New Prognostic Frontiers for Lung Neuroendocrine Tumors

2022 ◽  
Author(s):  
Anna La Salvia ◽  
Irene Persano ◽  
Alessandra Siciliani ◽  
Monica Verrico ◽  
Massimiliano Bassi ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Neuroendocrine Tumors ◽  
Progression Free Survival ◽  
Mitotic Count ◽  
Tnm Stage ◽  
Histopathological Diagnosis ◽  
High Power Field ◽  
Primary Tumors ◽  
Well Differentiated ◽  
Indolent Disease

Abstract Purpose Well-differentiated lung neuroendocrine tumors (Lu-NET) are classified as typical (TC) and atypical (AC) carcinoids, based on mitotic counts and necrosis. However, prognostic factors, other than tumor node metastasis (TNM) stage and the histopathological diagnosis, are still lacking. The current study is aimed to identify potential prognostic factors to better stratify lung NET, thus, improving patients’ treatment strategy and follow-up. Methods A multicentric retrospective study, including 300 Lung NET, all surgically removed, from Italian and Spanish Institutions. Results Median age 61 years (13-86), 37.7% were males, 25.0% were AC, 42.0% were located in the lung left parenchyma, 80.3% presented a TNM stage I-II. Mitotic count was ≥2 per 10 high power field (HPF) in 24.7%, necrosis in 13.0%. Median overall survival (OS) was 46.1 months (0.6-323), median progression free survival (PFS) was 36.0 months (0.3-323). Female sex correlated with a more indolent disease (T1; N0; lower Ki67; lower mitotic count and the absence of necrosis). Left-sided primary tumors were associated with higher mitotic count and necrosis. At Cox multivariate regression model, age, left-sided tumors and nodal (N) positive status resulted independent negative prognostic factors for OS and PFS. Conclusions This study confirms the prognostic relevance of TNM stage and diagnosis to stratify LuNET. However, the current analysis suggests a wider spectrum of clinical and pathological prognostic factors, including age and primary tumor’s location. These parameters could help clinicians to personalize the management of Lu-NET.

scholarly journals FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

2021 ◽  
Author(s):  
Jane E. Rogers ◽  
Michael Lam ◽  
Daniel M. Halperin ◽  
Cecile G. Dagohoy ◽  
James C. Yao ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Prior Therapy ◽  
Well Differentiated ◽  
Grade 3 ◽  
Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

scholarly journals Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study

2019 ◽  
Vol 37 (28) ◽  
pp. 2571-2580 ◽  
Author(s):  
Alberto Carmona-Bayonas ◽  
Paula Jiménez-Fonseca ◽  
Ángela Lamarca ◽  
Jorge Barriuso ◽  
Ángel Castaño ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Failure Time ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Accelerated Failure Time Model ◽  
Endocrine Tumors ◽  
First Line ◽  
Ki 67 ◽  
Free Survival ◽  
Well Differentiated

PURPOSE Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients. PATIENTS AND METHODS We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom). RESULTS We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively. CONCLUSION The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.

scholarly journals Prevention and Management of Hormonal Crisis during Theragnosis with LU-DOTA-TATE in Neuroendocrine Tumors. A Systematic Review and Approach Proposal

2020 ◽  
Vol 9 (7) ◽  
pp. 2203 ◽  
Author(s):  
Maria Isabel del Olmo-García ◽  
Maria Angustias Muros ◽  
Martín López-de-la-Torre ◽  
Marc Agudelo ◽  
Pilar Bello ◽  
...  
Keyword(s):  
Systematic Review ◽  
Neuroendocrine Tumors ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Progression Free Survival ◽  
Metabolic Complications ◽  
Literature Searches ◽  
Prisma Statement ◽  
Well Differentiated ◽  
Meta Analyses

Neuroendocrine tumors (NETs) frequently overexpress somatostatin receptors (SSTR) on their cell surface. The first-line pharmacological treatment for inoperable metastatic functioning well-differentiated NETs are somatostatin analogs. On second line, Lu-DOTA-TATE (177Lu-DOTA0 Tyr 3 octreotate) has shown stabilization of the disease and an increase in progression free survival, as well as effectiveness in controlling symptoms and increasing quality of life. The management of functional NETs before and during LU-DOTA-TATE treatment is specially challenging, as several complications such as severe carcinoid and catecholamine crisis have been described. The aim of this review is to establish practical guidance for the management and prevention of the most common hormonal crises during radionuclide treatment with Lu-DOTA-TATE: carcinoid syndrome (CS) and catecholamine hypersecretion, as well as to provide a brief commentary on other infrequent metabolic complications. To establish a practical approach, a systematic review was performed. This systematic review was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and conducted using MEDLINE (accessed from PubMed), Google Scholar and ClinicalTrials.gov. Literature searches found 449 citations, and finally nine were considered for this systematic review.

Outcomes of patients treated with capecitabine and temozolamide (CapTem) for advanced pancreatic neuroendocrine tumors (PNETs) and non-PNETs.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 343-343 ◽  
Author(s):  
Renata D'Alpino Peixoto ◽  
Krista Noonan ◽  
Hagen F. Kennecke ◽  
Howard John Lim
Keyword(s):  
Progression Free Survival ◽  
Median Number ◽  
First Line ◽  
Primary Tumors ◽  
Free Survival ◽  
Entire Cohort ◽  
First Line Therapy ◽  
Poor Tolerance ◽  
Well Differentiated ◽  
Number Of Cycles

343 Background: Retrospective studies have demonstrated high response rates among patients with advanced PNETs treated with CapTem while responses are infrequently seen among non-PNETs. The objective of the study was to describe progression free survival (PFS) and overall survival (OS) among sequential NET patients treated with CapTem and to identify factors associated with response. Methods: Patients who initiated therapy with CapTem between 2009 and 2013 for advanced NETs and referred to one of 6 provincial cancer treatment centers were included. Patients received Cap 2000 mg/m2 day 1-14 and TMZ 200 mg/m2 on days 10-14 every 28 days. Their characteristics and outcomes were retrospectively analyzed. Results: In our cohort, 29 patients (16 male) with a median age of 59 (range 26 – 76) received palliative CapTem, 15 of them as first-line chemotherapy and 14 as subsequent lines. Primary tumors included pancreas (48.3%), small bowel (20.7%), lung (10.3%), unknown (10.3), rectum (6.9%) and appendix (3.4%). Median number of cycles was 3. For the entire cohort, median PFS and OS were 4.7 and 20.2 months, respectively. Although pancreatic NETs (PNETs) had shorter OS (18.8 months versus not reached, p=0.37), their PFS was longer than non-PNETs (4.9 versus 2.8 months, p=0.178). There was no difference in PFS between first or subsequent lines of therapy. Patients with Ki67 above 10% had a shorter PFS when compared to lower Ki67 (3.1 versus 5.5 months, p = 0.028). Three patients had to discontinue CapTem due to poor tolerance (2 intractable nauseas and 1 myocardial infarction). There were no treatment-related deaths. Conclusions: CapTem showed good activity among NETs, especially for PNETS, who derived the greatest benefit. Effectiveness was not exclusive to first-line therapy and seems better for well-differentiated tumors.

Prognostic Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Patients with Neuroendocrine Tumors: An Izmir Oncology Group Study

Chemotherapy ◽  
2016 ◽  
Vol 61 (6) ◽  
pp. 281-286 ◽  
Author(s):  
Tarik Salman ◽  
Seher Nazli Kazaz ◽  
Umut Varol ◽  
Utku Oflazoglu ◽  
Ilkay Tugba Unek ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Neuroendocrine Tumors ◽  
Progression Free Survival ◽  
Laboratory Findings ◽  
Strong Negative Correlation ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Pretreatment Period ◽  
Embryonic Origin ◽  
Pancreatic Net

Background: Several studies evaluating the prognostic factors of gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs) have been published. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been accepted as prognostic factors for cancer patients. Materials and Methods: This study included 132 patients diagnosed with GEP-NETs. Peripheral blood samples were collected before the pretreatment period. Results: NLR and PLR were increased as the grade increased in NETs. The embryonic origin analysis revealed higher NLR and PLR rates in NETs of foregut origin. NLR and PLR were also higher in pancreatic NET patients compared to the gastroenteric NET patients. Analysis of NETs by TNM indicated that an advanced stage was accompanied by significantly higher NLR and PLR. We found a strong negative correlation between progression-free survival and NLR and PLR. Conclusion: The study verified that NLR and PLR are simple laboratory findings that can be used to identify NETs with a worse outcome.

Survival and prognostic factors in well-differentiated pancreatic neuroendocrine tumors

2014 ◽  
Vol 49 (6) ◽  
pp. 734-741 ◽  
Author(s):  
Raziye Boyar Cetinkaya ◽  
Morten Vatn ◽  
Lars Aabakken ◽  
Deidi S. Bergestuen ◽  
Espen Thiis-Evensen
Keyword(s):  
Prognostic Factors ◽  
Neuroendocrine Tumors ◽  
Pancreatic Neuroendocrine Tumors ◽  
Well Differentiated

Ki-67 proliferative index predicts progression-free survival of patients with well-differentiated ileal neuroendocrine tumors

2012 ◽  
Vol 43 (4) ◽  
pp. 489-495 ◽  
Author(s):  
Deepti Dhall ◽  
Richard Mertens ◽  
Catherine Bresee ◽  
Rugvedita Parakh ◽  
Hanlin L. Wang ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Progression Free Survival ◽  
Proliferative Index ◽  
Ki 67 ◽  
Free Survival ◽  
Well Differentiated

scholarly journals Multicenter Analysis of Treatment Outcomes for Systemic Therapy in Well Differentiated Grade 3 Neuroendocrine Tumors (NET G3)

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1936
Author(s):  
Leonidas Apostolidis ◽  
Arianna Dal Buono ◽  
Elettra Merola ◽  
Henning Jann ◽  
Dirk Jäger ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Progression Free Survival ◽  
First Line ◽  
Treatment Protocols ◽  
First Line Therapy ◽  
Line Therapy ◽  
Multicenter Analysis ◽  
Net G3 ◽  
Well Differentiated ◽  
Grade 3

Well-differentiated grade 3 neuroendocrine tumors (NET G3) have been distinguished from poorly differentiated neuroendocrine carcinomas (NEC) in the most current WHO classifications. Commonly applied first-line chemotherapy protocols with cisplatin or carboplatin in combination with etoposide (PE) are less effective in NET G3 than NEC. Suggested alternative treatment protocols have not been studied in first-line therapy of NET G3 so far. We performed a retrospective analysis of patients with NET G3 in the databases of 3 German cancer centers. Out of 142 patients, 136 patients received palliative first-line therapy: overall response rate (ORR) was 35.1% for PE (n = 37), 56.4% for FOLFOX (n = 39), 27.3% for temozolomide/capecitabine (TEM/CAP) (n = 22), 45.0% for streptozotocin/5-fluorouracil (STZ/5-FU) (n = 20), and 16.7% for other (n = 18). Median progression-free survival (PFS) for PE was 6.9 months. Compared to PE, PFS in the other treatment groups was 6.9 months for FOLFOX (p = 0.333), 12.0 months for TEM/CAP (p = 0.093), 4.8 months for STZ/5-FU (p = 0.919), and 14.1 months for other (p = 0.014). In a univariate setting, all non-PE patients combined showed a significantly prolonged PFS vs. PE (9.0 months; p = 0.049) which could not be confirmed in a multivariate analysis. In conclusion, NET G3 with FOLFOX showed the highest ORR, and with TEM/CAP showed the longest PFS. Further prospective evaluation of the optimal therapeutic strategy for this tumor entity is needed.

scholarly journals Survival Nomograms for Patients with Pancreatic Neuroendocrine Tumors: A Population-based Study

2020 ◽  
Author(s):  
Bi Lin ◽  
Dinglai Yu ◽  
Shengchuan Chen ◽  
Daojie Wang ◽  
Chaohao Huang
Keyword(s):  
Risk Factors ◽  
Prognostic Factors ◽  
Neuroendocrine Tumors ◽  
Predictive Accuracy ◽  
Primary Site ◽  
Tnm Stage ◽  
Pancreatic Neuroendocrine Tumors ◽  
Multivariate Models ◽  
Training Set ◽  
Discrimination Power

Abstract Background: Although Pancreatic neuroendocrine tumors(PNETs) considered as indolent tumors, most patients are diagnosed at an advanced stage. Herein, we aimed to establish a nomogram to predict the survival of PNETs patients for clinical use via Surveillance, Epidemiology, and End Results (SEER) database. Methods: Based on the SEER program, the data of 1103 patients with PNETs were enrolled and randomly divided into training set and validation set. We performed Kaplan-Meier analysis, Cox proportional hazard regression analysis in training set to evaluate the value of prognostic factors. A nomogram was constructed obtained these independent prognostic factors for predicting overall survival(OS) and specific-cancer survival(CSS). C-index, calibration curve, decision curve analysis were used to evaluate the predictive accuracy of the nomogram. Results: Age, primary site, TNM stage, grade, and surgery were associated with OS and CSS in the multivariate models. Nomograms were established depend on these risk factors and had a better discrimination power than TMN stage. The validation technologies showed that the nomogram was able to predict 3- and 5-year OS and CSS accurately, and also proved the superiority. Age, primary site, TNM stage, grade, and surgery were associated with OS and CSS in the multivariate models. Conclusions: Nomograms were established depend on these risk factors and had a better discrimination power than TMN stage. The validation technologies showed that the nomograms were able to predict 3- and 5-year OS and CSS accurately, and also proved the superiority.

Ribociclib and everolimus in well-differentiated foregut neuroendocrine tumors

2021 ◽  
Vol 28 (4) ◽  
pp. 237-246
Author(s):  
Nitya Raj ◽  
Youyun Zheng ◽  
Haley Hauser ◽  
Joanne Chou ◽  
Johnathan Rafailov ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Treatment Interruption ◽  
Tissue Samples ◽  
Free Survival ◽  
Well Differentiated

The mammalian target of rapamycin inhibitor everolimus is an established therapy for well-differentiated (WD) foregut neuroendocrine tumors (NETs). Pre-clinical data demonstrates a potential synergistic role for cyclin dependent kinase 4/6 inhibition and everolimus to treat this disease. In this phase II multicenter study, patients with advanced foregut WDNETs received combination ribociclib and everolimus until confirmed disease progression or unacceptable toxicity. The first 12 patients received ribociclib 300 mg three weeks in a row with a 1 week break and everolimus 2.5 mg daily (recommended phase II dose). Due to unexpected hematologic and infectious toxicities, the trial was put on hold, modified, and an additional 9 patients received ribociclib 200 mg and everolimus 2.5 mg daily. The primary end point was progression-free survival. Archived pre-treatment tumor was profiled by next-generation sequencing to evaluate for genomic markers of drug response. Twenty-one patients were treated (median age, 56; range, 24 to 77). The study did not meet the pre-specified criteria to advance to stage two. No patients experienced an objective response. Thirteen patients (62%) experienced stable disease. Median progression-free survival was 7.7 months (95% CI, 2.8 months to not reached). Eleven of the first 12 patients (92%) developed grade 2 or more myelosuppression. Ten patients (84%) experienced treatment interruption and 8 patients (67%) required dose reduction. Genetic testing in archival tumor tissue samples failed to identify a predictive biomarker of disease stabilization. The combination of ribociclib and everolimus had insufficient activity to warrant further investigation in foregut WDNETs.

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