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Background: Metastatic neuroendocrine carcinoma (NEC) is associated with short survival. Other than platinum-based chemotherapy, there is no clear standard regimen. Current guidelines suggest that combination treatment with BRAF-inhibitors should be considered for patients with BRAF V600E-mutated NEC. However, since only eight such patients have been reported in the literature, our object was to confirm the validity of this recommendation. Methods: This was a single-center retrospective cohort study conducted at Uppsala University Hospital. The included patients 1) had a histopathologically confirmed diagnosis of NEC, 2) were diagnosed between January 1st, 2018 and December 31st, 2023, 3) had tumor tissue genetically screened by a broad next-generation sequencing (NGS) panel, and 4) showed a tumor mutation for which there is a currently available targeted therapy. Results: We screened 48 patients diagnosed with NEC between January 1st, 2018 and December 31st, 2023. Twelve had been analyzed with a broad NGS-panel, and two had a targetable mutation. Both these patients harbored a BRAF V600E-mutated colon-NEC and were treated with BRAF- and MEK-inhibitors dabrafenib and trametinib in second-line. At first radiological evaluation (RECIST 1.1), both patients had a reduction of tumor size, which decreased by 31 and 40%. Both had short response periods, and their overall survival was 12 and 9 months. Conclusions: BRAF-mutated NEC is sensitive to treatment with BRAF- and MEK-inhibitor combination. These results further support that DNA sequencing should be considered as standard of care in NECs to screen for potential treatment targets.
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Carcinoma Neuroendocrino , Oximas , Inhibidores de Proteínas Quinasas , Proteínas Proto-Oncogénicas B-raf , Piridonas , Pirimidinonas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/tratamiento farmacológico , Secuenciación de Nucleótidos de Alto Rendimiento , Imidazoles/uso terapéutico , Imidazoles/administración & dosificación , Mutación , Oximas/uso terapéutico , Oximas/administración & dosificación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , Piridonas/uso terapéutico , Piridonas/administración & dosificación , Pirimidinonas/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Several inflammation scores have shown association with survival outcomes for patients with neuroendocrine tumours (NET) treated with peptide receptor radionuclide therapy (PRRT). However, whether these scores add value to established prognostic factors remains unknown. In this retrospective, cohort study of 557 NET patients undergoing PRRT in a tertiary referral centre from 2005 to 2015, we examined inflammatory markers and scores previously associated with cancer outcomes, using Cox proportional hazard models and Akaike's information criterion. Lower albumin (hazard ratio [95% confidence interval], .91 [.87-.95] per unit), as well as higher C-reactive protein (CRP; 1.02 [1.01-1.02]), Glasgow Prognostic Score (GPS; 1 vs. 0: 1.67 [1.14-2.44], 2 vs. 0 3.60 [2.24-5.79]), CRP/albumin ratio (1.84 [1.43-2.37]) and platelet count (Plt) × CRP, but not white blood cell, neutrophil and thrombocyte counts or derived neutrophil to lymphocyte ratio (dNLR), were associated with shorter median overall survival (OS) in an adjusted analysis. The addition of parameters based on albumin and CRP, but not dNLR, to a base model including age, chromogranin A, the cell proliferation marker Ki-67, performance status, tumour site and previous treatments improved the predictive accuracy of the base model. In an exploratory analysis of patients with available erythrocyte sedimentation rate (ESR) and CRP, ESR emerged as the most powerful predictor. When added to a prognostic model for OS in NET patients treated with PRRT, most inflammation scores further improved the model. Albumin was the single marker adding most value to the set of established prognostic markers, whereas dNLR did not seem to improve the model's prognostic ability.
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Tumour evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumours (PanNETs) in particular, show frequent progression from a low/intermediate to a high-grade disease. To understand the molecular mechanisms underlying this phenomenon, we performed multi-omics analysis of 32 longitudinal samples from six metastatic PanNET patients. Following MEN1 inactivation, PanNETs exhibit genetic heterogeneity on both spatial and temporal dimensions with parallel and convergent tumuor evolution involving the ATRX/DAXX and mTOR pathways. Following alkylating chemotherapy treatment, some PanNETs develop mismatch repair deficiency and acquire a hypermutator phenotype. This DNA hypermutation phenotype was only found in cases that also showed transformation into a high-grade PanNET. Overall, our findings contribute to broaden the understanding of metastatic PanNET, and suggests that therapy driven disease evolution is an important hallmark of this disease.
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This ENETS guidance paper aims to provide practical advice to clinicians for the diagnosis, treatment and follow-up of functioning syndromes in pancreatic neuroendocrine tumours (NET). A NET-associated functioning syndrome is defined by the presence of a clinical syndrome combined with biochemical evidence of inappropriately elevated hormonal levels. Different hormonal syndromes can be encountered in pancreatic NET patients, including insulinoma, gastrinoma as well as the rare glucagonoma, VIPoma, ACTHoma, PTHrPoma, carcinoid syndrome, calcitoninoma, GHRHoma and somatostatinoma. The recommendations provided in this paper focus on the biochemical, genetic and imaging work-up as well as therapeutic management of the individual hormonal syndromes in well-differentiated, grade 1-3, functioning NET with the primary tumour originating in the pancreas, and for specific subtypes also in the duodenum.
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Gastrinoma , Glucagonoma , Insulinoma , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Insulinoma/diagnóstico , Insulinoma/terapia , Gastrinoma/diagnóstico , Gastrinoma/terapia , Glucagonoma/diagnóstico , Glucagonoma/terapiaRESUMEN
Lung neuroendocrine neoplasms (NEN) are a heterogeneous population of neoplasms with different pathology, clinical behavior, and prognosis compared to the more common lung cancers. The diagnostic work-up and treatment of patients with lung- NEN has undergone major recent advances and new methods are currently being introduced into the clinic. These Nordic guidelines summarize and update the Nordic Neuroendocrine Tumor Group's current view on how to diagnose and treat lung NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients. This review reflects our view of the current state of the art of diagnosis and treatment of patients with lung-NEN. Small cell lung carcinoma (SCLC) is not included in these guidelines.
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Carcinoma Neuroendocrino , Neoplasias Pulmonares , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/terapia , Tumores Neuroendocrinos/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Pronóstico , Pulmón/patología , Neoplasias Pancreáticas/patologíaRESUMEN
Small intestinal neuroendocrine tumours (Si-NET) are often studied as a uniform group. Proliferation index Ki-67 influences prognosis and determines tumour grade. We hypothesized that Si-NET grade 2 (G2) tumours, which have a higher Ki-67 than G1 tumours, might benefit less from established treatments for metastatic disease. We conducted a retrospective cohort study of 212 patients with metastatic Si-NET G2 treated in two Swedish hospitals during 20 years (2000-2019). Median cancer-specific survival on first-line somatostatin analogues (SSA) was 77 months. Median progression-free survival (PFS) was 12.4 months when SSA was given as monotherapy and 19 months for all patients receiving first-line SSA. PFS after SSA dose escalation was 6 months in patients with radiological progression. Treatment efficacies of SSA and peptide receptor radionuclide treatment (PRRT) were studied separately in patients with Ki-67 of 3-5%, 5-10% and 10-20%. For SSA, PFS was significantly shorter at higher Ki-67 levels (31, 18 and 10 months, respectively), while there was only a minor difference in PFS for PRRT (29, 25 and 25 months). Median PFS for sequential treatment with interferon-alpha (IFNα), everolimus and chemotherapy was 6, 5 and 9 months. IFNα seemed to be effective in tumours with low somatostatin-receptor expression. In conclusion, established treatments appeared effective in Si-NET G2, despite their higher proliferation index compared to G1 tumours. However, efficacy of SSA but not PRRT was reduced at higher Ki-67 levels. SSA dose escalation provided limited disease stabilization.
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Tumores Neuroendocrinos , Octreótido , Humanos , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/radioterapia , Tumores Neuroendocrinos/metabolismo , Estudios Retrospectivos , Antígeno Ki-67/metabolismo , Resultado del Tratamiento , Somatostatina/uso terapéutico , Radioisótopos/uso terapéuticoRESUMEN
BACKGROUND: The use of liver transplantation (LT) in patients with stage IV neuroendocrine pancreatic tumors (pan-NET) is under debate. Previous studies report a 5-year survival of 27-53% after LT in pan-NET and up to 92.7% in patients with mixed NETs. This study aimed to determine survival rates of patients with stage IV pan-NET meeting criteria for LT while only subjected to multimodal treatment. METHODS: Medical records of patients with pan-NET diagnosed from 2000 to 2021 at a tertiary referral center were evaluated for eligibility. Patients without liver metastases, who did not undergo primary tumor surgery, age > 75 years and with grade 3 tumors were excluded. The patients were divided into groups; all included patients, patients meeting the Milan, the United Network for Organ Sharing (UNOS) or the European Neuroendocrine Tumor Society (ENETS) criteria for LT. Kaplan-Meier survival analysis was used to calculate overall survival. RESULTS: Out of 519 patients with pan-NET, 41 patients were included. Mean follow-up time was 5.4 years. Overall survival was 9.3 years (95% Cl 6.8-11.7), and 5-year survival was 64.7% (95% CI 48.2-81.2). Patients meeting the Milan, ENETS and UNOS criteria for LT had a 5-year survival of 64.9% (95% CI 32.2-97.6), 85.7% (95% CI 59.8-100.0) and 55.4% (95% CI 26.0-84.8), respectively. CONCLUSIONS: In patients with stage IV pan-NET, grade 1 and 2, with no extra abdominal disease, 5-year survival was 64.7% (95% CI 48.2-81.2). As these survival rates exceed previously published series of LT for pan-NET, the evidence base for this treatment is very weak.
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Neoplasias Hepáticas , Trasplante de Hígado , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Anciano , Neoplasias Hepáticas/secundario , Estimación de Kaplan-Meier , Neoplasias Pancreáticas/cirugía , Tumores Neuroendocrinos/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Hemangioblastomas of the central nervous system are a prominent feature of von Hippel-Lindau-disease (vHL). Hemangioblastomas are known to secrete vascular endothelial growth factor (VEGF), suggesting a potential role of VEGF as a biomarker for tumor growth. METHODS: Plasma VEGF samples from 24 patients with von Hippel-Lindau disease were analyzed by solid-phase proximity ligation assay (PLA). Levels were monitored over time together with numeric and volumetric CNS tumor burden, and compared to plasma VEGF levels in healthy controls. RESULTS: The mean yearly progression in tumor volume was 65.5%. Yearly risk of developing one or several new CNS tumor(s) was 50%. No significant correlation between tumor burden and levels of VEGF was seen. VEGF levels in patients (31.55-92.04; mean 55.83, median 56.41) as measured by immunodetection in a solid-phase PLA did not differ significantly from controls (37.38-104.56; mean 58.89, median 54.12) (p = 0,266). CONCLUSION: The increase in total CNS tumor volume in vHL occurred in a saltatory manner. The risk of developing a new lesion was 50% per year. We found no evidence for VEGF secretion from CNS hemangioblastomas in vHL in circulating blood. Other potential biomarkers should be explored to assess progression of tumor burden in vHL.
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Neoplasias del Sistema Nervioso Central , Hemangioblastoma , Enfermedad de von Hippel-Lindau , Humanos , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular , Sistema Nervioso CentralRESUMEN
Paragangliomas of the head and neck are rare tumours arising from extraadrenal ganglia. They are highly vascular lesions and are normally benign and not hormone secreting. Symptoms are usually discreet and the tumours often present as a lump in the neck or are diagnosed incidentally. Evaluation of paragangliomas of the head and neck, and surgery when indicated, is highly specialized care to be performed at two hospitals nationwide (in Region Uppsala and Region Skåne). Historically, treatment has mainly been surgical. However, with a multidisciplinary evaluation of each case recommendations can be individualized and treatment options may include surgery, radiotherapy or watchful waiting (wait-and-scan). When surgery is recommended for paragangliomas of the neck, it is best performed in collaboration between head-neck surgeons and vascular surgeons. Follow up in benign cases is mainly done through imaging.
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Tumor Glómico , Neoplasias de Cabeza y Cuello , Paraganglioma , Humanos , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/terapia , Paraganglioma/diagnóstico , Paraganglioma/cirugía , Diagnóstico por ImagenRESUMEN
There is an unmet need for novel biomarkers to diagnose and monitor patients with neuroendocrine neoplasms. The EXPLAIN study explores a multi-plasma protein and supervised machine learning strategy to improve the diagnosis of pancreatic neuroendocrine tumors (PanNET) and differentiate them from small intestinal neuroendocrine tumors (SI-NET). At time of diagnosis, blood samples were collected and analyzed from 39 patients with PanNET, 135 with SI-NET (World Health Organization Grade 1-2) and 144 controls. Exclusion criteria were other malignant diseases, chronic inflammatory diseases, reduced kidney or liver function. Prosed Oncology-II (i.e., OLink) was used to measure 92 cancer related plasma proteins. Chromogranin A was analyzed separately. Median age in all groups was 65-67 years and with a similar sex distribution (females: PanNET, 51%; SI-NET, 42%; controls, 42%). Tumor grade (G1/G2): PanNET, 39/61%; SI-NET, 46/54%. Patients with liver metastases: PanNET, 78%; SI-NET, 63%. The classification model of PanNET versus controls provided a sensitivity (SEN) of 0.84, specificity (SPE) 0.98, positive predictive value (PPV) of 0.92 and negative predictive value (NPV) of 0.95, and area under the receiver operating characteristic curve (AUROC) of 0.99; the model for the discrimination of PanNET versus SI-NET providing a SEN 0.61, SPE 0.96, PPV 0.83, NPV 0.90 and AUROC 0.98. These results suggest that a multi-plasma protein strategy can significantly improve diagnostic accuracy of PanNET and SI-NET.
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Neoplasias Intestinales , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Anciano , Biomarcadores , Proteínas Sanguíneas , Femenino , Humanos , Neoplasias Intestinales/diagnóstico , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologíaRESUMEN
In May 1982, the US Food and Drug Administration (FDA) approved the use of streptozotocin to treat pancreatic neuroendocrine tumors (panNETs). Thus, this year marks 40 years since that landmark date. This review of streptozotocin to treat panNETs is intended to commemorate this anniversary. A historical perspective of the chemical structure, pharmacokinetics, and mechanism of action of streptozotocin is followed by data from prospective and retrospective clinical studies. The last section of the review addresses the latest aspects and takes note of the prospects that lie ahead on the future horizon of the use of streptozotocin to treat panNETs, including ongoing clinical trials.
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Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/patología , Estreptozocina/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patologíaRESUMEN
Lutetium peptide receptor radio nuclide therapy (Lu-PRRT) is an effective treatment for progressive, metastatic, somatostatin-receptor-positive, well-differentiated neuroendocrine tumours (WD-NETs). Here, we report a single centre experience of real-world efficacy, long-term side effects, and challenges of this treatment. This was a retrospective analysis. All patients linked with our centre who had Lu-PRRT were included. Clinicopathological data were analysed using descriptive statistics, Kaplan-Meier, and Cox regression. A total of 45 patients had Lu-PRRT, of those 30 (67%) were males, and 13 (29%) were more than 65 years old. The primary site was small intestine in 30 (67%) patients, pancreas in seven (16%) patients, and lung in three (7%) patients. The tumor was grade 1 in 15 (35%) patients, grade 2 in 22 (48%) patients, and grade 3 in six (13%) patients. A total of 41 (91%) patients had liver metastasis, and 20 (44%) patients had carcinoid syndrome. Lu-PRRT was the second-line therapy in all patients. Krenning's score was 4 in 36 (80%) patients and 3 in nine (20%) patients. The median waiting time to start Lu-PRRT therapy was 87 days. The median follow-up was 41 months. A total of 23 (51%) patients had a partial response, 18 (40%) patients had stable disease, and four (9%) patients had progression. None of the patients had a complete response. The median progression-free survival (PFS) was 38 months (95% CI: 25.8-50.1). The median overall survival (OS) was not reached. Nine patients died during follow-up (death from any cause). Prior treatment with targeted therapies or high dose somatostatin analogues were negative predictors of Lu-PRRT outcome (p-values of < .001 and < .045, respectively). There were two serious haematological toxicities, one patient developed acute myeloid leukaemia (AML), and the other developed chronic myeloid leukaemia (CML). Lu-PRRT is an effective second-line treatment for metastatic WD-NETs. The effect of targeted therapies on Lu-PRRT outcome was significant and needs to be clarified in further studies.
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Tumores Neuroendocrinos , Anciano , Femenino , Humanos , Lutecio/uso terapéutico , Masculino , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/radioterapia , Radioisótopos/uso terapéutico , Receptores de Péptidos , Estudios Retrospectivos , SomatostatinaRESUMEN
Longitudinal changes in pancreatic neuroendocrine tumor (panNET) cell proliferation correlate with fast disease progression and poor prognosis. The optimal treatment strategy for secondary panNET grade (G)3 that has progressed from a previous low- or intermediate-grade to high-grade panNET G3 is currently unknown. This was a single-center retrospective cohort study aimed to characterize treatment patterns and outcomes among patients with secondary panNET-G3. Radiological responses were assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A total of 22 patients were included and received a median of 2 (range, 1-4) treatment lines in 14 different combinations. Median overall survival (OS) was 9 months (interquartile range (IQR): 4.25-17.5). For the 15 patients who received platinum-etoposide chemotherapy, median OS was 7.5 months (IQR: 3.75-10) and median progression-free survival (PFS) was 4 months (IQR: 2.5-5.5). The 15 patients who received conventional panNET therapies achieved a median OS of 8 months (IQR: 5-16.75) and median PFS was 5.5 months (IQR: 2.75-8.25). We observed one partial response on 177Lu DOTA-TATE therapy. In conclusion, this hypothesis-generating study failed to identify any promising treatment alternatives for patients with secondary panNET-G3. This demonstrates the need for both improved biological understanding of this particular NET entity and for designing prospective studies to further assess its treatment in larger patient cohorts.
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The European Neuroendocrine Tumor Society (ENETS) promotes practices and procedures that aim to improve the standard of care delivered to patients diagnosed with or suspected of having neuroendocrine neoplasia (NEN). At its annual Scientific Advisory Board Meeting in 2018, experts in imaging, pathology and clinical care of patients with NEN drafted guidance for the standardised reporting of diagnostic studies critical to the diagnosis, grading, staging and treatment of NEN. These included pathology, radiology, endoscopy and molecular imaging procedures. In an iterative process, a synoptic reporting template for molecular imaging procedures was developed to guide personalised therapies. Following pilot implementation and refinement within the ENETS Center of Excellence network, harmonisation with specialist imaging societies including the Society of Nuclear Medicine, European Association of Nuclear Medicine and the International Cancer Imaging Society will be pursued.
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Tumores Neuroendocrinos , Humanos , Imagen Molecular , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , SociedadesRESUMEN
Objective: To determine the association of primary tumor resection in stage IV pancreatic neuroendocrine tumors (Pan-NET) and survival in a propensity-score matched study. Background: Pan-NET are often diagnosed with stage IV disease. The oncologic benefit from primary tumor resection in this scenario is debated and previous studies show contradictory results. Methods: Patients from 3 tertiary referral centers from January 1, 1985, through December 31, 2019: Uppsala University Hospital (Uppsala, Sweden), Sahlgrenska University Hospital (Gothenburg, Sweden), and Brigham and Women's Hospital/Dana-Farber Cancer Institute (Boston, USA) were assessed for eligibility. Patients with sporadic, grade 1 and 2, stage IV pan-NET, with baseline 2000-2019 were divided between those undergoing primary tumor resection combined with oncologic treatment (surgery group [SG]), and those who received oncologic treatment without primary tumor resection (non-SG). A propensity-score matching was performed to account for the variability in the extent of metastatic disease and comorbidity. Primary outcome was overall survival. Results: Patients with stage IV Pan-NET (n = 733) were assessed for eligibility, 194 were included. Patients were divided into a SG (n = 65) and a non-SG (n = 129). Two isonumerical groups with 50 patients in each group remained after propensity-score matching. The 5-year survival was 65.4% (95% CI, 51.5-79.3) in the matched SG and 47.8% (95% CI, 30.6-65.0) in the matched non-SG (log-rank, P = 0.043). Conclusions: Resection of the primary tumor in patients with stage IV Pan-NET and G1/G2 grade was associated with prolonged overall survival compared to nonoperative management. A surgically aggressive regime should be considered where resection is not contraindicated.
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INTRODUCTION: Telotristat ethyl is indicated for use in combination with somatostatin analogs (SSAs) to treat carcinoid syndrome (CS) diarrhea uncontrolled by SSAs alone in adults, but long-term safety and efficacy data beyond 48 weeks are needed. OBJECTIVES: The aims of the study were to evaluate the long-term safety and tolerability of telotristat ethyl and its effect on quality of life (QOL) in patients with CS. METHODS: In this phase 3, nonrandomized, multicenter, open-label, long-term extension study (TELEPATH), patients who participated in phase 2 or 3 trials of telotristat ethyl continued treatment at their present dose level (250 or 500 mg thrice daily) for 84 weeks. Safety and tolerability, the primary endpoint, were assessed by monitoring adverse events (AEs), serious AEs, AEs of special interest (AESIs; including liver-related AEs, depression, and gastrointestinal AEs), and deaths. The secondary objective was to evaluate changes in patients' QOL using validated cancer questionnaires and a subjective global assessment of CS symptoms. RESULTS: In 124 patients exposed to telotristat ethyl for a mean of 102.6 ± 53.2 weeks, the type and frequency of AEs were consistent with those reported in previous trials. The occurrence of AESIs was not related to dosage or duration of therapy. Most AEs were mild to moderate in severity, and no deaths were related to telotristat ethyl. QOL scores remained stable, and the majority of patients reported adequate symptom relief throughout the study. CONCLUSIONS: Safety results of TELEPATH support the long-term use of telotristat ethyl in patients with CS diarrhea. Telotristat ethyl was well-tolerated and associated with sustained improvement in QOL scores (NCT02026063).
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Síndrome Carcinoide Maligno , Calidad de Vida , Adulto , Humanos , Síndrome Carcinoide Maligno/tratamiento farmacológico , Fenilalanina/efectos adversos , Fenilalanina/análogos & derivados , Pirimidinas , Resultado del TratamientoRESUMEN
Neuroendocrine neoplasms (NENs) causing ectopic Cushing's syndrome (ECS) are rare and challenging to treat. In this retrospective cohort study, we aimed to evaluate different approaches for bilateral adrenalectomy (BA) as a treatment option in ECS. Fifty-three patients with ECS caused by a NEN (35 females/18 men; mean ± SD age: 53 ± 15 years) were identified from medical records. Epidemiological and clinical parameters, survival, indications for surgery and timing, as well as duration of surgery, complications and surgical techniques, were collected and further analysed. The primary tumour location was thorax (n = 30), pancreas (n = 14) or unknown (n = 9). BA was performed in 37 patients. Median time from diagnosis of ECS to BA was 2 months (range 1-10 months). Thirty-two patients received different steroidogenesis inhibitors before BA to control hypercortisolaemia. ECS resolved completely after surgery in 33 patients and severe peri- or postoperative complications were detected in 12 patients. There were fewer severe complications in the endoscopic group compared to open surgery (p = .030). Posterior retroperitoneoscopic BA performed simultaneously by a two surgeon approach had the shortest operating time (p = .001). Despite the frequent use of adrenolytic treatment, BA was necessary in a majority of patients to gain control over ECS. Complication rate was high, probably as a result of the combination of metastatic disease and metabolic disorders caused by high cortisol levels. The two surgeon approach BA may be considered as the method of choice in ECS compared to other BA approaches as a result of fewer complications and a shorter operating time.
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Síndrome de ACTH Ectópico/cirugía , Adrenalectomía/métodos , Síndrome de Cushing/cirugía , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/epidemiología , Adrenalectomía/estadística & datos numéricos , Adulto , Anciano , Estudios de Cohortes , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Suecia/epidemiologíaRESUMEN
OPINION STATEMENT: Treatment recommendations for advanced gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are based on uncontrolled, mainly retrospective data. Chemotherapy can offer palliative relief, but long-lasting complete responses or cures are rare. The European Neuroendocrine Tumour Society (ENETS) and European Society for Medical Oncology (ESMO) recommend platinum-based chemotherapy as first-line treatment. This has been the golden standard since the late 1980s and has been evaluated in mostly retrospective clinical studies. However, progression is inevitable for most patients. Unfortunately, data on effective second-line treatment options are scant, and ENETS and ESMO recommendations propose fluorouracil- or temozolomide-based chemotherapy schedules. As such, there is a huge unmet need for improved care. Improved knowledge on GEP-NEC biology may provide a pathway towards more effective interventions including chemotherapy, targeted gene therapy, peptide receptor radionuclide therapy, as well as immune checkpoint inhibitors. The review summarises this current state of the art as well as the most promising developments for systemic therapy in GEP-NEC patients.
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Carcinoma Neuroendocrino/tratamiento farmacológico , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Carcinoma Neuroendocrino/clasificación , Carcinoma Neuroendocrino/genética , Neoplasias Gastrointestinales/genética , Humanos , Neoplasias Pancreáticas/genéticaRESUMEN
BACKGROUND: The diagnostic work-up and treatment of patients with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) has undergone major advances and new methods are introduced. Furthermore, an update of the WHO classification has resulted in a new nomenclature for GEP-NEN that is implemented in the clinic. AIM: These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group's current view on how to diagnose and treat GEP-NEN patients and aims to be useful in the daily practice for clinicians.
Asunto(s)
Neoplasias Gastrointestinales , Neoplasias Intestinales , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Neoplasias Intestinales/diagnóstico , Neoplasias Intestinales/tratamiento farmacológico , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapiaRESUMEN
The present study aimed to assess gadoxetate disodium contrast-enhanced (CE) positron emission tomography (PET)/magnetic resonance imaging (MRI) with 68 Ga-DOTATOC and 11 C-5-Hydroxy-tryptophan (11 C-5-HTP) in comparison with iodine CE 68 Ga-DOTATOC-PET/computed tomography (CT) for neuroendocrine tumour imaging. Detection rate and reader's confidence were evaluated for each separate image volume: CE-CT, CE-MRI including diffusion-weighted imaging, 68 Ga-DOTATOC-PET performed at PET/CT, 68 Ga-DOTATOC-PET performed at PET/MRI and 11 C-5-HTP-PET, and for the three combined hybrid examinations 68 Ga-DOTATOC-PET/MRI, 11 C-5-HTP-PET/MRI and 68 Ga-DOTATOC-PET/CT. In 11 patients, 255 lesions were depicted. 68 Ga-DOTATOC-PET performed at PET/MRI depicted 72.5%, 68 Ga-DOTATOC-PET performed at PET/CT depicted 62.7%, 11 C-5-HTP-PET depicted 68.2% and CE-CT depicted 53% of lesions. 68 Ga-DOTATOC-PET performed at PET/MRI (P < 0.001) and PET/CT (P = 0.02), 11 C-5-HTP-PET (P < 0.001) and MRI (P < 0.001) were superior to CT. 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI detected 92.5% and 92% of lesions, respectively, and both outperformed 68 Ga-DOTATOC-PET/CT (65%) (P < 0.001). For liver metastasis imaging, MRI alone was unsurpassed (P < 0.01) and 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI outperformed 68 Ga-DOTATOC-PET/CT (P < 0.001). For lymph node metastasis diagnosis, 68 Ga-DOTATOC-PET performed at PET/MRI and PET/CT and 11 C-5-HTP-PET detected 94%, 94% and 94% of lesions, respectively, and outperformed MRI and CE-CT alone (P < 0.001). For bone metastasis imaging, 68 Ga-DOTATOC-PET performed at PET/MRI and PET/CT and 11 C-5-HTP-PET performed equally well (P = 0.05) and better than MRI. Reader's confidence was better for 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI than for 68 Ga-DOTATOC-PET/CT. The tumour maximum standardised uptake value and tumour-to-liver ratio were both approximately twice as high as for 68 Ga-DOTATOC than for 11 C-5-HTP. 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI provided the highest detection rates and reader's confidence and were both superior to 68 Ga-DOTATOC-PET/CT, mainly because of the MRI component. The imaging contrast with 68 Ga-DOTATOC was superior to that of 11 C-5-HTP.