scholarly journals Unique Metastatic Patterns in Neuroendocrine Neoplasms of Different Primary Origin

2020 ◽  
Author(s):  
B C. M. Hermans ◽  
J de Vos - Geelen ◽  
J L Derks ◽  
L Latten ◽  
I H Liem ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Metastatic Disease ◽  
Reference Network ◽  
Neuroendocrine Neoplasms ◽  
Screening Methods ◽  
Special Focus ◽  
Additional Information ◽  
Netherlands Cancer Registry ◽  
Metastatic Patterns ◽  
Primary Origin

Introduction Neuroendocrine neoplasms (NEN) can originate in different organs, e.g. the gastroenteral tract (GE), pancreas (Pan) or lung (L). Our aim was to examine metastatic patterns for patients with NEN of various primary origins with a special focus on brain metastases to indicate utility for screening. Methods All NEN patients except for small cell lung cancer registered in the Netherlands Cancer Registry from 2008-2018 were selected. Metastatic patterns at initial diagnosis for NEN with different primary origin were compared. In a subcohort of patients from two referral hospitals (2014-2019), additional information on for example development of metastases after initial presentation was available. Results In the nationwide cohort 4,768/11,120 (43%) patients had metastatic disease at diagnosis (GE 1,504/4,710 (32%), Pan 489/1,150 (43%), L 1,230/2,978 (41%)). For GE- and Pan-NEN, the most prevalent metastatic site was the liver (25% and 39%), followed by distant lymph nodes (8% and 8%), whereas only few patients with brain metastases were identified (0% in both). In contrast, for L-NEN, prevalence of metastases in liver (19%), brain (9%), lung (7%) and bone (14%) was more equal. In the reference network cohort, slightly more NEN patients had metastatic disease (260/539, 48%) and similar metastatic patterns were observed. Conclusion Almost half of NEN patients were diagnosed with synchronous metastatic disease. L-NEN have a unique metastatic pattern compared to GE- and Pan-NEN. Remarkably, an important part of L-NEN metastases were in the brain, whereas brain metastases were almost absent in GE- and Pan-NEN, indicating utility of screening in L-NEN.

scholarly journals The Diagnostic Value of Chromogranin A in Neuroendocrine Neoplasms is Potentiated by Clinical Factors and Inflammatory Markers

Endocrines ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 1-12
Author(s):  
Olga Papalou ◽  
Melpomeni Peppa ◽  
Eleni Kandaraki ◽  
Evanthia Diamanti-Kandarakis ◽  
George Nikou
Keyword(s):  
Metastatic Disease ◽  
Chromogranin A ◽  
Clinical Laboratory ◽  
Probability Model ◽  
Diagnostic Value ◽  
Initial Diagnosis ◽  
Neuroendocrine Neoplasms ◽  
Special Focus ◽  
Accurate Identification ◽  
Increased Risk

Objective: Neuroendocrine neoplasms (NENs) are a heterogenous group of indolent tumors, with variable clinical behavior and steadily rising incidence. The aim of this study is to investigate the clinical and laboratory factors that contribute in predicting the aggressiveness and invasiveness of NENs. Special focus is given to clinical parameters that would enhance the diagnostic value of chromogranin A (CgA), via formalizing an integrated probability model, which would contribute to the timely and accurate identification of patients at high risk for metastatic disease at initial diagnosis. Designs and Methods: We identified a total of 93 patients with NENs, recruited at a specialized academic center in Athens, Greece. Anthropometric, clinical, laboratory, and pathological data were obtained from every patient before any therapeutic intervention. Results: Age over 50 years and male gender were accompanied by increased risk for metastases at the time of initial diagnosis. Additionally, when these parameters were combined with CgA levels, they were shown to enhance the predictive capacity of CgA. Different patient scenarios combining age, gender, and CgA levels are associated with different probabilities for metastatic disease, demonstrated schematically in a gradually escalating model, as age and CgA levels increase in both males and females. The lowest risk is observed in women aged <50 years old with CgA levels <200 ng/dl (6.5%), while the highest one is in males over 50 years old with CgA > 200 ng/dl (62.9%). Finally, it was shown that c-reactive protein (CRP) can predict disease extent at the time of diagnosis. Conclusions: CgA levels can not only be used as a direct predictor of tumor load in patients with NENs, but also, when interpolated with the effects of age and gender, cumulatively predict whether a NEN would be metastatic or not at the time of initial diagnosis, via a risk-escalating probability model.

Current concepts in the diagnosis and management of neuroendocrine neoplasms of unknown primary origin

2020 ◽  
Vol 44 (4) ◽  
Author(s):  
Krystallenia I. Alexandraki ◽  
Marina Tsoli ◽  
Georgios Kyriakopoulos ◽  
Anna Angelousi ◽  
Georgios Nikolopoulos ◽  
...  
Keyword(s):  
Unknown Primary ◽  
Neuroendocrine Neoplasms ◽  
Diagnosis And Management ◽  
Primary Origin ◽  
Unknown Primary Origin

scholarly journals Leptomeningeal Carcinomatosis: A Clinical Dilemma in Neuroendocrine Neoplasms

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 277
Author(s):  
Leonidas Apostolidis ◽  
Jörg Schrader ◽  
Henning Jann ◽  
Anja Rinke ◽  
Sebastian Krug
Keyword(s):  
Brain Metastases ◽  
Median Overall Survival ◽  
Case Reports ◽  
Individual Case ◽  
Leptomeningeal Carcinomatosis ◽  
Neuroendocrine Neoplasms ◽  
Cns Involvement ◽  
Ki 67 ◽  
Sensory Deficits ◽  
Clinical Dilemma

Central nervous system (CNS) involvement by paraneoplastic syndromes, brain metastases, or leptomeningeal carcinomatosis (LC) in patients with neuroendocrine neoplasms (NEN) has only been described in individual case reports. We evaluated patients with LC in four neuroendocrine tumor (NET) centers (Halle/Saale, Hamburg, Heidelberg, and Marburg) and characterized them clinically. In the study, 17 patients with a LC were defined with respect to diagnosis, clinic, and therapy. The prognosis of a LC is very poor, with 10 months in median overall survival (mOS). This is reflected by an even worse course in neuroendocrine carcinoma (NEC) G3 Ki-67 >55%, with a mOS of 2 months. Motor and sensory deficits together with vigilance abnormalities were common symptoms. In most cases, targeted radiation or temozolomide therapy was used against the LC. LC appears to be similarly devastating to brain metastases in NEN patients. Therefore, the indication for CNS imaging should be discussed in certain cases.

Colorectal cancer and brain metastases: An aggressive disease with a different response to treatment

2018 ◽  
Vol 105 (5) ◽  
pp. 427-433 ◽  
Author(s):  
Georges Chahine ◽  
Tony Ibrahim ◽  
Tony Felefly ◽  
Abir El-Ahmadie ◽  
Pamela Freiha ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Brain Metastases ◽  
Median Survival ◽  
Metastatic Disease ◽  
Antiangiogenic Therapy ◽  
Response To Treatment ◽  
Aggressive Disease ◽  
Dismal Prognosis ◽  
Poor Outcomes ◽  
Different Response

Introduction: Brain metastases (BM) are rare in colorectal cancer (CRC) and are associated with a dismal prognosis. This work aims to report the rate of BM in CRC patients treated in a single institution, along with survival and prognostic factors. Methods: Medical charts for patients with histologically proven CRC were retrospectively reviewed. Results: A total of 538 patients were identified, of whom 33% developed any metastatic disease and 4.4% presented BM. Lung was the most frequently associated metastatic site (in 68% of the cases). The only factor independently associated with BM development was the presence of metastatic disease at the time of initial presentation. The median duration from initial diagnosis to BM development was 38.6 months (SD 29.1 months). Median survival after BM development was 62 days (95% confidence interval [CI] 56–68). Patients diagnosed with BM within 1 year of cancer diagnosis responded significantly better to treatment than those who acquired BM later, with a median survival after BM diagnosis of 261 days versus 61 days, respectively ( p = .002). Patients with BM who received antiangiogenic therapy had an improved median survival compared to those who did not (151 days vs 59 days, p = 0.02; hazard ratio for death 0.29 [95% CI 0.09–0.94]). Conclusion: CRC with BM is an aggressive disease resistant to standard treatment and is associated with poor outcomes. Adding antiangiogenic therapy might be of value for those patients. Patients with BM developing early in the disease course might respond better to treatment.

scholarly journals Patient-derived models of brain metastases recapitulate the histopathology and biology of human metastatic cancers

2020 ◽  
Author(s):  
Claudia C. Faria ◽  
Carlos Custódia ◽  
Rita Cascão ◽  
Eunice Paisana ◽  
Tânia Carvalho ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Anticancer Drugs ◽  
Cancer Progression ◽  
Metastatic Disease ◽  
Great Majority ◽  
Tumor Formation ◽  
Preclinical Studies ◽  
Primary Tumors ◽  
The Brain

ABSTRACTPurposeDissemination of cancer cells from primary tumors to the brain is observed in the great majority of cancer patients, contributing to increased morbidity and being the main cause of death. Most mechanistic and preclinical studies have relied on aggressive cancer cell lines, which fail to represent tumor heterogeneity and are unsuitable to validate therapies due to fast cancer progression in vivo.Experimental designWe established a unique library of subcutaneous and intracardiac patient-derived xenografts (PDXs) of brain metastases (BMs) from eight distinct primary tumor origins. Cancer progression in mice was compared to the matched patient clinical outcome, metastatic dissemination pattern and histopathological features. Preclinical studies with FDA approved drugs were performed.ResultsIn vivo tumor formation of flank-implanted BMs correlated with patients’ poor survival and serial passaging increased tumor aggressiveness. Subcutaneous xenografts originated spontaneous metastases in 61% of the cases, including in the leptomeningeal space (21%). The intracardiac model increased the tropism to the brain and leptomeninges (46%). Strikingly, 62% of intracardiac PDXs shared metastatic sites with the donor patients, including the primary cancer organ and the central nervous system (CNS). Of therapeutic relevance, PDX-derived cultures and corresponding mouse xenografts can be effectively treated with targeted anticancer drugs.ConclusionsPatient-derived models of BMs recapitulate the biology of human metastatic disease and can be a valuable translational platform for precision medicine.TRANSLATIONAL RELEVANCESubcutaneous and intracardiac mouse xenografts of human brain metastases exhibit a spontaneous dissemination pattern that resembles patients’ metastatic disease. The preclinical testing of targeted anticancer drugs using patient-derived cultures and patient-derived xenografts of brain metastasis showed an effective therapeutic response. These translational models represent an outstanding tool to advance the understanding of the biology of brain metastases and to foster the rapid discovery of novel therapeutics.

scholarly journals A filter-flow perspective of hematogenous metastasis offers a non-genetic paradigm for personalized cancer therapy

2013 ◽  
Author(s):  
Jacob G Scott ◽  
Alexander G Fletcher ◽  
Philip K Maini ◽  
Alexander R A Anderson ◽  
Philip Gerlee
Keyword(s):  
Metastatic Disease ◽  
Efficiency Index ◽  
Rational Method ◽  
Hematogenous Metastasis ◽  
Primary Target ◽  
Large Dataset ◽  
Oligometastatic Disease ◽  
Metastatic Patterns ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer

Background: Research into mechanisms of hematogenous metastasis has largely become genetic in focus, attempting to understand the molecular basis of `seed-soil' relationships. However, preceding this biological mechanism is the physical process of dissemination of circulating tumour cells (CTCs) in the circulatory network. We utilize a novel, network perspective of hematogenous metastasis and a large dataset on metastatic patterns to shed new light on this process. %a fundamental gap in our knowledge of this process. Experimental Design: The metastatic efficiency index (MEI), previously suggested by Weiss, quantifies the process of hematogenous metastasis by taking the ratio of metastatic incidence for a given primary-target organ pair and the relative blood flow between the two sites. In this paper we extend the methodology by taking into account the reduction in CTC number that occurs in capillary beds and a novel network model of CTC flow. Results: By applying this model to a dataset of metastatic incidence, we show that the MEI depends strongly on the assumptions of micrometastatic lesions in the lung and liver. Utilizing this framework we can represent different configurations of metastatic disease and offer a rational method for identifying patients with oligometastatic disease for inclusion in future trials. Conclusions:We show that our understanding of the dynamics of CTC flow is significantly lacking, and that this specifically precludes our ability to predict metastatic patterns in individual patients. Our formalism suggests an opportunity to go a step further in metastatic disease characterization by including the distribution of CTCs at staging, offering a rational method of trial design for oligometastatic disease.

Circulating tumor DNA mutation as a prognostic marker in melanoma with brain metastasis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21560-e21560
Author(s):  
Tapas Ranjan Behera ◽  
Jung Min Song ◽  
Donald Matthew Eicher ◽  
Brian Gastman ◽  
Daniel H. Farkas ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Metastatic Disease ◽  
Braf Mutation ◽  
Mutation Detection ◽  
Objective Response ◽  
Unmet Need ◽  
Circulating Tumor Dna ◽  
Metastatic Setting ◽  
Tumor Dna

e21560 Background: Prognosis in melanoma with brain metastasis is poor with a median survival of four months and a one-year survival rate of 10–20%. There is an unmet need for surveillance methods that can supplement imaging at regular intervals. Serial analysis of circulating tumor DNA (ctDNA) may aid surveillance and prognostication. A PCR-based, “specimen in/result out” testing device was employed to detect BRAF variants in plasma-derived ctDNA to evaluate the utility of rapid biomarker detection in the management of melanoma with brain metastasis. Methods: Serial blood samples from patients diagnosed with BRAF mutation-positive metastatic melanoma were collected at regular intervals. We employed a real-time PCR-based automated mutation detection system (Idylla; Biocartis, Belgium) to interrogate the plasma samples. The ctDNA mutation detection trend was analyzed relative to disease progression. Results: 39 patients with BRAF mutation positive melanoma were enrolled. 29 patients were treated in the metastatic setting, 10 in the adjuvant setting. 18 of the 29 patients with metastatic disease (62%) had brain metastases. Circulating BRAF mutation was detected in 17 of the 29 (59%) patients with metastatic disease, and was not detected in any patients treated adjuvantly. In the group with metastatic disease, this circulating biomarker changed from undetectable to detectable in eight (28%) and detectable to undetectable in three (10%). No change in circulating mutation status occurred in 18 (62%). In the eight patients who had an initial negative test that later became positive, seven (87%) had brain metastases. In three patients, ctDNA mutation detection occurred before the diagnosis of brain metastases on imaging, with a median lead time of five weeks (range, 3-12 weeks). In one patient with de novo metastatic disease admitted to the ICU, tissue was unavailable for BRAF testing but plasma was found to be positive for ctDNA BRAF detection. BRAF/MEK targeted therapy resulted in a sustained objective response. Five of six (83%) patients that had persistent ctDNA positivity had brain metastases. Among patients with brain metastases, median overall survival (mOS) of patients demonstrating >50% test positivity was numerically longer than those with <50% positivity (mOS 12.3 vs 53.5 months; p = 0.133). Conclusions: Plasma-based, rapid ctDNA testing may be useful as an aid in detecting progression and gauging prognosis in patients with melanoma treated in the metastatic setting. The dynamics of ctDNA test positivity may indicate a need for more urgent imaging, particularly of the brain. Blood-based, semi-automated ctDNA detection may serve as an attractive adjunct to scheduled imaging surveillance in melanoma.

Universal Screening Methods and Models: Diagnostic Accuracy of Reading Assessments

2018 ◽  
Vol 45 (4) ◽  
pp. 255-265
Author(s):  
Kalie VanMeveren ◽  
David Hulac ◽  
Sarah Wollersheim-Shervey
Keyword(s):  
Student Performance ◽  
Upper Elementary ◽  
Fifth Grade ◽  
Screening Methods ◽  
Elementary Grades ◽  
High Stakes ◽  
Additional Information ◽  
Fifth Grade Students ◽  
Statewide Assessment ◽  
Student Risk

Reading screening assessments help educators identify students who are at risk of reading and determine the need for intervention and supports. However, some schools screen and assess students more often than needed, and the additional information does not improve the accuracy of decisions. This may be especially true for students at the upper elementary grades who have already taken high-stakes tests. This exploratory study evaluated how accurately a variety of screening measures predicted performance on a high-stakes end of year test for fourth- and fifth-grade students. Results of this study indicated that previous scores on the statewide assessment and computer-adaptive assessment best predicted student performance on a high-stakes reading test (Minnesota Comprehensive Assessment—Third Edition). When comparing screening models, a two-gate approach appeared to be the best method for identifying student risk.

scholarly journals NEN: Advancement in Diagnosis and Minimally Invasive Therapy

2019 ◽  
Vol 192 (05) ◽  
pp. 422-430
Author(s):  
Daniel Putzer ◽  
Peter Schullian ◽  
Werner Jaschke ◽  
Reto Bale
Keyword(s):  
Metastatic Disease ◽  
Symptom Control ◽  
Distant Metastases ◽  
Neuroendocrine Neoplasms ◽  
Clinical Expertise ◽  
Systemic Treatments ◽  
Therapeutic Procedures ◽  
Unresectable Liver Metastases ◽  
Frequent Site ◽  
Metastatic Involvement

Neuroendocrine neoplasms (NEN) are a heterogeneous type of malignant disease and frequently present with symptoms caused by the secretion of metabolically active substances or the manifestation of distant metastases, with the liver being the most frequent site of spreading. Early diagnosis of metastatic disease is recognized as the major prognostic factor in NEN patients. Complete surgical resection is feasible in only selected cases. For patients with unresectable liver metastases, various locoregional treatment approaches are available. Over the last decade, therapeutic procedures including locoregional and systemic treatments have been investigated for gastroenteropancreatic NEN (GEP-NEN), especially for metastatic disease to the liver. Only a few prospective clinical trials have compared these approaches, and the management of individual patients remains subject to clinical expertise and judgement. Locoregional treatments are applicable in patients with limited metastatic involvement of the liver, and may be used for tumor debulking and symptom control in patients with diffuse liver involvement. Key Points: Citation Format

scholarly journals 66. CLINICAL CHARACTERISTICS AND RESULTS OF PEDIATRIC SOLID TUMORS WITH BRAIN METASTASES: EXPERIENCE FROM A SINGLE REFERRAL CANCER CENTER

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii14-ii14
Author(s):  
Clarissa Aguilar ◽  
Víctor Toro ◽  
Rina Medina
Keyword(s):  
Brain Metastases ◽  
Childhood Cancer ◽  
Solid Tumors ◽  
Metastatic Disease ◽  
Cancer Center ◽  
Middle Income ◽  
Middle Income Countries ◽  
Pediatric Solid Tumors ◽  
Low Middle Income Countries

Abstract BACKGROUND 80% of childhood cancer are located in low- and middle-income countries (LMIC). The most common form of presentation is disseminated or metastatic disease. The rate of survival has not been equitable across the world, since in these countries only 1 of 5 children are cured. OBJECTIVE To evaluate the clinical and histopathological features of patients with metastatic pediatric solid tumors, in a single referral cancer center in Honduras. METHODS We conducted a retrospective review of patients diagnosed with pediatric solid tumors from January 2010 to April 2020. Among the 260 patients through a collection form, we obtained: sociodemographic characteristics, clinical presentation at diagnosis, common histological subtypes, sites of metastasis, treatment and outcome at the time of follow-up. RESULTS During the last 10 years, 260 cases of childhood cancer were referred to our center for treatment. 127 patients (48.8%), have a solid tumor, patients ranged in age from 1 to 18 years and distribution for sex were 38% for males and 62% females. At the time of initial diagnosis 40/127 (31%) have advanced disease (stages III and IV). We found brain metastases in 22/40 cases (55%), the primary cancer was localized at CNS in 13/22 (59%) and the most common extracranial tumors causing brain metastases were neuroblastoma (4/22), rhabdomyosarcoma (3/22), retinoblastoma (2/22). Currently in the follow-up there were 18/22 (82%) died and 4/22 (18%) are in treatment with palliative intent. CONCLUSION There is a lack of information about the epidemiology of brain metastases among children with solid tumors in the low/middle income countries (LMIC) where the prognosis of metastatic disease is very poor, despite efforts, multimodal therapy and multidisciplinary management, in absence of other options like bone marrow transplantation, and reliable access to high-quality medicines. For our countries, timely diagnosis is still the main determining factor for cure.

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