Adjuvant chemotherapy following trimodality therapy for esophageal carcinoma-Is the evidence sufficient?
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ABSTRACT:
SUBMITTER: Atay SM
PROVIDER: S-EPMC5723781 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Oesophageal cancer (OC) survival rates have improved since the widespread adoption of neoadjuvant chemoradiation therapy (NACRT) followed by oesophagectomy (trimodality therapy). Unfortunately, the overall prognosis for patients with locally advanced disease remains poor. In this study, we sought to assess the effect of adjuvant chemotherapy (AC) in patients treated with trimodality therapy.Using the National Cancer Database we retrospectively identified 6785 patients with locally advanced (cT1b-T4a, N0-N+, M0) OC who were treated with trimodality therapy from 2006 to 2014. Patients were separated based on receipt of AC (n=463), as well as clinical and pathological lymph node involvement. Overall survival (OS) between groups was compared using the Kaplan-Meier method and Cox proportional hazard modelling.Based on multivariate analysis, AC was associated with a statistically significantly reduced risk of death (HR 0.77, p<0.001). Subgroup analysis revealed that AC was associated with reduced risk of death compared with NACRT alone in the cN+/pN0 (median OS 64 vs 43 months; p=0.019) and the cN+/pN+ (median OS 27 vs 22 months; p=0.010) groups, but not in the cN0/pN0 (median OS 48 vs 49 months; p=0.253) or cN0/pN+ (median OS 31 vs 24 months; p=0.077) groups.AC following trimodality therapy may improve survival in patients with locally advanced OC. Patients who undergo lymph node downstaging may be the most likely to benefit from AC. Prospective studies are needed to confirm this finding.
| S-EPMC6069924 | biostudies-other
Project description:BackgroundMost patients with resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma (AC) receive concurrent chemoradiation (CRT) followed by esophagectomy. The majority of patients do not achieve pathologic complete response (pCR) with neoadjuvant CRT, and the relapse rate is high among these patients.MethodsWe conducted a phase II study (ClinicalTrials.gov Identifier: NCT02639065) evaluating the efficacy and safety of PD-L1 inhibitor durvalumab in patients with locally advanced esophageal and GEJ AC who have undergone neoadjuvant CRT followed by R0 resection with evidence of persistent residual disease in the surgical specimen. Patients received durvalumab 1500 mg IV every 4 weeks for up to 1 year. The primary endpoint was 1-year relapse free survival (RFS). Secondary endpoint was safety and tolerability of durvalumab following trimodality therapy. Exploratory endpoints included correlation of RFS with PD-L1 expression, HER-2 expression, and tumor immune cell population.ResultsThirty-seven patients were enrolled. The majority (64.9%) had pathologically positive lymph nodes. The most common treatment related adverse events were fatigue (27%), diarrhea (18.9%), arthralgia (16.2%), nausea (16.2%), pruritus (16.2%), cough (10.8%), and increase in AST/ALT/bilirubin (10.8%). Three (8.1%) patients developed grade 3 immune mediated adverse events. One-year RFS was 73% (95% CI, 56-84%) with median RFS of 21 months (95% CI, 14-40.4 months). Patients with GEJ AC had a trend toward superior 1-year RFS compared to those with esophageal AC (83% vs. 63%, p = 0.1534). There was a numerical trend toward superior 1-year RFS among patients with PD-L1 positive disease compared to those with PD-L1 negative disease, using CPS of ≥10 (100% vs. 66.7%, p = 0.1551) and ≥1 (84.2% vs. 61.1%, p = 0.1510) cutoffs. A higher relative proportion of M2 macrophages and CD4 memory activated T cells was associated with improved RFS (HR = 0.16; 95% CI, 0.05-0.59; p = 0.0053; and HR = 0.37; 95% CI, 0.15-0.93, p = 0.0351, respectively).ConclusionsAdjuvant durvalumab in patients with residual disease in the surgical specimen following trimodality therapy for locally advanced esophageal and GEJ AC led to clinically meaningful improvement in 1-year RFS compared to historical control rate. Higher PD-L1 expression may have a correlation with the efficacy of durvalumab in this setting. Higher proportion of M2 macrophages and CD4 memory activated T cells was associated with superior RFS.
| S-EPMC8484871 | biostudies-literature
Project description:Correlative analysis using RNA-seq was performed on tumor samples from patients with locally advanced esophageal and gastroesophageal junction adenocarcinoma treated with adjuvant durvalumab as part of a Phase II trial. The primary goal of this correlative analysis was to perform immune deconvolution using CIBERSORTx in order to determine the relative proportion of immune cell types in each sample. The immune components were then associated with relapse free survival.
2021-09-12 | GSE183924 | GEO
Project description:PurposeWhile trimodality therapy for esophageal cancer has improved patient outcomes, surgical complication rates remain high. The goal of this study was to identify modifiable factors associated with postoperative complications after neoadjuvant chemoradiation.Methods and materialsFrom 1998 to 2011, 444 patients were treated at our institution with surgical resection after chemoradiation. Postoperative (pulmonary, gastrointestinal [GI], cardiac, wound healing) complications were recorded up to 30 days postoperatively. Kruskal-Wallis tests and χ(2) or Fisher exact tests were used to assess associations between continuous and categorical variables. Multivariate logistic regression tested the association between perioperative complications and patient or treatment factors that were significant on univariate analysis.ResultsThe most frequent postoperative complications after trimodality therapy were pulmonary (25%) and GI (23%). Lung capacity and the type of radiation modality used were independent predictors of pulmonary and GI complications. After adjusting for confounding factors, pulmonary and GI complications were increased in patients treated with 3-dimensional conformal radiation therapy (3D-CRT) versus intensity modulated radiation therapy (IMRT; odds ratio [OR], 2.018; 95% confidence interval [CI], 1.104-3.688; OR, 1.704; 95% CI, 1.03-2.82, respectively) and for patients treated with 3D-CRT versus proton beam therapy (PBT; OR, 3.154; 95% CI, 1.365-7.289; OR, 1.55; 95% CI, 0.78-3.08, respectively). Mean lung radiation dose (MLD) was strongly associated with pulmonary complications, and the differences in toxicities seen for the radiation modalities could be fully accounted for by the MLD delivered by each of the modalities.ConclusionsThe radiation modality used can be a strong mitigating factor of postoperative complications after neoadjuvant chemoradiation.
| S-EPMC3786201 | biostudies-literature
Project description:BackgroundThe role of adjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC) remains controversial. This study aimed to evaluate the impact of adjuvant chemotherapy on survival in patients with positive nodes after surgery for ESCC.MethodsWe retrospectively reviewed the survival outcomes of node-positive patients with ESCC who underwent curative resection with or without adjuvant chemotherapy between January 1994 and December 2015.ResultsWe analyzed 460 patients (333 adjuvant chemotherapy, 127 surgery alone). The surgery-alone group was older (64 vs. 60 years, p < 0.001) and had more comorbidities (p = 0.004) than the adjuvant chemotherapy group. After propensity score matching, overall survival (OS) and recurrence-free survival (RFS) of the adjuvant chemotherapy group were better than those of the surgery-alone group: 5-year OS rate 62.7% (95% confidence interval [CI] 54.4-72.3%) vs. 46.8% (95% CI 38.5-57%, p = 0.001) and 5-year RFS rate 53.9% (95% CI 45.4-63.9%) vs. 36.2% (95% CI 28.3-46.3%, p < 0.001). Notably, in patients with pT3-4 stage, the adjuvant chemotherapy group had significantly better 5-year OS rate (41.3% [95% CI 29.3-58.3%] vs. 18% [95% CI 10-32.5%], p = 0.01) and 5-year RFS rate (37% [95% CI 25.3-53.9%] vs. 12% [95% CI 5.7-25.4%], p < 0.001) than in the surgery-alone group. In multivariable analysis, adjuvant chemotherapy had a favorable effect on both OS (hazard ratio [HR] 0.562, 95% CI 0.426-0.741, p < 0.001) and RFS (HR 0.702, 95% CI 0.514-0.959; p = 0.026).ConclusionAdjuvant chemotherapy may improve survival in node-positive patients with ESCC, especially in those with pT3-4 stage.
| S-EPMC9968597 | biostudies-literature
Project description:Purpose/objectivePostoperative toxicity for esophageal cancer impacts patient quality of life and potentially overall survival (OS). We studied whether patient and toxicity parameters post-chemoradiation therapy predict for post-surgical cardiopulmonary total toxicity burden (CPTTB) and whether CPTTB was associated with short and long-term outcomes.Materials/methodsPatients had biopsy-proven esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. CPTTB was derived from total perioperative toxicity burden (Lin et al. JCO 2020). To develop a CPTTB risk score predictive for major CPTTB, recursive partitioning analysis was used.ResultsFrom 3 institutions, 571 patients were included. Patients were treated with 3D (37%), IMRT (44%), and proton therapy (19%). 61 patients had major CPTTB (score ≥ 70). Increasing CPTTB was predictive of decreased OS (p<0.001), lengthier post-esophagectomy length of stay (LOS, p<0.001), and death or readmission within 60 days of surgery (DR60, p<0.001). Major CPTTB was also predictive of decreased OS (hazard ratio = 1.70, 95% confidence interval: 1.17-2.47, p=0.005). The RPA-based risk score included: age ≥ 65, grade ≥ 2 nausea or esophagitis attributed to chemoradiation, and grade ≥ 3 hematologic toxicity attributed to chemoradiation. Patients treated with 3D radiotherapy had inferior OS (p=0.010) and increased major CPTTB (18.5% vs. 6.1%, p<0.001).ConclusionCPTTB predicts for OS, LOS, and DR60. Patients with 3D radiotherapy or age ≥ 65 years and chemoradiation toxicity are at highest risk for major CPTTB, predicting for higher short and long-term morbidity and mortality. Strategies to optimize medical management and reduce toxicity from chemoradiation should be strongly considered.
| S-EPMC9948243 | biostudies-literature
Project description:ObjectiveNo standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma (ESCC). This is a study to explore the effect of postoperative paclitaxel (PTX) and cisplatin (DDP) in lymph node-positive, completely resected thoracic ESCC patients.MethodsWe conducted a prospective phase II trial. Patients had pathologically node-positive thoracic ESCC with negative margins. Outcomes of disease-free survival (DFS) and overall survival (OS) were compared with a matched historical control cohort. The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d.ResultsForty-three patients were accrued from December 2007 to May 2012 at Cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy. The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time. Of the 43 patients with adjuvant chemotherapy, 37 (86.0%) patients completed 4 to 6 cycles of chemotherapy. The 3-year DFS rates were 56.3% in the adjuvant group and 34.6% in the control group (P=0.006). The 3-year OS rates were 55.0% in the adjuvant group and 37.5% in the control group (P=0.013). Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS (P=0.005).ConclusionsBiweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive, curatively resected thoracic ESCC patients. These conclusions warrant further study in randomized phase III clinical trials.
| S-EPMC5422417 | biostudies-literature
Project description:BackgroundThe comparative effectiveness of trimodality therapy vs definitive chemoradiation for treating locally advanced esophageal cancer in older adults is uncertain. Existing trials lack generalizability to older adults, a population with heightened frailty. We sought to emulate a hypothetical trial comparing these treatments using real-world data.MethodsA cohort of adults aged 66-79 years diagnosed with locally advanced esophageal cancer between 2004 and 2017 was identified in the Surveillance Epidemiology and End Results-Medicare database. The clone-censor-weight method was leveraged to eliminate time-related biases when comparing outcomes between treatments. Outcomes included overall mortality, esophageal cancer-specific mortality, functional adverse events, and healthy days at home.ResultsA total of 1240 individuals with adenocarcinomas and 661 with squamous cell carcinomas were identified. For adenocarcinomas, the standardized 5-year risk of mortality was 73.4% for trimodality therapy and 83.8% for definitive chemoradiation (relative risk [RR] = 0.88, 95% confidence interval [CI] = 0.82 to 0.95). Trimodality therapy was associated with mortality risk reduction for squamous cell carcinomas (RR = 0.87, 95% CI = 0.70 to 1.01). The 1-year incidence of functional adverse events was higher in the trimodality group (adenocarcinomas RR = 1.40, 95% CI = 1.22 to 1.65; squamous cell carcinomas RR = 1.21, 95% CI = 1.00 to 1.49). Over 5 years, trimodality therapy was associated with 160 (95% CI = 67 to 229) and 177 (95% CI = 51 to 313) additional home days in individuals with adenocarcinomas and squamous cell carcinomas, respectively.ConclusionsCompared with definitive chemoradiation, trimodality therapy was associated with reduced mortality but increased risk of function-related adverse events. Discussing these tradeoffs may help optimize care plans.
| S-EPMC9623425 | biostudies-literature
Project description:BackgroundBladder-sparing chemoradiation therapy is a definitive first-line treatment option for muscle-invasive bladder cancer. Randomized trials have demonstrated that the addition of neoadjuvant chemotherapy to radical cystectomy or radiation monotherapy results in a survival benefit. Whether neoadjuvant chemotherapy improves outcomes when used with definitive chemoradiation is unknown.Patients and methodsWe identified 2566 patients in the National Cancer Data Base with cT2-4N0M0 urothelial cell carcinoma of the bladder treated with definitive intent concurrent chemoradiation from 2004 to 2015. The exposure of interest was receipt of neoadjuvant chemotherapy versus those without neoadjuvant chemotherapy. The primary outcome was overall survival defined from the time of diagnosis. Kaplan-Meier and multivariable Cox proportional hazard analyses were used to compare survival between groups. Sensitivity analyses tested (1) an interaction term for clinical T stage and (2) defining survival from start of radiation (as opposed to time of diagnosis) to address potential leading time bias.ResultsWe identified 462 patients treated with neoadjuvant chemotherapy followed by chemoradiation and 2104 patients treated with chemoradiation alone. With a median follow-up of 6.2 years, we found no difference in survival between groups: 5-year or 10-year overall survival of 30.6% (95% confidence interval [CI], 28.4%-32.9%) in the neoadjuvant group versus 31.8% (95% CI, 27.0%-36.8%) in the standard chemoradiation therapy group and 13.3% (95% CI, 11.2%-15.5%) in the neoadjuvant group versus 13.0% (95% CI, 8.4%-18.7%) in the standard chemoradiation therapy group, respectively (log-rank P = .19). On multivariable analysis we found no association between receipt of neoadjuvant chemotherapy and overall survival (hazard ratio, 1.01; 95% CI, 0.88-1.15; P = .921). The sensitivity analyses did not identify any differential effect by clinical T stage nor by defining survival from start of radiation.ConclusionThese results do not support the routine addition of neoadjuvant chemotherapy to definitive chemoradiation for bladder cancer, and optimizing the chemotherapy sequencing and regimens for bladder-preserving approaches to muscle invasive bladder cancer should continue to be studied under prospective clinical trials.
| S-EPMC8376795 | biostudies-literature
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