Dataset Information

Impact of the interval between neoadjuvant immunotherapy and surgery on prognosis in esophageal squamous cell carcinoma (ESCC): a real-world study.

ABSTRACT:

Background

The time interval between neoadjuvant immunotherapy and surgery is 6 weeks for esophageal squamous cell carcinoma (ESCC), but whether delayed surgery affects prognosis remains unclear.

Methods

Clinical data of locally advanced ESCC who underwent neoadjuvant immunotherapy followed by esophagectomy from November 2019 to December 2022 were collected. The surgery outcomes and prognosis were compared between short-interval (time to surgery ≤ 6 weeks) and long-interval groups (time to surgery > 6 weeks).

Results

152 patients were enrolled totally, with a ratio of 91:61 between short-interval and long-interval groups. The rate of pathological complete response in the short-interval and long-interval groups were 34.1% and 24.6% (P = 0.257). Delayed surgery did not have a significantly impact on the number of lymph node dissections (P = 0.133), operative duration (P = 0.689), blood loss (P = 0.837), hospitalization duration (P = 0.293), chest drainage duration (P = 0.886) and postoperative complications (P > 0.050). The 3-year Overall survival (OS) rates were 85.10% in the short-interval group, and 82.07% in the long-interval group (P = 0.435). The 3-year disease-free survival (DFS) rates were 83.41% and 70.86% in the two groups (P = 0.037). Subgroup analysis revealed that patients with a favorable response to immunotherapy (tumor regression grade 0) exhibited inferior 3-year OS (long-interval vs. short-interval: 51.85% vs. 91.08%, P = 0.035) and DFS (long-interval vs. short-interval: 47.40% vs. 91.08%, P = 0.014) in the long-interval group.

Conclusions

Delayed surgery after neoadjuvant immunotherapy does not further improve pathological response; instead, it resulted in a poorer DFS. Especially for patients with a favorable response to immunotherapy, delayed surgery increases the risk of mortality and recurrence.

SUBMITTER: Yang G

PROVIDER: S-EPMC11303633 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Impact of the interval between neoadjuvant immunotherapy and surgery on prognosis in esophageal squamous cell carcinoma (ESCC): a real-world study.

Yang Guozhen G Hong Yutong Y Zhang Xiaomin X Zeng Chufeng C Tan Linyu L Zhang Xu X

Cancer immunology, immunotherapy : CII 20240806 10

<h4>Background</h4>The time interval between neoadjuvant immunotherapy and surgery is 6 weeks for esophageal squamous cell carcinoma (ESCC), but whether delayed surgery affects prognosis remains unclear.<h4>Methods</h4>Clinical data of locally advanced ESCC who underwent neoadjuvant immunotherapy followed by esophagectomy from November 2019 to December 2022 were collected. The surgery outcomes and prognosis were compared between short-interval (time to surgery ≤ 6 weeks) and long-interval groups ...[more]

PMID: 39105817

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Project description:BackgroundThere is currently no consensus on whether intensive cycles of neoadjuvant immunochemotherapy provide greater benefit than do less intensive cycles (two cycles) in esophageal cancer (EC). Therefore, in this study, we assessed the efficacy and safety of three to four cycles of neoadjuvant immunochemotherapy compared to two cycles for treating patients with locally advanced esophageal squamous cell carcinoma (ESCC).MethodsThis is a retrospective study of patients enrolled on previous clinical studies involving locally/regionally advanced ESCC (St. II-IVA) who received preoperative immunochemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine from 2019 to 2021. In this study, patients were planned to receive 2-4 cycles of chemoimmunotherapy. In this secondary analysis, patients who received three to four cycles of neoadjuvant immunochemotherapy were compared to those receiving two cycles in terms of safety and oncologic outcomes. The follow-up duration required for inclusion was at least one year following surgery, or until the patient died or independently elected to cease treatment if less than one year.ResultsOur study identified a total of 142 participants, who were categorized into two groups based on the number of neoadjuvant treatment cycles: the two cycles group (2 cycles) (n=65) and the three to four cycles group (3-4 cycles) (n=77). Regarding the rate of major pathologic response (MPR), the rates for the 3-4 cycles and 2 cycles groups were 22.1% and 20.0%, respectively, although this difference was not statistically significant (P=0.25). Similarly, the rate of pathologic complete remission (pCR) was higher in the 3-4 cycles group at 14.3% compared to 7.7% in the 2 cycles group, but the difference did not reach statistical significance (P=0.07). However, the incidence of adverse events (AEs) classified as grade 3 or 4 was significantly higher in the 3-4 cycles group than in the 2 cycles group (36.4% vs. 18.5%; P=0.02). The median disease-free survival (DFS) for the 3-4 cycles group was 30.8 months [95% confidence interval (CI): not reached to not reached] and was not reached in the 2 cycles group (hazard ratio 2.35, 95% CI: 1.134-4.86; P=0.02). The 2 cycles group did not reach the median overall survival (OS) (hazard ratio 2.47, 95% CI: 1.08-5.53; P=0.045), with that in the 3-4 cycles group 34.9 months (95% CI: 24.5 to not reached). Interestingly, the survival outcomes were more favorable in the 2 cycles group for certain subgroups of patients: those who were male, those with a history of smoking, those with a history of drinking, and those who did not achieve MPR.ConclusionsTwo cycles of neoadjuvant immunochemotherapy can be considered in locally advanced ESCC at high risk of developing toxicity with 3-4 cycles with similar oncologic outcomes.

Project description:BackgroundThere are also differences in survival prognosis among esophageal squamous cell carcinoma (ESCC) patients with a complete regression of the primary tumor (ypT0) after Neoadjuvant chemoradiotherapy (NCRT) followed by surgery. And the purpose of this study was to investigate influencing factors from these different prognostic outcomes and their possible causes.MethodsThe clinical data of 88 cases of ESCC patients with ypT0 after NCRT followed by surgery between 2011 and 2019 were retrospectively analyzed. The clinical and pathological prognostic factors that affect the survival were analyzed.ResultsSex, number of lymph nodes dissected, and pathologic positivity of lymph nodes may be significant in univariate analysis (P<0.1). Further multivariate analysis suggested that the pathologic positivity of the lymph nodes was an independent factor affecting prognosis (HR: 4.757, 95% CI: 2.195-10.313, P=0.000). Subsequently, the whole group was divided into a positive lymph node group (group LN+) and a negative lymph node group (group LN-) for comparison. The overall survival (OS) of group LN+ was significantly worse (HR: 0.211, 95% CI: 0.0336-0.239; P<0.0001), and recurrence-free survival (RFS) was significantly poorer in the LN+ group (HR: 0.0679, 95% CI: 0.0239-0.1923, P<0.0001). There were 14 cases of recurrence and metastasis in the LN+ group (14/21, 66.7%) and 10 cases in the group LN- (10/67, 14.9%). Among the sites of recurrence and metastasis, there were 10 (10/14, 71.4%) and 4 (4/14, 28.6%) cases of distant metastasis, respectively, and 4 (4/14, 28.6%) cases of local metastasis in the LN+ group; meanwhile, there were 8 (8/10, 80.0%) cases of distant metastasis and 2 (2/10, 20.0%) cases of local metastasis in the LN- group.ConclusionsThe independent risk factor for survival prognosis in ESCC patients with ypT0 after NCRT followed by surgery was positive postoperative pathological lymph nodes. The reason for the shortened survival time associated with this group of patients was their susceptibility to recurrence and metastasis.

Project description:PurposeThe present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario.Materials and methodsIn this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared.ResultsOne hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery.ConclusionOur results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

Project description:BackgroundCurrent paradigms of anti-tumor therapies are not qualified to evacuate the malignancy ascribing to cancer stroma's functions in accelerating tumor relapse and therapeutic resistance. Cancer-associated fibroblasts (CAFs) has been identified significantly correlated with tumor progression and therapy resistance. Thus, we aimed to probe into the CAFs characteristics in esophageal squamous cancer (ESCC) and construct a risk signature based on CAFs to predict the prognosis of ESCC patients.MethodsThe GEO database provided the single-cell RNA sequencing (scRNA-seq) data. The GEO and TCGA databases were used to obtain bulk RNA-seq data and microarray data of ESCC, respectively. CAF clusters were identified from the scRNA-seq data using the Seurat R package. CAF-related prognostic genes were subsequently identified using univariate Cox regression analysis. A risk signature based on CAF-related prognostic genes was constructed using Lasso regression. Then, a nomogram model based on clinicopathological characteristics and the risk signature was developed. Consensus clustering was conducted to explore the heterogeneity of ESCC. Finally, PCR was utilized to validate the functions that hub genes play on ESCC.ResultsSix CAF clusters were identified in ESCC based on scRNA-seq data, three of which had prognostic associations. A total of 642 genes were found to be significantly correlated with CAF clusters from a pool of 17080 DEGs, and 9 genes were selected to generate a risk signature, which were mainly involved in 10 pathways such as NRF1, MYC, and TGF-Beta. The risk signature was significantly correlated with stromal and immune scores, as well as some immune cells. Multivariate analysis demonstrated that the risk signature was an independent prognostic factor for ESCC, and its potential in predicting immunotherapeutic outcomes was confirmed. A novel nomogram integrating the CAF-based risk signature and clinical stage was developed, which exhibited favorable predictability and reliability for ESCC prognosis prediction. The consensus clustering analysis further confirmed the heterogeneity of ESCC.ConclusionThe prognosis of ESCC can be effectively predicted by CAF-based risk signatures, and a comprehensive characterization of the CAF signature of ESCC may aid in interpreting the response of ESCC to immunotherapy and offer new strategies for cancer treatment.

Dataset Information

Impact of the interval between neoadjuvant immunotherapy and surgery on prognosis in esophageal squamous cell carcinoma (ESCC): a real-world study.

Background

Methods

Results

Conclusions

Publications

Impact of the interval between neoadjuvant immunotherapy and surgery on prognosis in esophageal squamous cell carcinoma (ESCC): a real-world study.

Similar Datasets

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