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Tsoli, M., Alexandraki, K. I., Spei, M.-E., Kaltsas, G. A. & Daskalakis, K. (2020). Anti-Tumor Activity and Safety of Multikinase Inhibitors in Advanced and/or Metastatic Thyroid Cancer: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. Hormone and Metabolic Research, 52(1), 25-31
Open this publication in new window or tab >>Anti-Tumor Activity and Safety of Multikinase Inhibitors in Advanced and/or Metastatic Thyroid Cancer: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
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2020 (English)In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 52, no 1, p. 25-31Article, review/survey (Refereed) Published
Abstract [en]

Many trials have demonstrated prime antitumor activity of novel, small molecule multikinase inhibitors (MKIs) in advanced and/or metastatic thyroid cancer (TC). In this work, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, and clinicaltrials.gov databases were searched. Quality/risk of bias were assessed using GRADE criteria. Randomized clinical trials (RCTs) comparing two or more systemic therapies in patients with advanced and/or metastatic thyroid cancer were assessed. A total of 1347 articles and 548 clinical trials in clinicaltrials.gov were screened. We included seven relevant RCTs comprising 1934 unique patients assigned to different MKIs. Two separate network meta-analyses included four RCTs in radioiodine refractory well-differentiated thyroid cancer (RR-WDTC) and three RCTs in medullary thyroid cancer (MTC), respectively; all with a low risk of bias. We identified three therapies for RR-WDTC: sorafenib [disease control rate (DCR) odds ratio (OR): 0.11 (95% CI: 0.03–0.40); progression-free survival (PFS) hazard ratio (HR): 1.99 (95% CI: 1.62–2.46)], vandetanib [DCR_OR:0.26 (95% CI: 0.06–1.24); PFS_HR: 0.99 (95% CI: 0.82–1.20)] and lenvatinib [DCR_OR: 0.26 (95% CI: 0.05–1.33); PFS_HR: 0.99 (95% CI: 0.81–1.22)]; and the following therapies for MTC: vandetanib 300 mg [objective response rate (ORR)_OR: 3.31 (95% CI: 0.68–16.22); vandetanib 150 mg ORR_OR: 0.60 (95% CI: 0.16–2.33)]; and cabozantinib [ORR_OR: 85.32 (95% CI: 5.22–1395.15)]. Serious side effect (SE) analysis per organ/system demonstrated a varying MKI SE profile across both RR-WDTC and MTC diagnoses, more commonly involving metabolic/nutritional disorders [OR: 2.07 [95% CI: 0.82–5.18)] and gastrointestinal SE [OR: 1.63 (95% CI: 1.0–2.66)]. This network meta-analysis on advanced and/or metastatic TC points towards a higher efficacy of lenvatinib in RR-WDTC. The included MKIs exhibit a varying SE profile across different organs/systems favoring a patient-tailored approach with the anticipated toxicities guiding clinicians’ decisions.

Keywords
multikinase inhibitors, advanced, metastatic thyroid cancer, network meta-analysis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-407173 (URN)10.1055/a-1023-4214 (DOI)000508192600003 ()31665790 (PubMedID)
Available from: 2020-03-23 Created: 2020-03-23 Last updated: 2020-03-23Bibliographically approved
Chatzellis, E., Daskalakis, K., Angelousi, A., Tsoli, M., Alexandraki, K. I., Wachula, E., . . . Kaltsas, G. (2020). Authors' Response to the Letter by Lamarca et al. Entitled "Temozolomide-Capecitabine Chemotherapy for Neuroendocrine Neoplasms: The Dilemma of Treatment Duration" Regarding "Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms" [Letter to the editor]. Neuroendocrinology, 110(1-2), 158-160
Open this publication in new window or tab >>Authors' Response to the Letter by Lamarca et al. Entitled "Temozolomide-Capecitabine Chemotherapy for Neuroendocrine Neoplasms: The Dilemma of Treatment Duration" Regarding "Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms"
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2020 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 110, no 1-2, p. 158-160Article in journal, Letter (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-407164 (URN)10.1159/000503999 (DOI)000507623200016 ()31597137 (PubMedID)
Available from: 2020-03-20 Created: 2020-03-20 Last updated: 2020-03-20Bibliographically approved
Chatzellis, E., Angelousi, A., Daskalakis, K., Tsoli, M., Alexandraki, K. I., Wachula, E., . . . Kaltsas, G. (2019). Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms. Neuroendocrinology, 109(4), 333-345
Open this publication in new window or tab >>Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 109, no 4, p. 333-345Article in journal (Refereed) Published
Abstract [en]

Background: Capecitabine and temozolomide combination (CAPTEM) is associated with high response rates in patients with advanced neuroendocrine neoplasms (NENs). We evaluated the real-world activity and safety of CAPTEM from 3 NEN centers. Methods: Clinicopathological characteristics and outcomes of patients treated with CAPTEM for bulky or progressive disease (PD) were retrospectively analyzed. -Results: Seventy-nine patients with gastroenteropancreatic (grades 1-2 [n = 38], grade 3 [n = 24]) and lung/thymic (n = 17) NENs were included. Median treatment duration was 12.1 months (range 0.6-55.6). Overall, partial responses (PRs) occurred in 23 (29.1%), stable (SD) in 24 (30.4%), and PD in 28 (35.4%) patients. Median progression-free survival (PFS) and overall survival (OS) were 10.1 (6-14.2) and 102.9 months (43.3-162.5), respectively. On univariate analysis, NENs naive to chemotherapy and low Ki67 were associated with favorable responses (partial response [PR] + SD; p = 0.011 and 0.045), PFS (p < 0.0001 and 0.002) and OS (p = 0.005 and 0.001). Primary site (pancreas and lung/thymus) was also a significant prognostic factor for PFS (p < 0.0001) and OS (p < 0.0001). On multivariate analysis, gastrointestinal and unknown primary NENs (hazard ratio [HR] 0.3, 95% CI 0.1-0.8, p = 0.009 and p = 0.018) and prior surgery (HR 2.4, 95% CI 11-4.9, p = 0.021) were independent prognostic factors for PFS. Ki-67 was a poor predictor for favorable response in receiver operating characteristic analysis (area under the curve 0.678). Safety analysis of CAPTEM indicated rare events of serious (grades 3-4) toxicities (n = 4) and low discontinuation rates (n = 8) even in patients with prolonged administration (>12 months). Conclusions: CAPTEM treatment can be an effective and safe treatment even after prolonged administration for patients with NENs of various sites and Ki67 labeling index, associated with significant favorable responses and PFS.

Place, publisher, year, edition, pages
S. Karger, 2019
Keywords
Temozolomide, Capecitabine, Capecitabine and temozolomide combination, TEMCAP, Neuroendocrine neoplasms, Neuroendocrine tumors
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-398579 (URN)10.1159/000500135 (DOI)000497719000005 ()31167197 (PubMedID)
Available from: 2019-12-09 Created: 2019-12-09 Last updated: 2019-12-09Bibliographically approved
Daskalakis, K., Tsoli, M., Angelousi, A., Kassi, E., Alexandraki, K. I., Kolomodi, D., . . . Koumarianou, A. (2019). Anti-tumour activity of everolimus and sunitinib in neuroendocrine neoplasms. Endocrine Connections, 8(6), 641-653
Open this publication in new window or tab >>Anti-tumour activity of everolimus and sunitinib in neuroendocrine neoplasms
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2019 (English)In: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 8, no 6, p. 641-653Article in journal (Refereed) Published
Abstract [en]

Comparisons between everolimus and sunitinib regarding their efficacy and safety in neuroendocrine neoplasms (NENs) are scarce. We retrospectively analysed the clinicopathological characteristics and outcomes in 92 patients with well-differentiated (WD) NEN of different origin (57 pancreatic NENs (PanNENs)), treated with molecular targeted therapy (MTT) with everolimus or sunitinib, first- (73: 19) or second-line (sequential; 12: 22) for progressive disease. Disease control rates (DCR: partial response or stable disease) at first-line were higher in all patients treated with everolimus than sunitinib (64/73 vs 12/19, P = 0.012). In PanNENs, DCR at first-line everolimus was 36/42 versus 9/15 with sunitinib (P = 0.062). Progression-free survival (PFS) at first-line everolimus was longer than sunitinib (31 months (95% CI: 23.1-38.9) vs 9 months (95% CI: 0-18.5); log-rank P < 0.0001) in the whole cohort and the subset of PanNENs (log-rank P < 0.0001). Median PFS at second-line MTT was 12 months with everolimus (95% CI: 4.1-19.9) vs 13 months with sunitinib (95% CI: 9.3-16.7; log-rank P = 0.951). Treatment with sunitinib (HR: 3.47; 95% CI: 1.5-8.3; P value: 0.005), KI67 > 20% (HR: 6.38; 95% CI: 1.3-31.3; P = 0.022) and prior chemotherapy (HR: 2.71; 95% CI: 1.2-6.3; P = 0.021) were negative predictors for PFS at first line in multivariable and also confirmed at multi-state modelling analyses. Side effect (SE) analysis indicated events of serious toxicities (Grades 3 and 4: n = 13/85 for everolimus and n = 4/41 for sunitinib). Discontinuation rate due to SEs was 20/85 for everolimus versus 4/41 for sunitinib (P = 0.065). No additive toxicity of second-line MTT was confirmed. Based on these findings, and until reliable predictors of response become available, everolimus may be preferable to sunitinib when initiating MTT in progressive NENs.

Place, publisher, year, edition, pages
Bioscientifica, 2019
Keywords
neuroendocrine neoplasms, molecular targeted therapy, everolimus, sunitinib
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-390599 (URN)10.1530/EC-19-0134 (DOI)000472586000004 ()31026812 (PubMedID)
Funder
Swedish Society of Medicine
Available from: 2019-08-13 Created: 2019-08-13 Last updated: 2019-08-13Bibliographically approved
Daskalakis, K., Norlén, O., Hellman, P. & Stålberg, P. (2019). Applying the use of novel biomarkers for neuroendocrine tumors in the clinic: where are we now?. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY, 6(1), Article ID IJE14.
Open this publication in new window or tab >>Applying the use of novel biomarkers for neuroendocrine tumors in the clinic: where are we now?
2019 (English)In: INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY, ISSN 2045-0869, Vol. 6, no 1, article id IJE14Article in journal, Editorial material (Other academic) Published
Keywords
biomarkers, neuroendocrine tumors, prognosis, targeted therapy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-399971 (URN)10.2217/ije-2017-0012 (DOI)000498810800003 ()
Available from: 2019-12-18 Created: 2019-12-18 Last updated: 2019-12-18Bibliographically approved
Daskalakis, K., Chatzelis, E., Tsoli, M., Papadopoulou-Marketou, N., Dimitriadis, G. K., Tsolakis, A. V. & Kaltsas, G. (2019). Endocrine paraneoplastic syndromes in patients with neuroendocrine neoplasms. Endocrine (Basingstoke), 64(2), 384-392
Open this publication in new window or tab >>Endocrine paraneoplastic syndromes in patients with neuroendocrine neoplasms
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2019 (English)In: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 64, no 2, p. 384-392Article in journal (Refereed) Published
Abstract [en]

Objective: Our aim was to assess the prevalence of endocrine paraneoplastic syndromes (EPNS) in neuroendocrine neoplasms (NENs) and estimate its impact on patient outcomes.

Design: This is a retrospective analysis of 834 patients with NENs (611 gastrointestinal, 166 thoracic, 57 of unknown and various other primary origin). We included 719 consecutive NEN patients treated at EKPA-Laiko Hospital, Athens, Greece and 115 patients with lung carcinoid (LC) treated at Uppsala University Hospital, Uppsala, Sweden. EPNS diagnosis was based on standard criteria.

Methods: Twenty-one patients with EPNS were detected: 16 with ectopic Cushing's syndrome (ECS), one with hypercalcaemia due to parathyroid hormone-related protein (PTHrP) secretion, three with hypercalcitonaemia and one patient with dual secretion of calcitonin and beta-human chorionic gonadotropin (-HCG). All tumours were well-differentiated; 10 patients had Stage IV disease at diagnosis.

Results: The prevalence of EPNS in the Greek cohort was 1.9%, whereas that of ECS among LC patients in both centres was 6.7%. Median overall survival (OS) for patients with EPNS was 160.7 months (95%CI, 86-235.4) and median event-free survival (EFS) was 25.9 months (95%CI, 0-57.2). Patients presenting with EPNS prior to NEN diagnosis had longer EFS compared to patients with synchronous or metachronous EPNS (log-rank P=0.013). Patients with ECS of extra-thoracic origin demonstrated shorter OS and EFS compared to patients with ECS of lung or thymic origin (log-rank P=0.001 and P<0.001, respectively). LC patients with and without ECS were comparable in 5-year and 10-year OS rates (66.7% and 33.3% versus 89.8% and 60.2%, respectively; 95%CI [189.6-300.4 months], log-rank P=0.94) and in median EFS, 67 versus 183 months, 95%CI [50.5-207.5], log-rank P=0.12).

Conclusion: EPNS are relatively rare in patients with NENs and mainly concern well-differentiated tumours of the foregut. Among patients with EPNS, LC-related ECS may not adversely affect patient outcomes when diagnosed prior to NEN and effectively been treated.

Place, publisher, year, edition, pages
SPRINGER, 2019
Keywords
Paraneoplastic syndrome, Neuroendocrine tumours, Ectopic Cushing's syndrome, Hypercalcitonaemia, PTHrP secretion
National Category
Endocrinology and Diabetes Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-386165 (URN)10.1007/s12020-018-1773-3 (DOI)000468840200021 ()30280284 (PubMedID)
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-06-20Bibliographically approved
Tsolakis, A. V., Ragkousi, A., Vujasinovic, M., Kaltsas, G. & Daskalakis, K. (2019). Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis. World Journal of Gastroenterology, 25(35), 5376-5387
Open this publication in new window or tab >>Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis
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2019 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 25, no 35, p. 5376-5387Article, review/survey (Refereed) Published
Abstract [en]

BACKGROUND

To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated.

AIM

To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters.

METHODS

The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis.

RESULTS

We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3% (25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8; heterogeneity: P = 0.126; I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2; 95%CI: 1.8-161.1; heterogeneity: P = 0.165; I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2; 95%CI: 0.3-11.6; heterogeneity: P = 0.304; I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3; 95%CI: 0.1-1.1; heterogeneity: P = 0.173; I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively.

CONCLUSION

This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5-year disease-specific survival rates reported; hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Place, publisher, year, edition, pages
BAISHIDENG PUBLISHING GROUP INC, 2019
Keywords
Gastric neuroendocrine neoplasms type 1, Meta-analysis, Lymph node metastasis, Tumor size, Invasion, Endoscopy, Surgery
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-395747 (URN)10.3748/wjg.v25.i35.5376 (DOI)000487245400012 ()31558880 (PubMedID)
Funder
Swedish Society of Medicine, SLS-785911
Available from: 2019-10-24 Created: 2019-10-24 Last updated: 2019-10-24Bibliographically approved
Daskalakis, K., Tsoli, M., Srirajaskanthan, R., Chatzellis, E., Alexandraki, K., Angelousi, A., . . . Weickert, M. O. (2019). Lung Metastases in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Neoplasms: An Appraisal of the Validity of Thoracic Imaging Surveillance. Neuroendocrinology, 108(4), 308-316
Open this publication in new window or tab >>Lung Metastases in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Neoplasms: An Appraisal of the Validity of Thoracic Imaging Surveillance
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2019 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 4, p. 308-316Article in journal (Refereed) Published
Abstract [en]

Background/Aims: To evaluate the impact of lung metastases (LM) on overall survival (OS) in well-differentiated (WD) stage IV gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) patients along with developing surveillance strategies for thoracic imaging. Methods: Thirty-four patients with LM, from 3 centres, were identified (22 small intestine/12 pancreatic; 17 grade 1/15 grade 2/2 of unknown grade). For comparison, we used 106 stage IV WD, grade 1 and 2 GEP-NEN patients with metastatic disease confined in the abdomen. Results: LM prevalence was 4.9% (34/692). Eleven patients (32%) presented with synchronous LM whereas 23 (68%) developed metachronous LM at a median of 25 months (range 1-150 months). Patients with metachronous LM had already established liver and/or para-aortic lymph node metastases. Eighteen of 23 patients (78%) with metachronous LM exhibited concomitant progression in the abdomen. Median OS of WD GEP-NEN patients with LM was shorter than for those with stage IV disease without extra-abdominal metastases (56 [95% CI 40.6-71.6] vs. 122.7 [95% CI 70.7-174.8] months; log-rank p = 0.001). Among patients with progressive stage IV disease, the subset of patients with LM exhibited shorter OS (log-rank p = 0.005). LM were also confirmed as an independent prognostic factor for survival in multivariable analysis (HR 0.18; 95% CI 0.07-0.45; p< 0.0001). Conclusion: LM, although relatively rare in patients with WD stage IV GEP-NENs, may impact patients' outcome. The development of metachronous LM is associated with concomitant disease progression in established abdominal metastases in most patients. These patient-related parameters could be utilized for a stratified surveillance approach, mainly reserving thoracic imaging for GEP-NEN patients with progressive disease in the abdomen.

Place, publisher, year, edition, pages
KARGER, 2019
Keywords
Lung metastases, Well-differentiated neoplasms, Gastroenteropancreatic neuroendocrine neoplasms
National Category
Endocrinology and Diabetes Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-389989 (URN)10.1159/000497183 (DOI)000471962300004 ()30673674 (PubMedID)
Available from: 2019-08-02 Created: 2019-08-02 Last updated: 2019-08-02Bibliographically approved
Daskalakis, K., Tsoli, M., Alexandraki, K. I., Angelousi, A., Chatzellis, E., Tsolakis, A. V., . . . Kaltsas, G. (2019). Magnetic Resonance Imaging or Endoscopic Ultrasonography for Detection and Surveillance of Pancreatic Neuroendocrine Neoplasms in Patients with Multiple Endocrine Neoplasia Type 1?. Hormone and Metabolic Research, 51(9), 580-585
Open this publication in new window or tab >>Magnetic Resonance Imaging or Endoscopic Ultrasonography for Detection and Surveillance of Pancreatic Neuroendocrine Neoplasms in Patients with Multiple Endocrine Neoplasia Type 1?
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2019 (English)In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 51, no 9, p. 580-585Article in journal (Refereed) Published
Abstract [en]

Our aim was to compare the clinical utility of Magnetic Resonance Imaging (MRI) and Endoscopic Ultrasonography (EUS) in identifying Pancreatic Neurondocrine Neoplasms (PanNENs) and monitoring size alterations in Multiple Endocrine Neoplasia type 1 (MEN1) patients. Thirty-one MEN1 patients with PanNENs and concurrent screening by EUS and abdominal MRI were included and 129 pancreatic lesions were detected in total. MRI detected fewer lesions than EUS (n=73 vs. 110, p=0.006). MRI sensitivity and specificity compared to EUS at 20 and 10 mm cut-offs of maximal lesion diameter were 96 and 88% (20 mm cut-off) and 90 and 82%(10 mm cut-off), respectively (concordance rates of 97 and 87% and Cohen's kappa=0.912 and 0.718, respectively). Lesions<1 cm were more often detected with EUS (p=0.025). Data from sequential concurrent imaging on lesion growth rate [n=7 (mean +/- SD: 2 mm/year +/- 3.4 mm vs. 1.9 mm/year +/- 3.6 mm)] over a period of at least two years as well as pathology data in connection to preoperative concurrent imaging were available in a small number of patients (n=7, p=0.933 for mean differences in maximal lesion diameter). MRI of the pancreas was more readily available and less expensive than EUS in an outpatient setting. In conclusion, MRI performs well compared to EUS for the detection and subsequent surveillance of MEN1-related panNENs larger than 10 mm and seems to be cost-effective. Both modalities could be used at initial assessment and MRI alone could be utilized thereafter in patient surveillance. EUS retains its value in surgical planning and the detection of small mostly functional PanNENs.

Place, publisher, year, edition, pages
GEORG THIEME VERLAG KG, 2019
Keywords
multiple endocrine neoplasia type 1, neuroendocrine tumor, magnetic resonance imaging, endoscopic ultrasonography
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-394691 (URN)10.1055/a-0931-7005 (DOI)000485005700004 ()31295747 (PubMedID)
Available from: 2019-10-24 Created: 2019-10-24 Last updated: 2019-10-24Bibliographically approved
Daskalakis, K., Tsoli, M., Karapanagioti, A., Chrysochoou, M., Thomas, D., Sougioultzis, S., . . . Alexandraki, K. I. (2019). Recurrence and metastatic potential in Type 1 gastric neuroendocrine neoplasms. Clinical Endocrinology, 91(4), 534-543
Open this publication in new window or tab >>Recurrence and metastatic potential in Type 1 gastric neuroendocrine neoplasms
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2019 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 91, no 4, p. 534-543Article in journal (Refereed) Published
Abstract [en]

Background The aim of our study was to assess clinico-pathological and biochemical parameters of Type 1 Gastric Neuroendocrine Neoplasms (GNEN1) with respect to tumours propensity for recurrence and metastasis. Methods Hospital charts of GNEN1 patients were reviewed at a single tertiary referral centre. Results We included 114 consecutive patients (74 women; age at baseline 54.5 +/- 12.7 years [mean +/- SD]) with GNEN1. All tumours (n = 114) were well differentiated; Grade 1 (G1) accounted for 56 patients (49%), whereas 46 (40%) were Grade 2 (G2) and 12 (11%) of unknown Grade. Overall follow-up encompassed 45.3 +/- 46 (mean +/- SD) months in 84 patients who were subjected to annual surveillance; 44 (52%) developed recurrence in the stomach during follow-up with 22 experiencing multiple recurrences; three (2.6%) presented with metastases in locoregional lymph nodes (n = 3) and/or the liver (n = 2); No metastasis or death was reported during follow-up. Median recurrence-free survival (RFS) was 31 months (95% CI: 7.6-54.4). Among clinico-pathological and biochemical parameters investigated, endoscopic intervention compared with surgery (P-value = .009) and higher serum-gastrin levels (s-gastrin) at baseline and first-year follow-up were associated with recurrence (P-value = .022 and .003 respectively) and also shorter RFS (log-rank P = .009 for type of intervention and .014 for s-gastrin, respectively). Receiver Operator Curve analysis of s-gastrin levels at first-year follow-up for recurrence demonstrated an area under the curve of 0.702. Conclusion Despite the relatively high prevalence of G2 tumours, endoscopically and/or surgically treated GNEN1 remains an indolent disease with a low metastatic propensity and no disease-specific mortality reported in our series. Many patients though will experience local recurrence, warranting long-term endoscopic surveillance with s-gastrin biomarker being a complementary tool in recurrence prediction.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
gastrin, recurrence, Type 1 gastric neuroendocrine neoplasm
National Category
Endocrinology and Diabetes Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-396147 (URN)10.1111/cen.14055 (DOI)000474457100001 ()31254407 (PubMedID)
Available from: 2019-11-04 Created: 2019-11-04 Last updated: 2019-11-04Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-4224-8912

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