Adjuvant immunotherapy in resected esophageal squamous cell carcinoma: a gospel to the non-pCRs.
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ABSTRACT:
SUBMITTER: Zhang Z
PROVIDER: S-EPMC8382737 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
Publications
Adjuvant immunotherapy in resected esophageal squamous cell carcinoma: a gospel to the non-pCRs.
Zhang Zhihui Z Sun Nan N He Jie J
Signal transduction and targeted therapy 20210823 1
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Project description:BackgroundThe aim of this study was to evaluate the impact of adjuvant chemotherapy in patients with radically resected esophageal squamous cell carcinoma (ESCC).MethodsPatients with esophageal cancer who underwent esophagectomy at our hospital from 2010 to 2019 were retrospectively analyzed. Only patients with radically resected ESCC who did not receive neoadjuvant therapy or adjuvant radiotherapy were enrolled in this study. Propensity score matching (1:1) was used to balance the baseline.ResultsA total of 1,249 patients met the inclusion criteria and were enrolled in the study, and 263 patients received adjuvant chemotherapy. After matching, 260 pairs were analyzed. The 1-, 3-, and 5-year overall survival (OS) rates were 93.4%, 66.1% and 59.6%, respectively, for patients with adjuvant chemotherapy compared with 83.8%, 58.4% and 48.8%, respectively, for patients with surgery alone (P = 0.003). The 1-, 3-, and 5-year disease-free survival (DFS) rates were 82.3%, 58.8% and 51.3%, respectively, for patients with adjuvant chemotherapy compared with 68.0%, 48.3% and 40.8%, respectively, for patients with surgery alone (P = 0.002). In multivariate analyses, adjuvant chemotherapy was found to be an independent prognostic factor. In subgroup analyses, only the patients in certain subgroups were found to benefit from adjuvant chemotherapy, such as patients who underwent right thoracotomy, pT3 diseases, pN1-pN3 diseases, or pTNM stage III and IVA diseases.ConclusionsPostoperative adjuvant chemotherapy can improve the OS and DFS of ESCC patients after radical resection but may only work for patients in certain subgroups.
| S-EPMC10188986 | biostudies-literature
Project description:Esophageal squamous cell carcinoma have been frustrating to treat, with slow progress made on extending survival. Immunotherapy targeting immune checkpoints, T cells, and infiltrating lymphocytes has shown promise in early studies. The efficacy of pembrolizumab and nivolumab is encouraging. Anti-chemokine receptors and oncolytic viruses are also making headway against these stubborn tumors; improved results when immune checkpoint inhibitors are combined with radiation therapy are eagerly anticipated. Adoptive T cell therapy and vaccines are also under development. The importance of a multidisciplinary approach cannot be emphasized enough.
| S-EPMC5374168 | biostudies-literature
Project description:Tertiary lymphoid structures (TLSs) are considered to have a good prognosis in multiple solid tumors. However, the prognostic value of TLS in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we retrospectively enrolled 185 ESCC patients who underwent surgical resection. Hematoxylin and eosin staining was performed to investigate the presence, the abundance, the maturation, and the location of TLSs. We explored the cellular composition of TLSs using traditional immunohistochemistry in serial sections. The prognostic value of TLSs was investigated by univariate and multivariate analyses. A nomogram was constructed to predict the prognosis. TLS-positive tumors were infiltrated with more CD45+ leukocytes, CD20+ B cells, CD4+ and CD8+ T cells, and CD11c+ dendritic cells（DCs） compared with negative tumors. Kaplan-Meier curves showed that the presence and the abundance of TLSs were associated with longer disease-free survival (DFS) (p = 0.0130) and overall survival (OS) (p = 0.0164). In addition, patients with tumors containing more CD20+ B cell infiltration had longer DFS (p = 0.0105) and OS (p = 0.0341). Multivariate analyses demonstrated that the presence of TLSs was an independent prognostic factor for DFS (hazard ratio [HR] = 0.384, p < 0.001) and OS (HR = 0.293, p < 0.001). The nomogram that integrated the tumor stage, histologic grade, and TLS presence had higher prognostic accuracy. Our study suggests that ESCC-related TLSs can be used as a new biomarker for the prognosis of ESCC patients, and further understanding of their formation and mechanism of induction can provide a possible direction and target for immunotherapy of ESCC.
| S-EPMC9353661 | biostudies-literature
Project description:Cancer vaccines and immune checkpoint inhibitors (ICI) have recently been employed as immunotherapies for esophageal squamous cell carcinoma (ESCC). Cancer vaccines for ESCC have yielded several promising results from investigator-initiated phase I and II clinical trials. Furthermore, a Randomized Controlled Trial as an adjuvant setting after curative surgery is in progress in Japan. On the other hand, ICI, anti-CTLA-4 mAb and anti-PD-1 mAb, have demonstrated tumor shrinkage and improved overall survival in patients with multiple cancer types. For ESCC, several clinical trials using anti-PD-1/anti-PD-L1 mAb are underway with several recent promising results. In this review, cancer vaccines and ICI are discussed as novel therapeutic strategies for ESCC.
| S-EPMC6141453 | biostudies-literature
Project description:BackgroundNeoadjuvant chemoradiotherapy (nCRT) and surgery have been recommended as the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC). In addition, nodal metastases decreased in frequency and changed in distribution after neoadjuvant therapy. This study aimed to examine the optimal strategy for lymph node dissection (LND) in patients with ESCC who underwent nCRT.MethodsThe hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were calculated using the Cox proportional hazard model. To determine the minimal number of LNDs (n-LNS) or least station of LNDs (e-LNS), the Chow test was used.ResultsIn total, 333 patients were included. The estimated cut-off values for e-LNS and n-LNS were 9 and 15, respectively. A higher number of e-LNS was significantly associated with improved OS (HR: 0.90; 95% CI 0.84-0.97, P = 0.0075) and DFS (HR: 0.012; 95% CI: 0.84-0.98, P = 0.0074). The e-LNS was a significant prognostic factor in multivariate analyses. The local recurrence rate of 23.1% in high e-LNS is much lower than the results of low e-LNS (13.3%). Comparable morbidity was found in both the e-LNS and n-LND subgroups.ConclusionThis cohort study revealed an association between the extent of LND and overall survival, suggesting the therapeutic value of extended lymphadenectomy during esophagectomy. Therefore, more lymph node stations being sampled leads to higher survival rates among patients who receive nCRT, and standard lymphadenectomy of at least 9 stations is strongly recommended.
| S-EPMC10845591 | biostudies-literature
Project description:We aimed to report patients' survival after surgical resection of eSCC and to ascertain the clinical, imaging, and pathological factors related to patient prognosis. This retrospective study included 435 patients with eSCC of <stage T2 (median follow-up period, 49.3 months). A total of 103 (23.7%) patients died, and 89 (20.5%) experienced recurrence during follow-up. The maximum standardized uptake value (SUVmax) on positron emission tomography (PET)/computed tomography (CT) of the primary tumor was significantly correlated with tumor length, nodal metastasis, and pathologic T stage in a positive linear fashion. In the multivariate analysis, higher SUVmax on PET/CT was a negative prognostic factor for both disease-free survival (DFS) and overall survival (OS). Contrarily, the presence of nodal metastasis was a prognostic factor only for DFS, and pathologic T stage only for OS. By applying SUVmax cut-off, both DFS and OS were significantly different among three groups when divided by cut-off values (A: SUVmax ≤ 3.05, B: SUVmax 3.06 - 5.64, C: SUVmax ≥ 5.65). In patients with a surgically resectable eSCC, measuring the SUVmax of the primary tumor during PET/CT can help predict patient survival. Additionally, PET/CT renders triage criterion for endoscopic submucosal dissection (ESD; T1a cancer and SUVmax, ≤3.05).
| S-EPMC7081270 | biostudies-literature
Project description:BackgroundThe prognosis of patients with resected esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy is particularly poor in those who were staged as ypT3/T4 and/or ypN+. This study investigated whether adjuvant chemoradiotherapy was associated with improved clinical outcomes in these patients.Methodswe identified patients with esophageal squamous cell carcinoma who were staged as ypT3/T4 and/or ypN+ after being treated with neoadjuvant chemoradiotherapy followed by esophagectomy between the years 2013 and 2019. Patients were divided into two groups based on whether they received adjuvant chemoradiotherapy. The Kaplan-Meier method and Cox regression modeling were performed for survival analyses and multivariable analysis, respectively.Results76 eligible patients were included in the analyses. The median follow-up for the study cohort was 43.4 months. On Kaplan-Meier analyses of the overall population, adjuvant chemoradiotherapy was associated with significantly improved median overall survival (31.7 months vs. 16.3 months, p = 0.036). On Kaplan-Meier analyses of the 35 matched pairs generated by propensity score matching, adjuvant chemoradiotherapy was associated with significantly longer median overall survival (31.7 months vs. 14.3 months; p = 0.004) and median recurrence-free survival (18.9 months vs. 11.7 months; p = 0.020). In multivariable analysis, adjuvant chemoradiotherapy was independently associated with a 60% reduction in mortality (p = 0.003) and a 48% reduction in risk of recurrence (p = 0.035) after adjusting for putative confounders. In addition, microscopic positive resection margin and Mandard tumor regression grade 3-4 were independently associated with increased mortality and risk of recurrence. While a greater number of lymph nodes dissected was independently associated with significantly improved overall survival, the number of positive lymph nodes was independently associated with significantly worse overall survival and a trend (p = 0.058) towards worse recurrence-free survival.ConclusionsThis study demonstrated that adjuvant CRT was independently associated with a significantly improved survival and lower risk of recurrence than observation in esophageal squamous cell carcinoma patients staged as ypT3 and/or ypN+ after receiving neoadjuvant chemoradiotherapy and radical surgery. The results of this study have implications for the design of future clinical trials and may improve treatment outcomes of patients in this setting who cannot afford or are without access to adjuvant nivolumab.
| S-EPMC9687609 | biostudies-literature
Project description:Postoperative non-small cell lung cancer (NSCLC) patients require adjuvant therapy to improve their prognosis. In this study, we investigated the efficacy of a sequential combination of autologous cellular immunotherapy (CIT) and chemotherapy for postoperative NSCLC. This retrospective study included 120 postoperative NSCLC patients: 60 cases received only chemotherapy; 33 cases received chemotherapy and sequential CIT with cytokine-induced killer (CIK) cells; and 27 cases received chemotherapy and sequential CIT with alternate CIK and natural killer (NK) cells. Survival analysis showed significantly higher overall survival rates in the CIT group compared with the control group. Overall survival was higher in patients who received CIT with alternate CIK and NK cells than those who received treatment with only CIK cells. Multivariate analysis showed that adjuvant CIT was an independent prognostic factor for overall survival of patients with NSCLC. In subgroup analyses, adjuvant CIT significantly improved the overall survival of patients with less than 60 y old and positive lymph node. In conclusions, these data indicate that adjuvant CIT, especially with alternate application of CIK and NK cells, is an effective therapeutic approach to prolong survival of patients with NSCLC, particularly for patients ≤60 y old with positive lymph nodes.
| S-EPMC4570139 | biostudies-literature
Project description:Esophageal cancer (EC) ranks among the most prevalent malignant tumors affecting the digestive tract. Esophageal squamous cell carcinoma (ESCC) stands as the prevailing pathological subtype, encompassing approximately 90% of all EC patients. In clinical stage II-IVA locally advanced ESCC cases, the primary approach to treatment involves a combination of neoadjuvant therapy and surgical resection. Despite concerted efforts, the long-term outcomes for ESCC patients remain unsatisfactory, with dismal prognoses. However, recent years have witnessed remarkable strides in immunotherapy, particularly in the second- and first-line treatment of advanced or metastatic ESCC, with the development of monoclonal antibodies that inhibit programmed death 1 or programmed death ligand 1 demonstrating encouraging responses and perioperative clinical benefits for various malignancies, including ESCC. This comprehensive review aims to present the current landscape of perioperative immunotherapy for resectable ESCC, focusing specifically on the role of immune checkpoint inhibitors during the perioperative period. Additionally, the review will explore promising biomarkers and offer insights into future prospects.
| S-EPMC10518742 | biostudies-literature
Project description:Despite a series of attempts during the last decades, the prognosis of esophageal squamous cell carcinoma (ESCC) remains poor. Different responses of individual tumors encouraged us to look for valuable prognostic markers. As a key regulator controlling the anabolic ketogenic pathway, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) has been reported to play a crucial role in colorectal cancer and prostate cancer. However, its importance to ESCC has not been verified. Therefore, a large cohort retrospective study was planned, to investigate the relationship between HMGCS2 expression and ESCC prognosis. By adopting real-time polymerase chain reaction (PCR) and immunohistochemical (IHC) staining, HMGCS2 expression was examined in tissues of 300 ESCC patients with complete resection. Besides, the association between HMGCS2 protein expression and survival time was evaluated through chi-square test and Kaplan-Meier analysis. With the use of Cox-proportional hazards model, the prognostic impact of clinicopathologic variables and biomarker expression was evaluated. Compared with their non-tumor counterparts, HMGCS2 downregulation occurred in 65.5% and 37.6% of primary ESCCs on the mRNA and protein levels (P<0.001), respectively. On the protein level, HMGCS2 expression was associated with tumor cell differentiation (P=0.003), pT status (P=0.006), and TNM stage (P=0.010). In the down-HMGCS2 expression group, the 5-year overall survival (OS) and relapse-free survival (RFS) are poorer than those in the normal expression group (19 months vs 24 months, P=0.002; 13 months vs 17 months, P=0.007, respectively). According to the TNM stage, stratified analysis revealed that its discernibility on RFS was only pronounced in patients with advanced clinical stage (P=0.001). In addition, multivariate Cox regression analysis showed that HMGCS2 expression was an independent risk factor for RFS (P=0.032) instead of OS (P=0.099). The findings of this study provided the evidence that HMGSC2 represented a potential novel prognostic biomarker for ESCC patients.
| S-EPMC5438074 | biostudies-literature