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Diagnostic and Management Pathways for Pulmonary Carcinoid Tumours in the United Kingdom: Results from the National Lung Neuroendocrine Tumour Pathway Project.

ABSTRACT: There is inconsistency among published guidelines for the optimal diagnostic and management pathways for patients with typical (TC) or atypical (AC) pulmonary carcinoid tumours. We conducted a UK-wide clinician survey to assess current practice for the diagnosis, management, and follow-up of patients with TC/AC and descriptively compared management between European Neuroendocrine Tumor Society (ENETS) accredited centres of excellence (CoE) and nonaccredited centres (non-CoE). Twenty-seven clinicians (10 CoE; 17 non-CoE) participated. Computed tomography of thorax, abdomen, and pelvis was the most commonly reported diagnostic tool (96% of respondents), and bone scans and gallium somatostatin receptor scintigraphy positron emission tomography (SRS PET) were the least commonly reported (30% and 37% of respondents, respectively). Adjuvant therapy is considered for resected TC/AC by <5% of respondents for patients with stage N0 M0 AC or TC, up to 48% of respondents for patients with AC with R1 disease. Somatostatin analogues were the most commonly reported first-line treatment (63% of respondents), and chemotherapy was the most commonly reported second-line therapy and third-line therapy (33% and 41%, respectively) for unresectable and metastatic disease. Reported frequency of initial follow-up after primary surgery ranged from every 2 months to annual, and total follow-up duration ranged from 2 years to indefinite depending on disease type (TC/AC) and stage. For most diagnostic investigations, the highest reported frequency of use was in CoE, most notably gallium SRS PET (70% CoE vs. 18% non-CoE respondents). 93% of respondents (100% CoE; 88% non-CoE) reported having neuroendocrine tumour- (NET-) specialist multidisciplinary team meetings at their centre; 59% (90% CoE; 41% non-CoE) had a NET Clinical Nurse Specialist (CNS) and 48% (80% CoE; 29% non-CoE) had a lung NET patient database. The survey results suggest variability between UK centres in diagnostic pathways and management of patients with TC/AC and suggest that CoE may be able to offer an improved service to patients.

SUBMITTER: Mansoor W

PROVIDER: S-EPMC7064844 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Diagnostic and Management Pathways for Pulmonary Carcinoid Tumours in the United Kingdom: Results from the National Lung Neuroendocrine Tumour Pathway Project.

Mansoor Wasat W Ferguson Stuart S Ross Victoria V Talbot Denis D

International journal of endocrinology 20200228

There is inconsistency among published guidelines for the optimal diagnostic and management pathways for patients with typical (TC) or atypical (AC) pulmonary carcinoid tumours. We conducted a UK-wide clinician survey to assess current practice for the diagnosis, management, and follow-up of patients with TC/AC and descriptively compared management between European Neuroendocrine Tumor Society (ENETS) accredited centres of excellence (CoE) and nonaccredited centres (non-CoE). Twenty-seven clinic ...[more]

PMID: 32190050

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Project description:Neuroendocrine tumours (NETs) can secrete bioactive amines into the bloodstream, causing carcinoid syndrome, with symptoms including flushing and diarrhoea. However, carcinoid syndrome frequency in the NET population has never been rigorously assessed, nor has its relationship to presenting clinicopathological characteristics. This analysis assessed the proportion of patients with NETs and carcinoid syndrome in the USA and associated clinical factors.We identified patients (?65 years of age) from the Surveillance, Epidemiology, and End Results-Medicare database, excluding those with pancreatic tumours or small-cell or large-cell lung cancer, as well as those without complete data. We assessed the incidence of patients with at least two insurance claims of flushing, diarrhoea, or carcinoid syndrome during the 3 months before and after NET diagnosis. We compared demographic and clinical characteristics between patients with and without carcinoid syndrome using ?2 tests. We used the Cochran-Armitage trend test to identify trends in carcinoid syndrome incidence and Cox regression to assess the relationship between carcinoid syndrome and survival.Between April 1, 2000, and Dec 31, 2011, 9512 eligible patients were diagnosed with NETs, of whom 1786 (19%) had carcinoid syndrome. The number of patients with NETs and carcinoid syndrome increased from 50 (11%) of 465 patients in 2000 to 160 (19%) of 854 in 2011 (p<0·0001). The proportion of patients with carcinoid syndrome compared with those without did not differ significantly with respect to age at diagnosis (p=0·65), geographical region (p=0·054), or urban versus rural status (p=0·53). Patients with carcinoid syndrome were more frequently female than male (p=0·0003). Race was associated with a significant difference in the reported incidence of carcinoid syndrome (p<0·0001), as was tumour grade, stage, and primary tumour site (all p<0·0001). Patients with carcinoid syndrome had a shorter overall survival (median 5 years [95% CI 4·5-5·4]) than did those without carcinoid syndrome (5·6 years [5·4-5·9]; hazard ratio 1·102 [1·016-1·194]; p=0·019). Use of octreotide (p<0·0001) and chemotherapy (p=0·003) were more common in patients with carcinoid syndrome than in those without it, whereas surgery was used more frequently in patients without carcinoid syndrome (p=0·009); use of radiotherapy was not significantly associated with the presence of carcinoid syndrome at diagnosis (p=0·07).This population-based analysis reveals that carcinoid syndrome is significantly associated with tumour grade, stage, and primary tumour site, and leads to shorter survival compared with those patients without carcinoid syndrome. An improved understanding of the heterogeneity of presenting symptoms among patients with NETs might permit more tailored assessment and management than at present and enable future research into the effect of carcinoid syndrome control on patient survival.Ipsen.

Project description:Non-tumoural cells within the tumour microenvironment (TME) influence tumour proliferation, invasiveness and angiogenesis. Little is known about TME in pituitary neuroendocrine tumours (PitNETs). We aimed to characterise the role of TME in the aggressive behaviour of PitNETs, focusing on immune cells and cytokines. The cytokine secretome of 16 clinically non-functioning PitNETs (NF-PitNETs) and 8 somatotropinomas was assessed in primary culture using an immunoassay panel with 42 cytokines. This was correlated with macrophage (CD68, HLA-DR, CD163), T-lymphocyte (CD8, CD4, FOXP3), B-lymphocyte (CD20), neutrophil (neutrophil elastase) and endothelial cells (CD31) content, compared to normal pituitaries (NPs, n?=?5). In vitro tumour-macrophage interactions were assessed by conditioned medium (CM) of GH3 (pituitary tumour) and RAW264.7 (macrophage) cell lines on morphology, migration/invasion, epithelial-to-mesenchymal transition and cytokine secretion. IL-8, CCL2, CCL3, CCL4, CXCL10, CCL22 and CXCL1 are the main PitNET-derived cytokines. PitNETs with increased macrophage and neutrophil content had higher IL-8, CCL2, CCL3, CCL4 and CXCL1 levels. CD8+ T-lymphocytes were associated to higher CCL2, CCL4 and VEGF-A levels. PitNETs had more macrophages than NPs (p?<?0.001), with a 3-fold increased CD163:HLA-DR macrophage ratio. PitNETs contained more CD4+ T-lymphocytes (p?=?0.005), but fewer neutrophils (p?=?0.047) with a 2-fold decreased CD8:CD4 ratio. NF-PitNETs secreted more cytokines and had 9 times more neutrophils than somatotropinomas (p?=?0.002). PitNETs with higher Ki-67 had more FOXP3+ T cells, as well as lower CD68:FOXP3, CD8:CD4 and CD8:FOXP3 ratios. PitNETs with "deleterious immune phenotype" (CD68hiCD4hiFOXP3hiCD20hi) had a Ki-67???3%. CD163:HLA-DR macrophage ratio was positively correlated with microvessel density (p?=?0.015) and area (p?<?0.001). GH3 cell-CM increased macrophage chemotaxis, while macrophage-CM changed morphology, invasion, epithelial-to-mesenchymal transition and secreted cytokines of GH3 cells. PitNETs are characterised by increased CD163:HLA-DR macrophage and reduced CD8:CD4 and CD8:FOXP3 T cell ratios. PitNET-derived chemokines facilitate macrophage, neutrophil and T cell recruitment into the tumours which can determine aggressive behaviour.

Project description:This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Significantly new data have been published on laryngeal cancer management since the last edition of the guidelines. This paper discusses the evidence base pertaining to the management of laryngeal cancer and provides updated recommendations on management for this group of patients receiving cancer care. Recommendations • Radiotherapy (RT) and transoral laser microsurgery (TLM) are accepted treatment options for T1a-T2a glottic carcinoma. (R) • Open partial surgery may have a role in the management of selected tumours. (R) • Radiotherapy, TLM and transoral robotic surgery are reasonable treatment options for T1-T2 supraglottic carcinoma. (R) • Supraglottic laryngectomy may have a role in the management of selected tumours. (R) • Most patients with T2b-T3 glottic cancers are suitable for non-surgical larynx preservation therapies. (R) • Concurrent chemoradiotherapy should be regarded as the standard of care for non-surgical management. (R) • Subject to the availability of appropriate surgical expertise and multi-disciplinary rehabilitation services, TLM or open partial surgical procedures ± post-operative RT, may be also be appropriate in selected cases. (R) • In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-operative RT) is recommended to at least lymph node levels II, III and IV bilaterally. In node positive disease, it is recommended that lymph node levels II-V should be treated on the involved side. If level II nodes are involved, then elective irradiation of ipsilateral level Ib nodes may be considered. (R) • Most patients with T3 supraglottic cancers are suitable for non-surgical larynx preservation therapies. (R) • Concurrent chemoradiotherapy should be regarded as the standard of care for non-surgical management. (R) • Subject to the availability of appropriate surgical expertise and multi-disciplinary rehabilitation services, TLM or open partial surgical procedures ± post-operative RT, may also be appropriate in selected cases. (R) • In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-operative RT) is recommended to at least lymph node levels II, III and IV bilaterally. In node positive disease, lymph node levels II-V should be treated on the involved side. (R) • As per the PET-Neck clinical trial, patients with N2 or N3 neck disease who undergo treatment with chemoradiotherapy to their laryngeal primary and experience a complete response with a subsequent negative post-treatment positron emission tomography combined with computed tomography (PET-CT) scan do not require an elective neck dissection. In contrast, patients who have a partial response to treatment or have increased uptake on a post-treatment PET-CT scan should have a neck dissection. (R) • Larynx preservation with concurrent chemoradiotherapy should be considered for T4 tumours, unless there is tumour invasion through cartilage into the soft tissues of the neck, in which case total laryngectomy yields better outcomes. (R) • In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-operative RT) is recommended to bilateral lymph node levels II, III, IV, V and VI. (R).

Project description:BackgroundLung cancer is the leading cause of cancer-related deaths worldwide. The typical and atypical carcinoid (TC and AC), the large-cell neuroendocrine carcinoma (LCNEC) and the small-cell lung cancers (SCLC) are subgroups of pulmonary tumours that show neuroendocrine differentiations. With the rising impact of molecular pathology in routine diagnostics the interest for reliable biomarkers, which can help to differentiate these subgroups and may enable a more personalised treatment of patients, grows.MethodsA collective of 70 formalin-fixed, paraffin-embedded (FFPE) pulmonary neuroendocrine tumours (17 TCs, 17 ACs, 19 LCNECs and 17 SCLCs) was used to identify biomarkers by high-throughput sequencing. Using the Illumina TruSeq Amplicon-Cancer Panel on the MiSeq instrument, the samples were screened for alterations in 221 mutation hot spots of 48 tumour-relevant genes.ResultsAfter filtering >26 000 detected variants by applying strict algorithms, a total of 130 mutations were found in 29 genes and 49 patients. Mutations in JAK3, NRAS, RB1 and VHL1 were exclusively found in SCLCs, whereas the FGFR2 mutation was detected in LCNEC only. KIT, PTEN, HNF1A and SMO were altered in ACs. The SMAD4 mutation corresponded to the TC subtype. We prove that the frequency of mutations increased with the malignancy of tumour type. Interestingly, four out of five ATM-mutated patients showed an additional alteration in TP53, which was by far the most frequently altered gene (28 out of 130; 22%). We found correlations between tumour type and IASLC grade for ATM- (P=0.022; P=0.008) and TP53-mutated patients (P<0.001). Both mutated genes were also associated with lymph node invasion and distant metastasis (P⩽0.005). Furthermore, PIK3CA-mutated patients with high-grade tumours showed a reduced overall survival (P=0.040) and the mutation frequency of APC and ATM in high-grade neuroendocrine lung cancer patients was associated with progression-free survival (PFS) (P=0.020).ConclusionsThe implementation of high-throughput sequencing for the analysis of the neuroendocrine lung tumours has revealed that, even if these tumours encompass several subtypes with varying clinical aggressiveness, they share a number of molecular features. An improved understanding of the biology of neuroendocrine tumours will offer the opportunity for novel approaches in clinical management, resulting in a better prognosis and prediction of therapeutic response.

Dataset Information

Diagnostic and Management Pathways for Pulmonary Carcinoid Tumours in the United Kingdom: Results from the National Lung Neuroendocrine Tumour Pathway Project.

Publications

Diagnostic and Management Pathways for Pulmonary Carcinoid Tumours in the United Kingdom: Results from the National Lung Neuroendocrine Tumour Pathway Project.

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