Outcome and prognostic factors of multimodal therapy for pulmonary large-cell neuroendocrine carcinomas.
BACKGROUND
There is controversy whether patients diagnosed with large-cell neuroendocrine carcinoma (LCNEC) should be treated according to protocols for non-small cell lung cancers (NSCLC) or small cell lung cancers (SCLC), especially with regard to the administration of prophylactic cranial irradiation (PCI). This study was set up to determine the incidence of brain metastases and to investigate the outcome following multimodal treatment in 70 patients with LCNEC.


METHODS
Seventy patients with histologically confirmed LCNEC were treated at the University Hospital of Heidelberg between 2001 and 2014. Data were collected retrospectively. Al most all patients received thoracic surgery as initial treatment (94 %). Chemotherapy was administered in 32 patients as part of the initial treatment. Fourteen patients were treated with adjuvant or definitive thoracic radiotherapy according to NSCLC protocols. Cranial radiotherapy due to brain metastases, mostly given as whole brain radiotherapy (WBRT), was received by fourteen patients. Statistical analysis was performed using the long-rank test and the Kaplan-Meier method.


RESULTS
Without PCI, the detected rate for brain metastases was 25 % after a median follow-up time of 23.4 months, which is comparable to NSCLC patients in general. Overall (OS), local (LPFS), brain metastases-free survival (BMFS) and extracranial distant progression-free survival (eDPFS) was 43, 50, 63 and 50 % at 5 years, respectively. Patients with incomplete resection showed a survival benefit from adjuvant radiotherapy. The administration of adjuvant chemotherapy improved the general worse prognosis in higher pathologic stages.


CONCLUSIONS
In LCNEC patients, the administration of radiotherapy according to NSCLC guidelines appears reasonable and contributes to acceptable results of multimodal treatment regimes. The low incidence of spontaneous brain metastases questions a possible role of PCI.
Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. juliane.rieber@med.uni-heidelberg.de.|Heidelberg Institute of Radiation Oncology, Heidelberg, Germany. juliane.rieber@med.uni-heidelberg.de.
Juliane
J
Rieber
Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. Julian.schmitt@stud.uni-heidelberg.de.|Heidelberg Institute of Radiation Oncology, Heidelberg, Germany. Julian.schmitt@stud.uni-heidelberg.de.
Julian
J
Schmitt
Institute for Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. arne.warth@med.uni-heidelberg.de.
Arne
A
Warth
Translational Research Unit, Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. thomas.muley@med.uni-heidelberg.de.
Thomas
T
Muley
Translational Research Unit, Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. jutta.kappes@med.uni-heidelberg.de.|Department of Thoracic Oncology, Thoraxklinik, Heidelberg University, Amalienstraße 20, 69126, Heidelberg, Germany. jutta.kappes@med.uni-heidelberg.de.
Jutta
J
Kappes
Translational Research Unit, Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. florian.eichhorn@med.uni-heidelberg.de.|Department of Thoracic Surgery, Thoraxklinik, Heidelberg University, Amalienstraße 20, 69126, Heidelberg, Germany. florian.eichhorn@med.uni-heidelberg.de.
Florian
F
Eichhorn
Translational Research Unit, Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. hans.hoffmann@med.uni-heidelberg.de.|Department of Thoracic Surgery, Thoraxklinik, Heidelberg University, Amalienstraße 20, 69126, Heidelberg, Germany. hans.hoffmann@med.uni-heidelberg.de.
Hans
H
Hoffmann
Translational Research Unit, Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. clauspeter.heussel@med.uni-heidelberg.de.|Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik gGmbH, University Hospital Heidelberg, Heidelberg, Germany. clauspeter.heussel@med.uni-heidelberg.de.|Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany. clauspeter.heussel@med.uni-heidelberg.de.
Claus Peter
CP
Heussel
Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. thomas.welzel@med.uni-heidelebrg.de.|Heidelberg Institute of Radiation Oncology, Heidelberg, Germany. thomas.welzel@med.uni-heidelebrg.de.
Thomas
T
Welzel
Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. juergen.debus@med.uni-heidelberg.de.|Heidelberg Institute of Radiation Oncology, Heidelberg, Germany. juergen.debus@med.uni-heidelberg.de.
Jürgen
J
Debus
Translational Research Unit, Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. michael.thomas@med.uni-heidelberg.de.|Department of Thoracic Oncology, Thoraxklinik, Heidelberg University, Amalienstraße 20, 69126, Heidelberg, Germany. michael.thomas@med.uni-heidelberg.de.
Michael
M
Thomas
Translational Research Unit, Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Im Neuenheimer Feld 430, 69120, Heidelberg, Germany. martin.steins@med.uni-heidelberg.de.|Department of Thoracic Oncology, Thoraxklinik, Heidelberg University, Amalienstraße 20, 69126, Heidelberg, Germany. martin.steins@med.uni-heidelberg.de.
Martin
M
Steins
Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. stefan.rieken@med.uni-heidelberg.de.|Heidelberg Institute of Radiation Oncology, Heidelberg, Germany. stefan.rieken@med.uni-heidelberg.de.
Stefan
S
Rieken
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D018278:Carcinoma, Neuroendocrine / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D059248:Chemoradiotherapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome