Lung Metastases in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Neoplasms: An Appraisal of the Validity of Thoracic Imaging Surveillance

Daskalakis, Kosmas; Tsoli, Marina; Srirajaskanthan, Raj; Chatzellis, Eleftherios; Alexandraki, Krystallenia Ι.; Angelousi, Anna; Pizanias, Michail; Randeva, Harpal S.; Kaltsas, Gregory; Weickert, Martin O.

doi:10.1159/000497183

Cited by 11 publications

(12 citation statements)

References 21 publications

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“…The presence of carcinoid heart disease, mesenteric lymph node metastases, distant abdominal lymph node metastases, liver metastatic burden, extra-abdominal metastases, skeletal involvement and peritoneal carcinomatosis (PC) are independent prognostic factors for OS in SBNEN [157]. Bone metastases have a distinct prognostic impact to that of other distant metastases (inferior OS with the former) [158], and although occurring only in approximately 5% of metastatic GEP NEN, lung metastases have significant detriment to OS which is in addition to that presented by distant metastases at other sites [159]. Multivariate prognostic scores have been developed for both SBNEN and PanNEN in terms of OS or recurrence post-surgery [160][161][162][163].…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

et al. 2019

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The traditionally promulgated perspectives of neuroendocrine neoplasms (NEN) as rare, indolent tumours are blunt and have been outdated for the last 2 decades. Clear increments in their incidence over the past decades render them increasingly clinically relevant, and at initial diagnosis many present with nodal and/or distant metastases (notably hepatic). The molecular pathogenesis of these tumours is increasingly yet incompletely understood. Those arising from the small bowel (SB) or pancreas typically occur sporadically; the latter may occur within the context of hereditary tumour predisposition syndromes. NENs can also be associated with endocrinopathy of hormonal hypersecretion. Tangible advances in the development of novel biomarkers, functional imaging modalities and therapy are especially applicable to this sub-set of tumours. The management of SB and pancreatic neuroendocrine tumours (NET) may be challenging, and often comprises a multidisciplinary approach wherein surgical, medical, interventional radiological and radiotherapeu-tic modalities are implemented. This review provides a comprehensive overview of the epidemiology, pathophysiology, diagnosis and treatment of SB and pancreatic NETs. Moreover, we provide an outlook of the future in these tumour types which will include the development of precision oncology frameworks for individualised therapy, multi-analyte predictive biomarkers, artificial intelligence-derived clinical decision support tools and elucidation of the role of the microbiome in NEN development and clinical behaviour.According to SEER version 18, SBNEN and PanNEN incidences are currently estimated at 1.2 and 0.7 per 100,000, respectively [5]. The overall 20-year duration prevalence of all NEN is estimated at 171,321; SBNEN constituting 32,122 patients with 3-fold fewer PanNEN (10,707) [5]. Possible attributable factors for this increase evolving epidemiology include increased use of endoscopy and also improvements in the sensitivity of widely used imaging modalities, leading to increased detection of early-stage, asymptomatic disease [5].The median overall survival (OS) for NEN (irrespective of site and grade) is 9.3 years [5]. For SB (median OS: 14 years), this ranges from 70 months (advanced disease with distant metastases) to 170 months (localised disease) and from 30 months (Grade 3) to 160 months (Grade 1). For pancreas (median OS: 3.6 years): 21 months (advanced) to 235 months (localised disease) and from 15 months (Grade 3) to 140 months (Grade 1) [5].Multivariable analyses have identified that ethnicity, age, differentiation, stage and site all have statistically significant correlations with survival. In general, Caucasian ethnicity, age (< 50 years) and localised, well-differentiated NEN exhibit the best survival. SB tumour patients are approximately 1.5 times more likely to survive longer than those with PanNEN [19]. Many of these correlations are self-evident since they pertain to degree of malignancy, disease duration and patient performance status.OS (median 5-year) app...

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Section: Therapeutic Strategiesmentioning

confidence: 99%

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

et al. 2019

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“…However, extra-abdominal distant metastases, mainly to the bones and the lungs, are encountered in only up to 6.1% of SI-NET patients at presentation. Importantly, distant extrahepatic metastases to the para-aortic lymph nodes, bones, and lungs have been recognized as independent prognostic factors for survival [ 2 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of Small Intestinal Neuroendocrine Tumors Metastasis: Biologic Patterns of a Series with Virchow’s Node Involvement

Wedin

Tsoli

Wallin

et al. 2022

Cancers

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Small intestinal neuroendocrine tumors (SI-NETs) may rarely metastasize to the left supraclavicular lymph nodes, also known as Virchow’s node metastasis (VM). Data on prevalence, prognostic significance, and clinical course of disease for SI-NET patients with VM is limited. In this retrospective analysis of 230 SI-NET patients treated at two tertiary referral centers, we found nine patients with VM (prevalence 3.9%). Among those, there were 5 females and median age at SI-NET and VM diagnosis was 61 and 65 years, respectively. Two patients had G1 tumors and five G2, while two tumors were of unspecified grade (median Ki67: 7%, range 2–15%). Four patients presented with synchronous VM, whereas five developed metachronous VM after a median of twenty-four months (range: 4.8–117.6 months). Hepatic metastases were present in seven patients, extrahepatic metastases (EM) in eight (six para-aortic distant lymph node metastases, one lung and one pancreatic metastasis), whereas peritoneal carcinomatosis (PC) in two patients. We used a control group of 18 age- and sex-matched SI-NET patients from the same cohort with stage IV disease but no extra-abdominal metastases. There was no difference in best-recorded response to first line treatment according to RECIST 1.1 as well as progression-free survival (PFS) between patients with VM and those in the control group (Chi-square test p = 0.516; PFS 71.7 vs. 106.9 months [95% CI 38.1–175.8]; log-rank p = 0.855). In addition, median overall survival (OS) of SI-NET patients with VM did not differ from those in the control group (138.6 [95% CI 17.2–260] vs. 109.9 [95% CI 91.7–128] months; log-rank p = 0.533). In conclusion, VM, although relatively rare in patients with SI-NETs, is more often encountered in patients with G2 tumors and established distant para-aortic lymph node metastases. The presence of VM in SI-NET patients does not seem to impact patients’ survival outcomes and treatment responses, when compared to age- and sex-matched SI-NET patients with stage IV disease confined in the abdomen.

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“…Data with a promising effect are retrospective and should be warranted with caution. In pNET, lung metastasis is relatively rare (around 5%) and usually goes together with progressive disease in the abdomen [104]. Resection of extrahepatic metastasis in low-grade pNET is technically possible and associated with acceptable outcomes in selected cases [17].…”

Section: Pnet With Extensive Liver Metastasis (>50%) or Extrahepatic ...mentioning

confidence: 99%

Orchestrating Treatment Modalities in Metastatic Pancreatic Neuroendocrine Tumors—Need for a Conductor

Siebenhüner

Langheinrich

Friemel

et al. 2022

Cancers

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Pancreatic neuroendocrine tumors (pNETs) are a vast growing disease. Over 50% of these tumors are recognized at advanced stages with lymph node, liver, or distant metastasis. An ongoing controversy is the role of surgery in the metastatic setting as dedicated systemic treatments have emerged recently and shown benefits in randomized trials. Today, liver surgery is an option for advanced pNETs if the tumor has a favorable prognosis, reflected by a low to moderate proliferation index (G1 and G2). Surgery in this well-selected population may prolong progression-free and overall survival. Optimal selection of a treatment plan for an individual patient should be considered in a multidisciplinary tumor board. However, while current guidelines offer a variety of modalities, there is so far only a limited focus on the right timing. Available data is based on small case series or retrospective analyses. The focus of this review is to highlight the right time-point for surgery in the setting of the multimodal treatment of an advanced pancreatic neuroendocrine tumor.

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Lung Metastases in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Neoplasms: An Appraisal of the Validity of Thoracic Imaging Surveillance

Cited by 11 publications

References 21 publications

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

Heterogeneity of Small Intestinal Neuroendocrine Tumors Metastasis: Biologic Patterns of a Series with Virchow’s Node Involvement

Orchestrating Treatment Modalities in Metastatic Pancreatic Neuroendocrine Tumors—Need for a Conductor

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