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Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

ABSTRACT: Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in "real-world" treatment/survival outcomes between small-cell (SC) versus (vs.) non-SC EP-NECs. One-hundred and seventy patients were included: 77 (45.3%) had SC EP-NECs and 93 (54.7%) had non-SC EP-NECs. Compared to the SC subgroup, the non-SC subgroup had the following features: (1) a lower mean Ki-67 index (69.3% vs. 78.7%; p = 0.002); (2) a lower proportion of cases with a Ki-67 index of ≥55% (73.9% vs. 88.7%; p = 0.025); (3) reduced sensitivity to first-line platinum/etoposide (objective response rate: 31.6% vs. 55.1%, p = 0.015; and disease control rate; 59.7% vs. 79.6%, p = 0.027); (4) worse progression-free survival (PFS) (adjusted-HR = 1.615, p = 0.016) and overall survival (OS) (adjusted-HR = 1.640, p = 0.015) in the advanced setting. Within the advanced EP-NEC cohort, subgroups according to morphological subtype and Ki-67 index (<55% vs. ≥55%) had significantly different PFS (adjusted-p = 0.021) and OS (adjusted-p = 0.051), with the non-SC subgroup with a Ki-67 index of <55% and non-SC subgroup with a Ki-67 index of ≥55% showing the best and worst outcomes, respectively. To conclude, the morphological subtype of EP-NEC provides complementary information to the Ki-67 index and may aid identification of patients who could benefit from alternative first-line treatment strategies to platinum/etoposide.

SUBMITTER: Frizziero M

PROVIDER: S-EPMC8392018 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

Frizziero Melissa M Durand Alice A Taboada Rodrigo G RG Zaninotto Elisa E Luchini Claudio C Chakrabarty Bipasha B Hervieu Valérie V Claro Laura C L LCL Zhou Cong C Cingarlini Sara S Milella Michele M Walter Thomas T Riechelmann Rachel S RS Lamarca Angela A Hubner Richard A RA Mansoor Wasat W Valle Juan W JW McNamara Mairéad G MG

Cancers 20210818 16

Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in "real-world" treatment/survival outcomes between small-cell (SC) versus (vs.) non-SC EP-NECs. One-hundred and seventy patients were included: 77 ( ...[more]

PMID: 34439308

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Project description:ObjectivesPost-imaging mathematical prediction models (MPMs) provide guidance for the management of solid pulmonary nodules by providing a lung cancer risk score from demographic and radiologists-indicated imaging characteristics. We hypothesized calibrating the MPM risk score threshold to a local study cohort would result in improved performance over the original recommended MPM thresholds. We compared the pre- and post-calibration performance of four MPM models and determined if improvement in MPM prediction occurs as nodules are imaged longitudinally.Materials and methodsA common cohort of 317 individuals with computed tomography-detected, solid nodules (80 malignant, 237 benign) were used to evaluate the MPM performance. We created a web-based application for this study that allows others to easily calibrate thresholds and analyze the performance of MPMs on their local cohort. Thirty patients with repeated imaging were tested for improved performance longitudinally.ResultsUsing calibrated thresholds, Mayo Clinic and Brock University (BU) MPMs performed the best (AUC = 0.63, 0.61) compared to the Veteran's Affairs (0.51) and Peking University (0.55). Only BU had consensus with the original MPM threshold; the other calibrated thresholds improved MPM accuracy. No significant improvements in accuracy were found longitudinally between time points.ConclusionsCalibration to a common cohort can select the best-performing MPM for your institution. Without calibration, BU has the most stable performance in solid nodules ≥ 8 mm but has only moderate potential to refine subjects into appropriate workup. Application of MPM is recommended only at initial evaluation as no increase in accuracy was achieved over time.Key points• Post-imaging lung cancer risk mathematical predication models (MPMs) perform poorly on local populations without calibration. • An application is provided to facilitate calibration to new study cohorts: the Mayo Clinic model, the U.S. Department of Veteran's Affairs model, the Brock University model, and the Peking University model. • No significant improvement in risk prediction occurred in nodules with repeated imaging sessions, indicating the potential value of risk prediction application is limited to the initial evaluation.

Project description:BackgroundPulmonary adenocarcinoma with neuroendocrine differentiation (ADE_ned) is a relatively uncommon pathological classification, and there exists considerable debate regarding its prognosis and treatment. The purpose of this study was to analyze the survival difference between patients with neuroendocrine carcinoma (NEC), adenocarcinoma (ADE), or ADE_ned and to investigate the prognostic factors influencing the outcomes of individuals diagnosed with pulmonary ADE_ned.MethodsWe retrieved information on 316 cases of ADE_ned, 188,823 cases of ADE, and 71,154 cases of NEC diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. To account for potential confounding variables, propensity score matching (PSM) was employed. Comparative analyses were conducted to estimate the overall survival (OS) and cancer-specific survival (CSS). Finally, the Cox regression models were used to identify prognostic factors associated with pulmonary ADE_ned.ResultsPrior to PSM, patients with lung ADE_ned had a worse OS rate than did those with lung ADE or NEC (5-year OS rate: 13.3% vs. 26.6% vs. 15.6%; P<0.001 and P=0.009, respectively). In terms of CSS, the 5-year CSS rate of patients with ADE_ned was superior to that of NEC but inferior to that of ADE (28.7% vs. 26.8% vs. 43.8%; P=0.006 and P<0.001, respectively). Following PSM, the 5-year survival rate of patients with ADE_ned remained lower than that of individuals with ADE or NEC in terms of OS (13.3% vs. 24.4% vs. 23.0%; P<0.001 and P<0001, respectively) and CSS (28.8% vs. 58.6% vs. 43.1%; P<0.001 and P=0.006, respectively). Finally, the results of the competitive risk regression analysis demonstrated that several variables, including sex, T stage, N stage, M stage, and surgery, were found to be independent prognostic factors for patients diagnosed with pulmonary ADE_ned (all P values <0.05).ConclusionsPatients with lung ADE_ned had a significantly poorer survival outcome compared to those with lung ADE or NEC. Furthermore, sex, tumor-node-metastasis (TNM) stage, and surgery were found to be independent prognostic indicators for cases with lung ADE_ned.

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Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

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Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

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