Background In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for treatment locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks high‐level clinical evidence. This study aimed to compare safety and long‐term efficacy NAIC followed by minimally invasive esophagectomy (MIE) with those chemotherapy (NAC) MIE. Methods A prospective, single‐center, open‐label, randomized phase III trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned receive either toripalimab (240 mg) plus paclitaxel (175 mg/m 2 ) + cisplatin (75 (toripalimab group) or alone (chemotherapy every 3 weeks cycles. After surgery, group received mg up 6 months). The primary endpoint event‐free survival (EFS). pathological complete response (pCR) overall (OS) key secondary endpoints. Adverse events (AEs) quality life also assessed. Results Between May 15, 2020 August 13, 2021, 252 ESCC patients ranging from T1N1‐3M0 T2‐3N0‐3M0 enrolled interim analysis, 127 in 125 group. 1‐year EFS rate 77.9% compared 64.3% (hazard ratio [HR] = 0.62; 95% confidence interval [CI] 0.39 1.00; P 0.05). OS rates 94.1% 83.0% groups, respectively (HR 0.48; CI 0.24 0.97; 0.037). had a higher pCR (18.6% vs. 4.6%; 0.001). postoperative Clavien‐Dindo grade IIIb morbidity 9.8% 6.8% group, no significant difference observed ( 0.460). 4 treatment‐related AEs did not differ between two groups (12.5% versus 12.4%). Conclusions results this ongoing showed that resectable ESCC, addition perioperative NAC safe, may improve might change standard future.

Язык: Английский

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Perioperative the BTLA inhibitor (tifcemalimab) combined with toripalimab and chemotherapy for resectable locally advanced thoracic esophageal squamous cell carcinoma trial (BT-NICE trial): a prospective, single-arm, exploratory study

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 10, 2025

The treatment of cancer has brought about a paradigm shift with the introduction immune checkpoint blockade (ICB) therapy, which is mostly dependent on inhibiting PD-1/PD-L1 and CTLA-4. However, recent studies have shown limited efficacy this in esophageal squamous cell carcinoma (ESCC). Preliminary found that tifcemalimab (the world's first anti-BTLA blocking monoclonal antibody) combined toripalimab (PD-1) chemotherapy favorable safety several solid cancers. This study aimed to evaluate neoadjuvant following esophagectomy for resectable ESCC, association adjuvant immunotherapy improved survival outcomes. Patients pathologically confirmed cT1b-3N1-3M0 or cT2-3N0M0 thoracic ESCC were treated (200mg, iv, d1) combination (240mg, (paclitaxel 135-175 mg/m2, d1 + cisplatin 75 every 3 weeks 2 cycles. undergoing pathological complete response (pCR) administered up 15 cycles (200 mg) (240 mg), whereas patients without pCR received cycles, followed by 13 patient incomplete resection was decided receive radiotherapy after multidisciplinary consultation. primary endpoint rate. secondary endpoints include major rate (MPR), objective (ORR), disease control (DCR), adverse events, R0 rate, event-free (EFS), overall (OS). Ethics Committee Henan Provincial People's Hospital approved protocol (No 2024-132-03). prospective clinical trial BTLA inhibitor PD-1 as neoadjuvant/adjuvant therapy locally advanced ESCC. We predicted perioperative potentially preferred effective strategy may lead better

Язык: Английский

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Pathologic responses and surgical outcomes after neoadjuvant immunochemotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Ноя. 17, 2022

Background Currently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared efficacy immunochemotherapy (NICT) and chemoradiotherapy (NCRT). Our study aimed to compare treatment response postoperative complications after NICT followed by surgery that conventional NCRT ESCC. Methods Of 468 ESCC, 154 received NCRT, whereas 314 NICT. Treatment response, mortality between two groups were compared. Pathological primary tumor was evaluated using Mandard regression grade (TRG) scoring system. complete (pCR) metastatic lymph nodes (LNs) defined as no viable within all resected LNs. According directionality, pattern summarized into four categories: type I, toward lumen; II, invasive front; III, concentric regression; IV, scattered regression. Inverse probability propensity score weighting performed minimize influence confounding factors. Results After adjusting baseline characteristics, R0 resection rates (90.9% vs. 89.0%, P=0.302) pCR (ypT0N0) (29.8% 34.0%, P=0.167) comparable groups. Patients receiving showed lower TRG (P&lt;0.001) higher major pathological (MPR) rate (64.7% 53.6%, P=0.001) those However, brought a LNs than (53.9% 37.1%, P&lt;0.001). The I/II/III/IV patterns 44.6%, 6.8%, 11.4% 37.1% group, 16.9%, 8.2%, 18.3% 56.6% indicating significant difference (P&lt;0.001). Moreover, there differences incidence total (35.8% 39.9%, P=0.189) 30-d (0.0% 1.1%, P=0.062). Conclusion For without increased mortality. Notablely, might bring promising

Язык: Английский

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