Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung Carcinoma
BackgroundLarge-cell neuroendocrine lung carcinoma (LCNEC) is a rare pulmonary neoplasm with poor prognosis and limited therapeutic options.MethodsWe retrospectively analyzed all patients with metastatic LCNEC in the records of a large German academic center since 2010.Results191 patients were ident...
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Frontiers Media S.A.
2021-07-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.673901/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David Fisch Farastuk Bozorgmehr Farastuk Bozorgmehr Daniel Kazdal Daniel Kazdal Jonas Kuon Jonas Kuon Laura V. Klotz Laura V. Klotz Rajiv Shah Rajiv Shah Florian Eichhorn Florian Eichhorn Mark Kriegsmann Mark Kriegsmann Marc A. Schneider Marc A. Schneider Thomas Muley Thomas Muley Albrecht Stenzinger Albrecht Stenzinger Helge Bischoff Petros Christopoulos Petros Christopoulos |
spellingShingle |
David Fisch Farastuk Bozorgmehr Farastuk Bozorgmehr Daniel Kazdal Daniel Kazdal Jonas Kuon Jonas Kuon Laura V. Klotz Laura V. Klotz Rajiv Shah Rajiv Shah Florian Eichhorn Florian Eichhorn Mark Kriegsmann Mark Kriegsmann Marc A. Schneider Marc A. Schneider Thomas Muley Thomas Muley Albrecht Stenzinger Albrecht Stenzinger Helge Bischoff Petros Christopoulos Petros Christopoulos Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung Carcinoma Frontiers in Oncology large-cell neuroendocrine lung carcinoma immunotherapy platinum chemotherapy local therapies overall survival de novo metastatic |
author_facet |
David Fisch Farastuk Bozorgmehr Farastuk Bozorgmehr Daniel Kazdal Daniel Kazdal Jonas Kuon Jonas Kuon Laura V. Klotz Laura V. Klotz Rajiv Shah Rajiv Shah Florian Eichhorn Florian Eichhorn Mark Kriegsmann Mark Kriegsmann Marc A. Schneider Marc A. Schneider Thomas Muley Thomas Muley Albrecht Stenzinger Albrecht Stenzinger Helge Bischoff Petros Christopoulos Petros Christopoulos |
author_sort |
David Fisch |
title |
Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung Carcinoma |
title_short |
Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung Carcinoma |
title_full |
Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung Carcinoma |
title_fullStr |
Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung Carcinoma |
title_full_unstemmed |
Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung Carcinoma |
title_sort |
comprehensive dissection of treatment patterns and outcome for patients with metastatic large-cell neuroendocrine lung carcinoma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-07-01 |
description |
BackgroundLarge-cell neuroendocrine lung carcinoma (LCNEC) is a rare pulmonary neoplasm with poor prognosis and limited therapeutic options.MethodsWe retrospectively analyzed all patients with metastatic LCNEC in the records of a large German academic center since 2010.Results191 patients were identified with a predominance of male (68%) smokers (92%) and a median age of 65 years. The single most important factor associated with outcome was the type of systemic treatment, with a median overall survival (OS) of 26.4 months in case of immune checkpoint inhibitor administration (n=13), 9.0 months for other patients receiving first-line platinum doublets (n=129), and 4.0 months with non-platinum chemotherapies (n=17, p<0.01). Other patient characteristics independently associated with longer OS were a lower baseline serum LDH (hazard ratio [HR] 0.54, p=0.008) and fewer initial metastatic sites (HR 0.52, p=0.006), while the platinum drug type (cisplatin vs. carboplatin) and cytotoxic partner (etoposide vs. paclitaxel), patients’ smoking status and baseline levels of tumor markers (NSE, CYFRA 21-1, CEA) did not matter. 12% (23/191) of patients forewent systemic treatment, mainly due to tumor-related clinical deterioration (n=13), while patient refusal of therapy (n=5) and severe concomitant illness (n=5) were less frequent. The attrition between successive treatment lines was approximately 50% and similar for platinum-based vs. other therapies, but higher in case of a worse initial ECOG status or higher serum LDH (p<0.05). 19% (36/191) of patients had secondary stage IV disease and showed fewer metastatic sites, better ECOG status and longer OS (median 12.6 vs. 8.7 months, p=0.030). Among the 111 deceased patients with palliative systemic treatment and complete follow-up, after exclusion of oligometastatic cases (n=8), administration of local therapies (n=63 or 57%) was associated with a longer OS (HR 0.58, p=0.008), but this association did not persist with multivariable testing.ConclusionsHighly active systemic therapies, especially immunotherapy and platinum doublets, are essential for improved outcome in LCNEC and influence OS stronger than clinical disease parameters, laboratory results and other patient characteristics. The attrition between chemotherapy lines is approximately 50%, similar to other NSCLC. Patients with secondary metastatic disease have a more favorable clinical phenotype and longer survival. |
topic |
large-cell neuroendocrine lung carcinoma immunotherapy platinum chemotherapy local therapies overall survival de novo metastatic |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.673901/full |
work_keys_str_mv |
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doaj-e1f6b634e2764da99e782889394b37102021-07-08T06:41:33ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-07-011110.3389/fonc.2021.673901673901Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung CarcinomaDavid Fisch0Farastuk Bozorgmehr1Farastuk Bozorgmehr2Daniel Kazdal3Daniel Kazdal4Jonas Kuon5Jonas Kuon6Laura V. Klotz7Laura V. Klotz8Rajiv Shah9Rajiv Shah10Florian Eichhorn11Florian Eichhorn12Mark Kriegsmann13Mark Kriegsmann14Marc A. Schneider15Marc A. Schneider16Thomas Muley17Thomas Muley18Albrecht Stenzinger19Albrecht Stenzinger20Helge Bischoff21Petros Christopoulos22Petros Christopoulos23Department of Thoracic Oncology, Thoraxklinik and National Center for Tumor diseases (NCT), Heidelberg University Hospital, Heidelberg, GermanyDepartment of Thoracic Oncology, Thoraxklinik and National Center for Tumor diseases (NCT), Heidelberg University Hospital, Heidelberg, GermanyTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, GermanyTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, GermanyInstitute of Pathology, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Thoracic Oncology, Thoraxklinik and National Center for Tumor diseases (NCT), Heidelberg University Hospital, Heidelberg, GermanyTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, GermanyTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, GermanyDepartment of Thoracic Surgery, Thoraxklinik at Heidelberg University Hospital, Heidelberg, GermanyDepartment of Thoracic Oncology, Thoraxklinik and National Center for Tumor diseases (NCT), Heidelberg University Hospital, Heidelberg, GermanyTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, GermanyTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, GermanyDepartment of Thoracic Surgery, Thoraxklinik at Heidelberg University Hospital, Heidelberg, GermanyTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, GermanyInstitute of Pathology, Heidelberg University Hospital, Heidelberg, GermanyTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, GermanyTranslational Research Unit, Thoraxklinik at Heidelberg University Hospital, Heidelberg, GermanyTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, GermanyTranslational Research Unit, Thoraxklinik at Heidelberg University Hospital, Heidelberg, GermanyTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, GermanyInstitute of Pathology, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Thoracic Oncology, Thoraxklinik and National Center for Tumor diseases (NCT), Heidelberg University Hospital, Heidelberg, GermanyDepartment of Thoracic Oncology, Thoraxklinik and National Center for Tumor diseases (NCT), Heidelberg University Hospital, Heidelberg, GermanyTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, GermanyBackgroundLarge-cell neuroendocrine lung carcinoma (LCNEC) is a rare pulmonary neoplasm with poor prognosis and limited therapeutic options.MethodsWe retrospectively analyzed all patients with metastatic LCNEC in the records of a large German academic center since 2010.Results191 patients were identified with a predominance of male (68%) smokers (92%) and a median age of 65 years. The single most important factor associated with outcome was the type of systemic treatment, with a median overall survival (OS) of 26.4 months in case of immune checkpoint inhibitor administration (n=13), 9.0 months for other patients receiving first-line platinum doublets (n=129), and 4.0 months with non-platinum chemotherapies (n=17, p<0.01). Other patient characteristics independently associated with longer OS were a lower baseline serum LDH (hazard ratio [HR] 0.54, p=0.008) and fewer initial metastatic sites (HR 0.52, p=0.006), while the platinum drug type (cisplatin vs. carboplatin) and cytotoxic partner (etoposide vs. paclitaxel), patients’ smoking status and baseline levels of tumor markers (NSE, CYFRA 21-1, CEA) did not matter. 12% (23/191) of patients forewent systemic treatment, mainly due to tumor-related clinical deterioration (n=13), while patient refusal of therapy (n=5) and severe concomitant illness (n=5) were less frequent. The attrition between successive treatment lines was approximately 50% and similar for platinum-based vs. other therapies, but higher in case of a worse initial ECOG status or higher serum LDH (p<0.05). 19% (36/191) of patients had secondary stage IV disease and showed fewer metastatic sites, better ECOG status and longer OS (median 12.6 vs. 8.7 months, p=0.030). Among the 111 deceased patients with palliative systemic treatment and complete follow-up, after exclusion of oligometastatic cases (n=8), administration of local therapies (n=63 or 57%) was associated with a longer OS (HR 0.58, p=0.008), but this association did not persist with multivariable testing.ConclusionsHighly active systemic therapies, especially immunotherapy and platinum doublets, are essential for improved outcome in LCNEC and influence OS stronger than clinical disease parameters, laboratory results and other patient characteristics. The attrition between chemotherapy lines is approximately 50%, similar to other NSCLC. Patients with secondary metastatic disease have a more favorable clinical phenotype and longer survival.https://www.frontiersin.org/articles/10.3389/fonc.2021.673901/fulllarge-cell neuroendocrine lung carcinomaimmunotherapyplatinum chemotherapylocal therapiesoverall survivalde novo metastatic |