scholarly journals Clinicopathological and Prognostic Significance of CD47 Expression in Lung Neuroendocrine Tumors

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mario Orozco-Morales ◽  
Alejandro Avilés-Salas ◽  
Norma Hernández-Pedro ◽  
Rodrigo Catalán ◽  
Graciela Cruz-Rico ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Neuroendocrine Tumors ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Large Cell ◽  
Ki 67 ◽  
Typical Carcinoid ◽  
Free Survival ◽  
Wide Range

Background. Lung neuroendocrine tumors account for approximately 15% of all lung cancer cases. LNET are subdivided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small-cell lung cancer (SCLC). The Ki-67 index has been used for decades to evaluate mitotic counts however, the role of Ki-67 as a biomarker for assessing prognosis and guiding therapy in metastatic LNET still lacks feasible clinical validation. Recent clinical trials have indicated that inhibition of CD47 with anti-CD47 antibodies exerts a promising antitumor effect against several human malignancies, including NSCLC, melanoma, and hematologic malignancies. However, the clinical relevance of CD47 expression in LNET has remained unclear. Methods. We performed a retrospective study in which we analyzed tumor biopsies from 51 patients with a confirmed diagnosis of LNET that received treatment at our hospital. Then, we analyzed if there was any correlation between CD47 expression with any clinical or pathological characteristic. We also analyzed the prognostic significance of CD47, assessed as progression-free survival and overall survival. Results. A total of 51 patients with LNET were enrolled in our study. The mean age at diagnosis was 57.6 (±11.6) years; 30 patients were women (59%). 27.5% of patients were positive for CD47 expression, and 72.5% of patients showed a CD47 expression of less than 1% and were considered as negatives. In patients with high-grade tumors (this time defined as Ki ‐ 67 > 40 % ), the positive expression of CD47 was strongly associated with an increased PFS. Albeit, these differences did not reach statistical significance when analyzing OS. Conclusion. Contrary to what happens in a wide range of hematologic and solid tumors, a higher expression of CD47 in patients with LNET is associated with a better progression-free survival, especially in patients with a Ki ‐ 67 ≥ 40 % . This “paradox” remains to be confirmed and explained by larger studies.

scholarly journals Outcome of Patients With Metastatic Lung Neuroendocrine Tumors Submitted to First Line Monotherapy With Somatostatin Analogs

2021 ◽  
Vol 12 ◽  
Author(s):  
Elisa Lenotti ◽  
Andrea Alberti ◽  
Francesca Spada ◽  
Vito Amoroso ◽  
Patrick Maisonneuve ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumors ◽  
Somatostatin Analogs ◽  
Case Series ◽  
Progression Free Survival ◽  
First Line ◽  
Ki 67 ◽  
Typical Carcinoid ◽  
Free Survival ◽  
Metastatic Lung

ObjectiveAntiproliferative activity of somatostatin analogs (SSAs) has been demonstrated in digestive neuroendocrine tumors (NETs), but few data have been published in patients with pulmonary NETs. We therefore conducted a retrospective study to provide additional data on the outcome of patients with metastatic lung NETs submitted to front line SSAs.Research Design and MethodsPatients with metastatic lung NET treated with first line SSA-monotherapy (octreotide or lanreotide) in two different reference Institutions were reviewed. Outcome measures were progression-free survival (PFS) overall survival (OS), overall response rate and safety. We also explored prognostic factors associated with PFS.MethodsThe outcome of consecutive patients (pts) with metastatic lung NETs, who underwent first-line treatment with SSAs, recruited from 2014 on 2019 in two Italian reference Institutions, was retrospectively evaluated.ResultsThirty-one patients entered the study: 14 (45.2%) with typical and 17 (54.8%) atypical carcinoid. Six patients (19.4%) had a carcinoid syndrome. 60.0% of patients had Ki-67 ≤ 10%. Two (6.5%) patients obtained a partial response, 24 (77.4%) disease stabilization while 5 (16.1%) had progressive disease. Median progression free survival (PFS) was 28.6 months, median overall survival (OS) was not attained. Ki-67 ≤ 10%, typical carcinoid histotype and non-functioning disease, were associated with a non-significant PFS prolongation. PFS in patients with atypical carcinoids and in those with Ki-67 >10% was greater than 19 months.ConclusionsThe long PFS and OS obtained in this case series suggest that SSAs could be effective as first line approach in the management of patients with progressive, metastatic pulmonary NET.

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.

Prognostic Significance of Cell of Origin Subclassification in Diffuse Large B Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5081-5081
Author(s):  
Muath Dawod ◽  
Juan Gomez-Gelvez ◽  
Ahmad Mattour ◽  
Kedar V. Inamdar ◽  
Nalini Janakiraman
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Free Survival ◽  
Large B Cell Lymphoma

Abstract Abstract 5081 Background: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that has been divided into three different prognostic subgroups: Germinal Center B cell-like (GC), Activated B cell-like (ABC) and type 3 according to gene expression profile using cDNA. Immunohistochemistry (IHC) has been used as surrogate to identify these cell-of-origin subgroups. Data about the prognostic value of IHC has been conflicting. Patients and methods: In this retrospective study, we reviewed the charts of 252 patients diagnosed with DLBCL at Henry Ford Hospital from 1999 to 2012. We excluded patients with HIV, transformed lymphomas and unavailable samples. Data was collected on a total of 157 patients. The following data was gathered: age, sex, race, IPI score, disease stage, hemoglobin, white blood and platelet counts, best response achieved and dates of treatment start, relapse, death or last follow up. Tissue microarray slides with the following IHC stains (CD10, MUM1, Bcl6) were prepared and reviewed when needed. Using Hans Algorithm, samples were divided into two major groups (GC-like and non-GC-like). 3-year progression free and overall survivals were compared between all subgroups using a log-rank test. Continuous variables were reported as median and range, and compared using Wilcoxon rank-sum tests. Categorical variables were reported as median and range, and compared using Chi-square tests. Statistical significance was set at p<0. 05. Results: Eighty patients (51%) were classified as GC-like, and 77 patients (49%) as non-GC-like. GC-like subgroup had a significantly longer 3-year progression free survival (90% vs 74%, P=0. 024), as compared with the non-GC-like subgroup. There was a trend toward longer overall survival but it didn't reach statistical significance (74% vs 67%, P=0. 161). For all patients, IPI stands as a strong prognostic index with 3-year overall survival of (85% and 46%, P=<. 001) in patients with low IPI (0 to 2) and high IPI (3 to 5) respectively. Interestingly, in patients with low IPI, cell of origin stands as a prognostic factor with 3-year progression free survival of (96% and 81%, P=0. 032) in GC-like and non-GC-like groups respectively. While in patients with high IPI, there was no significant difference in progression free survival in cell-of-origin subgroups. Conclusion: Cell of origin subclassification as determined by IHC surrogate markers predict for better progression free survival in GC-like subgroup but not for overall survival. While this prognostic value was maintained in patients with low IPI, there was no prognostic significance in patients with high IPI. IPI is still a valuable prognostic tool in patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

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 The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events

2021 ◽  
Vol 11 ◽  
Author(s):  
Toshiya Fujisaki ◽  
Satoshi Watanabe ◽  
Takeshi Ota ◽  
Kohei Kushiro ◽  
Yusuke Sato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Continuous Administration ◽  
Free Survival ◽  
Programmed Cell Death 1 ◽  
Third Line ◽  
Nsclc Patients

ObjectivesAlthough immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs.MethodsWe retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors.ResultsOf 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) vs. not reached (95% CI: 22.4–NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) vs. not reached (95% CI: 8.4–NE); p = 0.031].ConclusionThe current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs.

scholarly journals Significance of Chromogranin A in Diagnosis and Prognosis of Neuroendocrine Tumors

2019 ◽  
Vol 2 (17) ◽  
pp. 19-22 ◽  
Author(s):  
N. V. Lyubimova ◽  
Yu. S. Timofeev ◽  
T. K. Churikova ◽  
A. E. Kuzminov ◽  
N. E. Kushlinsky
Keyword(s):  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
High Efficiency ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Healthy Individuals ◽  
Free Survival ◽  
Diagnosis And Prognosis ◽  
Different Types ◽  
The Comparative Study

We present the comparative study of plasma chromogranin A (CgA) levels measured in 232 patients with different types of neuroendocrine tumors (NETs) and 66 healthy individuals using enzyme immunoassay Chromogranin A ELISA kit (Dako). CgA levels were significantly higher in patients with all types of NETs than in healthy subjects. CgA secretion were highly variable. The study demonstrate high diagnostic sensitivity of CgA, which was 80.6 % in overall group of NETs with specificity 98.5 %. We confirmed the prognostic significance of CgA, in this case the high basal levels of CgA (above 100 U/l) were significantly associated with less favorable prognosis of progression free survival after different types of treatment. The data confirms high efficiency of CgA as biomarker, which measurement enhances the accuracy of diagnosis and prognosis of NETs.

Neuroendocrine Tumors of the Lung: An Update

2010 ◽  
Vol 134 (11) ◽  
pp. 1628-1638 ◽  
Author(s):  
Natasha Rekhtman
Keyword(s):  
Neuroendocrine Tumors ◽  
Who Classification ◽  
Large Cell ◽  
Mitotic Rate ◽  
World Health ◽  
Diagnostic Tools ◽  
Ki 67 ◽  
Typical Carcinoid ◽  
Pathologic Features ◽  
Health Organization

AbstractContext.—The 2004 World Health Organization (WHO) classification recognizes 4 major types of lung neuroendocrine tumors: typical carcinoid, atypical carcinoid, small cell lung cancer, and large cell neuroendocrine carcinoma. Markedly different prognostic implications and treatment paradigms for these tumors underscore the importance of accurate pathologic diagnosis.Objective.—To detail the clinical and pathologic features of lung neuroendocrine tumors, with emphasis on diagnostic criteria, differential diagnoses, and application of immunohistochemistry. The emerging evidence for the utility of Ki-67 (MIB1) in the diagnosis of lung neuroendocrine tumors, particularly in small biopsy and cytology, is emphasized.Data Sources.—The 2004 WHO classification, other published literature, and primary material from the author's institution.Conclusions.—The current WHO classification of neuroendocrine tumors is based on morphologic features in combination with precisely defined mitotic rate and absence or presence of necrosis. Ki-67 (MIB1) is emerging as a useful ancillary tool in the diagnosis of these tumors. Continued research efforts are needed to identify additional immunohistochemical and molecular biomarkers that can serve as ancillary diagnostic tools and as potential therapeutic targets for these diseases.

scholarly journals The impact of tumor invasion to muscularis mucosaevascular plexus on patient outcome in pT1 bladder urothelial carcinoma

2020 ◽  
Vol 92 (3) ◽  
Author(s):  
Ahmet Sahan ◽  
Fatma Gerin ◽  
Asgar Garayev ◽  
Emine Bozkurtlar ◽  
Alkan Çubuk ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Urothelial Carcinoma ◽  
Tumor Invasion ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Free Survival ◽  
Bladder Urothelial Carcinoma ◽  
Wide Range ◽  
The Impact

Objectives: T1 bladder cancer has a wide range of tumor behavior and lamina propria invasion depth has a high potential risk of disease progression. To evaluate the patient outcome according to the tumor invasion to the muscularis mucosae-vascular plexus (MM-VP) in pT1 bladder urothelial carcinoma (BUC). Materials and methods: This study is a retrospective analysis of patients consecutively recorded from 2007 to 2013. A total of 93 patients with a history of primary pT1 BUC and complete follow-up were included. We used a pathological substaging system according to the tumor invasion regarding the MM-VP: pT1a (invasion above MM-VP) and pT1b (MM-VP invasion). We evaluated recurrence-free survival (RFS), progression- free survival (PFS), disease-specific-survival (DSS) based on this sub-staging system. Results: Pathological evaluation regarding the MM-VP invasion revealed 53 patients (57%) as pT1a BUC and 40 patients (43%) as pT1b BUC. The mean follow-up was 78.8 months. During the follow-up period; 60 patients (64.5%) had tumor recurrences, 32 patients (34.4%) had progression to invasive disease, 18 patients (19.4 %) died during follow-up related to the BUC. In 29 (54.7%) of pT1a and in 31(77.5%) of pT1b tumors, the recurrent disease was recorded during the followup period (p = 0.023). DSS rates at 5 years for pT1a and pT1b were 80.2% and 60.8%, respectively. PFS, RFS, and DSS rates were similar for pT1a/pT1b and did not reach statistical significance (p > 0.05). Conclusions: Sub-staging of pT1 BUC according to the MM-VP invasion showed a limited impact on the outcome in our patient cohort. However, the presence of pT1b disease caused a significantly higher rate of recurrence.

scholarly journals Prognostic Value of the Advanced Lung Cancer Inflammation Index in Patients with Lung Cancer: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yi Zhang ◽  
Bo Chen
Keyword(s):  
Lung Cancer ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Advanced Lung Cancer ◽  
Free Survival ◽  
Online Databases ◽  
Hazard Ratios ◽  
Cancer Inflammation

Background. The advanced lung cancer inflammation index (ALI) has been related to tumor survival in lung cancer (LC) patients. However, these findings regarding the prognostic relevance of ALI in LC were inconsistent. Our study is aimed at characterizing the prognostic significance of low pretreatment ALI in LC cases. Methods. Relevant published studies were systematically searched in several online databases. The combined hazard ratios (HRs) were applied to assess the correlation between ALI and overall/recurrence-free/progression-free survival (OS/PFS/RFS) in LC. Results. A total of 1587 LC patients from eight articles were recruited. Pooled results indicated that pretreatment ALI was significantly associated with prognosis in cases with LC. Compared to those with high-ALI, LC cases in the low-ALI group had a poorer OS (HR: 1.64, 95% CI: 1.34-1.93, p<0.001). Subgroup analyses further revealed the negative significant prognostic value of low ALI in LC. In addition, low ALI had obvious connection with inferior PFS/RFS (HR: 1.71, 95% CI: 1.35-2.07, p<0.001) in LC patients. Conclusions. Low ALI before treatments indicates poor prognosis in LC patients. Serum ALI may serve as a promising predictive tumor marker of survival in LC sufferers.

scholarly journals Prognostic Significance of PD-L1 Expression In Patients With Primary Oropharyngeal Squamous Cell Carcinoma: A Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jerry Polesel ◽  
Anna Menegaldo ◽  
Giancarlo Tirelli ◽  
Vittorio Giacomarra ◽  
Roberto Guerrieri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Free Survival ◽  
Hpv Status

BackgroundAt present, the prognostic significance of programmed cell death receptor ligand 1 (PD-L1) expression in oropharyngeal squamous cell carcinoma (OPSCC) patients is still controversial. In this study, we aim to synthesize relevant studies that have assessed the prognostic value of PD-L1 in patients with primary OPSCC treated according to the current standard-of-care.MethodsA systematic search of Medline/PubMed, Cochrane, Embase, Web of Science, and Scopus was conducted to define the prognostic role of PD-L1 expression in OPSCC. All studies published before July 31, 2021 were screened. Summary hazard ratios (sHR) with 95% confidence intervals (CIs) were calculated using a random-effects model.ResultsA total of 1522 OPSCC patients from 12 studies were included. PD-L1 expression in OPSCC tumor cells (TCs) was significantly associated with longer overall survival (sHR=0.63, 95% CI 0.50-0.79), and progression-free survival (sHR=0.62, 95% CI 0.49-0.79). A benefit in survival was also observed in PD-L1-positive OPSCC patients who underwent surgery (sHR=0.34, 95% CI 0.18-0.65). Finally, although PD-L1-positive expression was related to better outcomes both in HPV-negative and HPV-positive OPSCC, the difference reached the statistical significance only in the HPV-positive subgroup (sHR=0.37, 95% CI 0.19-0.73). No heterogeneity emerged between studies for all considered outcomes, with I2 ranging from 0% for progression-free survival to 11% for overall survival.ConclusionsPD-L1 expression on TCs associated with improved survival in OPSCC. In particular, HPV-positive OPSCC most benefited from PD-L1 expression when compared to the PD-L1 negative counterpart. Thus, PD-L1 might represent a useful biomarker to stratify prognosis in OPSCC in addition to HPV status.

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