Survival benefit of surgery in patients with clinical T4 esophageal cancer who achieved complete or partial response after neoadjuvant chemoradiotherapy or radiotherapy
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ABSTRACT: Objective:
This study aimed to determine the long-term survival of patients with cT4
SUBMITTER: Gao L
PROVIDER: S-EPMC9340417 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Project description:Although it was controversial for treating locally advanced resectable esophageal squamous cell carcinoma (ESCC), neoadjuvant chemoradiotherapy (NACR) was more widely accepted rather than neoadjuvant chemotherapy (NAC) worldwide. With the development of paclitaxel, a high response rate to NAC was reported in many studies. Our hypothesis is that lots of patients could get a response from NAC alone and avoid unnecessary NACR. Those who had no response from NAC could still response from the followed radiotherapy. We attempted to circumvent the controversy over the use of NAC, NACR and made a combined version, NAC ± neoadjuvant radiotherapy (NAR).The retrospective study compared NAC ± NAR with NACR between June 30, 2015 and October 31, 2016. Sixty consecutive borderline resectable ESCC were included: thirty-one in NAC ± NAR group and 29 in NACR group. The toxicities, response rates, operative data, complications, length of stay, and overall survival (OS) rates were evaluated.The response rate to NAC ± NAR was 93.5%; to NACR was 86.2%. There was no grade 3-4 non-hematologic adverse events after NAC ± NAR, but three in the NACR group. Arrhythmias (6.5% vs. 37.9%, P=0.003), pneumonitis (25.8% vs. 51.7%, P=0.039) and anastomotic leakage (0% vs. 13.8%, P=0.049) were more likely in NACR group. Postoperative hospitalization stays were significantly prolonged in the NACR (9 vs. 16 d, P<0.001). A point estimate of the 2-year OS rate of the NAC ± NAR group was 84.0%, the NACR group 80.7% (P=0.410).Compared with NACR, the NAC ± NACR provided the same survival benefits but low post operation complication rate. In the future, it might be a choice for locally advanced ESCC.
| S-EPMC6129884 | biostudies-other
Project description:Neoadjuvant radiochemotherapy (nRCT) followed by surgery has become the gold standard treatment in patients with locally advanced esophageal cancer. The pathological response is an important predictor in such patients. This work represents a single-center analysis investigating the impact of pathological complete response (pCR) on treatment outcome.All patients treated with nRCT followed by surgery between January 2005 and December 2015 were reviewed. The patients were categorized into two groups according to the pathological response following nRCT: pCR group and non-pCR group.Fifty-six patients with invasive cancer, 23 patients (41.1%) achieved pCR and 33 patients had non-pCR (58.9%) following nRCT. The average age was 62 years (±9.1), and most patients were males (83.9%). Histological types included squamous cell carcinoma (75%) and adenocarcinoma (25%). The total radiation dose was 45 Gy in 76.8% of the patients and 50.4 Gy in 23.2%. The median overall survival (OS) of the entire group was 3.5±1.2 years, and the 5-year OS rate was 38.2%, while the median disease-free survival (DFS) was 2.1±0.4 years and the 5-year DFS rate was 33.1%. The patients who achieved pCR had significantly higher 5-year OS and 5-year DFS rates: 47.2% and 48% compared to 27.3% and 21% for the non-pCR patients respectively (P=0.04, 0.03). The median time of local recurrence was 3.8±0.4 years in pCR group and 1.8±0.2 years in non-pCR group (P=0.01), while the median time of distant metastases in pCR group was 1.2±0.5 years and 1.1±0.2 years in non-pCR group (P=0.6).Complete pathological response predicts significantly higher rates of OS and DFS in patients with locally advanced esophageal cancer treated with nRCT followed by surgery.
| S-EPMC6106005 | biostudies-other
Project description:BackgroundThe impact of neoadjuvant chemoradiotherapy (nCRT) on early stage esophageal cancer is unknown. Here, we compared the outcomes after esophagectomy alone or nCRT plus surgery for clinically staged node-negative esophageal cancer.MethodsWe searched the Surveillance, Epidemiology, and End Results database for patients with clinically node-negative (cN0) esophageal cancer from 2004 to 2016 who underwent surgery alone or nCRT plus surgery. Propensity score matching and Cox regression analysis were used to identify covariates associated with overall survival and cancer-specific survival.ResultsA total of 1587 patients were retrospectively identified, of whom 49.8% (n = 791) received nCRT and 80.2% (n = 1273) were truly node-negative diseases. For the entire cohort, surgery alone was associated with a statistically significant but modest absolute increase in survival outcomes (P < 0.01). After matching, nCRT was associated with improved five-year overall survival for pT3-4N0 (localized) disease (59.6% vs. 37.7%; P < 0.001) and pathological node-positive disease (60.5% vs. 40.7%; P = 0.002). Cox multivariate regression analysis revealed that the addition of nCRT for truly node-negative patients with tumor length ≥ 3 cm, pT1-2N0 (early-staged) and localized disease were independent risk factors for survival than surgery alone (P < 0.01).ConclusionsCompared with surgery alone, patients with cN0 esophageal cancer with pathological node-positive or localized true node-negative disease gain a significant survival benefit from nCRT. However, nCRT plus surgery was associated with decreased survival for early-staged true node-negative patients. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN0 disease.
| S-EPMC7471040 | biostudies-literature
Project description:BackgroundNeoadjuvant 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.MethodsWe 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.ResultsSix 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).ConclusionOmitting 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.
| S-EPMC8591817 | biostudies-literature
Project description:BackgroundsIn this study, we evaluated the factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma (ESCC).MethodsPre-nCRT parameters in ESCC patients treated between 1999 and 2006 were analyzed to identify predictors of pCR. All patients received 5-fluorouracil/cisplatin-based chemotherapy and external beam radiation followed by scheduled esophagectomy. Variables were analyzed using univariate and multivariate analyses with pCR as the dependent variable. Estimated pCR rate was calculated with a regression model.ResultsFifty-nine (20.9%) of 282 patients achieved pCR. Univariate analysis identified four patient factors (age, smoking status, drinking history and hypertension), one pre-nCRT parameter (tumor length) as significant predictors of pCR (all P <0.05). On multivariate analysis, tumor length ≤3 cm (favorable, odds ratio (OR): 4.85, P = 0.001), patient age >55 years (favorable, OR: 1.95, P = 0.035), and being a non-smoker (favorable, OR: 3.6, P = 0.003) were independent predictors of pCR. The estimated pCR rates based on a logistic regression including those three predictors were 71%, 35 to approximately 58%, 19 to approximately 38%, and 12% for patients with 3, 2, 1 and 0 predictors, respectively.ConclusionAge, smoking habit and tumor length were important pCR predictors. These factors may be used to predict outcomes for ESCC patients receiving nCRT, to develop risk-adapted treatment strategies, and to select patients who could participate in trials on new therapies.
| S-EPMC4050419 | biostudies-literature
Project description:OBJECTIVE:Definitive chemoradiotherapy (CRT) remains the most commonly used treatment for locally advanced esophageal squamous cell carcinoma (SCC), because of perceptions that esophagectomy offers an unclear survival advantage. We compare recurrence, overall survival (OS), and disease-free survival (DFS) in patients treated with definitive CRT or neoadjuvant CRT followed by surgery (trimodality). METHODS:This was a retrospective cohort study of patients with stage II and III SCC of the middle and distal esophagus in patients who completed CRT. Treatment groups were matched (1:1) on covariates using a propensity score-matching approach. The effect of trimodality treatment, compared with definitive CRT, on OS, DFS, and site-specific recurrence was evaluated as a time-dependent variable and analyzed using Cox regression with a gamma frailty term for matched units. RESULTS:We included 232 patients treated between 2000 and 2016: 124 (53%) with definitive CRT and 108 (47%) with trimodality. Trimodality was used less frequently over time (61% before 2009 and 29% after 2009; P < .0001). After matching, each group contained 56 patients. Median OS and DFS were 3.1 and 1.8 years for trimodality versus 2.3 and 1.0 years for CRT. Surgery was independently associated with improved OS (hazard ratio, 0.57; 95% confidence interval, 0.34-0.97; P = .039) and DFS (hazard ratio, 0.51; 95% confidence interval, 0.32-0.83; P = .007). CONCLUSIONS:CRT followed by surgery might decrease local recurrence and increase DFS and OS in patients with esophageal SCC. Until better tools to select patients with pathological complete response are available, surgery should remain an integral component of the treatment of locally advanced esophageal SCC.
| S-EPMC5960990 | biostudies-literature
Project description:Esophageal cancer has high incidence rate in China. Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for esophageal squamous cell carcinoma (ESCC). However, there are few reliable epigenetic parameters for patients with ESCC undergoing neoadjuvant therapy. Genomic extract from tumor tissue was amplified and sequenced using the Illumina HiSeq4000 to quantify genes associated methylation or hydromethylation in 12 patients with ESCC undergoing nCRT. The genome-wide hydroxymethylation were analyzed by methylated and hydroxymethylated DNA immunoprecipitation sequencing by MACS2 software and UCSC RefSeq database. Abnormal DNA methylation was statistically different between nCRT-well (showed a pathological complete response to nCRT) and nCRT-poor (showed incomplete pathological response to nCRT) patients. Levels of ten-eleven translocation 1, 2 and 3 mRNA and protein were higher in tumor tissue in nCRT-well group patients than in nCRT-poor group patients. Illumina HiSeq 4000 sequencing identified 2925 hypo-differentially hydroxymethylated region (DhMRs) and 292 hyper-DhMRs in promoter between nCRT-well and nCRT-poor patients. Biological processes associated with hyper-DhMRs included 'snRNA processing', 'hormone-mediated signaling pathway' and 'cellular response'. Metabolic processes were associated with hypo-DhMRs. These data may explain the functional response to nCRT in patients with abnormal promoter of methylation gene-associated mRNA expression. The present results implied that hyper-DhMRs and hypo-DhMRs affect molecular pathways, such as hippo and Notch signaling pathways, highlighting epigenetic modifications associated with clinical response to nCRT in patients with esophageal cancer.
| S-EPMC9748644 | 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:BackgroundThe outcome of patients with T4 esophageal squamous cell carcinoma (ESCC) is extremely poor. Two distinct therapeutic options are currently available for T4 esophageal cancers: neochemoradiotherapy followed by surgery (CRT-S) and definitive chemoradiotherapy (D-CRT). This study aimed to investigate the clinicopathologic characteristics of T4 ESCC in Chinese patients and compare the survival between the two therapeutic options.MethodsWe retrospectively analyzed 125 patients with clinically unresectable T4 ESCC in Tianjin Medical University Cancer Institute and Hospital from January 2010 to December 2020. Overall survival (OS), progression-free survival (PFS) and associated factors were analyzed.ResultsA total of 106 of 125 T4 ESCC patients were downstaged of the tumor by neoadjuvant CRT. Among 106 patients, 32 patients underwent CRT-S, and 74 patients underwent D-CRT. Patients in the CRT-S group had a higher OS (20.4 months vs. un-reached median OS, p = 0.037) and PFS (8.6 months vs. 21.0 months, p = 0.008) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor of PFS. After propensity score matching (PSM), 50 patients (CRT-S = 25; D-CRT = 25) were matched. Among these 50 patients, patients in the CRT-S group had a higher OS (15.6 months vs. un-reached median OS, p = 0.025) and PFS (7.2 months vs. 18.8 months, p = 0.026) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor for PFS.ConclusionWe demonstrated that CRT-S was superior to D-CRT for T4 ESCC patients who were downstaged by neo-CRT with respect to longer OS and PFS. Randomized controlled trials involving large population samples are needed to define the standard treatment for T4 ESCC.
| S-EPMC9396773 | biostudies-literature
Project description:Background and purpose: Although patients with esophageal squamous cell carcinoma (ESCC) can achieve a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) followed by surgery, one-third of these patients with a pCR may still experience recurrence. The aim of this study is to develop and validate a predictive model to estimate recurrence-free survival (RFS) in those patients who achieved pCR. Materials and methods: Two hundred six patients with ESCC were enrolled and divided into a training cohort (n = 146) and a validation cohort (n = 60). Radiomic features were extracted from contrast-enhanced computed tomography (CT) images of each patient. Feature reduction was then implemented in two steps, including a multiple segmentation test and least absolute shrinkage and selection operator (LASSO) Cox proportional hazards regression method. A radiomics signature was subsequently constructed and evaluated. For better prediction performance, a clinical nomogram based on clinical risk factors and a nomogram incorporating the radiomics signature and clinical risk factors was built. Finally, the prediction models were further validated by calibration and the clinical usefulness was examined in the validation cohort to determine the optimal prediction model. Results: The radiomics signature was constructed using eight radiomic features and displayed a significant correlation with RFS. The nomogram incorporating the radiomics signature with clinical risk factors achieved optimal performance compared with the radiomics signature (P < 0.001) and clinical nomogram (P < 0.001) in both the training cohort [C-index (95% confidence interval [CI]), 0.746 (0.680-0.812) vs. 0.685 (0.620-0.750) vs. 0.614 (0.538-0.690), respectively] and validation cohort [C-index (95% CI), 0.724 (0.696-0.752) vs. 0.671 (0.624-0.718) vs. 0.629 (0.597-0.661), respectively]. The calibration curve and decision curve analysis revealed that the radiomics nomogram outperformed the other two models. Conclusions: A radiomics nomogram model incorporating radiomics features and clinical factors has been developed and has the improved ability to predict the postoperative recurrence risk in patients with ESCC who achieved pCR after nCRT followed by surgery.
| S-EPMC7431604 | biostudies-literature