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

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107598 - 107598

Published: Jan. 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.

Language: Английский

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Neoadjuvant Chemoradiotherapy vs Chemoimmunotherapy for Esophageal Squamous Cell Carcinoma

JAMA Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: March 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 &amp;lt; .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.

Language: Английский

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Neoadjuvant immunotherapy for resectable esophageal cancer: A review

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 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.

Language: 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, Journal Year: 2023, Volume and Issue: 14(17), P. 1556 - 1566

Published: April 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

Language: Английский

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Advances in targeted therapy and immunotherapy for esophageal cancer

Chinese Medical Journal, Journal Year: 2023, Volume and Issue: 136(16), P. 1910 - 1922

Published: July 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.

Language: 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, Journal Year: 2023, Volume and Issue: 4(3), P. 100972 - 100972

Published: March 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.

Language: Английский

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Single-cell sequencing reveals immune features of treatment response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 22, 2024

Neoadjuvant immunochemotherapy (nICT) has dramatically changed the treatment landscape of operable esophageal squamous cell carcinoma (ESCC), but factors influencing tumor response to nICT are not well understood. Here, using single-cell RNA sequencing paired with T receptor sequencing, we profile tissues from ESCC patients accepting and characterize microenvironment context. CXCL13+CD8+ Tex cells, a subset exhausted CD8+ revealed highly infiltrate in pre-treatment tumors show prominent progenitor exhaustion phenotype post-treatment samples responders. We validate cells as predictor improved reveal CXCL13 potentiate anti-PD-1 efficacy vivo. Post-treatment non-responders enriched for notably remarkable TNFRSF4+CD4+ Tregs activated immunosuppressive function significant clone expansion. Several critical markers therapeutic resistance also identified, including LRRC15+ fibroblasts SPP1+ macrophages, which may recruit form an landscape. Overall, our findings unravel immune features distinct treatment, providing rationale optimizing individualized neoadjuvant strategy ESCC. The tumour (ESCC) remain be explored. single TCR on pre- post- identifies presence enrichment marker resistance.

Language: 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, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 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

Language: Английский

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Nab-Paclitaxel in the Treatment of Gastrointestinal Cancers—Improvements in Clinical Efficacy and Safety

Biomedicines, Journal Year: 2023, Volume and Issue: 11(7), P. 2000 - 2000

Published: July 15, 2023

Taxanes (paclitaxel and docetaxel) are one of the most useful classes anticancer drugs. highly hydrophobic; therefore, these drugs must be dissolved in organic solvents (polysorbate or Cremophor EL), which contribute to their toxicities. To reduce this toxicity enhance efficacy, novel formulations have been developed. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an albumin-stabilized, Cremophor-free, water-soluble nanoparticle formulation paclitaxel. Nab-paclitaxel has better solubility less infusion-associated compared solvent-based Additionally, nab-paclitaxel can given at higher doses concentrations with Based on its superior clinical efficacy safety profile, received FDA approval for metastatic breast cancer (2008) NSCLC (2011). Among gastrointestinal cancers, it now approved USA treating patients adenocarcinoma pancreas as first-line therapy combination gemcitabine. Furthermore, several trials suggested potential a single agent other agents treatment esophageal, gastric, bowel, biliary tract cancers. demonstrated greater overall response rates (ORR) enhanced progression-free survival (PFS), (OS) profile fewer adverse effects This review summarizes advantages associated nab-paclitaxel-based regimens terms improving upper cancer.

Language: Английский

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The survival outcomes of neoadjuvant sintilimab combined with chemotherapy in patients with locally advanced esophageal squamous cell carcinoma

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 19, 2023

Background Neoadjuvant programmed death receptor-1 (PD-1) inhibitor combined with chemotherapy has been reported to improve the pathological response of locally advanced esophageal squamous cell carcinoma (ESCC), but systematic report on survival follow-up is quite few. This study we will outcomes after a median 21.1 months. Methods was real-world retrospective study. Locally ESCC patients treated neoadjuvant sintilimab albumin-bound paclitaxel and nedaplatin followed by surgery completed at least 1-year were reviewed. The primary outcome disease-free (DFS) 24 secondary overall (OS) Results Ninety eligible included in analysis between July 2019 October 2021. number cycles 3 (range 2-4). All achieved R0 resection. With months 14.0-39.0), DFS OS had not reached, 2-year rate 78.3% (95%CI 68.8%-89.1%) 2-years 88.0% 80.6%-96.0%). Postoperative stage, pCR, MPR, tumor down-staging significantly correlated favorable outcome. Univariable multivariable Cox regression identified cycle treatment as independent predictor DFS. Conclusion Our results preliminarily show benefit ESCC.

Language: Английский

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