No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Validation of the Eighth Clinical American Joint Committee on Cancer Stage Grouping for Esophageal Cancer
Future Oncology
Abstract
Aim:
To validate the American Joint Committee on Cancer (AJCC) clinical staging system for esophageal cancer using Surveillance, Epidemiology and End Results database.
Methods:
Cancer-specific survival analyses for clinically-staged patients with esophageal cancer according to both seventh and eighth editions were conducted through Kaplan-Meier analysis.
Results:
For cancer-specific survival according to both seventh and eighth clinical systems, p-values for pairwise comparisons were nonsignificant in many comparisons. C-index for adenocarcinoma was: 0.671 according to the seventh AJCC and 0.671 according to the clinical eighth AJCC. C-index for squamous cell carcinoma according to the seventh AJCC was: 0.634 and 0.643 according to clinical eighth AJCC.
Conclusion:
Minimal improvement was achieved by the eighth clinical AJCC staging system for esophageal cancer.
... While the clinical staging approach serves as a fundamental framework for assessing the prognosis of patients at various stages, its ability to predict survival in individuals with identical disease stages is restricted. Furthermore, some studies have provided evidence indicating that the clinical staging system lacks reliability in its ability to predict survival outcomes among individuals diagnosed with locally advanced EC [8][9][10]. ...
Objectives
The purpose of this study was to investigate the prognostic significance of radiomics in conjunction with hematological parameters in relation to the overall survival (OS) of individuals diagnosed with esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy (dCRT).
Methods
In this retrospective analysis, a total of 122 patients with locally advanced ESCC were included. These patients were randomly assigned to either the training cohort (n = 85) or the validation cohort (n = 37). In the training group, the least absolute shrinkage and selection operator (LASSO) regression was utilized to choose the best radiomic features for calculating the Rad-score. To develop a nomogram model, both univariate and multivariate analyses were conducted to identify the clinical factors and hematologic parameters that could predict the OS. The performance of the predictive model was evaluated using the C-index, while the accuracy was assessed through the calibration curve.
Results
The Rad-score was calculated by selecting 10 radiomic features through LASSO regression. OS was predicted independently by neutrophil-to-monocyte ratio (NMR) and Rad-score according to the results of multivariate analysis. Patients who had a Rad-score > 0.47 and an NMR > 9.76 were at a significant risk of mortality. A nomogram was constructed using the findings from the multivariate analysis. In the training cohort, the nomogram had a C-index of 0.619, while in the validation cohort, it was 0.573. The model’s accuracy was demonstrated by the calibration curve, which was excellent.
Conclusion
A prognostic model utilizing radiomics and hematologic parameters was developed, enabling the prediction of OS in patients with ESCC following dCRT.
Critical relevance statement
Patients with esophageal cancer who underwent definitive chemoradiotherapy may benefit from including CT radiomics in the nomogram model.
Key points
• Predicting the prognosis of ESCC patients before treatment is particularly important.
• Patients with a Rad-score > 0.47 and neutrophil-to-monocyte ratio > 9.76 had a high risk of mortality.
• CT-based radiomics nomogram model could be used to predict the survival of patients.
Graphical Abstract
... The screening items included: Complete blood count (CBC), comprehensive chemistry profile, esophageal barium swallow, upper gastrointestinal (GI) endoscopic ultrasonography (EUS) and biopsy and chest/upper abdomen computed tomography (CT) with intravenous (IV) contrast. The histopathologic features of cancerous specimens were classified in accordance with the 8th AJCC (American Joint Committee on Cancer) criteria on esophageal cancer (22,23), and the TNM staging system as well (24). Patients receiving induction chemotherapy, however, would not undergo surgery until down-staging was achieved and surgical indication was met. ...
The present study aimed to introduce a novel method of cervical esophagogastric anastomosis, so-called 'modified one-piece mechanical anastomosis' (MOMA) in McKeown esophagogastrectomy and to compare its feasibility, efficacy and safety with those of 'conventionally double-layer hand-sewn anastomosis' (CDHA). Between March 2016 and March 2018, 80 consecutive patients with thoracic esophageal squamous cell carcinoma undergoing McKeown esophagogastrectomy with a curative intent were included in the present study. Among them, 40 received MOMA and the other 40 received CDHA. Their medical records, including operation time, anastomotic time, estimated blood loss, postoperative complications within 30 days, as well as survival rate, were retrospectively reviewed, analyzed and compared. Total operation time, anastomotic time and estimated blood loss in the MOMA group were significantly decreased compared with those in the CDHA group (207.73±2.66 vs. 225.40±3.43 min; 10.95±0.44 vs. 23.03±0.47 min; 144.50±21.14 vs. 241.75±23.75 ml; all P<0.01). Anastomotic leakage was present in 1 patient in the CDHA group, but no patients in the MOMA group (P=1.000). Anastomotic stenosis was documented in 4 and 2 patients in the MOMA and CDHA group, respectively (P=0.392). The 30-day operative mortality was 0% and no significant difference was demonstrated in postoperative complications within groups (P>0.05). Furthermore, the disease-free and overall survival was compared by means of Kaplan-Meier survival estimates and log-rank tests and no statistical difference was determined (P=0.5114 and P=0.7875, respectively). McKeown esophagogastrectomy with MOMA may be a feasible, effective and reproducible alternative with relatively satisfactory postoperative outcomes for the treatment of TE-SCC, providing shorter operation and anastomosis times, and less estimated intraoperative blood loss.
... Although the clinical stage system provides important insights for evaluating outcomes of patients with different stages, its role in survival prediction among patients with the same disease stage is non-significant. Indeed, previous studies have shown that the clinical stage system fails to predict heterogeneous outcomes of patients with locally advanced disease following CCRT [6][7][8]. A variety of other clinical factors and biomarkers have also been assessed for their prognostic potential [9][10][11]. ...
Background
This study aimed to evaluate the predictive potential of contrast-enhanced computed tomography (CT)-based imaging biomarkers (IBMs) for the treatment outcomes of patients with oesophageal squamous cell carcinoma (OSCC) after definitive concurrent chemoradiotherapy (CCRT).
Methods
Altogether, 154 patients with OSCC who underwent definitive CCRT were included in this retrospective study. All patients were randomised to the training cohort (n = 99) or the validation cohort (n = 55). Pre-treatment contrast-enhanced CT scans were obtained for all patients and used for the extraction of IBMs. An IBM score, was constructed by using the least absolute shrinkage and selection operator with Cox regression analysis, which was equal to the log-partial hazard of the Cox model in the training cohort and tested in the validation cohort. IBM nomograms were built based on IBM scores for individualised survival estimation. Finally, a decision curve analysis was performed to estimate the clinical usefulness of the nomograms.
Results
Altogether, 96 IBMs were extracted from each contrast-enhanced CT scan. IBM scores were constructed from 11 CT-based IBMs for overall survival (OS) and 8 IBMs for progression-free survival (PFS), using the LASSO-Cox regression method in the training cohort. Multivariate analysis revealed that IBM score was an independent prognostic factor correlated with OS and PFS. In the training cohort, the C-indices of IBM scores were 0.734 (95% CI 0.664–0.804) and 0.658 (95% CI 0.587–0.729) for OS and PFS, respectively. In the validation cohort, C-indices were 0.672 (95% CI 0.578–0.766) and 0.666 (95% CI 0.574–0.758) for OS and PFS, respectively. Kaplan–Meier survival analysis showed a significant difference between risk subgroups in the training and validation cohorts. Decision curve analysis confirmed the clinical usefulness of the IBM score.
Conclusions
The IBM score based on pre-treatment contrast-enhanced CT could predict the OS and PFS for patients with OSCC after definitive CCRT. Further multicentre studies with larger sample sizes are warranted.
... The N stage has typically been de ned by the American Joint Committee on Cancer (AJCC) as the number of positive lymph node (PLN),but a new N stage was proposed by the Japanese Society for Esophageal Diseases (JSED) [3,4]. The JSED N stage is de ned according to the site of PLN. ...
Background:
The study aimed to propose a modified N stage of esophageal cancer (EC) on the basis of the number of positive lymph node (PLN) and the number of negative lymph node (NLN) simultaneously.
Method:
Data from 13,491 patients with EC registered in the SEER database were reviewed. The parameters related to prognosis were investigated using a Cox proportional hazards regression model. A modified N stage was proposed based on the cut-off number of the re-adjusted ratio of the number of PLN (numberPLN) to the number of NLN (numberNLN), which were derived from the comparison of the hazard rate (HR) of numberPLN and numberNLN. The modified N stage was confirmed using the cross-validation method with the training and validation cohort, and it was also compared to the N stage from the American Joint Committee on Cancer (AJCC) staging system (7th edition) using Receiver Operating Characteristic (ROC) curve analysis.
Results:
The numberPLN on prognosis was 1.042, while numberNLN was 0.968. The modified N stage was defined as follows: N1 stage: the ratio range was from 0 to 0.21; N2 stage: more than 0.21, but no more than 0.48; N3 stage: more than 0.48. The log-rank test indicated that significant survival differences were confirmed among the N1, N2 and N3 sub-groups of patients in the training population. The difference of all the patients using the modified N stage method were more significant than AJCC N stage. The result of ROC analysis indicated that the modified N stage could represent the N stage of EC more accurately.
Conclusion:
The modified N stage based on the re-adjusted ratio of numberPLN to numberNLN can evaluate tumor stage more accurately than the traditional N stage.
... However, at present, the definition of N stage is controversial. The N stage has typically been defined by the American Joint Committee on Cancer (AJCC) as the number of positive lymph node (PLN),but a new N stage was proposed by the Japanese Society for Esophageal Diseases (JSED) [3,4]. The JSED N stage is defined according to the site of PLN. ...
Background
The study aimed to propose a modified N stage of esophageal cancer (EC) on the basis of the number of positive lymph node (PLN) and the number of negative lymph node (NLN) simultaneously.
Method
Data from 13,491 patients with EC registered in the SEER database were reviewed. The parameters related to prognosis were investigated using a Cox proportional hazards regression model. A modified N stage was proposed based on the cut-off number of the re-adjusted ratio of the number of PLN (numberPLN) to the number of NLN (numberNLN), which were derived from the comparison of the hazard rate (HR) of numberPLN and numberNLN. The modified N stage was confirmed using the cross-validation method with the training and validation cohort, and it was also compared to the N stage from the American Joint Committee on Cancer (AJCC) staging system (7th edition) using Receiver Operating Characteristic (ROC) curve analysis.
Results
The numberPLN on prognosis was 1.042, while numberNLN was 0.968. The modified N stage was defined as follows: N1 stage: the ratio range was from 0 to 0.21; N2 stage: more than 0.21, but no more than 0.48; N3 stage: more than 0.48. The log-rank test indicated that significant survival differences were confirmed among the N1, N2 and N3 sub-groups of patients in the training population. The difference of all the patients using the modified N stage method were more significant than AJCC N stage. The result of ROC analysis indicated that the modified N stage could represent the N stage of EC more accurately.
Conclusion
The modified N stage based on the re-adjusted ratio of numberPLN to numberNLN can evaluate tumor stage more accurately than the traditional N stage.
... Although the clinical stage system provides important insights for evaluating outcomes of patients with different stages, its role in survival prediction among patients with the same disease stage is non-signi cant. Indeed, previous studies have shown that the clinical stage system fails to predict heterogeneous outcomes of patients with locally advanced disease following CCRT [6][7][8]. A variety of other clinical factors and biomarkers have also been assessed for their prognostic potential [9][10][11]. ...
Background: This study aimed to evaluate the predictive potential of contrast-enhanced computed tomography (CT)-based imaging biomarkers (IBMs) for the treatment outcomes of patients with oesophageal squamous cell carcinoma (OSCC) after definitive concurrent chemoradiotherapy (CCRT).
Methods: Altogether, 154 patients with OSCC who underwent definitive CCRT were included in this retrospective study. All patients were randomised to the training cohort (n=99) or the validation cohort (n=55). Pre-treatment contrast-enhanced CT scans were obtained for all patients and used for the extraction of IBMs. An IBM score, was constructed by using the least absolute shrinkage and selection operator with Cox regression analysis, which was equal to the log-partial hazard of the Cox model in the training cohort and tested in the validation cohort. IBM nomograms were built based on IBM scores for individualised survival estimation. Finally, a decision curve analysis was performed to estimate the clinical usefulness of the nomograms.
Results: Altogether, 96 IBMs were extracted from each contrast-enhanced CT scan. IBM scores were constructed from 11 CT-based IBMs for overall survival (OS) and 8 IBMs for progression-free survival (PFS), using the LASSO-Cox regression method in the training cohort. Multivariate analysis revealed that IBM score was an independent prognostic factor correlated with OS and PFS. In the training cohort, the C-indices of IBM scores were 0.734 (95%CI, 0.664–0.804) and 0.658 (95%CI, 0.587–0.729) for OS and PFS, respectively. In the validation cohort, C-indices were 0.672 (95%CI, 0.578–0.766) and 0.666 (95%CI, 0.574–0.758) for OS and PFS, respectively. Kaplan-Meier survival analysis showed a significant difference between risk subgroups in the training and validation cohorts. Decision curve analysis confirmed the clinical usefulness of the IBM score.
Conclusions: The IBM score based on pre-treatment contrast-enhanced CT could predict the OS and PFS for patients with OSCC after definitive CCRT. Further multicentre studies with larger sample sizes are warranted.
... The N stage has typically been de ned by the American Joint Committee on Cancer (AJCC) as the number of positive lymph node (PLN),but a new N stage was proposed by the Japanese Society for Esophageal Diseases (JSED) [3,4]. The JSED N stage is de ned according to the site of PLN. ...
Background: The study aimed to propose a modified N stage of esophageal cancer (EC) on the basis of the number of positive lymph node (PLN) and the number of negative lymph node (NLN) simultaneously.
Method: Data from 13,491 patients with EC registered in the SEER database were reviewed. The parameters related to prognosis were investigated using a Cox proportional hazards regression model. A modified N stage was proposed based on the cut-off number of the re-adjusted ratio of the number of PLN (numberPLN) to the number of NLN (numberNLN), which were derived from the comparison of the hazard rate (HR) of numberPLN and numberNLN. The modified N stage was confirmed using the cross-validation method with the training and validation cohort, and it was also compared to the N stage from the American Joint Committee on Cancer (AJCC) staging system (7th edition) using Receiver Operating Characteristic (ROC) curve analysis.
Results: The numberPLN on prognosis was 1.042, while numberNLN was 0.968. The modified N stage was defined as follows: N1 stage: the ratio range was from 0 to 0.21; N2 stage: more than 0.21, but no more than 0.48; N3 stage: more than 0.48. The log-rank test indicated that significant survival differences were confirmed among the N1, N2 and N3 sub-groups of patients in the training population. The difference of all the patients using the modified N stage method were more significant than AJCC N stage. The result of ROC analysis indicated that the modified N stage could represent the N stage of EC more accurately.
Conclusion: The modified N stage based on the re-adjusted ratio of numberPLN to numberNLN can evaluate tumor stage more accurately than the traditional N stage.
... Although the clinical stage system provides important insights for evaluating outcomes of patients with different stages, its role in survival prediction among patients with the same disease stage is non-signi cant. Indeed, previous studies have shown that the clinical stage system fails to predict heterogeneous outcomes of patients with locally advanced disease following CCRT [6][7][8]. A variety of other clinical factors and biomarkers have also been assessed for their prognostic potential [9][10][11]. ...
Background: This study aimed to evaluate the predictive potential of contrast-enhanced computed tomography (CT)-based imaging biomarkers (IBMs) for the treatment outcomes of patients with oesophageal squamous cell carcinoma (OSCC) after definitive concurrent chemoradiotherapy (CCRT).
Methods: Altogether, 154 patients with OSCC who underwent definitive CCRT were included in this retrospective study. All patients were randomised to the training cohort (n=99) or the validation cohort (n=55). Pre-treatment contrast-enhanced CT scans were obtained for all patients and used for the extraction of IBMs. An IBM score was constructed by using the least absolute shrinkage and selection operator with Cox regression analysis in the training cohort and tested in the validation cohort. IBM nomograms were built based on IBM scores for individualised survival estimation. Finally, a decision curve analysis was performed to estimate the clinical usefulness of the nomograms.
Results: Altogether, 96 IBMs were extracted from each contrast-enhanced CT scan. IBM scores were constructed from 11 CT-based IBMs for overall survival (OS) and 8 IBMs for progression-free survival (PFS), using the LASSO-Cox regression method in the training cohort. Multivariate analysis revealed that IBM score was an independent prognostic factor correlated with OS and PFS. In the training cohort, the C-indices of IBM scores were 0.734 (95%CI, 0.664–0.804) and 0.658 (95%CI, 0.587–0.729) for OS and PFS, respectively. In the validation cohort, C-indices were 0.672 (95%CI, 0.578–0.766) and 0.666 (95%CI, 0.574–0.758) for OS and PFS, respectively. Kaplan-Meier survival analysis showed a significant difference between risk subgroups in the training and validation cohorts. Decision curve analysis confirmed the clinical usefulness of the IBM score.
Conclusions: The IBM score based on pre-treatment contrast-enhanced CT could predict the OS and PFS for patients with OSCC after definitive CCRT. Further multicentre studies with larger sample sizes are warranted.
... Although the clinical stage system could provide important insights for evaluating outcomes of patients with different stages, its role in survival prediction among patients with the same disease stage is non-signi cant. Indeed, previous studies have shown that the clinical stage system fails to predict heterogeneous outcomes of patients with locally advanced disease following CCRT [6][7][8]. A variety of other clinical factors and biomarkers have also been assessed for their prognostic potential [9][10][11]. ...
Background: This study aimed to evaluate the predictive potential of contrast-enhanced computed tomography (CT)-based imaging biomarkers (IBMs) for the treatment outcomes of oesophageal squamous cell carcinoma (OSCC) patients after definitive concurrent chemoradiotherapy (CCRT).
Methods: Altogether, 154 patients with OSCC who underwent definitive CCRT were included in this retrospective study. All patients were separated randomly to a training cohort (n=99) and the validation cohort (n=55). Pre-treatment contrast-enhanced CT scans were obtained for all patients and used for the extraction of IBMs. An IBM score was constructed by using the least absolute shrinkage and selection operator with Cox regression analysis in the training cohort and tested in the validation cohort. IBM nomograms were built based on IBM scores for individualized survival estimation. Finally, a decision curve analysis was performed to estimate the clinical usefulness of the nomograms.
Results: Altogether, 96 IBMs were extracted from each contrast-enhanced CT scan. The IBM score constructed by 11 CT-based IBMs, using LASSO-Cox regression method in training cohort. The multivariate analysis revealed that IBM score was the independent prognostic factor correlated with overall survival (OS) and progression-free survival (PFS). In the training cohort, the C-indices of IBM scores were 0.734 (95%CI, 0.664–0.804) and 0.678 (95%CI, 0.607–0.745) for OS and PFS, respectively. In the validation cohort, C-indices were 0.672 (95%CI, 0.578–0.766) and 0.662 (95%CI, 0.573–0.751) for OS and PFS, respectively. Kaplan-Meier survival analysis showed significantly different between risk subgroups in training and validation cohort. The decision curve showed the clinical usefulness of IBM score.
Conclusions: The IBM score based on pre-treatment contrast-enhanced CT could predict the OS and PFS for patients with OSCC after definitive CCRT. Further multicentre studies with larger sample sizes are warranted.
... However, at present, the de nition of N stage is controversial. The N stage has typically been de ned by the American Joint Committee on Cancer (AJCC) as the number of positive lymph node (PLN),but a new N stage was proposed by the Japanese Society for Esophageal Diseases (JSED) [3,4]. The JSED N stage is de ned according to the site of PLN. ...
Objective: The study aimed to propose a modified Nodal stage of esophageal cancer (EC) on basis of the number of positive lymph node (PLN) and the number of negative lymph node (NLN) simultaneously.
Method: Data from 13,491 patients with EC registered in the SEER database were reviewed. The parameters related to prognosis were investigated using a Cox proportional hazards regression model. A modified N stage was proposed based on the cut-off number of the re-adjusted ratio of the number of PLN (numberPLN) to the number of NLN (numberNLN), which were derived from the comparison of the hazard rate (HR) of numberPLN and numberNLN. The modified N stage was confirmed using the cross-validation method with the training and validation cohort, and it was also compared to the N stage from the American Joint Committee on Cancer (AJCC) staging system (7th edition) using Receiver Operating Characteristic (ROC) curve analysis.
Results: The numberPLN on prognosis was 1.064, while numberNLN was 0.962. The modified N stage was defined as follows: N1 stage: the ratio range was from 0 to 0.08; N2 stage: more than 0.08, but no more than 0.63; N3 stage: more than 0.63. Cross-validation method within the cohort identified the predictive accuracy of this modified N stage, and ROC curve analysis demonstrated the relative superiority of the modified N stage over that of the AJCC N stage.
Conclusion: The modified N stage based on the re-adjusted ratio of numberPLN to numberNLN can evaluate tumor stage relative accurately than the traditional N stage.
... The N stage has typically been de ned by the American Joint Committee on Cancer (AJCC) as the number of positive lymph node (PLN),but a new N stage was proposed by the Japanese Society for Esophageal Diseases (JSED) [3,4]. The JSED N stage is de ned according to the site of PLN. ...
Objective:
The study aimed to propose a modified N stage of esophageal cancer (EC) on basis of based on the number of positive lymph node (PLN) and the number of negative lymph node (NLN) simultaneously.
Method:
Data from 13,491 patients with EC registered in the SEER database were reviewed. The parameters related to prognosis were investigated using a Cox proportional hazards regression model. A modified N stage was proposed based on the cut-off number of the re-adjusted ratio of the number of PLN (numberPLN) to the number of NLN (numberNLN), which derived from the comparison of the hezode rate (HR) of numberPLN and numberNLN. The modified N stage was confirmed using the cross-validation method with the training and validation cohort, and it was also compared to the N stage from the American Joint Committee on Cancer (AJCC) staging system (7th edition) using Receiver Operating Characteristic (ROC) curve analysis.
Results:
The numberPLN on prognosis was 1.042, while numberNLN was 0.968. The modified N stage was defined as follows: N1 stage: the ratio range was from 0 to 0.21; N2 stage: more than 0.21, but no more than 0.48; N3 stage: more than 0.48. Cross-validation method within the cohort identified the predictive accuracy of this modified N stage, and ROC curve analysis demonstrated the superiority of this modified N stage over that of the AJCC.
Conclusion:
The modified N stage based on the re-adjusted ratio of numberPLN to numberNLN can evaluate tumor stage more accurately than the traditional N stage.
... Although the clinical staging system could provide important insights for evaluating outcomes of patients with different stages, its role in survival prediction among patients with the same disease stage is insigni cant. Indeed, previous studies have shown that the clinical staging system fails to predict heterogeneous outcomes of patients with locally advanced disease after CCRT [6][7][8]. A variety of other clinical factors and biomarkers have also been assessed for their prognostic potential [9][10][11]. ...
Background: This study aimed to evaluate the predictive potential of contrast-enhanced computed tomography (CT)-based imaging biomarkers (IBMs) for the treatment outcomes of oesophageal squamous cell carcinoma (OSCC) patients after definitive concurrent chemoradiotherapy (CCRT).
Methods: A total of 151 ESCC patients who underwent definitive CCRT were included in this retrospective study. All patients were separated randomly to a training cohort (n=97) and the validation cohort (n=54). Pre-treatment contrast-enhanced CT scans were obtained for all patients and used for the extraction of IBMs. An IBM score was constructed by using the least absolute shrinkage and selection operator with logistic regression analysis in training cohort and tested in the validation cohort. IBMsnomograms were built based on IBM score. The concordance index (C-index) was used to assess the performance of the nomograms. Finally, decision curve analysis was performed to estimate the clinical usefulness of the nomograms.
Results: A total of 96 IBMs were extracted from each contrast-enhanced CT scan. The IBM score were consisted of 13 CT-based IBMs and were significantly correlated with 3-year overall survival (OS) and 3-year progression-free survival (PFS). Multivariate analysis revealed that IBM score was the independent prognostic factor. In the training cohort, the IBM score yielded an area under the curves (AUCs) of 0.802 (95% CI: 0.713–0.891, p<0.001) and 0.742 (95% CI: 0.620–0.889, p<0.001) in terms of 3-year OS and 3-year PFS, respectively. In validation cohort, the AUCs were 0.761(95% CI: 0. 639–0.900, p<0.001) and 0.761(95% CI: 0.629–0.893, p=0.001) for 3-year OS and 3-year PFS,respectively. Kaplan-Meier survival analysis showed significantly different between risk subgroups in training and validation cohort. The nomograms were built based on the IBM score showed good discrimination. In the training cohort, with the C-indices of IBMsnomograms were 0.732 (95%CI, 0.661–0.803) and 0.670(95%CI, 0.595–0.745) for OS and PFS, respectively. In the validation cohort C-indices were 0.677(95%CI, 0.583–0.771) and 0.678(95%CI, 0.591–0.765) for OS and PFS, respectively. The decision curve showed the clinical usefulness of nomograms.
Conclusions: TheIBM score based on pre-treatment contrast-enhanced CT could predict the 3-year OS and 3-year PFS for OSCC patients after definitive CCRT. Further multicenter studies with larger sample sizes are warranted.
Objective:
The study aimed to propose a modified Nodal stage of esophageal cancer (EC) on basis of the number of positive lymph node (PLN) and the number of negative lymph node (NLN) simultaneously.
Method:
Data from 13,491 patients with EC registered in the SEER database were reviewed. The parameters related to prognosis were investigated using a Cox proportional hazards regression model. A modified N stage was proposed based on the cut-off number of the re-adjusted ratio of the number of PLN (numberPLN) to the number of NLN (numberNLN), which were derived from the comparison of the hazard rate (HR) of numberPLN and numberNLN. The modified N stage was confirmed using the cross-validation method with the training and validation cohort, and it was also compared to the N stage from the American Joint Committee on Cancer (AJCC) staging system (7th edition) using Receiver Operating Characteristic (ROC) curve analysis.
Results:
The numberPLN on prognosis was 1.064, while numberNLN was 0.962. The modified N stage was defined as follows: N1 stage: the ratio range was from 0 to 0.08; N2 stage: more than 0.08, but no more than 0.63; N3 stage: more than 0.63. Cross-validation method within the cohort identified the predictive accuracy of this modified N stage, and ROC curve analysis demonstrated the relative superiority of the modified N stage over that of the AJCC N stage.
Conclusion:
The modified N stage based on the re-adjusted ratio of numberPLN to numberNLN can evaluate tumor stage relative accurately than the traditional N stage.
The new 8th edition of the TNM classification system for esophageal and cardia or esophagogastric junction cancer provides important innovations in the TNM stages. Two classifications are presented, updated by stages, clinical (cTNM) and pathological (pTNM) methods, together with another pathological classification applicable to cases receiving neoadjuvant treatment (ypTNM). There is a notable increase in complexity compared to previous versions, but it is still early to determine whether the current modifications will result in a clear improvement in the prognostic discrimination of survival among the patient groups (which is their main objective), although the initial expectations are favorable.
Resumen
La nueva 8.ª edición del sistema de clasificación TNM para el cáncer de esófago y cardias, o de la unión esofagogástrica, aporta importantes novedades en la confección de los estadios TNM. Se presentan 2 clasificaciones actualizadas por estadios, clínicos (cTNM) y patológicos (pTNM), junto a otra clasificación patológica aplicable a los casos que reciben tratamiento neoadyuvante (ypTNM). Hay un notable aumento de la complejidad con respecto a versiones anteriores, pero aún es pronto para conocer si las actuales modificaciones redundarán, como es su objetivo principal, en una manifiesta mejora de la discriminación pronóstica de la supervivencia entre los grupos de pacientes que configuran, si bien las expectativas iniciales son favorables.
Aim:
To evaluate the accuracy of contemporary N-staging and provide radiological-pathological correlation in patients with lymph node metastases (LNMs) that were radiologically staged N0.
Materials and methods:
One hundred and twelve patients were included who underwent surgery alone (n=41) or neoadjuvant therapy (n=71) between October 2010 and December 2015. Contrast-enhanced computed tomography (CECT), endoscopic ultrasound (EUS), and combined positron-emission tomography (PET) and CT N-stage were compared to pathological N-stage [node-negative (N0) versus node-positive (N+) groups]. Fifty LNMs from 15 patients preoperatively staged as N0 were measured and the maximum size recorded.
Results:
Accuracy, sensitivity, and specificity of N0 versus N+ disease with CECT, EUS, and PET/CT was 54.5%, 39.7% and 77.3%, 55.4%, 42.6% and 75%, and 57.1% 35.3%, and 90.9%, respectively. All techniques were more likely to under-stage nodal disease; CECT (X(2) 32.890, df=1, p<0.001), EUS (X(2) 28.471, df=1, p<0.001), and PET/CT (X(2) 50.790, df=1, p<0.001). PET/CT was more likely to under-stage nodal disease than EUS (p=0.031). Median LNM size was 3?mm, with 41 (82%) of LNMs measuring <6?mm and 22 (44%) classified as micro-metastases (?2?mm).
Conclusion:
This study has demonstrated poor N-staging accuracy in the modern era of radiological staging. Eighty-two percent of LNMs measured <6?mm, making direct identification extremely challenging on medical imaging. Future research should focus on investigating and developing alternative surrogate markers to predict the likelihood of LNMs.
To evaluate the prognostic factors and tumor stages of the 7(th) edition TNM classification for esophageal cancer.
In total, 1033 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgical resection with or without (neo)adjuvant therapy between January 2003 and June 2012 at the Thoracic Surgery Department II of the Beijing Cancer Hospital, Beijing, China were included in this study. The following eligibility criteria were applied: (1) squamous cell carcinoma of the esophagus or gastroesophageal junction identified by histopathological examination; (2) treatment with esophagectomy plus lymphadenectomy with curative intent; and (3) complete pathologic reports and follow-up data. Patients who underwent non-curative (R1) resection and patients who died in hospital were excluded. Patients who received (neo)adjuvant therapy were also included in this analysis. All patients were restaged using the 7(th) edition of the Union for International Cancer Control and the American Joint Committee on Cancer TNM staging systems. Univariate and multivariate analyses were performed to identify the prognostic factors for survival. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to evaluate differences between the subgroups.
Of the 1033 patients, 273 patients received (neo)adjuvant therapy, and 760 patients were treated with surgery alone. The median follow-up time was 51.6 mo (range: 5-112 mo) and the overall 5-year survival rate was 36.4%. Gender, "pT" and "pN" descriptors, (neo)adjuvant therapy, and the 7(th) edition TNM stage grouping were independent prognostic factors in the univariate and multivariate analyses. However, neither histologic grade nor cancer location were independent prognostic factors in the univariate and multivariate analyses. The 5-year stage-based survival rates were as follows: IA, 84.9%; IB, 70.9%; IIA, 56.2%; IIB, 43.3%; IIIA, 37.9%; IIIB, 23.3%; IIIC,12.9% and IV, 3.4%. There were significant differences between each adjacent staging classification. Moreover, there were significant differences between each adjacent pN and pM subgroup. According to the pT descriptor, there were significant differences between each adjacent subgroup except between pT3 and pT4 (P = 0.405). However, there was no significant difference between each adjacent histologic grade subgroup and between each adjacent cancer location subgroup.
The 7(th) edition is considered to be valid for patients with resected ESCC. However, the histologic grade and cancer location were not prognostic factors for ESCC.
BACKGROUND
The advantages of endoscopic ultrasound (EUS) and computed tomography (CT)–positron emission tomography (PET) with respect to survival for esophageal cancer patients are unclear. This study aimed to assess the effects of EUS, CT-PET, and their combination on overall survival with respect to cases not receiving these procedures.METHODS
Patients who were ≥66 years old when diagnosed with esophageal cancer were identified in the Surveillance, Epidemiology, and End Results–Medicare linked database. Cases were split into 4 analytic groups: EUS only (n = 318), CT-PET only (n = 853), EUS+CT-PET (n = 189), and no EUS or CT-PET (n = 2439). Survival times were estimated with the Kaplan-Meier method and were compared with the log-rank test for each group versus the no EUS or CT-PET group. Multivariate Cox proportional hazards models were used to compare 1-, 3-, and 5-year survival rates.RESULTSKaplan-Meier analyses showed that EUS, CT-PET, and EUS+CT-PET patients had improved survival for all stages (with the exception of stage 0 disease) in comparison with patients undergoing no EUS or CT-PET. Receipt of EUS increased the likelihood of receiving endoscopic therapies, esophagectomy, and chemoradiation. Multivariate Cox proportional hazards models showed that receipt of EUS was a significant predictor of improved 1- (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.39-0.59; P < .0001), 3- (HR, 0.57; 95% CI, 0.48-0.66; P < .0001), and 5-year survival (HR, 0.59; 95% CI, 0.50-0.68). Similar results were noted when the results were stratified on the basis of histology and for the CT-PET and EUS+CT-PET groups.CONCLUSIONS
Receipt of either EUS or CT-PET alone in esophageal cancer patients was associated with improved 1-, 3-, and 5-year survival. Future studies should identify barriers to the dissemination of these staging modalities. Cancer 2014. © 2014 American Cancer Society.
The new 7th edition of the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC) tumor, node, metastasis (TNM) staging system is the ratification of data-driven recommendations from the Worldwide Esophageal Cancer Collaboration database. Generalizability remains questionable for single institutions. The present study serves as a validation of the 7th edition of the TNM system in a prospective cohort of patients with predominantly adenocarcinomas from a single institution.
Included were patients who underwent transhiatal esophagectomy with curative intent between 1991 and 2008 for invasive carcinoma of the esophagus or gastroesophageal junction. Excluded were patients who had received neoadjuvant chemo(radio)therapy, patients after a noncurative resection and patients who died in the hospital. Tumors were staged according to both the 6th and the 7th editions of the UICC-AJCC staging systems. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed with a Cox regression model. The likelihood ratio chi-square test related to the Cox regression model and the Akaike information criterion were used for measuring goodness of fit.
A study population of 358 patients was identified. All patients underwent transhiatal esophagectomy for adenocarcinoma. Overall 5-year survival rate was 38%. Univariate analysis revealed that pT stage, pN stage, and pM stage significantly predicted overall survival. Prediction was best for the 7th edition, stratifying for all substages.
The application of the 7th UICC-AJCC staging system results in a better prognostic stratification of overall survival compared to the 6th edition. The fact that the 7th edition performs better predominantly in patients with adenocarcinomas who underwent a transhiatal surgical approach, in addition to findings from earlier research in other cohorts, supports its generalizability for different esophageal cancer practices.
Background:
Esophageal cancer represents a heterogeneous malignancy mostly diagnosed in advanced stages. Worldwide, squamous cell carcinomas (SCCs) continue to be the most prevalent subtype; however, in the Western countries, the incidence of adenocarcinomas is increasing and will exceed that of SCC in the near future. During the last decade, several landmark trials contributed to a better understanding of the disease and emphasized the importance of multimodal treatment protocols.
Summary:
With the introduction of perioperative or neoadjuvant approaches, the survival of both subtypes of esophageal cancer has significantly improved. Several trials confirmed a survival benefit for perioperative chemotherapy or neoadjuvant chemoradiation, respectively, for patients with resectable locally advanced adenocarcinomas. However, the question of whether perioperative chemotherapy or neoadjuvant chemoradiation is more effective for the long-term survival in this population has yet to be fully elucidated. In SCCs, neoadjuvant chemoradiation followed by surgery or definitive chemoradiation in case of functional inoperability represent the preferred treatment options. Compared to neoadjuvant protocols, adjuvant chemotherapy or chemoradiation have only minor effects and are associated with enhanced toxicities. Current preclinical and clinical trials investigate efficacy and tolerability of novel drugs aiming to modulate immune check-points and dual inhibition of HER2. In this "to-the-point" article, we review the current standard and summarize the most recent and encouraging therapeutic advances in esophageal cancer. Multimodal treatment approaches for esophageal cancer should be discussed in a multidisciplinary team based on histology, tumor localization, and patient performance status. Neoadjuvant chemoradiation is beneficial for patients with locally advanced SCC and adenocarcinomas of the esophagus and the gastroesophageal junction (GEJ), with perioperative chemotherapy representing a valid alternative for GEJ adenocarcinomas. Combination therapies are indicated for metastatic adenocarcinomas, while the benefit of palliative chemotherapy in SCC remains controversial. Trastuzumab is indicated in HER2+ metastatic adenocarcinomas.
We report analytic and consensus processes that produced recommendations for neoadjuvant pathologic stage groups (ypTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 7,773 had pathologic assessment after neoadjuvant therapy. Risk-adjusted survival for each patient was developed. Random forest analysis identified data-driven neoadjuvant pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. An additional analysis produced data-driven anatomic neoadjuvant pathologic stage groups based only on ypT, ypN, and ypM categories. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus neoadjuvant pathologic stage groups. Grade and location were much less discriminating for stage grouping ypTNM than pTNM. Data-driven stage grouping without grade and location produced nearly identical groups for squamous cell carcinoma and adenocarcinoma. However, ypTNM groups and their associated survival differed from pTNM. The need for consensus process was minimal. The consensus groups, identical for both cell types were as follows: ypStage I comprised ypT0-2N0M0; ypStage II ypT3N0M0; ypStage IIIA ypT0-2N1M0; ypStage IIIB ypT3N1M0, ypT0-3N2, and ypT4aN0M0; ypStage IVA ypT4aN1-2, ypT4bN0-2, and ypTanyN3M0; and ypStage IVB ypTanyNanyM1. Absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories ypTisN0-3M0 and ypT0N0-3M0, dissimilar stage group compositions, and markedly different early- and intermediate-stage survival necessitated a unified, unique set of stage grouping for patients of either cell type who receive neoadjuvant therapy.
We report analytic and consensus processes that produced recommendations for pathologic stage groups (pTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 13,300 without preoperative therapy had pathologic assessment after esophagectomy or endoscopic treatment. Risk-adjusted survival for each patient was developed using random survival forest analysis to identify data-driven pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus pathologic stage groups. For pT1-3N0M0 squamous cell carcinoma (SCC) and pT1-2N0M0 adenocarcinoma, pT was inadequate for grouping; subcategorizing pT1 and adding histologic grade enhanced staging; cancer location improved SCC staging. Consensus eliminated location for pT2N0M0 and pT3N0M0G1 SCC groups, and despite similar survival, restricted stage 0 to pTis, excluding pT1aN0M0G1. Metastases markedly reduced survival; pT, pN, and pM sufficiently grouped advanced cancers. Stage IIA and IIB had different compositions for SCC and adenocarcinoma, but similar survival. Consensus stage IV subgrouping acknowledged pT4N+ and pN3 cancers had poor survival, similar to pM1. Anatomic pathologic stage grouping, based on pTNM only, produced identical consensus stage groups for SCC and adenocarcinoma at the cost of homogeneity in early groups. Pathologic staging can neither direct pre-treatment decisions nor aid in prognostication for treatment other than esophagectomy or endoscopic therapy. However, it provides a clean, single therapy reference point for esophageal cancer.
We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was “pinched,” with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved.
Purpose:
The extremely high incidence of esophageal cancer in certain rural areas of China has prompted significant intellectual curiosity and research efforts both in China and abroad.
Methods:
We summarize the research progress over the past several decades in high-risk areas (Linxian, Cixian, Shexian, and Yanting) based on literature research and our field trip (2012-2013).
Results:
Considerable progress in clarifying the environmental risk factors and pathogenesis of esophageal cancer in high-risk areas has been achieved over the past several decades. Epidemiologic evidence suggests that carcinogen exposure and nutritional deficiency, rather than smoking and drinking, may be the major risk factors for esophageal cancer in the Taihang Mountains region, where the incidence of esophageal cancer is among the highest in the world. Two genome-wide association studies have identified variants in PLCE1 at 10q23 that are significantly associated with esophageal cancer risk. Recent whole-exome studies have revealed a comprehensive mutation pattern, in which the C>T transition is the predominant mutation type.
Conclusions:
Despite extensive research, the main causative factors that contribute to esophageal cancer in high-risk areas have not yet been elucidated. Challenges in this research area include determining the causative role of nitrosamine, identifying other potential carcinogens, and conducting fruitful international collaborative studies based on a multidisciplinary approach. Increased international collaboration will contribute to a better understanding of the etiology of esophageal cancer.
This primer for eighth edition staging of esophageal and esophagogastric epithelial cancers presents separate classifications for the clinical (cTNM), pathologic (pTNM), and postneoadjuvant pathologic (ypTNM) stage groups, which are no longer shared.
For pTNM, pT1 has been subcategorized as pT1a and pT1b for the subgrouping pStage I adenocarcinoma and squamous cell carcinoma. A new, simplified esophagus-specific regional lymph node map has been introduced. Undifferentiated histologic grade (G4) has been eliminated; additional analysis is required to expose histopathologic cell type. Location has been removed as a category for pT2N0M0 squamous cell cancer. The definition of the esophagogastric junction has been revised. ypTNM stage groups are identical for both histopathologic cell types, unlike those for cTNM and pTNM.
Background:
To assess and evaluate the prognostic value of the 7(th) edition of the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC) tumor, node, metastasis (TNM) staging system for Chinese patients with esophageal cancer in comparison with the 6(th) edition.
Methods:
A retrospective review was performed on 766 consecutive esophageal cancer patients treated with esophagectomy between 2008 and 2012. Patients were staged according to the 6(th) and 7(th) editions for esophageal cancer respectively. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed using Cox regression model.
Results:
Overall 3-year survival rate was 59.5%. There were significant differences in 3-year survival rates among T stages both according to the 6(th) edition and the 7(th) edition (P<0.001). According to the 7(th) edition, the 3-year survival rates of N0 (75.4%), N1 (65.2%), N2 (39.7%) and N3 (27.3%) patients were significant differences (P<0.001). Kaplan-Meier curve revealed a good discriminatory ability from stage I to IV, except for stage IB, IIA and IIB in the 7(th) edition staging system. Based on the 7(th) edition, the degree of differentiation, tumor length and tumor location were not independent prognostic factors on multivariate analysis. The multivariate analyses suggested that pT-, pN-, pTNM-category were all the independent prognostic factors based on the 6(th) and 7(th) edition staging system.
Conclusions:
The 7(th) edition of AJCC TNM staging system of esophageal cancer should discriminate pT2-3N0M0 (stage IB, IIA and IIB) better when considering the esophageal squamous cell cancer patients. Therefore, to improve and optimize the AJCC TNM classification for Chinese patients with esophageal cancer, more considerations about the value of tumor grade and tumor location in pT2-3N0M0 esophageal squamous cell cancer should be taken in the next new TNM staging system.
Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ.
Copyright © 2015 by the National Comprehensive Cancer Network.