Colorectal Neuroendocrine Tumors Research Articles

Treatment indicators and prognostic factors in colorectal neuroendocrine neoplasms and adenocarcinoma with neuroendocrine differentiation: a single center retrospective study.

This study compared survival and metastasis occurrence between colorectal neuroendocrine neoplasms (cNEN) and colorectal adenocarcinoma with neuroendocrine differentiation (cNED) and further explored their prognostic factors and treatment indicators. Patients diagnosed as cNEN and cNED in West China Hospital from January 2009 to December 2020 were enrolled. The diagnosis and metastasis rates were calculated. Univariate and multivariate Cox analyses were conducted for progression-free survival (PFS) in cNEN surgical patients, and generalized linear regression was used for metastatic disease. The study enrolled 435 patients, including 257 neuroendocrine tumors (NET), 52 neuroendocrine carcinomas (NEC), 29 mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN), and 97 NED patients, of whom 202 received local resection, and 233 received radical resection. Metastasis rates were higher in MiNEN and NEC groups compared to other groups (NED: 28.9%, MiNEN: 58.6%, NEC: 65.4%, NET: 8.6%, p < 0.001). The liver is the main metastatic site in cNEN, whereas cNED metastasized to various sites. For NEC and MiNEN patients, colon location (p = 0.002) and T stage > 2 (p = 0.040) were associated with disease progression separately. Independent risk factors for metastatic NET included tumor grade G2/G3 (p < 0.001), colon location (p = 0.001), size ≥ 1cm (p = 0.005), and CK20 partial positive (p < 0.001). cNEN show high metastatic capacity and are challenging to diagnose. More aggressive treatment and follow-up strategies are necessary for those patients. NET tumor grade higher than G2, size larger than 1cm, or located in the colon should be managed with radical surgery.

Demographic Characteristics and Survival in Young-Onset Colorectal Neuroendocrine Neoplasms.

Recent epidemiological studies have revealed an upward trend in young-onset colorectal cancer (YOCRC) overall, whereas specific data on young-onset colorectal neuroendocrine neoplasms (YONEN) remain limited. This study investigated the demographic characteristics and survival trends in YONEN and compared these with those of young-onset colorectal adenocarcinoma (YOADC), the most common histologic subtype of YOCRC. A retrospective analysis was conducted from 2000 to 2019 using the Surveillance, Epidemiology, and End Results (SEER) database. Survival outcomes were assessed using univariate and multivariable Cox proportional models, with demographic differences evaluated via Wilcoxon rank sum and Chi-square tests. Out of 61,705 patients aged 20-49 with colorectal cancer, 8% had NEN, and 92% had adenocarcinoma. The YONEN cohort had a higher proportion of Black patients and a lower proportion of White patients than the YOADC cohort (21% vs. 13% and 44% vs. 57%, respectively). NEN was more commonly found in the rectum (79%), and adenocarcinoma was mostly colonic (57%) in origin. YONEN patients had better survival than YOADC patients. Multivariate analysis in YONEN patients revealed that Hispanic patients had better overall survival compared to White patients (HR 0.67, 95% CI 0.47-0.95, p = 0.024). Racial disparities should be investigated further to aid in policymaking and targeted interventions.

Deep learning model with pathological knowledge for detection of colorectal neuroendocrine tumor

Colorectal neuroendocrine tumors (NETs) differ significantly from colorectal carcinoma (CRC) in terms of treatment strategy and prognosis, necessitating a cost-effective approach for accurate discrimination. Here, we propose an approach for distinguishing between colorectal NET and CRC based on pathological images by utilizing pathological prior information to facilitate the generation of robust slide-level features. By calculating the similarity between morphological descriptions and patches, our approach selects only 2% of the diagnostically relevant patches for both training and inference, achieving an area under the receiver operating characteristic curve (AUROC) of 0.9974 on the internal dataset, and AUROCs of 0.9724 and 0.9513 on two external datasets. Our model effectively identifies NETs from CRCs, reducing unnecessary immunohistochemical tests and enhancing the precise treatment for patients with colorectal tumors. Our approach also enables researchers to investigate methods with high accuracy and low computational complexity, thereby advancing the application of artificial intelligence in clinical settings.

Colorectal Neuroendocrine Neoplasm Detection Rate During Colonoscopy: Results From Large-Scale Data of Colonoscopies in Japan.

This study investigated the detection rate of colorectal neuroendocrine neoplasms (NENs) using large-scale colonoscopy data. This cross-sectional analysis used large-scale data from a Japanese multicenter observational study of colonoscopies performed from 2010 to 2020. Among 82,005 colonoscopy cases, colorectal NENs were identified in 71 (67 of which were neuroendocrine tumors), with a detection rate of 0.087% (95% confidence interval: 0.069-0.109). Most were small rectal lesions, with only 4 >10 mm in size and 3 located in the colon. The detection rate of colorectal NENs during colonoscopy is substantially higher than expected.

Endoscopic therapy versus surgical resection for elderly patients with colorectal neuroendocrine tumors

BackgroundEndoscopic therapy (ET) and surgical resection (SR) are common surgical methods for the treatment of colorectal neuroendocrine tumors (CRNETs). However, for elderly patients, it remains unclear which surgical method yields better long-term outcomes.MethodsElderly patients ≥ 65 years with CRNETs diagnosed from 2000 to 2020 were identified from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan–Meier method and Cox proportional hazards models were utilized to evaluate the effects of diverse demographic and clinical factors on overall survival (OS) and cancer-specific survival (CSS).ResultsA total of 2214 patients were included in the study, with 1417 patients in the ET group and 797 patients in the SR group. After PSM, the ET group outperformed the SR group in terms of OS (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.44–0.70) and CSS (HR 0.21, 95% CI 0.11–0.40). Similarly, the ET group maintained its advantage in mean 1-, 3-, and 5-year OS and CSS rates compared to the SR group (P < 0.001). Multivariate Cox regression analysis identified age, sex, grade, marital status, and treatment modality as independent risk factors affecting OS, while age, sex, marital status, and treatment modality were identified as independent risk factors affecting CSS.ConclusionsET offered superior long-term outcomes for elderly patients ≥ 65 years with CRNETs.

Clinical and pathological characteristics of and predictive model for colorectal neuroendocrine tumors

BackgroundThe incidence of colorectal neuroendocrine tumors (NETs) is increasing, causing a social burden. At present, there is no specific prognostic model for colorectal NETs. Thus, an accurate model is needed to predict the prognosis of patients with colorectal NETs. AimWe aimed to create a new nomogram to predict the prognosis of patients with colorectal NETs. Furthermore, we compared nomogram we established and the 8th edition of the AJCC TNM staging system in terms of prediction ability and accuracy. MethodsA total of 3353 patients with colorectal NETs were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier analyses were used to assess overall survival (OS) and cancer-specific survival (CSS). Additionally, LASSO regression was used to select variables for constructing the nomogram. Furthermore, the C-index and time-dependent receiver operating characteristic (tdROC) curve were used to evaluate the nomogram. Decision curve analysis (DCA) was performed to compare the clinical utility of the nomogram with that of the TNM system. An external validation cohort (N = 61) was established to evaluate the nomogram's prediction accuracy. ResultsA total of 9 factors (age, sex, marital status, tumor size, T stage, M stage, N stage, grade, and surgery) were selected based on the results of LASSO analysis. The C-indexes of the nomogram in the training and validation sets were 0.807 and 0.775, respectively, which indicated that the nomogram had better prediction accuracy than TNM staging (C-index = 0.700 in the training set and 0.652 in the validation set). The C-index of the nomogram in the external validation cohort was 0.954, indicating that the nomogram had satisfactory prediction accuracy. The results of DCA revealed that the survival nomogram possessed greater utility in clinical practice. ConclusionWe determined the OS and CSS of patients with colorectal NETs and developed a robust and clinically useful survival nomogram.

Correlation between Neurotransmitters (Dopamine, Epinephrine, Norepinephrine, Serotonin), Prognostic Nutritional Index, Glasgow Prognostic Score, Systemic Inflammatory Response Markers, and TNM Staging in a Cohort of Colorectal Neuroendocrine Tumor Patients.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

Different lymph node staging systems for predicting the prognosis of colorectal neuroendocrine neoplasms.

Colorectal neuroendocrine neoplasms (NENs) are a rare malignancy that primarily arises from the diffuse distribution of neuroendocrine cells in the colon and rectum. Previous studies have pointed out that the status of lymph node may be used to predict the prognosis. To investigate the predictive values of lymph node ratio (LNR), positive lymph node (PLN), and log odds of PLNs (LODDS) staging systems on the prognosis of colorectal NENs treated surgically, and compare their predictive values. This cohort study included 895 patients with colorectal NENs treated surgically from the Surveillance, Epidemiology, and End Results database. The endpoint was mortality of patients with colorectal NENs treated surgically. X-tile software was utilized to identify most suitable thresholds for categorizing the LNR, PLN, and LODDS. Participants were selected in a random manner to form training and testing sets. The prognosis of surgically treating colorectal NENs was examined using multivariate cox analysis to assess the associations of LNR, PLN, and LODDS with the prognosis of colorectal NENs. C-index was used for assessing the predictive effectiveness. We conducted a subgroup analysis to explore the different lymph node staging systems' predictive values. After adjusting all confounding factors, PLN, LNR and LODDS staging systems were linked with mortality in patients with colorectal NENs treated surgically (P < 0.05). We found that LODDS staging had a higher prognostic value for patients with colorectal NENs treated surgically than PLN and LNR staging systems. Similar results were obtained in the different G staging subgroup analyses. Furthermore, the area under the receiver operating characteristic curve values for LODDS staging system remained consistently higher than those of PLN or LNR, even at the 1-, 2-, 3-, 4-, 5- and 6-year follow-up periods. LNR, PLN, and LODDS were found to significantly predict the prognosis of patients with colorectal NENs treated surgically.

Evaluation of association between center colorectal neuroendocrine neoplasm volume and survival among patients with colorectal neuroendocrine carcinoma.

Although correlation between center volume and survival has been reported for several complex cancers, it remains unknown if this is true for colorectal neuroendocrine carcinomas (CRNECs). We hypothesized that higher center annual volume of colorectal neuroendocrine neoplasm resections would be associated with overall survival (OS) for patients with CRNECs. Patients in the National Cancer Database diagnosed with stages I-III CRNEC between 2006 and 2018 and who underwent surgical resection were identified. The mean annual colorectal neuroendocrine neoplasm resection volume threshold associated with significantly worse mortality hazard was determined using restricted cubic splines. Kaplan-Meier (KM) method was used to compare OS, while Cox proportional hazards model was used for multivariable analysis. There were 694 patients with CRNEC who met inclusion criteria across 1229 centers. Based on the cubic spline, centers treating fewer than one colorectal neuroendocrine neoplasm patient every 3 years on average had worse outcomes. Centers below this threshold were classified as low-volume (LV) centers corresponding with 42% of centers and about 15% of the patient cohort. In unadjusted survival analysis, LV patients had a median OS of 14 months (95% confidence interval [CI]: 10-19) while those treated at HV centers had a median OS of 33 months (95% CI: 25-49). In multivariable analysis, resection at a LV center was associated with increased risk of mortality (1.42 [95% CI: 1.01-2.00], p = 0.04). CRNEC patients have a dire prognosis; however, treatment at an HV center may be associated with decreased risk of mortality.

Comparing surgical and endoscopic resection approaches for colorectal neuroendocrine tumors within the diameter range of 10-20mm: an inverse probability weighting analysis based on the SEER database.

Currently, the primary treatment modalities for colorectal neuroendocrine tumors (CRNET) with a diameter between 10mm and 20mm are surgical resection (SR) and endoscopic resection (ER). However, it remains unclear which surgical approach yields the greatest survival benefit for patients. This study included data from patients diagnosed with CRNET with tumor diameters ranging from 10mm to 20mm between the years 2004 and 2019, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into ER and SR groups based on the respective surgical approaches. Inverse probability weighting (IPTW) was employed to mitigate selection bias. Kaplan-Meier analysis and log-rank tests were utilized to estimate overall survival (OS) and cancer-specific survival (CSS). Cox regression analysis (univariate and multivariate) was performed to evaluate potential factors influencing survival. A total of 292 CRNET patients were included in this study (ER group: 108 individuals, SR group: 184 individuals). Prior to IPTW adjustment, Kaplan-Meier analysis and Cox proportional hazard regression analysis demonstrated that the OS and CSS of the SR group were inferior to those of the ER group. However, after IPTW adjustment, no statistically significant differences in prognosis were observed between the two groups. Subgroup analyses revealed that patients with muscular invasion, positive lymph nodes, or distant metastasis derived greater survival benefits from SR. Significant differences in OS and CSS between the two groups were also observed across different age groups. For patients with mucosal-limited lesions and without local lymph node or distant metastasis, ER is the preferred surgical approach. However, for patients with muscular invasion or positive lymph nodes/distant metastasis, SR offers a better prognosis. The choice of surgical approach should be based on the specific clinical characteristics of patients within different subgroups.

Palliative primary tumor resection may not offer survival benefits for patients with unresectable metastatic colorectal neuroendocrine neoplasms, one multicenter retrospective cohort study

BackgroundThe efficacy of palliative primary tumor resection (PTR) in improving prognosis for patients with unresectable metastatic colorectal neuroendocrine neoplasms (NENs) has not been fully explored.MethodsWe performed one retrospective cohort study and recruited 68 patients with unresectable metastatic colorectal NENs from two Chinese medical centers between 2000 and 2022. All patients were assigned to PTR group and no PTR group. The clinicopathological manifestation data were carefully collected, and the survival outcomes were compared between the two groups using Kaplan–Meier methods. Propensity score matching (PSM) was conducted to minimize confounding bias. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify prognostic factors.ResultsA total of 32 patients received PTR, and the other 36 patients did not. The median progression-free survival (PFS) and overall survival (OS) times were 4 and 22 months in the whole cohort, respectively. For patients who received no PTR, the median OS was 16 months, and the 1-year OS rate and 3-year OS rate were 56.4% and 39.6%, respectively. For patients who received PTR, the median OS was 24 months, and the 1-year OS rate and 3-year OS rate were 67.9% and 34.1%, respectively. However, the Kaplan–Meier survival curves and log-rank test demonstrated no significant survival difference between the two groups (P = 0.963). Moreover, palliative PTR was also not confirmed as a prognostic factor in subsequent univariable and multivariable Cox proportional hazards regression analyses in both the original and matched cohorts. Only histological differentiation was identified as an independent prognostic factor affecting PFS [hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.02–3.41, P = 0.043] and OS [HR = 3.70, 95% CI: 1.09–12.48, P = 0.035] in the original cohort.ConclusionsPalliative PTR may not offer survival benefits for patients with unresectable metastatic colorectal NENs.

Short-term outcomes of endoscopic resection for colorectal neuroendocrine tumors: Japanese multicenter prospective C-NET STUDY.

The incidence of colorectal neuroendocrine tumors (NETs) has increased with colorectal cancer screening programs and increased colonoscopies. The management of colorectal NETs has recently shifted from radical surgery to endoscopic resection. We aimed to evaluate the short-term outcomes of various methods of endoscopic resection for colorectal NETs. Among those registered in the C-NET STUDY, patients with colorectal NETs who underwent endoscopic treatment as the initial therapy were included. Short-term outcomes, such as the en bloc resection rate and R0 resection (en bloc resection with tumor-free margin) rate, were analyzed based on treatment modalities. A total of 472 patients with 477 colorectal NETs received endoscopic treatment. Of these, 418 patients with 421 lesions who met the eligibility criteria were included in the analysis. The median age of the patients was 55 years, and 56.9% of them were men. The lower rectum was the most commonly affected site (88.6%), and lesions <10 mm accounted for 87% of the cases. Endoscopic submucosal resection with a ligation device (ESMR-L, 56.5%) was the most common method, followed by endoscopic submucosal dissection (ESD, 31.4%) and endoscopic mucosal resection using a cap (EMR-C, 8.5%). R0 resection rates <10 mm were 95.5%, 94.8%, and 94.3% for ESMR-L, ESD, and EMR-C, respectively. All 16 (3.8%) patients who developed treatment-related complications could be treated conservatively. Overall, 23 (5.5%) patients had incomplete resection without independent clinicopathological risk factors. ESMR-L, ESD, and EMR-C were equally effective and safe for colorectal NETs with a diameter <10 mm.

Analysis of the Genetic Characteristics and Metastatic Pathways of G1 and G2 Colorectal Neuroendocrine Neoplasms.

G1 and G2 colorectal neuroendocrine neoplasms (NENs) are a group of rare and indolent diseases. We aimed to delineate their genetic characteristics and explore their metastatic mechanisms. We used next-generation sequencing technology for targeted sequencing for 54 patients with G1 and G2 colorectal NENs. We delineated their genetic features and compared the genetic characteristics between metastatic NENs and nonmetastatic NENs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was utilized to explore their abnormal pathways and study their potential metastatic mechanisms. We collected 23 metastatic NENs and 31 nonmetastatic NENs. In the whole cohort, the common mutated genes were NCOR2, BRD4, MDC1, ARID1A, AXIN2, etc. The common copy number variations (CNVs) included amplification of HIST1H3D, amplification of HIST1H3E, and loss of PTEN. The KEGG enrichment analysis revealed that PI3K-Akt, MAPK, and Rap1 were the major abnormal pathways. There were significantly different genetic features between metastatic NENs and nonmetastatic NENs. The metastatic NENs shared only 47 (22.5%) mutated genes and 6 (13.3%) CNVs with nonmetastatic NENs. NCOR2, BRD4, CDKN1B, CYP3A5, and EIF1AX were the commonly mutated genes in metastatic NENs, while NCOR2, MDC1, AXIN2, PIK3C2G, and PTPRT were the commonly mutated genes in nonmetastatic NENs. Metastatic NENs presented a significantly higher proportion of abnormal pathways of cell senescence (56.5% vs 25.8%, P = .022) and lysine degradation (43.5% vs 16.1%, P = .027) than nonmetastatic NENs. G1 and G2 colorectal NENs are a group of heterogeneous diseases that might obtain an increased invasive ability through aberrant cell senescence and lysine degradation pathways.

Demographic characteristics and survival in young onset colorectal neuroendocrine tumors

Demographic characteristics and survival in young onset colorectal neuroendocrine tumors

Claudin 18.2 expression in digestive neuroendocrine neoplasms: a clinicopathological study.

Claudin 18.2-targeted therapy has shown significant efficacy in treating claudin 18.2-positive cancers. However, limited systematic studies have investigated characteristics of claudin 18.2 expression in neuroendocrine neoplasms (NENs). Data and specimens from 403 cases of digestive NENs were retrospectively collected, and claudin 18.2 expression was detected using immunochemical staining. Claudin 18.2 was positive in 19.6% (79/403) of the digestive NENs. The highest positive rate of claudin 18.2 was observed in gastric NENs (72/259, 27.8%), accounting for 91.1% (72/79) of all positive cases. The positivity rate was significantly higher in gastric NENs compared to pancreatic (2/78, 2.6%) or colorectal NENs (2/38, 5.3%; p < 0.05). For digestive NENs, claudin 18.2 positivity was significantly higher in neuroendocrine carcinomas (NECs) (37/144, 25.7%) than in neuroendocrine tumours (NETs; 14/160, 8.8%; p < 0.001), but no significant difference was found between gastric NECs (59/213, 27.7%) and gastric NETs (13/46, 28.3%; p > 0.05). The positivity was significantly higher in large-cell NECs (LCNECs; 28/79, 35.4%) and MiNEN (mixed neuroendocrine-non- neuroendocrine neoplasms)-LCNECs (23/66, 34.8%) compared to small-cell NECs (SCNECs; 9/65, 13.8%) and MiNEN-SCNECs (5/33, 15.2%; p < 0.05). Claudin 18.2 expression was more prevalent in gastric NENs than in pancreatic (12.5 ×; p = 0.001) and colorectal NENs (5.9 ×; p = 0.021). Claudin 18.2 staining was a useful method for identify the gastric origins of NETs, with a sensitivity of 28.3% and a specificity of 99.1%. The expression characteristics of claudin 18.2 in NENs were characterized, which may provide a clinicopathological reference for targeted therapies in patients with NENs.

Treatment strategy and post-treatment management of colorectal neuroendocrine tumor.

Following the increase in colorectal neuroendocrine tumors (NETs), there is a consequent increase in the importance of their appropriate treatment and post-treatment management. It is widely accepted that colorectal NETs sized ≥20mm and those with muscularis propria invasion are indicated for radical surgery, and those sized <10mm without the invasion are indicated for local resection. No consensus has been reached regarding the treatment strategy for those sized 10-19mm without the invasion. Endoscopic resection has become a primary option for the local resection of colorectal NETs. For rectal NETs sized <10mm, modified endoscopic mucosal resection, such as endoscopic submucosal resection with ligation device and endoscopic mucosal resection with a cap-fitted panendoscope, seems favorable because of its ability to achieve a high R0 resection rate, safety, and convenience. Endoscopic submucosal dissection can also be helpful for these lesions; however, this procedure may be more effective for large lesions or those in the colon. Management following local resection of colorectal NETs is based on the pathological evaluation of factors associated with metastasis, including tumor size, invasion depth, tumor cell proliferative activity (NET grading), presence of lymphovascular invasion, and resection margins. There remain unclear issues in managing cases with NET grading ≥2, positive lymphovascular invasion, and positive resection margins following local resection. In particular, there is confusion regarding managing positive lymphovascular invasion because positivity has become remarkably high with the increased use of the immunohistochemical/special staining. Further evidence based on long-term clinical outcomes is required to address these issues.

European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for colorectal neuroendocrine tumours.

This ENETS guidance paper, developed by a multidisciplinary working group, provides an update on the previous colorectal guidance paper in a different format. Guided by key clinical questions practical advice on the diagnosis and management of neuroendocrine tumours (NET) of the caecum, colon, and rectum is provided. Although covered in one guidance paper colorectal NET comprises a heterogeneous group of neoplasms. The most common rectal NET are often small G1 tumours that can be treated by adequate endoscopic resection techniques. Evidence from prospective clinical trials on the treatment of metastatic colorectal NET is limited and discussion of patients in experienced multidisciplinary tumour boards strongly recommended. Neuroendocrine carcinomas (NEC) and mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) are discussed in a separate guidance paper.

Risk prediction of second primary malignancies in primary colorectal neuroendocrine neoplasms patients: a population-based study.

In this study, we aimed to identify risk factors for developing second primary malignancies (SPMs) in colorectal neuroendocrine neoplasms (NENs) patients and develop a competing-risk nomogram to predict SPMs' probabilities quantitatively. Patients with colorectal NENs were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database during 2000-2013. Potential risk factors for SPMs' occurrence in colorectal NENs' patients were identified by the Fine and Gray's proportional sub-distribution hazards model. Then, a competing-risk nomogram was constructed to quantify SPMs' probabilities. The discriminative abilities and calibrations of this competing-risk nomogram were assessed by the area under the receiver-operating characteristic (ROC) curves (AUC) and calibration curves. We identified 11,017 colorectal NENs' patients, and randomly divided them into training (n = 7711 patients) and validation (n = 3306 patients) cohorts. In the whole cohort, 12.4% patients (n = 1369) had developed SPMs during the maximum follow-up of approximately 19years (median 8.9years). Sex, age, race, primary tumor location, and chemotherapy were identified as risk factors for SPMs' occurrence in colorectal NENs' patients. Such factors were selected to develop a competing-risk nomogram and showed excellent predictive ability for SPMs' occurrence (the 3-, 5-, and 10-year AUC values were 0.631, 0.632, and 0.629 in the training cohort and 0.665, 0.639, 0.624 in the validation cohort, respectively). This research identified risk factors for SPMs' occurrence in colorectal NENs' patients. Competing-risk nomogram was constructed and proved to have good performance.

Development of novel prediction models for nodal and distant metastasis in G1 and G2 colorectal neuroendocrine tumors

We aimed to construct novel nomograms for nodal and distant metastasis for patients with G1 and G2 colorectal neuroendocrine tumors (NETs). A training set and validation set were obtained by including G1 and G2 colorectal NET patients from the Surveillance, Epidemiology, and End Results database and the Cancer Hospital Chinese Academy of Medical Science, respectively. The area under curve (AUC) values under receiver operating characteristic (ROC) curves, calibration plots, and the Hosmer‒Lemeshow tests were used to evaluate the discriminability and calibration of nomograms. In total, 3690 and 172 patients were included in the training set and validation set, respectively. Tumor size, location, and T stage were included in the nomogram predicting nodal metastasis. The AUC values of the nomogram were 0.972 (95% confidence interval (CI): 0.964-0.980) and 0.897 (95% CI: 0.846-0.948) in the training set and validation set, respectively. The calibration plots and Hosmer‒Lemeshow test for the training set (P = 0.999) and validation set (P = 0.537) showed good model calibration. Tumor size, T stage, and N stage were incorporated into the nomogram predicting distant metastasis. The ROC curves demonstrated desirable discrimination both in the training set (AUC = 0.938 (95% CI: 0.921-0.954)) and validation set (AUC = 0.938 (95% CI: 0.890-0.988)). The calibration curves and Hosmer‒Lemeshow test indicated acceptable model calibration both in the training set (P = 0.908) and validation set (P = 0.722). The proposed nomograms may be used as a reliable tool to predict the nodal and distant metastasis in G1 and G2 colorectal NETs.

Epidemiological trends and novel prognostic evaluation approaches of patients with stage II-IV colorectal neuroendocrine neoplasms: A population-based study with external validation.

This study aimed to clarify the incidence trend of all-stage colorectal neuroendocrine neoplasms (CRNENs), overall survival (OS), and disease-specific survival (DSS) of patients with stage II-IV CRNENs, and to establish relevant nomograms for risk stratification. Among all patients diagnosed with CRNENs in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2019, temporal trends in incidence were assessed. Clinical data of 668 patients with stage II-IV CRNENs from 2010 to 2016 were extracted for survival analysis. Patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Univariate and multivariate cox regression analyses were utilized to identify independent prognostic factors affecting OS outcomes. Competing risk analysis was applied to investigate risk factors related to the DSS of CRNENs. Two nomograms specifically for OS and DSS were developed for patients with stage II-IV CRNENs, their prognostic capabilities were evaluated using calibration curves, receiver operating characteristic (ROC) curves, the time-dependent area under the curve (AUC), and decision-curve analysis (DCA). Our hospital's independent cohort of 62 patients with CRNENs was used as the external validation cohort. In the period of 1975-2019, the incidence of CRNENs increased steadily with an annual percentage change (APC) of 4.50 (95% confidence interval [CI]: 3.90-5.11, P < 0.05). In total, 668 patients with stage II-IV CRNENs were included in the survival analysis from 2010 and 2016. Independent adverse prognostic factors for both OS and DSS of CRNENs prior treatment included grade III/IV (HR for OS: 4.66, 95%CI: 2.92-7.42; HR for DSS: 4.79, 95%CI: 4.27-5.31), higher TNM stage ([stage III vs stage II] HR for OS: 2.22, 95%CI: 1.25-3.94; HR for DSS: 2.69, 95%CI: 1.96-3.42. [stage IV vs stage II] HR for OS: 3.99, 95%CI: 2.03-7.83; HR for DSS: 4.96, 95%CI: 4.14-5.78), liver metastasis (HR for OS: 1.61, 95%CI: 1.03-2.51; HR for DSS: 1.86, 95%CI: 1.39-2.32), and brain metastasis (HR for OS: 4.57, 95%CI: 1.66-12.58; HR for DSS: 5.01, 95%CI: 4.15-5.87). Advanced age was also identified as a risk factor for OS (HR: 2.03, 95%CI: 1.5-2.76) but not DSS. In terms of treatment, surgery can significantly prolong OS (HR: 0.62, 95%CI: 0.44-0.86) and DSS (HR: 0.67, 95%CI: 0.29-1.05), but chemotherapy and radiation failed to show significance. The respective nomograms for OS and DSS for stage II-IV CRNENs demonstrated high accuracy and robust prediction value in predicting 1-year, 3-year, and 5-year OS and DSS outcomes in training, internal validation, and external validation cohorts. Besides, two online tools regarding OS and DSS prediction were established, facilitating nomogram score calculation, risk group determination, as well as survival prediction for each individual patient. Over the past 40 years, the incidence of CRNENs presented increased steadily, along with improved survival outcomes. Grade III-IV, higher TNM stage, liver metastasis, brain metastasis, and without receiving surgery were found to be associated with worse OS and DSS. Advanced age was a risk factor for OS but not DSS. Nomograms for patients with stage II-IV stage CRNENs are capable of predicting the 1-, 3-, and 5-year OS and DSS rates with high accuracy, and realize risk stratification.