Esophageal Cancer-specific Survival Research Articles

Treatment and survival analysis for 40-year SEER data on upper esophageal cancer.

Upper esophageal cancer (UEC) is rare in both Eastern and Western countries. The epidemiological characteristics and long-term survival of UEC patients are less known. In addition, the choice of optimal treatment for UEC has been controversial. Cases of UEC (C15.3 and C15.0) arising during the period from 1973 to 2013 were identified and selected using the SEER database. Student's t-test and Pearson's chi-square test were used to compare the differences in parameters among different groups. Esophageal cancer-specific survival (ECSS) and overall survival (OS) rates were calculated by using the Kaplan-Meier method. Cox proportional hazard regression was used to analyze predictive factors. In the past 40 years, the cases of UEC have gradually increased, and the proportion of adenocarcinoma (AD) has gradually increased (from 3.6% to 11.8%, p < 0.001). There has been a significant increase (1973-1982 vs. 2004-2013) in median OS (7 months vs. 10 months, p < 0.001) and median ECSS (7 months vs. 11 months, p < 0.001) among UEC patients from 1973 to 2013. For the impact of different treatments, the results showed that the ECSS and OS of surgery without radiation (SWR) and radiation plus surgery (R+S) were superior to those of radiation without surgery (RWS). Subgroup analysis showed that ECSS and OS were highest among patients treated with SWR compared with R+S and RWS for patients with localized disease. For regional disease, ECSS and OS were highest among patients with R+S compared with SWR or RWS. Among patients with regional-stage squamous cell carcinoma (SCC), OS was higher with neoadjuvant radiotherapy or adjuvant radiotherapy compared with SWR. Multivariate analysis showed that radiotherapy sequence was dependently associated with OS among patients with regional-stage SCC. Although the long-term survival of UEC remains poor, it has gradually increased since 1973. This should be closely related to the improvement of medical care over the past 40 years. Different treatment methods have a great influence on the long-term survival of UEC. For localized diseases, surgery may be a better choice. For regional disease, surgery plus adjuvant or neoadjuvant radiotherapy may be more beneficial to improve the long-term prognosis of UEC patients.

Influence of adverse effects of neoadjuvant chemoradiotherapy on the prognosis of patients with early-stage esophageal cancer (cT1b-cT2N0M0) based on the SEER database.

To analyze the prognostic impact of neoadjuvant chemoradiotherapy (NCRT) on early-stage (cT1b-cT2N0M0) esophageal cancer (ESCA) and construct a prognostic nomogram for these patients. We extracted the clinical data about patients diagnosed with early-stage esophageal cancer from the 2004-2015 period of the Surveillance, Epidemiology, and End Results (SEER) database. We applied the independent risk factors affecting the prognosis of patients with early-stage esophageal cancer obtained after screening by univariate and multifactorial COX regression analyses to establish the nomogram and performed model calibration using bootstrapping resamples. The optimal cut-off point for continuous variables is determined by applying X-tile software. After balancing the confounding factors by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) method, Kaplan-Meier(K-M) curve, and log-rank test were applied to evaluate the prognostic impact of NCRT on early-stage ESCA patients. Among patients who met the inclusion criteria, patients in the NCRT plus esophagectomy (ES) group had a poorer prognosis for overall survival (OS) and esophageal cancer-specific survival (ECSS) than patients in the ES alone group (p < 0.05), especially in patients who survived longer than 1 year. After PSM, patients in the NCRT + ES group had poorer ECSS than patients in the ES alone group, especially after 6 months, while OS was not significantly different between the two groups. IPTW analysis showed that, prior to 6 months patients in the NCRT + ES group had a better prognosis than patients in the ES group, regardless of OS or ECSS, whereas after 6 months, patients in the NCRT + ES group had a poorer prognosis. Based on multivariate COX analysis, we established a prognostic nomogram which showed areas under the ROC curve (AUC) for 3-, 5-, and 10-year OS 0.707, 0.712, and 0.706, respectively, with the calibration curves showing that the nomogram was well calibrated. Patients with early-stage ESCA (cT1b-cT2) did not benefit from NCRT, and we established a prognostic nomogram to provide clinical decision aid for the treatment of patients with early-stage ESCA.

Prognostic analysis and nomogram establishment in patients with early esophageal cancer receiving endoscopic therapy: a population-based study.

The growing numbers of early esophageal cancer (EEC) have increased the demand for endoscopic therapy. To clarify the influential factors for the prognosis of patients with EEC receiving endoscopic surgery, and to construct a nomogram to evaluate the prognostic value of endoscopic therapy. Prognostic analysis study. Clinical data of EEC patients who received endoscopic therapy between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results database and used to construct the nomogram. The prognosis was analyzed by R language; the nomogram was constructed by Cox survival analysis; and the accuracy of the nomogram was verified by C index and the receiver operating characteristic (ROC) and calibration curves. X-Tile software was used to stratify the risk of patients. Our study constructed the nomogram of the prognosis of patients with EEC treated by endoscopic surgery, including 1118 patients and 5 independent prognostic factors of esophageal cancer-specific survival. The C index and the area under the ROC curve (AUC) of the training and verification cohorts were all >0.75. The calibration curve also reflected the good consistency of the model in predicting survival. Significant difference in the risk of patients from different stratifications with the same T staging existed, and the model had a better C index than that of the T staging. Our study reports potential influential factors affecting the prognosis of EEC patients who received endoscopic therapy and establishes a reliable nomogram to predict the risk and prognosis, which has certain advantages compared with traditional TNM staging system.

Patterns of care and prognostic evaluation for stage I–III upper esophageal squamous cell carcinoma: a population-based study

There is no strong evidence regarding the optimal treatment and specific prognosis prediction model for upper esophageal squamous cell carcinoma (UESCC). This study aimed to investigate the real-world treatment patterns and develop models to predict overall survival (OS) and esophageal cancer-specific survival (ECSS) in patients with stage I-III UESCC. Patients with T1-4N0-3M0 UESCC in the Surveillance, Epidemiology, and End Results (SEER) database were identified from 2010 to 2017, and randomized to a training cohort and a validation cohort. The effect of treatment patterns on survival were comprehensively analyzed. Nomograms were developed by incorporating independent prognostic factors analyzed by Cox regression in the training cohort and evaluated by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA) in two cohorts. A total of 677 patients were identified, including 452 in the training cohort and 225 in the validation cohort. Among all populations, 71.9% (487) received chemoradiotherapy without surgery, and chemoradiotherapy or/and surgery showed better survival than other treatments. However, surgery was rarely carried out for patients with stage II-III. T stage, N stage, surgery, chemotherapy, and radiotherapy were independent risks for both OS and ECSS, while age was also an independent risk for OS. The C-indexes for nomograms to predict OS (0.71 and 0.72) and ECSS (0.70 and 0.73) were greater than 7th AJCC staging system to predict OS (0.61 and 0.64) and ECSS (0.64 and 0.64) in both the training cohort and the validation cohort. Time-dependent ROC curves and DCA also suggested that nomograms performed consistently better than 7th AJCC staging system. The calibration curves demonstrated good consistency in predicting survival. Chemoradiotherapy was a major treatment with preferable survival for patients with stage I-III UESCC. We have firstly developed and validated prognostic nomograms in patients with stage I-III UESCC, which would play a supplementary role in the current staging system.

Development and validation of a deep learning model to predict survival of patients with esophageal cancer.

ObjectiveTo compare the performance of a deep learning survival network with the tumor, node, and metastasis (TNM) staging system in survival prediction and test the reliability of individual treatment recommendations provided by the network.MethodsIn this population-based cohort study, we developed and validated a deep learning survival model using consecutive cases of newly diagnosed stage I to IV esophageal cancer between January 2004 and December 2015 in a Surveillance, Epidemiology, and End Results (SEER) database. The model was externally validated in an independent cohort from Fujian Provincial Hospital. The C statistic was used to compare the performance of the deep learning survival model and TNM staging system. Two other deep learning risk prediction models were trained for treatment recommendations. A Kaplan–Meier survival curve was used to compare survival between the population that followed the recommended therapy and those who did not.ResultsA total of 9069 patients were included in this study. The deep learning network showed more promising results in predicting esophageal cancer-specific survival than the TNM stage in the internal test dataset (C-index=0.753 vs. 0.638) and external validation dataset (C-index=0.687 vs. 0.643). The population who received the recommended treatments had superior survival compared to those who did not, based on the internal test dataset (hazard ratio, 0.753; 95% CI, 0.556-0.987; P=0.042) and the external validation dataset (hazard ratio, 0.633; 95% CI, 0.459-0.834; P=0.0003).ConclusionDeep learning neural networks have potential advantages over traditional linear models in prognostic assessment and treatment recommendations. This novel analytical approach may provide reliable information on individual survival and treatment recommendations for patients with esophageal cancer.

Effect of prior cancer history on survival of patients with esophageal carcinoma: a propensity score matching, population-based study.

BackgroundWhen conducting esophageal cancer clinical trials, prior cancer history is frequently considered an exclusion criterion due to the assumption that prior malignancy may exert significant interference with the prognosis in patients with esophageal carcinoma. This study aimed to evaluate the impact of prior cancer on survival of patients with esophageal cancer and provide valuable assistance for trial design.MethodsData regarding patients diagnosed with esophageal cancer between 2011 and 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and divided into two groups depending on the presence or absence of prior cancer history. Propensity score matching (PSM) was performed to minimize the confounding bias caused by covariates. Subsequently, Kaplan-Meier analysis and multivariate Cox proportional hazards models were used to compare all-cause and esophageal cancer-specific survival between patients with and without prior cancer.ResultsAmong 17,123 patients with esophageal carcinoma included in this study, 2,224 (13%) patients had prior cancer history. Before PSM, Kaplan-Meier curves between the two groups classified by prior cancer history showed no significant differences in all-cause (HR =1.047, 95% CI: 0.995–1.102, P=0.077) and esophageal cancer-specific survival (HR =0.986, 95% CI: 0.928–1.048, P=0.65). Similar results were obtained after PSM. In multivariate Cox analysis, prior malignancy was not significantly associated with all-cause (HR =1.002, 95% CI: 0.936–1.072, P=0.965) and esophageal cancer-specific survival (HR =0.964, 95% CI: 0.890–1.045, P=0.374). Subgroup analysis stratified by timing of prior cancer demonstrated that prior cancer had no significant effect on prognosis in the recent latency period subgroups (P>0.05). Furthermore, patients with a prior cancer of lung and bronchus (P=0.013) or head and neck (P=0.012) displayed significantly worse survival than patients without prior cancer, while other types of prior cancer showed no significant effect.ConclusionsThe findings suggest that prior cancer is likely not a definite factor that has an impact on all-cause and esophageal cancer-specific survival. Therefore, exclusion criteria of prior cancer history in esophageal cancer clinical trials should be seriously reconsidered.

72 PHASE II ADJUVANT CANCER-SPECIFIC VACCINE THERAPY FOR ESOPHAGEAL CANCER PATIENTS CURATIVELY RESECTED AFTER PREOPERATIVE THERAPY WITH PATHOLOGICALLY POSITIVE NODES

Abstract Esophageal squamous cell carcinoma (ESCC) patients with pathologically positive nodes have a high risk for postoperative recurrence, despite curative resection after preoperative therapy. Subclinical micrometastases are an appropriate target for cancer vaccine. To elucidate the efficacy of adjuvant vaccine monotherapy using three HLA-A*24-restricted tumor-specific peptide antigens for ESCC, up-regulated lung cancer 10, cell division cycle associated 1 and KH domain-containing protein overexpressed in cancer 1, we conducted an exploratory prospective phase II clinical trial (UMIN000003557). Methods Patients with ESCC who underwent curative resection after preoperative therapy and were found pathologically positive lymph node metastasis were enrolled from December 2009 to September 2014 and allocated into the control and vaccine groups (CG and VG) based on the HLA-A*2402 positive or negative. One mg each of three epitope peptides mixed with 1 mL of Montanide ISA 51 VG was administered the first 10weekly injections followed by 10 additional biweekly injections to VG. No other adjuvant therapy was given until recurrence occurred. The primary endpoint was relapse-free survival (RFS) and the secondary endpoint was esophageal cancer-specific survival (ECSS). Results Thirty were in the CG and 33 in the VG. No significant difference was observed in RFS between the CG and VG (5-year RFS: 32.5% vs. 45.3%, p = 0.205 (one-sided)), but the recurrence rate significantly decreased with the number of peptides which induced antigen-specific cytotoxic T lymphocytes. The VG showed a significantly higher 5-year ECSS than the CG (60.0% vs. 32.4%, p = 0.045 (one-sided)) probably due to the better clinical responses in patients of the VG to the post-recurrence therapy and this difference was more prominent in patients with CD8+ and programmed death-ligand 1 double negative tumor (68.0% vs. 17.7%, p = 0.010 (two-sided)). Conclusion Our results suggested that the cancer peptide vaccine suppressed the postoperative recurrence, enhanced the post-recurrence therapy and improved the survival of ESCC patients, particularly in the cases without CD8 infiltration and PD-L1 expression. A phase III randomized controlled study has been conducted in response to these results, and the results are waiting to be published.

Efficacy and cost of high-frequency IGRT in elderly stage III non-small-cell lung cancer patients

BackgroundHigh-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC).MethodsWe selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods.ResultsOf the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86–1.09), ETFS (HR 1.05; 95% CI 0.93–1.18), CSS (HR 0.94; 95% CI 0.84–1.04), or OS (HR 0.95; 95% CI 0.87–1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively.ConclusionhfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost. hfIGRT deserves further scrutiny through a randomized controlled trial.

Prognostic value of the extent of lymphadenectomy for esophageal cancer-specific survival among T1 patients

BackgroundClinically, there are no clear guidelines on the extent of lymphadenectomy in patients with T1 esophageal cancer. Studying the minimum number of lymph nodes for resection may increase cancer-specific survival.MethodsPatients who underwent esophagectomy and lymphadenectomy at T1 stage were selected from the Surveillance, Epidemiology and End Results Program (United States, 1998–2014). Maximally selected rank and Cox proportional hazard models were used to examine three variables: the number of lymph nodes examined, the number of negative lymph nodes and the lymph node ratio.ResultsApproximately 18% had lymph node metastases, where the median values were 10, 10 and 0 for the number of lymph nodes examined, the number of negative lymph nodes and the lymph node ratio, respectively. All three examined variables were statistically associated with cancer-specific survival probability. Dividing patients into two groups shows a clear difference in cancer-specific survival compared to four or five groups for all three variables: there was a 29% decrease in the risk of death with the number of lymph nodes examined ≥14 vs < 14 (hazard ratio 0.71, 95% confidence interval: 0.57–0.89), a 35% decrease in the risk of death with the number of negative lymph nodes ≥13 vs < 13 (hazard ratio 0.65, 95% confidence interval: 0.52–0.81), and an increase of 1.21 times in the risk of death (hazard ratio 2.21, 95% confidence interval: 1.76–2.77) for the lymph node ratio > 0.05 vs ≤ 0.05.ConclusionsThe extent of lymph node dissection is associated with cancer-specific survival, and the minimum number of lymph nodes that need to be removed is 14. The number of negative lymph nodes and the lymph node ratio also have prognostic value after lymphadenectomy among T1 stage patients.

Lung Metastases in Newly Diagnosed Esophageal Cancer: A Population-Based Study.

BackgroundEsophageal cancer is one of the most common cancer types, with its most common distant metastatic site being the lung. Currently, population-based data regarding the proportion and prognosis of patients with esophageal cancer with lung metastases (ECLM) at the time of diagnosis is insufficient. Therefore, we aimed to determine the proportion of patients with ECLM at diagnosis, as well as to investigate the prognostic parameters of ECLM.MethodsThis population-based observational study obtained data from the Surveillance, Epidemiology, and End Results (SEER) database registered between 2010 and 2016. Multivariable logistic regression was performed to identify predictors of the presence of ECLM at diagnosis. Multivariable Cox regression and competing risk analysis were used to assess prognostic factors in patients with ECLM. Median survival was estimated using Kaplan–Meier curves.ResultsOf 10,965 patients diagnosed with esophageal cancer between 2010 and 2016, 713 (6.50%) presented with initial lung metastasis at diagnosis. Lung metastasis represented 27.15% of all cases with metastatic disease to any distant site. Considering all patients with esophageal cancer, multivariable logistic regression indicated that pathology grade, pathology type, T staging, N staging, race, and number of extrapulmonary metastatic sites were predictive factors for the occurrence of lung metastases at diagnosis. The median survival time of patients with ECLM was 4.0 months. Patients receiving chemotherapy or chemoradiotherapy had the longest median overall survival, 7.0 months. Multivariable Cox regression indicated that age, histology type, T2 staging, number of extrapulmonary metastatic sites, and treatment (chemotherapy, radiotherapy, or chemoradiotherapy) were independent predictors for overall survival (OS). Multivariable competing risk analysis determined that age, number of extrapulmonary metastatic sites, and treatment were independent predictors for esophageal cancer-specific survival (CSS).ConclusionThe findings of this study may provide important information for the early diagnosis of ECLM, as well as aid physicians in choosing appropriate treatment regimens for these patients.

Endoscopic resection versus esophagectomy for patients with small-sized T1N0 esophageal cancer: A propensity-matched study

Endoscopic resection (ER) has been rapidly adopted in the treatment of early-stage esophageal cancer. We aimed to compare the outcomes of ER with esophagectomy for patients with small-sized (≤2 cm) stage T1a and T1b esophageal cancer in a population-based cohort. We queried the Surveillance, Epidemiology, and End Results database for patients with T1N0M0 esophageal cancer who underwent ER or esophagectomy and generated a balanced cohort with 217 matched pairs using propensity score matching (PSM). Kaplan-Meier method and multivariable Cox regression analysis were employed to investigate the matched cohort. Subgroup analyses of T stage were also performed. We identified 702 patients; 309 (44.0 %) underwent ER, and 393 (56.0 %) underwent esophagectomy. In the unmatched cohort, patients who underwent ER were older, more likely to have a T1a stage, and less likely to receive lymph node sampling. In the entire matched cohort, multivariate analysis found esophagectomy were associated with better overall survival (OS) (HR: 0.62, 95 % CI: 0.40-0.96, p = 0.032) than ER, but no significant difference in esophageal cancer-specific survival (ECSS) (HR: 1.37, 95 % CI: 0.64-2.96, p = 0.420) between the two procedures. The results were similar for subgroup analyses of stage T1b patients. However, ER and esophagectomy were associated with similar OS (HR: 0.74, 95 % CI: 0.41-1.36; p = 0.334) and ECSS (HR: 3.69, 95 % CI: 0.95-14.39; p = 0.060) in patients with stage T1a disease. In patients with stage T1 esophageal cancer, ER was similar to esophagectomy in terms of oncologic outcomes. More prospective studies should be implemented to determine the optimal treatment for T1b esophageal cancer patients with risk factors.

Prognostic evaluation of esophageal cancer patients with stages I-III.

Purpose: The purpose of this study was to investigate the impact of clinicopathological factors and treatments on the overall survival (OS) and esophageal cancer-specific survival (ECSS) of stages I-III esophageal cancer (EC) patients and to establish a prognostic visual nomogram. Methods: We collected clinical data of patients diagnosed with stages I-III EC without receiving chemotherapy from 2004 to 2014 from the Surveillance, Epidemiology, and End Results (SEER) database. Prognoses were analyzed using the R language software, and nomograms were obtained according to the visual processing logistic regression model, which was verified using the Harrell C-index, receiver operating characteristic (ROC) curve, and calibration curve. Results: A total of 4,305 patients were selected, mostly white males. Most patients were over 60 years old and old age predicted poor prognosis. EC, primarily adenocarcinoma, occurred mostly in the lower third of the esophagus. About half of the patients had T1 (58.00%) and grade II (50.41%) cancer. Of all the patients, 2,448 was treated with surgery and the majority (n = 1,476; 64.85%) of these patients had stage I EC. Stages I-III patients underwent surgery had significantly better OS and ECSS, and endoscopic therapy was associated with the best outcome amongst all the surgical methods. 3.67% of the patients received radiotherapy, predominantly postoperative radiotherapy (2.69%). Older age, squamous cell carcinoma, overlapping lesion of the esophagus, and grades II and III were high-risk factors for poor OS and ECSS for stage I patients, whereas endoscopic therapy, esophagectomy, and esophagectomy with gastrectomy were low-risk factors. Stage II patients with older age, male sex, T3, N1, and grades II and III had shorter OS and ECSS, but patients with any surgical treatment had significantly longer OS and ECSS. T4, N1, and grade III correlated negatively with OS and ECSS in stage III patients, and any surgical treatment correlated positively with longer OS and ECSS. The OS and ECSS rates of stages I-III EC patients with a total score of more than 150 points in the nomogram were both only 40% after 3 years and 30% after 5 years. The C-index, ROC curve, and calibration curve indicated that the nomograms established in this study were suitable to assess patient prognosis. Conclusion: The nomogram established in this study is an effective clinical tool to predict the prognosis of stages I-III EC patients without chemotherapy.

Competing risk nomogram to predict cancer-specific survival in esophageal cancer during the intensity-modulated radiation therapy era: A single institute analysis.

The present study aimed to investigate the probability of cancer-associated mortality of patients with esophageal cancer undergoing intensity-modulated radiation therapy (IMRT), and to establish a competing risk nomogram to predict the esophageal cancer-specific survival (EC-SS) of these patients. A total of 213 patients with EC who underwent IMRT between January 2014 and May 2017 were selected to establish nomograms according to Fine and Gray's competing risk analysis. Predictive accuracy and discriminative ability of the model were determined using the concordance index (C-index), calibration curves and the area under receiver operating characteristic curves. Decision tree analysis was also constructed for patient grouping. With a median follow-up of 19 months (range, 3–50), the 2-year EC-specific mortality (EC-SM) and the non-esophageal cancer specific mortality (NEC-SM) of the cohort were 35.4 and 3.51%, respectively. Furthermore, an elevated 2-year EC-SM was observed in patients with tumor length ≥4.5 cm compared with patients with tumor length <4.5 cm (45.8% vs. 21.4%; P<0.001), patients with non-squamous cell carcinoma compared with patients with squamous cell carcinoma (49.9 vs. 33.7%; P=0.025) and patients with N3 stage (43.2%; P=0.005). The 2-year NEC-SM of patients with tumor length ≥4.5 cm was 6% vs. 0% in patients with tumor length <4.5 cm (P=0.016). Three independent risk factors for survival, including tumor length, histological type and N stage, were integrated to build competing nomograms for the EC-SS model (C-index=0.72; 95% confidence interval, 0.66–0.77). In addition, the nomograms displayed better discrimination power than the 7th edition of the Tumor-Node-Metastasis staging system for predicting EC-SS (area under the curve=0.707 vs. 0.634). Furthermore, the results from the classification tree analysis demonstrated that N stage was the initial node and that primary tumor length was a determinant for EC-SM in these patients. In conclusion, NEC-SM represented a competing event for patients with EC with a tumor length ≥4.5 cm. The competing risk nomograms may therefore be considered as convenient individualized predictive tools for cancer-specific survival in patients with EC undergoing IMRT treatment.

Competing Risk Nomogram to Predict Cancer-Specific Survival in Esophageal Cancer Patients During the Intensity-Modulated Radiation Therapy Era: A Single Institute Analysis

Recently, competing risk method based on the subdistribution hazard model is recommended to accurately determine the effects of risk factors on specific events, because it takes into account the informative nature of censoring. The aim of present study was to investigate the probability of cancer-specific mortality of esophageal cancer (ESC) patients undergoing intensity-modulated radiation therapy (IMRT) and establish a competing risk nomogram to predict esophageal cancer-specific survival (ESC-SS) of these patients. A total of 213 ESC patients undergoing IMRT were identified to establish nomograms based on Fine and Gray’s competing risk analysis. Predictive accuracy and discriminative ability of the model were performed using concordance index(C-index),calibration curve and the area under receiver operating characteristic (ROC) curve. Decision tree analysis was performed for patients grouping. With a median 19 month (range:3-50) follow-up, the 2-year ESC-specific mortality (ESC-SM) and non-cancer specific mortality (NC-SM) of the cohorts were 35.4% and 3.51% respectively, and elevated 2-year ESC-SM were observed in patients with tumor length≥4.5cm (45.8% vs. 21.4%, p<0.001), non-squamous cell carcinoma(non-SCC, 49.9% vs. 33.7%, p=0.025), and N3 stage (43.2%, p=0.005). The 2-year NC-SM was observed in tumor length≥4.5cm cohorts (6% vs. 0%, p=0.016). All validated factors including tumor length, histology type and N stage, were integrated into the competing nomograms into the ES-SCC model [concordance (c)-index=0.72, 95%CI: 0.66-0.77]. In addition, the nomograms displayed better discrimination power than 7th edition Tumor-Node-Metastasis (TNM) stage systems for predicting ESC-SS (the AUC value 0.707 vs. 0.634).The classification tree analysis also showed that N stage is the initial node, tumor length is also determinants for ESC-SM of this patients population. NC-SM represents a significant competing event for esophageal cancer with tumor length ≥4.5cm. The competing risk nomograms could be considered as convenient individualized predictive tools for cancer specific survival in esophageal cancer undergoing IMRT treatment.Abstract 2449; Table 1VariableUnivariateMultivariateSHR95%CIpSHR95%CIpGenderMale1---Female0.680.34-1.370.29---Age<601-≥600.840.54-1.330.47---Histologic TypesSCC11Non-SCC2.031.06-3.910.0342.711.48-4.930.001GradeHigh11Moderate/poor1.441.01-2.080.0461.140.75-1.740.61SurgeryYes11No0.620.40-0.960.0331.520.85-2.720.15Tumor length≤4.511＞4.5cm2.431.48-3.99《0.0011.801.03-3.160.04MetastasisYes11No2.121.08-4.130.0281.410.66-3.000.37 Open table in a new tab

Prognostic impact of examined lymph node count in pT1N0M0 esophageal cancer: A population-based study.

BackgroundResearch on the impact of examined lymph node (ELN) count on node‐negative esophageal cancer (EC) especially pT1N0M0 EC is inadequate. This study was designed to analyze the prognostic impact of ELN count on pT1N0M0 EC.MethodsData of resected pT1N0M0 EC patients between 1988 and 2015 were extracted from the United States Surveillance, Epidemiology, and End Results (SEER) database. The association between ELN count and overall survival (OS) or esophageal cancer‐specific survival (ECSS) were investigated. Factors that may predict the outcome were identified using the Kaplan‐Meier method and the Cox proportional‐hazards model.ResultsA total of 906 patients who underwent resection with at least one lymph node (LN) retrieved met our criteria. The cumulative 5‐year OS was 67.6%, while the cumulative 5‐year ECSS was 75.4%. X‐Tile analysis showed that 12 was the optimal cutoff value for ELN count in terms of both OS (χ2 = 28.764, P < 0.0001) and ECSS (χ2 = 15.668, P = 0.0026). A Kaplan‐Meier survival analysis and log‐rank comparison revealed that ELN > 12 was significantly associated with better OS (HR, 0.532; 95% CI, 0.421–0.672; P < 0.001) and ECSS (HR, 0.561; 95% CI, 0.420–0.749; P < 0.001) rates than ELN ≤12. The OS and ECSS benefit of increasing ELN count were also reflected in the multivariate analysis after adjustment for age, sex, race, marital status, location, T stage, tumor size, pathology, and differentiation.ConclusionsThese findings indicated that greater number of ELN count exhibits prognostic significance in pT1N0M0 EC. We recommend more than 12 LNs should be examined in pT1N0M0 EC.

Is the new distribution of early esophageal adenocarcinoma stages improving the prognostic prediction of the 8th edition of the TNM staging system for esophageal cancer?

The 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system released in 2017 reclassified the pTNM stage of early esophageal adenocarcinoma from stage IA in the 7th edition to stage IA and IB and from stage IB in the 7th edition to stage IC. In this study, we analyzed the reliability of the new staging system through clinical data analysis. We selected patient data from the Surveillance, Epidemiology, and End Results (SEER) database. From 2004 to 2014, data for a total of 714 patients were included in the study and were divided into groups representing stage IA (n=84), IB (n=386) and IC (n=244) according to the 8th edition. In the 8th edition, there was no significant difference between groups IA and IB in overall survival (OS) (P=0.331) or esophageal cancer-specific survival (ECSS) (P=0.341). However, the long-term survival rates of groups IA and IB were significantly higher than those of group IC. Cox regression analysis indicated that the use of new staging system does not affect prognosis. We also attempted to stratify the tumors by T stage and histological grade but found no significant difference. We used the SEER database to compare the staging of early esophageal adenocarcinomas between the 8th and 7th editions of the AJCC/UICC TNM staging system. Based on our data, the 8th edition is not superior to the 7th edition.

Neoadjuvant vs definitive concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma patients

BackgroundThe optimal treatment for locally advanced esophageal squamous cell carcinoma remains unclear. We compared the clinical outcomes of neoadjuvant concurrent chemoradiotherapy (CCRT) followed by esophagectomy [the surgery group] and CCRT without surgery [the CCRT group] in patients with squamous cell carcinoma from an Asian population.MethodsEligible patients diagnosed from 2008 to 2015 were identified through the Taiwan Cancer Registry. To balance observable potential confounders, we constructed a 1:1 propensity score-matched cohort [surgery vs CCRT]. We compared the hazard ratios between the surgery and CCRT groups for death using a robust variance estimator. We also evaluated the outcomes of patients for freedom from local regional recurrence (FFLRR) and esophageal cancer-specific survival (ECSS). Extensive supplementary analyses were performed to examine the robustness of our findings.ResultsOur study population included 298 patients balanced with respect to the observed covariables. The hazard ratio of death was 0.56 [95% confidence interval 0.42~0.75] when surgery was compared to CCRT. The results remained significant in the FFLRR and ECSS outcomes. In the supplementary analyses, our results also remained significant when additional covariables were taken into consideration or when the definition of the index date was changed.ConclusionsWhen compared to definitive CCRT, neoadjuvant CCRT followed by esophagectomy was associated with improved overall survival for locally advanced esophageal squamous cell carcinoma. However, given the nonrandomized nature of the study and the sensitivity to potentially unmeasured confounders, our results should be interpreted cautiously.

Esophageal cancer in patients under 50: a SEER analysis

Concomitant with rising rates of esophageal adenocarcinoma, there has been a significant increase of diagnoses among relatively younger individuals. However, most studies that focus on esophageal cancer (EC) in younger patients have had small sample sizes of patients treated at a single institute. The aim of this study was to analyze the clinical characteristics, outcomes and independent prognostic factors for EC in patients under 50-year-old using a large, multi-center dataset. The national Surveillance, Epidemiology, and End Results (SEER) database was analyzed for EC reported from 2004 to 2013. Patients were divided into two groups, those under 50-year-old and those 50 years or older, and comparisons were made regarding demographics, histology, stage distribution, treatment, overall survival (OS), and esophageal cancer-specific survival (ECSS). Multivariate Cox proportional hazard regression analyses were also used to identify independent prognostic factors. Among the 16,544 eligible patients, 1,385 (8.37%) were under 50 and 15,159 (91.63%) were over 50. Compared with the older group, patients under 50 were characterized by a higher frequency of males, lower esophagus involvement, adenocarcinoma histology, stage III/IV disease, and receiving esophagectomy or radiation therapy. The stage-wise OS and ECSS were significantly better in the younger group (P<0.001). The multivariate analysis indicated that African-American heritage, grade III or IV, later stage, and not undergoing surgical or radiation therapy were independent negative prognostic factors of ECSS for patients under 50. EC patients under 50-year-old had distinctive clinicopathological characteristics compared with patients over 50-year-old. Despite more often presenting with stage III and IV disease, survival rates were better in the younger cohort. Prognostic factors for ECSS in patients under 50 differed from those in all age patients.

Impact of prior malignancy on outcomes of stage IV esophageal carcinoma: SEER based study

ABSTRACT Introduction Usually, clinical trials on esophageal cancer exclude patients with a prior malignancy, assuming that this may influence survival outcomes. However, little is known about the impact of a prior malignancy on its prognosis. Methodology The Surveillance, Epidemiology, and End Results database (SEER) was used to review patients with stage IV squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus during 1973–2014. We calculated overall and esophageal cancer-specific survival using unadjusted Kaplan-Meier and multivariable covariate-adjusted Cox models. Results A total of 7,807 patients with stage IV SCC, and 11,238 patients with stage IV AC were reviewed, of which 652 and 840 patients, respectively, had a prior malignancy. Kaplan-Meier curves did not show difference in overall survival of SCC or AC in patients with prior malignancy. Stage IV AC patients with prior malignancy did not show different esophageal cancer-specific survival. However, esophageal cancer-specific survival was better among stage IV SCC patients with prior malignancy. Similar results were observed in Cox models after adjustment for: age, sex, race, marital status, grade, site in esophagus, and undergoing surgery. Conclusion Prior malignancy does not adversely impact survival of stage IV esophageal cancer. These results should be taken into consideration when designing clinical trials.

Endoscopic Treatment Versus Esophagectomy for Early-Stage Esophageal Cancer: a Population-Based Study Using Propensity Score Matching

BackgroundEndoscopic treatment (ET) is an alternative for selected patients with early-stage esophageal cancer. The primary aim of this study was to compare overall survival (OS) and esophageal cancer-specific survival (ECSS) of such patients after ET or esophagectomy. MethodsPropensity score matching (PSM) and Cox regression analysis were used to compare OS and ECSS of 2661 patients with ET or esophagectomy for early-stage (Tis–T1N0M0) disease. Patient information was retrieved from the Surveillance, Epidemiology, and End Results database. Subgroup analyses by T stage and tumor histology were also performed. ResultsThere were significant differences in age, sex ratio, year of diagnosis, cancer site, cancer stage, differentiation grade, tumor histology, tumor size, lymph nodes examined, and receipt of radiation therapy in the two treatment groups. PSM created 621 patient pairs. Multivariate analysis found no significant differences in OS (HR = 1.216, P = 0.279) or ECSS (HR = 0.692, P = 0.179) in the esophagectomy and ET groups. The results were similar for subgroup analyses limited to stage Tis, T1a, and T1b patients. ET was also associated with similar OS and ECSS in esophageal adenocarcinoma and squamous cell carcinoma patients. ConclusionIn this population-based study using PSM, patients with stage Tis and T1N0M0 esophageal cancer with ET had OS and ECSS comparable to those treated by esophagectomy after adjusting for clinical variables. The results support ET as an alternative to esophagectomy in early esophageal cancer.