Abstract
Background:
While sub-2 cm pancreatic neuroendocrine tumors (NETs) are often observed, small bowel-NETs undergo resection and lymphadenectomy regardless of size. Aim was to define the natural history of duodenal (D-NETs), determine the role of resection, and define the factors associated with overall survival (OS) after resection.
Methods:
National Cancer Database (2004-2014) was queried for the patients with nonmetastatic/nonfunctional D-NETs. Local resection (LR): local excision/polypectomy/excisional biopsy. Anatomic resection (AR): radical surgery. Tumor size was divided into less than 1cm, 1 to 2 cm, and ≥2 cm. Propensity score weighting was used to create balanced resection and no-resection cohorts. The primary endpoint was OS.
Results:
Among 5502 patient, the median age was 65 years. The median follow-up was 49 months. The median tumor size was 0.8 cm. Resection was performed in 72% (n = 3954; LR: 61%, AR: 39%). Lymph node (LN) resection was performed in 26% (43% had metastasis). A total of 74% had negative margins. Resection and no-resection cohorts were propensity score weighted for age/sex/race/Charlson-Deyo score/tumor grade (all independently associated with OS on multivariable analysis). Resection was associated with improved median OS compared to no resection in all sizes (<1 cm: median not reached vs 194 months; 1-2 cm: median not reached vs 56 months; >2 cm: median not reached vs 90 months; all P < .01). Subset analysis of each resection size cohort demonstrated that neither type of resection, LN retrieval, LN positivity, or margin status was associated with OS (all P > .05).
Conclusion:
Patients with nonmetastatic and nonfunctional D-NETS should be considered for resection regardless of tumor size. Given the lack of prognostic value, the resection type and extent of LN retrieval should be tailored to each patient’s clinical picture and safety profile.
Keywords: duodenal NETs, neuroendocrine tumors, small bowel NET
1 |. INTRODUCTION
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogenous group of neoplasms that arise from Kulchistsky or enterochromaffin cells in the gastrointestinal tract.1,2 Although the majority are largely indolent, the biologic behavior of GEP-NETs and their associated outcomes vary widely based on anatomic location and size of the primary tumor. To address the challenges that arise from the heterogeneity of these tumors, both the European Neuroendocrine Tumor Society (ENETS) and the North American Neuroendocrine Tumor Society (NANETS) have developed consensus guidelines for the diagnosis and management of GEP-NETs based on primary tumor site.3–6 Although initial guidelines considered duodenal neuroendocrine tumors (D-NETs) as a subset of small bowel GEP-NETs, updated guidelines acknowledge that D-NETs behave biologically different and are subject to different staging and management recommendations.
Pancreas neuroendocrine tumors (P-NETs) are the most common subgroup of GEP-NETs. Several clinicopathologic variables including tumor size and margin status have been found to be predictors of survival.7–12 However, the prognostic importance of nodal metastasis has remained controversial in several recent population-based studies.13–18 As a result, while early ENETS recommendations defined surgery as the only acceptable option for P-NETs, most recent guidelines recommend watchful observation in selected patients who might not benefit from immediate intervention.4 Despite a 6% to 10% risk of nodal metastasis reported in most surgical series, updated ENETS guidelines suggest that observation is reasonable for small, <2 cm tumors due to their excellent long-term survival particularly when considering the known morbidity of pancreatic surgery.4,18–21 Conversely, given their established propensity for distant metastasis, an oncologic resection is recommended for P-NETs ≥ 2 cm and operative approach spans enucleation with formal lymphadenectomy to anatomic resection (AR) including pancreaticoduodenectomy or distal pancreatectomy.4
In contrast to P-NETs, significant predictors of survival for small bowel neuroendocrine tumors (SB-NETs) include lymph node and distant metastasis for all tumor size categories.22 As a result, management guidelines for this group vary considerably from those of P-NETs. Considering improved 5- and 10-year overall survival (OS) after locoregional control for stage I-III patients, current ENETS recommendations for SB-NETs include routine segmental resection with wide lymphadenectomy regardless of the size of the primary tumor.5,23
When compared with pancreas and SB-NETs, the clinical behavior and clinicopathologic predictors of survival for D-NETs are less well defined. In addition, as a result of their low incidence, few studies have investigated the rationale for resection versus careful observation. The anatomic location of D-NETs between the pancreas and small bowel, however, highlights that the optimal management strategy for these tumors may lie somewhere between the guidelines for pancreas and SB-NETs. The prognostic role of lymph node metastasis in D-NETs is not well established in the literature and consequently the need for and extent of resection remains a matter of debate. While some have advocated for a formal pancreaticoduodenectomy and lymph node retrieval, others argue that formal resection carries high morbidity and may not be necessary given the lack of literature to support lymphadenectomy.1,2 Despite this controversy, current ENETs consensus guidelines recommend endoscopic mucosal resection for small less than 1 cm, nonfunctioning D-NETs as they have been shown to have a low rate of nodal disease ranging from 2% to 4.7%. As tumors greater than 2 cm have a higher risk of nodal involvement at approximately 20%, guidelines recommend routine radical resection with lymphadenectomy.24 For the management of 1- to 2-cm tumors, however, there is no firm consensus and management is largely based on tumor location and presence of nodal involvement on imaging.
Understanding the expected disease process for D-NETs is essential to guiding the development of definitive management strategies. To better define the prognostic characteristics and natural history of this rare disease, we reviewed data from a large, national cancer registry. The objective of the current study was to define the outcomes of D-NETs in a size-stratified analysis, and examine the role of curative-intent resection and the need for lymphadenectomy in a propensity score-weighted sample.
2 |. METHODS
2.1 |. Data source
The National Cancer Database (NCDB) is a hospital-based registry, a joint program of the American College of Surgeons Committee on Cancer and the American Cancer Society, with data sources from more than 1500 Commission on Cancer-accredited hospitals.25 A query of the NCDB registry from 2004 to 2014 was performed to identify patients with nonfunctional D-NETs according to ICD-3 codes including 8240 (carcinoid not otherwise specific) and 8246 (neuroendocrine carcinoma). The analysis further excluded patients with metastatic disease, palliative resections, or 30-day mortality. Patient demographics included age, race, sex, Charlson-Deyo score, and survival time in months. Clinicopathologic variables included tumor size, tumor grade, American Joint Committee on Cancer (AJCC) clinical and pathologic T and N stage, lymphovascular invasion, lymph node retrieval, and lymph node positivity. Tumor size was divided into three categories (<1, 1-2, and ≥2 cm). The type of operation was defined by site-specific surgery codes as provided by the NCDB. Local resection (LR) was defined as local tumor excision, electrocautery, laser ablation, polypectomy, or excisional biopsy. AR was defined as simple or partial removal, total surgical removal, debulking, or radical surgery.
2.2 |. Statistical analysis
Statistical analysis was conducted using SAS, version 9.4 (SAS Institute), and SAS macros or software developed at the Biostatistics and Bioinformatics at Winship Cancer Institute.26 Statistical significance was predefined as 2-tailed P < .05. Descriptive statistics for each variable were reported. The patients were divided into resection and no-resection cohorts. The χ2 test was used for comparison of discrete variables and the ANOVA test was used for comparison of continuous variables between the two cohorts. OS was calculated as the time from 6 months after diagnosis to the date of death or date of last available follow-up. Left truncation at 6 months was performed as 98% of patients who underwent resection had surgery performed within 6 months of initial diagnosis. This reduced guarantee-time bias between the resection and the no-resection cohorts.27 The median follow-up time was calculated based on the reversed Kaplan-Meier (KM) method. Univariate Cox regression was used to identify clinicopathologic factors associated with OS. Results were reported as hazard ratios (HR) with a 95% confidence interval (CI). A multivariable Cox proportional hazard model for OS was produced by backward elimination steps with an alpha level of 0.2 as removal criteria.
A propensity score overlap weighting schema was implemented to reduce selection bias in survival analysis between resection and no-resection cohorts. Propensity scores (PS) reflecting the conditional probability of undergoing resection were calculated by logistic regression. Patients in the resection cohort were assigned a weight with value 1-PS, while patients in the no-resection cohort were assigned a weight with value PS. The propensity model included variables independently associated with OS including age, sex, race, Charlson-Deyo score, and tumor grade. This weighting schema created a weighted sample of almost perfectly balanced covariates between the resection and no-resection cohorts. Cox regression and KM method were performed within the weighted sample to compare survival curves by study cohorts. Subgroup analyses within the resection cohort and by each stratum of tumor size were performed to evaluate the prognostic effect of type of resection, lymph node retrieval, lymph node positivity, or margin status.
3 |. RESULTS
3.1 |. Demographic and clinicopathologic characteristics
A total of 5502 patients with nonmetastatic D-NETs were identified in the NCDB. The median patient age at diagnosis was 65 years (interquartile range: 56-73) with a similar distribution of female (n = 2657, 48%) and male (n = 2845, 52%) patients. Median tumor size was 0.8 cm with 2558 (47%) tumors measuring greater than 1cm, 744 (14%) tumors measuring 1 to 1.99 cm, and 621 (11%) tumors measuring 2 cm or greater; 20% did not have size data available. Median follow-up for the entire cohort was 49 months (95% CI: 47-50). Data on complications and recurrence were not available from the NCDB source to evaluate.
Among all patients, 3954 (72%) underwent resection of which 2423 (61%) had LR and 1531 (39%) had AR. Patients who underwent resection compared with those who did not undergo resection were younger with an average age at diagnosis of 63 years vs 67 years (P <.01), had lower Charlson-Deyo scores (P < .01), more well-differentiated tumors (45% vs 33%; P < .01), and smaller average tumor size (1.35 cm vs 2.01 cm; P < .01). Within the resection cohort, at least one lymph node was retrieved in 1040 (26%), and among these patients, the average number of nodes examined was 1.5 ± 4.9 and 445 (43%) had lymph node metastases. On final pathology, negative margins were achieved in 2940 (74%) patients and a large proportion of patients had well-differentiated tumors (n = 1764, 45%). A summary of demographic and clinicopathologic variables for all patients and for the resection vs no-resection cohorts is presented in Table 1.
TABLE 1.
Demographic and clinicopathologic factors of the entire cohort and comparing resection vs no-resection cohorts
| All patients | Resection | No resection | Resection vs no-resection P value | |
|---|---|---|---|---|
| n = 5502 | n = 3954 | n = 1548 | ||
| Demographic variables | ||||
| Age at diagnosis (mean ± std) | 64 ± 12.9 | 63 ± 12.4 | 67 ± 13.4 | <.01 |
| Sex | ||||
| Female | 2657 (48) | 1904 (48) | 753 (49) | .74 |
| Male | 2845 (52) | 2050 (52) | 795 (51) | |
| Race | ||||
| White | 3855 (70) | 2832 (72) | 1023 (66) | <.01 |
| Black | 1366 (25) | 904 (22) | 462 (30) | |
| Other | 281 (5) | 218 (6) | 63 (4) | |
| Charlson-Deyo score | ||||
| 0 | 3657 (66) | 2681 (68) | 978 (63) | <.01 |
| 1 | 1257 (23) | 899 (23) | 358 (23) | |
| 2 | 588 (11) | 374 (9) | 214 (14) | |
| Clinicopathologic factors | ||||
| Tumor size (cm) | ||||
| <1cm | 2558 (47) | 2121 (54) | 437 (28) | <.01 |
| 1-1.99 cm | 744 (14) | 630 (16) | 114 (7) | |
| ≥2 cm | 621 (11) | 473 (12) | 148 (10) | |
| Grade | ||||
| Well differentiated | 2278 (41) | 1764 (45) | 514 (33) | <.01 |
| Moderately differentiated | 266 (5) | 217 (6) | 49 (3) | |
| Poorly/undifferentiated | 65 (1) | 46 (1) | 19 (1) | |
| Lymph nodes examined | 1040 (26) | |||
| Lymph node positive | … | 445 (43) | … | … |
| # Sampled lymph nodes (mean ± std) | … | 1.52 ± 4.87 | … | … |
| AJCC clinical T | ||||
| T1 | 1540 (28) | 1211 (31) | 339 (22) | <.01 |
| T2 | 392 (7) | 292 (7) | 100 (6) | |
| T3-4 | 100 (2) | 80 (2) | 20 (1) | |
| AJCC clinical N | ||||
| N0 | 2493 (45) | 1887 (48) | 606 (39) | <.01 |
| N1 | 119 (2) | 98 (2) | 20 (1) | |
| Lymph vascular invasion | 144 (3) | 141 (4) | 3 (0.002) | <.01 |
| Margin status | ||||
| Negative | … | 2940 (74) | … | … |
| Positive | … | 430 (11) | … | … |
| Type of resection | ||||
| Local resection | … | 2423 (61) | … | … |
| Anatomic resection | … | 1531 (39) | … | … |
| Median follow-up in monthsa (95% CI) | 49 (47-50) | 47 (45-49) | 55 (52-58) | <.01 |
| Median OS in months | 122 | MNR | 74 | <.01 |
Note: Percentages in parentheses are based on cohort size and do not account for missing data. Bold indicates statistical significance.
Abbreviations: CI, confidence interval.
Estimated by reversed Kaplan-Meier method.
3.2 |. Survival analysis in entire cohort
Median OS was 122 months with 1-, 3-, and 5-year OS being 94.0%, 84.3%, 76.1%, respectively, for the entire cohort. In univariate analysis, older age, male sex, non-white race, higher Charlson-Deyo score, tumor size 2 cm or greater, and poorly or undifferentiated tumor grade were significant predictors of worse OS (all P < .05). Importantly, lymph node positivity was not significantly associated with OS (HR: 0.77, 95% CI: 0.44-1.33, P = .34) and resection was associated with improved OS (HR: 0.41, 95% CI: 0.36-0.46, P < .01). On multivariable Cox regression analysis, all previous clinicopathologic variables remained independent predictors of worse OS (all P < .05), and resection remained predictive of improved OS (HR: 0.54, 95% CI: 0.47-0.62, P < .01) (Table 2).
TABLE 2.
Clinicopathologic factors associated with overall survival for entire cohort
| Univariable Cox regression |
Multivariable Cox regression |
|||
|---|---|---|---|---|
| Variable | HR (95% CI) | P value | HR (95% CI) | P value |
| Age at diagnosis | 1.06 (1.05-1.06) | <.01 | 1.05 (1.04-1.06) | <.01 |
| Sex | ||||
| Female | Reference | Reference | ||
| Male | 1.29 (1.14-1.46) | <.01 | 1.31 (1.16-1.48) | <.01 |
| Race | ||||
| White | Reference | Reference | ||
| Black | 1.15 (1.01-1.32) | .04 | 1.22 (1.06-1.40) | <.01 |
| Other | 0.58 (0.40-0.82) | <.01 | 0.65 (0.46-0.93) | .02 |
| Charlson-Deyo Score | ||||
| 0 | Reference | Reference | ||
| 1 | 1.52 (1.32-1.76) | <.01 | 1.38 (1.19-1.61) | <.01 |
| 2+ | 3.06 (2.61-3.60) | <.01 | 2.67 (2.26-3.14) | <.01 |
| Tumor size,cm | ||||
| <1cm | Reference | Reference | ||
| 1-1.99 cm | 1.13 (0.92-1.38) | .25 | 1.11 (0.90-1.38) | .33 |
| ≥2 cm | 1.27 (1.03-1.56) | .03 | 1.14 (0.91-1.43) | .25 |
| Tumor grade | ||||
| Well differentiated | Reference | Reference | ||
| Moderately differentiated | 1.06 (0.76-1.47) | .73 | 1.15 (0.83-1.60) | .41 |
| Poorly/undifferentiated | 4.58 (3.15-6.65) | <.01 | 3.70 (2.50-5.46) | <.01 |
| AJCC Pathologic T | ||||
| T1 | Reference | … | ||
| T2 | 1.05 (0.75-1.46) | .78 | … | |
| T3-4 | 1.48 (0.90-2.43) | .12 | … | |
| AJCC Pathologic N | ||||
| N0 | Reference | … | ||
| N1 | 0.77 (0.44-1.33) | .34 | … | |
| Lymph vascular invasion | ||||
| Absent | Reference | … | ||
| Present | 0.87 (0.46-1.67) | .68 | … | |
| Intervention | ||||
| No resection | Reference | Reference | ||
| Resection | 0.41 (0.36-0.46) | <.01 | 0.54 (0.47-0.62) | <.01 |
Note: For multivariable analysis, backward selection with an α level of removal of 0.2 was used.
Abbreviations: CI, confidence interval; HR, hazard ratio.
Bold indicates statistical significance.
3.3 |. Survival analysis in propensity weighted sample
Propensity score weighted matching was implemented to reduce selection bias between resection and no-resection cohorts based on the clinicopathologic variables independently associated with OS including age, sex, race, Charlson-Deyo score, and tumor grade. After this weighting schema was applied, a sample was generated in which the above-mentioned factors were well balanced between resection and no-resection cohorts.
On logrank analysis within this weighted sample, resection was associated with improved median OS for the entire cohort (MNR vs 94 months; P < .01; Figure 1A). A similar pattern was observed between resection and no-resection cohorts when stratifying by tumor size categories within the weighted sample (<1cm: MNR vs 194 months; Figure 1B; 1-2 cm: MNR vs 56 months; Figure 1C; ≥2 cm: MNR vs 90 months; Figure 1D; all P < .01).
FIGURE 1.
Kaplan-Meier curves comparing resection vs no resection of D-NETs in a propensity weighted sample further stratified by tumor size categories. D-NET, duodenal neuroendocrine tumor [Color figure can be viewed at wileyonlinelibrary.com]
3.4 |. Survival analysis in resection cohort
Within the original resection cohort, logrank analysis demonstrated that neither type of resection, lymph node retrieval, lymph node positivity nor margin status was associated with OS (all P > .05; Figure 2). This was further demonstrated on separate multivariable Cox regression analyses within each tumor size category when controlling for age, sex, race, Charlson-Deyo score, and tumor grade in each model (Table 3).
FIGURE 2.
Kaplan-Meier curves of resection cohort comparing type of resection, lymph node retrieval, lymph node positivity, and margin status [Color figure can be viewed at wileyonlinelibrary.com]
TABLE 3.
Clinicopathologic factors stratified by tumor size associated with survival after resection
| <1cm |
1-1.99 cm |
≥ 2 cm |
||||
|---|---|---|---|---|---|---|
| Variable | HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value |
| Type of resection | ||||||
| LR | Reference | Reference | Reference | |||
| AR | 1.02 (0.79-1.31) | .87 | 0.85 (0.58-1.23) | .39 | 1.02 (0.60-1.73) | .95 |
| LN retrieval | ||||||
| No | Reference | Reference | Reference | |||
| Yes | 1.13 (0.84-1.52) | .43 | 1.03 (0.69-1.53) | .89 | 0.85 (0.53-1.36) | .49 |
| LN status | ||||||
| Negative | Reference | Reference | Reference | |||
| Positive | 0.80 (0.43-1.48) | .48 | 1.13 (0.58-2.18) | .72 | 0.81 (0.43-1.51) | .50 |
| Margin status | ||||||
| Negative | Reference | Reference | Reference | |||
| Positive | 1.17 (0.81-1.69) | .39 | 1.57 (0.94-2.62) | .084 | 0.74 (0.32-1.71) | .48 |
Note: For multivariable analysis, backward selection with an α level of removal of 0.2 was used. Estimated stratified treatment effect was controlled by the following: age at diagnosis, sex, race, Charlson-Deyo score, and tumor grade
Abbreviations: AR, anatomic resection; CI, confidence interval; HR, hazard ratio; LR, local resection.
Bold indicates statistical significance.
4 |. DISCUSSION
D-NETs comprise 1% to 3% of all duodenal tumors and less than 4% of all gastrointestinal NETs, and are a clinical entity unique from pancreatic and other SB-NETs.28–30 Over the past three decades, there has been an increase in the incidence rate of D-NETs, currently with 1.1 cases per 100 000 diagnosed annually in the United States.31 Given this increasing disease burden, understanding the natural history of this disease process and developing robust management guidelines is of increased clinical relevance. Specifically, our study focused on identifying clinicopathologic factors associated with OS and the rationale for routine resection and need for lymphadenectomy in D-NETs.
The findings from this study continue to support the indolent nature of this disease process given a 5-year OS for the entire cohort of 76%. Importantly, however, patients who underwent resection had an improved OS compared with the patients who did not undergo resection regardless of tumor size, a finding that is concordant with ENETS guidelines which currently recommend resection, either endoscopic or anatomic, for all D-NETs.32 This result persisted even after controlling for potential confounding variables associated with OS including age, sex, race, Charlson-Deyo score, and tumor grade by a propensity score overlap weighting schema.
Clinicopathologic factors prognostic of long-term outcomes for D-NETs have been previously reported and of these, the association of tumor size and lymph node metastasis with long-term outcomes has been the focus of several recent studies. However, the association between lymph node retrieval or lymph node involvement and its prognostic effect on OS has not been well defined in the literature.1,2,33–37 Despite this, the current standard of care in the treatment of D-NETs is either endoscopic or segmental resection of all tumors regardless of size with lymphadenectomy for tumors ≥ 2 cm or tumors with suspected lymph node involvement on imaging.32 The current study found that several demographic and clinical factors were associated with OS including age, sex, race, Charlson-Deyo score, and tumor grade. However, despite a lymph node positivity rate of 43% of those who had lymph nodes retrieved in this series, nodal status was not an independent predictor of OS. In addition, although tumor size was ≥2 cm was associated with worse OS on univariate analysis, this finding did not persist in a multivariable model. It should be noted, however, that although a large proportion of the tumors in this series were well differentiated, poorly differentiated tumor grade was an independent predictor of outcome, a finding that has been illustrated universally and is a surrogate for tumor biology.1,30,38
As resection was associated with improved OS in our study of propensity weighted cohorts, another key point to consider in the management of D-NETs is the surgical approach and its associated oncologic outcomes. According to our findings, controversy still remains as to the most appropriate surgical strategy for resection of D-NETs regardless of size. Neither type of resection nor margin status was predictive of improved OS. Other investigators have also reported on the type of procedure used for resection and have not found an association with long-term outcomes.1,33,38 These findings highlight that although there is a clear indication to achieve local control with resection of the primary tumor, survival may not be affected by extent of resection largely due to the indolent nature of this disease. These data are essential to perioperative decision making as the decision for surgical approach should be largely based on the technical feasibility of the operation according to tumor size and location within the duodenum as well as safety when considering the patient’s age and comorbid status. In contrast to formal resection of SB-NETS, which can be routinely undertaken with a minimal complication profile, formal resection of D-NETS with lymphadenectomy may necessitate pancreaticoduodenectomy, a procedure that is known to have considerable perioperative complication rates. These findings further support that formal resection may be unwarranted if local control can be otherwise achieved via an endoscopic or segmental resection. This highlights the necessity of a thorough discussion with the patient to ensure their understanding of the risks and benefits of each operative strategy. Lastly, the results of this study demonstrate that the optimal management for D-NETs falls somewhere between the management guidelines for P-NETs, which suggest that lymph node retrieval is not always prognostic and hence not routinely necessary, and SB-NETS, which state that local control with segmental resection and lymphadenectomy results in an improvement in survival for all tumor sizes.
The data presented here are powered by large numbers and supported by strong statistical analysis, but nevertheless are subject to several limitations. First, the retrospective nature of these data introduces the known challenges of observational studies including limitations on survival data secondary to loss of follow-up as well as selection bias between resection and no-resection cohorts. Although propensity score weighting was performed to control for known confounding demographic and clinical variables between the two cohorts, without the benefit of prospective randomization, we cannot reliably reduce unmeasured factors that may account for imbalances between the groups. Finally, our study was limited by potential coding errors, missing data, and the absence of several variables within the NCDB including mitotic rates, Ki67, disease recurrence, and disease-specific survival. The lack of recurrence data poses a challenge when studying an indolent disease process in which OS may not be an ideal outcome to evaluate the natural history of the disease.
5 |. CONCLUSION
For D-NETs, any type of resection including endoscopic, local, or anatomic is associated with improved OS regardless of tumor size. In contrast to SB-NETs, lymph node retrieval or lymph node positivity was not prognostic. In determining the optimal treatment for this indolent disease process, it is important to take into consideration the tumor’s morphology, patient’s comorbid profile and potential longevity, and the complication rates of the planned procedure to offer a sound operation in the context of patient-centered care.
ACKNOWLEDGMENTS
The research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The research is also supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number TL1TR002382. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The data used in the study are derived from a deidentified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data by the investigator.
Funding information
National Center for Advancing Translational Sciences, Grant/Award Number: UL1TR002378/TL1TR002382
Abbreviations:
- D-NET
duodenal neuroendocrine tumor
- ENETS
European Neuroendocrine Tumor Society
- NANETS
North American Neuroendocrine Tumor Society
- NCDB
National Cancer Database
- OS
overall survival
- P-NET
pancreatic neuroendocrine tumor
- SB-NET
small bowel neuroendocrine tumor
Footnotes
CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the National Cancer Database but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.
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