Omitting Surgery In Esophageal Cancer Patients With Complete Response After Neoadjuvant Chemoradiotherapy: A Systematic Review And Meta-Analysis

2021 ◽  
Author(s):  
Jaehyeon Park ◽  
Ji woon Yea ◽  
Jaewon Park
Keyword(s):  
Esophageal Cancer ◽  
Risk Ratio ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Complete Response ◽  
Cochrane Library ◽  
Publication Date ◽  
Locoregional Failure

Abstract Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is a standard treatment modality for locally advanced esophageal cancer. However, patients who achieve clinical complete response (cCR) after nCRT have been reported to have better prognosis. Further, the role of surgery in these patients is controversial. Thus, this meta-analysis aimed to evaluate whether surgery is still useful in patients with cCR after nCRT. We systematically reviewed the MEDLINE, PubMed, Embase, Cochrane library, and Scopus databases for studies on surgical efficacy in complete responders after concurrent chemoradiotherapy for esophageal cancer. The publication date was set to January 1, 2010–January 31, 2020. The hazard ratio (HR) and risk ratio was used to compare 2-year overall survival (OS), disease-free survival (DFS), incidence of locoregional failure, distant metastasis and treatment mortality between the nCRT and the nCRT plus surgery groups. Six articles involving 609 patients were included. There was a significant benefit of nCRT for OS (HR = 0.80, 95% confidence interval [CI] = 0.64–0.99, p = 0.04), but not for DFS (HR = 1.19, 95% CI = 0.41–3.46, p = 0.75). The nCRT group tended to have lower mortality than the nCRT plus surgery group (risk ratio = 0.15, 95% CI = 0.02–1.18, p = 0.07). Omitting surgery provides better OS in complete responders after nCRT. Adding surgery could increase the morbidity and mortality and decrease the quality of life. Thus, nCRT alone could be a feasible approach for patients with cCR.

scholarly journals Omitting surgery in esophageal cancer patients with complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jaehyeon Park ◽  
Ji Woon Yea ◽  
Se An Oh ◽  
Jae Won Park
Keyword(s):  
Esophageal Cancer ◽  
Risk Ratio ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Complete Response ◽  
Cochrane Library ◽  
Publication Date ◽  
Locoregional Failure

Abstract Background Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is a standard treatment modality for locally-advanced esophageal cancer. However, patients who achieve clinical complete response (cCR) after nCRT have been reported to have better prognosis. Further, the role of surgery in these patients is controversial. Thus, this meta-analysis aimed to evaluate whether surgery is still useful in patients with cCR after nCRT. Methods We systematically reviewed the MEDLINE, PubMed, Embase, Cochrane library, and Scopus databases for studies on surgical efficacy in complete responders after concurrent chemoradiotherapy for esophageal cancer. The publication date was set to January 1, 2010–January 31, 2020. The hazard ratio (HR) and risk ratio were used to compare the 2-year overall survival (OS), disease-free survival (DFS), incidence of locoregional failure, distant metastasis, and treatment mortality between the nCRT and nCRT plus surgery groups. Results Six articles involving 609 patients were included. There was a significant benefit of nCRT for OS (HR = 0.80, 95% confidence interval [CI] 0.64–0.99, p = 0.04), but not for DFS (HR = 1.55, 95% CI 0.35–6.86, p = 0.56). The nCRT group tended to have lower mortality than the nCRT plus surgery group (risk ratio = 0.15, 95% CI 0.02–1.18, p = 0.07). Conclusion Omitting surgery provides better OS in complete responders after nCRT. Adding surgery could increase the morbidity and mortality and decrease the quality of life. Thus, nCRT alone could be a feasible approach for patients with cCR.

scholarly journals The Optimal Treatment for Resectable Esophageal Cancer: A Network Meta-Analysis of 6168 Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Meng Yuan ◽  
Yongxing Bao ◽  
Zeliang Ma ◽  
Yu Men ◽  
Yang Wang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Meta Analysis ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Optimal Treatment ◽  
Cochrane Library ◽  
Neoadjuvant Radiotherapy ◽  
Free Survival ◽  
Resectable Esophageal ◽  
Resectable Esophageal Cancer

The optimal treatment for resectable esophageal cancer remains unclear. This network meta-analysis compares the efficacy of different treatments. PubMed, Embase, and the Cochrane library were systematically screened. Randomized controlled trials comparing the efficacy of different treatments for resectable esophageal cancer were included. Hazard ratios (HR) for overall survival (OS), progression-free survival, or disease-free survival, and odds ratios for locoregional recurrence and distant metastasis rates were identified as the measurements of efficacy. A Bayesian network meta-analysis was performed. In this study, 26 studies were included. Patients received either surgery alone; neoadjuvant chemotherapy (CT), neoadjuvant radiotherapy (RT), or neoadjuvant chemoradiotherapy (CRT) followed by surgery; or surgery followed by adjuvant CT, adjuvant RT, or adjuvant CRT. Neoadjuvant CRT followed by surgery (pooled HR = 0.76, 95% credible interval: 0.67–0.85) and neoadjuvant CT followed by surgery compared with surgery alone were the only two showing statistically confident improvement on OS. Ranking analysis showed that neoadjuvant CRT with surgery was likely to be the best option in terms of efficacy. Therefore, for patients with resectable esophageal cancer, neoadjuvant CRT with surgery is the optimal treatment. Future studies should focus on the optimization of neoadjuvant CRT regimens.

scholarly journals The Impact of Preoperative Sarcopenia on Survival Prognosis in Patients Receiving Neoadjuvant Therapy for Esophageal Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Sheng-bo Jin ◽  
Zi-bin Tian ◽  
Xue-li Ding ◽  
Ying-jie Guo ◽  
Tao Mao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Esophageal Cancer ◽  
Neoadjuvant Therapy ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Survival Prognosis ◽  
Poor Prognostic Factor ◽  
The Impact

BackgroundSarcopenia is a poor prognostic factor in patients with esophageal cancer (EC). It can be aggravated by neoadjuvant therapy (NAT) that improves the prognosis of patients with EC. Until now, the impact of preoperative sarcopenia on survival prognosis in patients receiving NAT for EC remains unclear.MethodsWe systematically researched relevant studies in the PubMed, EMBASE, Web of Science, the Cochrane Library databases up to March 8, 2020. Prevalence of sarcopenia before and after NAT, overall survival (OS) and disease-free survival (DFS) were collected for analysis. Finally, eleven cohort studies were included.ResultsPooled analysis indicated that preoperative sarcopenia was negatively associated with OS. (HR = 1.290; 95% CI [1.078–1.543]; P = 0.005; I2 = 0.0%) and DFS (HR = 1.554; 95% CI [1.177–2.052]; P = 0.002; I2 = 0.0%) in the patients with EC receiving NAT. The prevalence of sarcopenia increased by 15.4% following NAT (95%CI [12.9%-17.9%]). Further subgroup analysis indicated that sarcopenia diagnosed following NAT (HR = 1.359; 95% CI [1.036–1.739]; P = 0.015; I2 = 6.9%) and age >65 years (HR = 1.381; 95% CI [1.090– 1.749]; P = 0.007; I2 = 0.0%) were the independent risk factors for decreased OS.ConclusionsClinicians should strengthen the screening of preoperative sarcopenia in patients of EC both receiving NAT and older than 65 years and give active nutritional support to improve the prognosis of patients.Systematic Review RegistrationInternational Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY), identifier INPLASY202050057.

scholarly journals Addition of Platinum Derivatives to Fluoropyrimidine-Based Neoadjuvant Chemoradiotherapy for Stage II/III Rectal Cancer: Systematic Review and Meta-Analysis

2019 ◽  
Vol 111 (9) ◽  
pp. 887-902 ◽  
Author(s):  
Felix J Hüttner ◽  
Pascal Probst ◽  
Eva Kalkum ◽  
Matthes Hackbusch ◽  
Katrin Jensen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Complete Response ◽  
Distant Recurrence ◽  
Stage Ii ◽  
Free Survival ◽  
Disease Free

Abstract Background Current guidelines recommend neoadjuvant therapy for patients with stage II or III rectal cancer. The addition of platinum derivatives to fluoropyrimidine-based chemoradiotherapy has been frequently investigated, but their role in this setting remains controversial. Methods PubMed, Cochrane Library, and Web of Science were systematically searched for randomized trials comparing chemoradiotherapy with or without platinum agents in stage II or III rectal cancer. Main outcome parameters were overall and disease-free survival, additional outcomes included pathological complete response, isolated local recurrence, distant recurrence, toxicity, and perioperative morbidity. Time-to-event data were pooled as hazard ratios (HRs) by the inverse variance method and binary outcomes as odds ratios (ORs) by the Peto method with their respective 95% confidence interval (CI). All statistical tests were two-sided. Results Ten randomized controlled trials with data on 5599 patients were included in the meta-analysis. Platinum derivatives did not statistically significantly improve overall survival (HR = 0.93, 95% CI = 0.82 to 1.05, P = .23), disease-free survival (HR = 0.91, 95% CI = 0.83 to 1.01, P = .07), or local recurrence (OR = 0.83, 95% CI = 0.66 to 1.05, P = .12). However, it led to a statistically significant increase of pathological complete response (OR = 1.31, 95% CI = 1.10 to 1.55, P = .002) and a statistically significant reduction of distant recurrence (OR = 0.78, 95% CI = 0.66 to 0.92, P = .004). Benefits were accompanied by higher rates of grade 3 or 4 toxicities. Conclusions Intensified neoadjuvant chemoradiotherapy with the addition of platinum derivatives cannot be recommended routinely because it did not improve overall or disease-free survival and was associated with increased toxicity. It needs to be elucidated whether the benefits in distant recurrence and pathological complete response may be advantageous for selected high-risk patients.

Outcomes of recurrence after complete response to definitive chemoradiotherapy for stage II/III (non–T4) esophageal squamous cell carcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 179-179
Author(s):  
Hiroki Kuwabara ◽  
Ken Kato ◽  
Yusuke Sasaki ◽  
Naoki Takahashi ◽  
Hirokazu Shoji ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Survival Time ◽  
Cox Regression ◽  
Performance Status ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Esophageal Cancer ◽  
Locoregional Failure ◽  
Distant Failure ◽  
Locally Advanced Esophageal Cancer

179 Background: Recurrence after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer is associated with poor outcome. We examined patterns of recurrence and clinical outcomes in patients with recurrence after complete response (CR) to dCRT. Methods: We retrospectively investigated 238 patients who had achieved initial CR after dCRT for locally advanced esophageal cancer between January 2000 and December 2010. From among these patients we selected 95 who had developed disease recurrence after CR. Overall survival was defined as survival time from recurrence to death and was calculated by using the Kaplan-Meier method. Univariate and multivariate analyses were performed with the Cox regression model to determine prognostic factors for survival. Results: The characteristics of the 95 patients were as follows: male: female = 84:11; median age = 64 years (range 46 to 80); clinical stage at diagnosis (UICC 6th edition) IIA/IIB/III = 20/31/44; and performance status at recurrence (0/1) = (51/44). Primary CRT consisted of 5-FU+cisplatin (n = 87), 5-FU+nedaplatin (n = 3), S-1+cisplatin (n = 3), 5-FU+cisplatin+ nimotuzumab (n = 1), or docetaxel (n = 1). The pattern of recurrence was locoregional failure (n = 53) or any distant failure (n = 42). Median time from the start of dCRT to recurrence was 13.0 months, and median survival time from recurrence to death was 19.6 months. Median survival time according to the pattern of failure was 34.7 months (locoregional failure) or 17.0 months (any distant failure). Application of the Cox regression model, including the additional prognostic variables of age, ECOG performance status, number of organs in which metastases were present, and LDH, revealed that any distant failure (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.2 to 4.1; P = 0.01) and recurrence before 13.0 months (HR 2.1; 95% CI 1.2 to 3.6; P = 0.01) were predictors of poor overall survival. Conclusions: Early recurrence and any distant failure were associated with poor prognosis after CR to dCRT for locally advanced esophageal cancer.

Multicenter, randomized phase II study of neoadjuvant pembrolizumab plus chemotherapy and chemoradiotherapy in esophageal adenocarcinoma (EAC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4005-4005
Author(s):  
Manish A. Shah ◽  
Khaldoun Almhanna ◽  
Syma Iqbal ◽  
Prashant Thakkar ◽  
Bryan J. Schneider ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Complete Response ◽  
Type I ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Grade 3

4005 Background: Recent transformative studies in the treatment of EAC support adjuvant nivolumab for patients with residual disease following neoadjuvant chemoradiotherapy (CRT) (Checkmate 577) and pembrolizumab (P) with chemotherapy in untreated metastatic disease (Keynote 590). We hypothesized that pre-operative P combined with CRT can further improve outcomes in patients with locally advanced EAC. Methods: Patients with cT3-4Nx or T2N1 M0 EAC or gastroesophageal junction (GEJ) adenocarcinoma eligible for curative surgery were randomized (1:1) to receive either full-dose paclitaxel (T)/ carboplatin (C) or T/C + P induction therapy. All patients then received CRT with weekly T/C, RT 41.4Gy in 23 fractions, and P every 3 weeks. Following resection, patients received P for one year. The primary endpoint is rate of major pathologic response (MPR), defined as pathologic complete response or near complete response ( < 10% residual cancer), with 80% power and 0.1 one-sided significance level to detect the difference between a MPR proportion of 30% (historical control) and an alternative hypothesis of 47% (with preoperative P). Tissue was collected for tumor immune microenvironment (TIME) analysis including bulk and single cell RNA(scRNA) expression analysis, DNA sequencing, and flow cytometry. Results: From 8/4/17 to 10/26/20, 40 patients were enrolled: median age 68 [38-81], male 32, esophagus/GEJ type I (n = 16), GEJ II/III (n = 24). CRT was well tolerated, with no grade 3-4 adverse events attributed to P. Notable toxicity included grade 3-4 pneumonitis (13%), anastomotic leak (13%), infection (35%). In 31 evaluable patients to date, the MPR rate was 50.0% (95% CI, 32.7%-67.3%). 1-yr disease free survival was 100% for patients with MPR vs. 31.8% without MPR, p = 0.002. Esophageal/GEJ type I cancers had a significantly higher MPR rate when compared with GEJ type II/III (76.9% vs 37.5%, p = 0.03). scRNA seq on > 100,000 tumor cells revealed EAC/GEJ type I had higher infiltration of activated dendritic cells (p = 0.12), whereas GEJ tumors have significantly higher infiltration of activated B cells (p = 0.02). Conclusions: The addition of P to preoperative CRT for EAC is safe and associated with a significantly higher MPR rate compared to historical data. We found MPR to be significantly enriched in EAC/GEJ type I tumors compared with GEJ II/III, associated with important differences in the baseline tumor immune microenvironment. Clinical trial information: NCT02998268.

scholarly journals Prognosis comparison between wait and watch and surgical strategy on rectal cancer patients after treatment with neoadjuvant chemoradiotherapy: a meta-analysis

2019 ◽  
Vol 12 ◽  
pp. 175628481989247 ◽  
Author(s):  
Kai Pang ◽  
Quan Rao ◽  
Shengqi Qin ◽  
Lan Jin ◽  
Hongwei Yao ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Surgical Treatment ◽  
Cancer Patients ◽  
Distant Metastasis ◽  
Meta Analysis ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Prognostic Indicators ◽  
Cochrane Library ◽  
Surgery Group

Background: After achieving a clinical complete response through neoadjuvant chemoradiotherapy, a nonoperative management approach for rectal cancer patients known as Wait and Watch (W&W) has gained increasing attention. However, the W&W strategy has been related to higher local recurrence and ambiguous long-term survival. This meta-analysis compared key prognosis indicators between W&W and surgical treatment in an effort to clarify some long-standing points of confusion. Methods: Pubmed, Web of Science, EMbase, Cochrane Library were searched for relevant researches comparing W&W with surgery treatment, with a time criteria set from 1 January 2002 to 4 July 2019. Endpoints were 2-year local regrowth/recurrence, 2-year distant metastasis (plus local regrowth/recurrence), 3- and 5-year disease-free survival (DFS), and overall survival (OS). Results: In total, nine studies with 801 patients were enrolled, of which 348 were managed by W&W and 453 by surgery. Surgery patients were further divided into a pathological complete response (pCR) group (all included patients achieved pCR) and a surgery group (consisting of both pCR and non-pCR patients without deliberate screening). Compared with the surgery group, W&W patients have higher 3- and 5-year OS, and are not inferior on 2-year local regrowth (LR), 2-year distant metastasis (DM)/DM+LR, and 3- and 5-year DFS. On the other hand, compared with the pCR group, the W&W group is inferior on 2-year LR, 3- and 5-year DFS, and 5-year OS, and not inferior on 2-year DM/DM+LR and 3-year OS. Conclusions: In contrast with patients undergoing surgical treatment, the W&W group has higher 3- and 5-year OS, and is not inferior on other major prognostic indicators, which, however, is based on the fact that the tumor stage in the W&W group is generally earlier. Versus surgically treated patients who acquired pCR, W&W group is inferior on all major prognostic indicators except 2-year DM/DM+LR and 3-year OS. Additionally, by comparison of cCR definitions across different studies, we conclude that implementation of the strictest cCR criteria is critical for W&W patients to acquire maximum prognostic benefit.

scholarly journals Adjuvant Second-Dose Chemotherapy before Surgery for Patients with Locally Advanced Rectal Malignancy Is Not Beneficial: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Min Chen ◽  
Xue Song ◽  
Liang-zhou Chen ◽  
Lin Xu ◽  
Yi-pu Lu ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Combination Chemotherapy ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Cochrane Library ◽  
Controlled Trials

Background. Preoperative chemoradiotherapy is the standard treatment for patients with locally advanced rectal cancer, although tumor responses vary widely; some patients may achieve a pathologic complete response rate (pCR) after chemoradiotherapy. Controversy exists with regard to the efficacy of different preoperative combination chemotherapy regimens and neoadjuvant chemoradiotherapy, compared with chemoradiotherapy alone. Methods. PubMed, the Cochrane Library, and Embase databases were searched for comparative studies of patients with locally advanced rectal cancer that were published between January 1991 and January 2016. Efficacies of different preoperative combination chemotherapy regimens and neoadjuvant chemoradiotherapy (group A) were compared with chemoradiotherapy alone (group B) in a meta-analysis using Review Manager v5.2. Results. Three prospective randomized controlled trials and two prospective nonrandomized controlled trials comprising 444 cases were eligible for analysis. No significant difference was detected in the rate of pCR (50/223, 22.4% versus 35/223, 15.7%; relative risk, RR: 1.42 [95% confidence interval, CI: 0.97–2.09], p=0.07) between the two groups. The rate of tumor regression was similar for both groups (122/203, 60.1% versus 111/203, 54.7%; RR: 1.11 [95% CI: 0.94–1.29], p=0.22). Conclusions. Adjuvant chemotherapy with preoperative chemoradiotherapy did not significantly improve the rate of pCR nor the rate of T and N downstaging.

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