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| 2. |
- Knigge, U., et al.
(author)
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ENETS Consensus Recommendations for the Standards of Care in Neuroendocrine Neoplasms : Follow-Up and Documentation
- 2017
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 105:3, s. 310-319
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Journal article (peer-reviewed)abstract
- ENETS consensus recommendations for the standards of care in neuroendocrine neoplasms (NEN) concerning follow-up and documentation are considered in this review. The documentation of patients with NEN should include the most relevant data characterizing an individual patient from the first contact with his/her physician/hospital until his/her last presentation during follow-up. It is advocated that follow-up occurs in specialized NEN centers with regular NEN tumor boards with expert panels. The follow-up should be in accordance with the ENETS consensus guidelines from 2011 and 2016, the present and coming WHO classification and ENETS/UICC recommendations for TNM staging. The recommendations for follow-up in patients with thymic, bronchopulmonary and gastroenteropancreatic NEN are given in Table 1. However, it should be stressed that evidence-based studies for follow-up are largely missing.
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| 4. |
- Baudin, Eric, et al.
(author)
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Unmet Medical Needs in Pulmonary Neuroendocrine (Carcinoid) Neoplasms
- 2019
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 108:1, s. 7-17
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Journal article (peer-reviewed)abstract
- Pulmonary carcinoids (PCs) display the common features of all well-differentiated neuroendocrine neoplasms (NEN) and are classified as low- and intermediate-grade malignant tumours (i.e., typical and atypical carcinoid, respectively). There is a paucity of randomised studies dedicated to advanced PCs and management principles are drawn from the larger gastroenteropancreatic NEN experience. There is growing evidence that NEN anatomic subgroups have different biology and different responses to treatment and, therefore, should be investigated as separate entities in clinical trials. In this review, we discuss the existing evidence and limitations of tumour classification, diagnostics and staging, prognostication, and treatment in the setting of PC, with focus on unmet medical needs and directions for the future.
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| 5. |
- Daskalakis, Kosmas, 1979-, et al.
(author)
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MODIFIED HISTOPATHOLOGICAL GRADING OPTIMIZES PREDICTION OF SURVIVAL OUTCOMES IN SMALL INTESTINAL NEUROENDOCRINE TUMOURS
- 2024
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In: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 111:Suppl. 4
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Journal article (other academic/artistic)abstract
- Background: We aimed to identify optimal grading Ki-67 cut-offs to delineate differences in prognosis of patients with small intestinal neuroendocrine tumours (SI-NETs) in terms of overall- and event-free survival rates.Methods: We included 551 patients with SI-NETs diagnosed from June 15th, 1993, through March 8th, 2021, identified using the SI-NET databases from five European referral centers.Results: Median age at baseline was 62.3(17-90) years; 252 patients were women (45.7%). All tumours were well-differentiated; 326 were G1 tumours (59.2%), 169 G2(30.7%), only 8 G3(1.5%), while 48 tumourswere of unspecified grade (8.7%). The median Ki67 was 2%(1-70%). 247 patients(44.8%) had distant metastases at baseline (stage IV), 217locoregional disease (41.1%; stage III), whereas 29(7.1%) and 25(4.5%) presented at stages II and I, respectively. Within a mean(SD) follow-up of 51.5(52.9) months, 94 patients(17.1%) died, whereas overall 188 experienced disease recurrence, progression and/or death(34.1%). The median OS was 214.7(95%CI: 152.7-276.6) months and the median EFS was 79.8(95%CI: 68.2-91.5) months, respectively. In multivariable Cox-regression OS analysis, age (HR=1.07, 95%CI: 1.04-1.09; p<0.001), Charlson Comorbidity Index(HR=1.1, 95%CI: 1.03-1.17; p=0.006) and the proposed modified histopathological Ki67 grading system(K67:5-10% group: HR=2.4, 95%CI: 1.3-4.5; p=0.007 and K67≥10% group: HR=5.1, 95%CI: 2.9-9.2; p<0.001) were independent predictors for death. Pertinent EFS analysis, confirmed age(HR=1.04, 95%CI: 1.02-1.05;p<0.001) and the proposed modified histopathological Ki67 grading system(K67≥10% group: HR=4; 95%CI:2.5-6.2;p<0.001) as independent predictors for recurrence, progression and/or death.Conclusions: Ki-67 proliferation index is an independent predictor of EFS and OS. A modified site-specific histopathological grading system applying Ki-67 cut-offs of 5% and 10% seems more optimal to predict differences in SI-NET patient prognosis
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| 7. |
- Kaltsas, G., et al.
(author)
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THE EFFECT OF PROPHYLACTIC RIGHT HEMICOLECTOMY ON SURVIVAL AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH WELL-DIFFERENTIATED APPENDICEAL NEUROENDOCRINE NEOPLASMS
- 2020
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In: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 107:Suppl. 2, s. 14-14
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Journal article (other academic/artistic)abstract
- Background: Long-term outcomes, including health-related quality of life (HRQoL) issues are understudied in patients with well-differentiated ppendiceal neuroendocrine neoplasms (WD-ANENs). We aimed to evaluate the validity of currently applied criteria for completion prophylactic right hemicolectomy (pRHC) and determine its association with patient outcomes.Methods: This cohort study included patients with WD-ANENs from five European Centers of Excellence for neuroendocrine tumors. Eligible patients were divided between those who underwent appendectomy alone and those who underwent pRHC. HRQoL EORTCqlqc30 questionnaires and cross-sectional imaging data were prospectively collected.Results: The 166 patients included 119 women (71.2%). Mean age was 31 ± 16 years. Mean follow-up was 51 ± 54 months. Most patients (152[92%]) had tumors≤20 mm. Fifty-eight patients (34.9%) underwent pRHC that was unnecessary in 65.5%(38/58); and in 79.1%(34/43) of tumors≤20 mm. In multivariable analysis, tumor size>20 mm was the only independent predictor for lymph node (LN) positivity(p = 0.021). No disease-specific mortality was reported. Three patients developed recurrence (n = 2inthepRHC group vs. n = 1 in the appendectomy group;p = 0.263). Although global HRQol was not significantly depreciated in patients undergoing pRHC compared to appendectomy alone (median scores 0.79[0.25-1] vs. 0.83[0.08-1], respectively; p = 0.738), impaired social functioning (p = 0.016), diarrhea (p = 0.003) and financial difficulties (0.024) were more frequently reported in the pRHC group. Furthermore, physical-(p = 0.066) and role functioning (p = 0.055), as well as constipation issues(p = 0.072) emerged in the pRHC group with marginal significance.Conclusion: pRHC in WD-ANENs comes at a high rate of unnecessary procedures, functional HRQoL issues and diarrhoea. LN positivity at pRHC may lack prognostic significance, as no disease-specific mortality and scarce recurrence was evident in this series. The validity of contemporary criteria and the value per se of pRHC to patients with WD-ANEN is challenged.
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| 8. |
- Matar, Somer, et al.
(author)
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Blood Chromogranin A Is Not Effective as a Biomarker for Diagnosis or Management of Bronchopulmonary Neuroendocrine Tumors/Neoplasms
- 2020
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 110:3-4, s. 185-197
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Journal article (peer-reviewed)abstract
- Background: Identification of circulating tumor markers for clinical management in bronchopulmonary (BP) neuroendocrine tumors/neoplasms (NET/NEN) is of considerable clinical interest. Chromogranin A (CgA), a "universal" NET biomarker, is considered controversial as a circulating biomarker of BPNEN.Aim: Assess utility of CgA in the diagnosis and management of BPNEN in a multicentric study.Material and Methods: CgA diagnostic metrics were assessed in lung NET/NENs (n = 200) and controls (n = 140), randomly assigned to a Training and Test set (100 BPC and 70 controls in each). Assay specificity was evaluated in neoplastic lung disease (n = 137) and nonneoplastic lung disease (n = 77). CgA efficacy in predicting clinical status was evaluated in the combined set of 200 NET/NENs. CgA levels in bronchopulmonary neuroendocrine tumor (BPNET) subtypes (atypical [AC] vs. typical [TC]) and grade was examined. The clinical utility of an alteration of CgA levels (+/- 25%) was evaluated in a subset of 49 BPNET over 12 months. CgA measurement was by NEOLISA(TM) kit (EuroDiagnostica).Results: Sensitivity and specificity in the training set were 41/98%, respectively. Test set data were 42/87%. Training set area under receiver operator characteristic analysis differentiated BPC from control area under the curve (AUC) 0.61 +/- 0.05 p = 0.015. Test set the data were AUC 0.58 +/- 0.05, p = 0.076. In the combined set (n = 200), 67% BPNET/NEN (n = 134) had normal CgA levels. CgA levels did not distinguish histological subtypes (TC vs. AC, AUC 0.56 +/- 0.04, p = 0.21), grade (p = 0.45-0.72), or progressive from stable disease (AUC 0.53 +/- 0.05 p = 0.47). There was no correlation of CgA with Ki-67 index (Pearson r = 0.143, p = 0.14). For nonneoplastic diseases (chronic obstructive pulmonary disorder and idiopathic pulmonary fibrosis), CgA was elevated in 26-37%. For neoplastic disease (NSCLC, squamous cell carcinoma), CgA was elevated in 11-16%. The neuroendocrine SCLC also exhibited elevated CgA (50%). Elevated CgA was not useful for differentiating BPNET/NEN from these other pathologies. Monitoring BPNET/NEN over a 12-month period identified neither CgA levels per se nor changes in CgA were reflective of somatostatin analog treatment outcome/efficacy or the natural history of the disease (progression).Conclusions: Blood CgA levels are not clinically useful as a biomarker for lung BPNET/NEN. The low specificity and elevations in both nonneoplastic as well as other common neoplastic lung diseases identified limited clinical utility for this biomarker.
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| 9. |
- Nesti, Cedric, et al.
(author)
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Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size : a retrospective, Europe-wide, pooled cohort study
- 2023
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In: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 24:2, s. 187-194
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Journal article (peer-reviewed)abstract
- BackgroundAwareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1–2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1–2 cm in size in patients with or without right-sided hemicolectomy.MethodsIn this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1–2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693.Findings282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1–2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0–15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 –21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36–2·17]; p=0·71).InterpretationThis study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1–2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort.
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