Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy for resectable esophageal cancer: a systematic review and meta-analysis
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SUBMITTER: Wang M
PROVIDER: S-EPMC11231810 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:BackgroundSignificant progress has been made in the investigation of neoadjuvant immune-chemoradiotherapy (NICRT) and neoadjuvant immune-chemotherapy (NICT) on the outcomes of esophageal cancer patients. To summarize the current developments, a systematic review and meta-analysis were conducted to evaluate the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy.MethodsA search strategy of prospective studies on esophageal cancer receiving neoadjuvant immunotherapy was predefined to scan PubMed, Embase, Cochrane, and additional major conferences for prospective studies. Efficacy was assessed by pathological complete response (pCR), major pathological response (MPR), and R0 resection rates. Safety was evaluated based on the incidence of grade ≥ 3 treatment-related adverse events (TRAEs), neoadjuvant therapy completion rate, surgical resection rate, and surgical delay rate. Differences between the NICRT and NICT groups were also analyzed.ResultsA total of 38 studies qualified for the analysis. The pooled pCR, MPR, and R0 resection rates were 30, 58, and 99%, respectively. The pCR and MPR in the NICRT vs. NICT group were 38% vs. 28% (p=0.078) and 67% vs. 57% (p=0.181), respectively. The pooled incidence of grade ≥ 3 TRAEs was 24% (NICRT,58%, I2 = 61% vs. NICT,18%, I2 = 79%; p<0.001). In addition, the pooled neoadjuvant therapy completion and surgical resection rates were 92% and 85%, respectively; the difference was not statistically significant between the NICRT and NICT groups.ConclusionsNeoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy is effective and safe in the short term for locally advanced esophageal cancer. However, further randomized trials are needed to confirm which combined model is more favorable.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284266, identifier CRD42021284266.
| S-EPMC9902949 | biostudies-literature
Project description:ObjectiveThe progress of neoadjuvant therapy for resectable locally advanced esophageal cancer has been stagnant. There has been much progress in immunotherapy for advanced esophageal cancer, but the efficacy and safety of neoadjuvant immunotherapy for resectable locally advanced esophageal cancer have not yet been definitively demonstrated.MethodsOriginal articles describing the safety and efficacy of neoadjuvant immunotherapy in resectable locally advanced esophagus published until July 2022 were retrieved from PubMed, Embase, and the Cochrane Library. The ratio (OR) and 95% confidence interval (CI) were calculated to conduct heterogeneity and subgroup analysis.ResultsIn total, 759 patients from 21 studies were enrolled. The effectiveness of neoadjuvant immunotherapy in combination with chemotherapy was evaluated using the major pathologic response (MPR) and pathologic complete response (PCR). In the enrolled patients, 677 were treated surgically and 664 achieved R0 resection. Major pathological remission was achieved in 52.0% (95% CI: 0.44-0.57) of patients on neoadjuvant immunotherapy combined with chemotherapy and complete pathological remission in 29.5% (95% CI: 0.25-0.32) of patients. The safety was primarily assessed by the incidence of treatment-related adverse events (TRAEs) and surgical resection rates. The incidence of TRAEs and the surgical resection rate combined ORs were 0.15 (95% CI: 0.09-0.22) and 0.86 (95% CI: 0.83-0.89), respectively.ConclusionNeoadjuvant immunotherapy combined with chemotherapy in locally advanced resectable esophageal cancer is effective and safe.
| S-EPMC9495441 | biostudies-literature
Project description:BackgroundEsophageal squamous cell cancer (ESCC) patients with the potentially resectable disease most would experience relapse after surgery. Immunotherapy has been reported to improve the prognosis of advanced esophageal cancer and may be a new strategy to prevent this urgent condition's recurrence. We first evaluated the efficacy and safety of neoadjuvant chemotherapy combined with immunotherapy in patients with resectable ESCC.MethodsAll patients with resectable locally advanced ESCC (clinical stage III-IVB). Received at least 1 cycle of neoadjuvant chemotherapy combined with immunotherapy (NACI), and the interval between each cycle and the operation should be at least 3 weeks. All patients were treated with standard surgery. The tumor imaginations were obtained at baseline and within a week before surgery. The efficacy endpoint was the rate of major pathologic response (MPR, 10% viable tumor cells). Expression of immunohistochemical-related molecules was investigated in surgical samples.ResultsA total of 38 patients with ESCC were included (36 males, median age 61 years), and most of them used Pembrolizumab (55.26%) and Camrelizumab (31.58%). We analyzed 19 patients and found that 13 patients (68.42%) achieved radiological partial response (PR) by CT images. R0 resection was performed in 35 patients (92.11%), and 10 patients (26.32%) developed postoperative complications. Through postoperative pathology, we found 13 (34.21%) patients had complete pathologic response (cPR), and 16 (42.11%) patients achieved MPR. We also found that none of the factors had a statistically significant impact on MPR. Still, the regression rate of Sum of lesion diameter (SLD) was significantly positively correlated with the pathological remission rate (P=0.012, r=0.565).ConclusionsThe rate of MPR in ESCC patients reached 42.11%. The use of the NACI regimen did not increase the occurrence of complications in neoadjuvant treatment and operation, and the SLD regression rate has a certain guiding significance for the effect of immunotherapy.
| S-EPMC8264718 | biostudies-literature
Project description:ImportanceA considerable number of clinical trials of neoadjuvant immunotherapy for patients with resectable esophageal cancer are emerging. However, systematic evaluations of these studies are lacking.ObjectiveTo provide state-of-the-art evidence and normative theoretical support for neoadjuvant immunotherapy for locally advanced resectable esophageal cancer.Data sourcesPubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for relevant original articles and conference proceedings that were published in English through April 1, 2022.Study selectionPublished phase 2 or 3 clinical trials that included patients with resectable stage I to IV esophageal cancer who received immune checkpoint inhibitors (ICIs) before surgery as monotherapy or in combination with other therapies.Data extraction and synthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines for meta-analysis were followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 statistic >50%); otherwise, the common-effects model was used. Data analyses were conducted from April 2 to 8, 2022.Main outcomes and measuresPathological complete response (pCR) rate and major pathological response (MPR) rate were considered to be the primary outcomes calculated for the clinical outcomes of neoadjuvant immunotherapy. Incidence of treatment-related severe adverse events was set as the major measure for the safety outcome. The rate of R0 surgical resection was summarized. Subgroup analyses were conducted according to histologic subtype and ICI types.ResultsA total of 27 clinical trials with 815 patients were included. Pooled rates were 31.4% (95% CI, 27.6%-35.3%) for pCR and 48.9% (95% CI, 42.0-55.9%) for MCR in patients with esophageal cancer. In terms of safety, the pooled incidence of treatment-related severe adverse events was 26.9% (95% CI, 16.7%-38.3%). Most patients achieved R0 surgical resection (98.6%; 95% CI, 97.1%-99.6%). Regarding histologic subtypes, the pooled pCR rates were 32.4% (95% CI, 28.2%-36.8%) in esophageal squamous cell carcinoma and 25.2% (95% CI, 16.3%-35.1%) in esophageal adenocarcinoma. The pooled MPR rate was 49.4% (95% CI, 42.1%-56.7%) in esophageal squamous cell carcinoma.Conclusions and relevanceThis study found that neoadjuvant immunotherapy with chemotherapy had promising clinical and safety outcomes for patients with resectable esophageal cancer. Randomized clinical trials with long-term follow-up are warranted to validate the findings and benefits of ICIs.
| S-EPMC9631099 | biostudies-literature
Project description:BackgroundThe prognosis of patients under existing neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy requires improvement. Whereas programmed cell death 1 (PD-1) inhibitors have shown promising response in advanced esophageal cancer, they have not been used in the perioperative treatment of resectable locally advanced esophageal cancer. Whether immunotherapy can be incorporated into neoadjuvant therapy has became a challenging question for researchers.Case presentationWe present a case of a 65-year-old male who had a history of progressive dysphagia for approximately 1 month. He underwent pertinent studies including computed tomography (CT)，gastroscopy，and pathological biopsy resulting in a diagnosis of medium-low differentiated squamous carcinoma of the thoracic segment of the esophagus (cT2N2M0 stage III). After 4 cycles of neoadjuvant chemotherapy combined with immunotherapy, gastroscopy showed the lesion in the esophagus was no longer present. Subsequently, the patient received thoracoscopic radical resection of esophageal cancer and achieved a pathological complete response (pCR) in postoperative pathological evaluation. During the whole treatment, no adverse effect was recorded and to date no evidence of recurrence has been recorded.ConclusionOur report suggest that neoadjuvant chemotherapy combined with immunotherapy not only improve the R0 resection and pCR rate in patients with resectable locally advanced esophageal cancer, but also the adverse effects are within the control range. However, the selection of therapeutic strategy, predictors of response to treatment, and interval time between neoadjuvant treatment and surgery still await more reliable evidence-based studies with large prospective samples.
| S-EPMC9414113 | biostudies-literature
Project description:ObjectiveThis systematic review and meta-analysis aimed to explore the efficacy and safety of neoadjuvant immunotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC).BackgroundSeveral studies have reported the outcomes of neoadjuvant immunotherapy in patients with ESCC. However, phase 3 randomized controlled trials (RCTs) with long-term outcomes and the comparison of different therapeutic strategies are lacking.MethodsStudies involving patients with advanced ESCC treated with preoperative neoadjuvant immune checkpoint inhibitors (ICIs) were searched through PubMed, Embase, and Cochrane Library up to July 1, 2022. The outcomes were presented as proportions and pooled respectively by fixed or random effect model depending on the heterogeneity between studies. All analyses were performed using the R packages meta 5.5-0 and meta-for 3.4-0.ResultsThirty trials involving 1406 patients were included in the meta-analysis. The pooled pathological complete response (pCR) rate for neoadjuvant immunotherapy was 0.30 (95% confidence interval [CI]: 0.26-0.33). The pCR rate of neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT) was significantly higher than that of neoadjuvant immunotherapy combined with chemotherapy (nICT) (nICRT: 0.48, 95% CI: 0.31-0.65; nICT: 0.29, 95% CI: 0.26-0.33; p=0.03). No significant difference in efficacy was observed between the different chemotherapy agents and treatment cycles. The incidences of grade 1-2 and 3-4 treatment-related adverse events (TRAEs) were 0.71 (95% CI: 0.56-0.84) and 0.16 (95% CI: 0.09-0.25), respectively. Patients treated with nICRT and carboplatin had a higher incidence of grade 3-4 TRAEs compared with those treated with nICT (nICRT: 0.46, 95% CI: 0.17-0.77; nICT: 0.14, 95% CI: 0.07-0.22; p=0.03) and cisplatin (carboplatin: 0.33, 95% CI: 0.15-0.53; cisplatin: 0.04, 95% CI: 0.01-0.09; p<0.01).ConclusionNeoadjuvant immunotherapy has good efficacy and safety profiles in patients with locally advanced ESCC. Additional RCTs with long-term survival data are warranted.
| S-EPMC9981949 | biostudies-literature
Project description:The efficacy of surgery alone for patients with locally advanced esophageal cancer (EC) is still unsatisfactory. Presently, induction therapy followed by surgery is the standard treatment. Preoperative chemotherapy (CT) and chemoradiation (CRT) are proven effective induction therapies; however, few sample studies have addressed these treatments, thus, their superiority remains uncertain. We performed a systemic review and meta analysis to test the hypothesis that induction CRT prior to surgery could improve survival compared with induction CT alone.A comprehensive search of PubMed and the Ovid database for relevant studies comparing EC patients undergoing resection after treatment with induction CT alone or induction CRT was conducted. Hazard ratios (HR) and 95% confidence intervals (95% CI) were extracted from these studies to provide pooled estimates of the effect of induction therapy on overall survival.Five studies met the criteria for analysis. Statistical analysis demonstrated a survival benefit of induction CRT compared with induction CT alone (HR0.73, 95% CI 0.61-0.89; P = 0.002). Further analysis showed that induction CRT perioperative mortality and complication rates were higher than for induction CT alone (HR 2.96, 95% CI 1.38-6.37; HR1.6, 95% CI 1.30-1.98; P = 0.01, respectively).Published evidence comparing the different efficacies of induction CT and induction CRT is sparse, with few samples of adenocarcinoma. This analysis supports the view that, compared with induction CT, induction CRT could achieve a long-term survival benefit in EC patients.
| S-EPMC4773296 | biostudies-other
Project description:BackgroundEsophageal cancer is a highly malignant cancer with a very poor prognosis. For resectable esophageal cancer, neoadjuvant treatment could improve the prognosis of esophageal cancer. However, current clinical neoadjuvant treatment options for esophageal cancer are still limited. The application of immunotherapy is a potentially beneficial new neoadjuvant treatment option for esophageal cancer. The objective of this meta-analysis is to evaluate the efficacy and safety of immunotherapy for the neoadjuvant treatment of esophageal cancer.MethodsWe will search Wanfang Database, SinoMed, China National Knowledge Infrastructure, Embase, Web of Science, Pubmed, and Cochrane Library for relevant articles published before July, 2021. We will also search the unpublished clinical trials of neoadjuvant immunotherapy in esophageal cancer in preprint website (such as bioRXiv and medRxiv) up to July, 2021. We will perform a meta-analysis to evaluate the efficacy and safety of neoadjuvant immunotherapy for resectable esophageal cancer. Randomized controlled trials (RCTs) will be included in this study. The risk of bias will be evaluated for each included study using the Cochrane Handbook for Systematic Reviews of Interventions. We will use RevMan 5.3 software for statistical analysis of the data.ResultsThe results of this study will provide evidence of immunotherapy using as neoadjuvant treatment for esophageal cancer. This meta-analysis will be submitted to a peer-reviewed journal seeking for publication.ConclusionThe results of this study will provide a reliable basis for clinicians and patients to formulate the best pre-surgical treatment plan for resectable esophageal cancer.Systematic review registrationINPLASY202120026.
| S-EPMC8177427 | biostudies-literature
Project description:BackgroundThe application of neoadjuvant immune checkpoint inhibitors combined with chemotherapy(NICT) in treating locally advanced esophageal squamous cell carcinoma (ESCC) is a subject of considerable research interest. In light of this, we undertook a comprehensive meta-analysis aiming to compare the efficacy and safety of this novel approach with conventional neoadjuvant chemotherapy (NCT) in the management of ESCC.MethodsA systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science to gather relevant literature on the efficacy and safety of NICT compared to conventional NCT in locally advanced ESCC published before June 2023. Effect indicators, including odds ratios (ORs) with associated 95% confidence intervals (CIs), were employed to evaluate the safety and efficacy outcomes. The risk of bias was assessed using the Cochrane bias risk assessment tool, and subgroup analysis and sensitivity analysis were conducted to investigate the findings further.ResultsA total of 9 studies qualified for the meta-analysis, all of which investigated the efficacy and safety of NICT compared to conventional NCT. The pooled rates of pathologic complete response (pCR) and major pathologic response (MPR) in the NICT group were significantly higher compared to the NCT group, with values of 26.9% versus 8.3% (P＜0.00001) and 48.1% versus 24.6% (P＜0.00001), respectively. The ORs for achieving pCR and MPR were 4.24 (95% CI, 2.84-6.32, I2=14%) and 3.30 (95% CI, 2.31-4.71, I2=0%), respectively, indicating a significant advantage for the NICT group. Regarding safety outcomes, the pooled incidences of treatment-related adverse events (TRAEs) and serious adverse events (SAEs) in the NICT group were 64.4% and 11.5%, respectively, compared to 73.8% and 9.3% in the NCT group. However, there were no significant differences observed between the two groups in terms of TRAEs (OR=0.67, 95% CI, 0.29-1.54, P=0.35, I2 =58%) or SAEs (OR=1.28, 95% CI, 0.69-2.36, P=0.43, I2=0%). Furthermore, no significant differences were found between the NICT and NCT groups regarding R0 resection rates, anastomotic leakage, pulmonary infection, and postoperative hoarseness.Conclusions:Neoadjuvant immune checkpoint inhibitors combined with chemotherapy demonstrate efficacy and safety in treating resectable esophageal squamous cell carcinoma. Nevertheless, additional randomized trials are required to confirm the optimal treatment regimen.
| S-EPMC10793745 | biostudies-literature
Project description:BackgroundNeoadjuvant immunotherapy has preliminarily been effective in multiple resectable cancers. However, its safety is still largely unknown.MethodsA systematic literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library up to February 28th, 2021. Pooled incidence and risk ratio (RR) of adverse events were calculated using the R software.ResultsTwenty-eight studies involving 2863 patients were included. First, the incidence for all-grade treatment-related adverse events (trAEs) was 94% (95% CI, 81%-98%), with 43% (95% CI, 24%-64%) for high-grade trAEs. For different treatment groups, neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy was associated with a higher incidence of all-grade [99% (95% CI, 98%-99%) vs. 76% (95% CI 47%-92%); P < 0.001] and high-grade [80% (58%-92%) vs. 15% (9%-24%); P < 0.001] trAEs compared with neoadjuvant ICIs alone. The most common high-grade trAEs were lipase increased (5%; 95% CI, 2%-10%), colitis (3%; 95% CI, 0-7%) and transaminitis (3%; 95% CI, 0-7%) for neoadjuvant ICIs, and neutropenia (53%; 95% CI, 31%-74%), anemia (8%; 95% CI, 3%-15%) and AST increased (4%; 95% CI, 2%-7%) for neoadjuvant ICIs plus chemotherapy. Furthermore, the incidence rates of progressive disease while on treatment, treatment-related surgical delays and deaths were 6% (95% CI, 4%-10%), 3.2% (12 of 377 patients) and 0.47% (5 of 1075 patients), respectively.ConclusionCompared with neoadjuvant ICIs alone, neoadjuvant ICIs plus chemotherapy had a higher incidence of trAEs. In addition, neoadjuvant immunotherapy had a low rate of progressive diseases, surgical delays and deaths.
| S-EPMC8841351 | biostudies-literature