Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype

B. C. M. Hermans; J. L. Derks; H. J. M. Groen; J. A. Stigt; R. J. van Suylen; L. M. Hillen; E. C. van den Broek; E. J. M. Speel; A-M C. Dingemans

doi:10.1530/EC-19-0372

Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype

B. C. M. Hermans
, J. L. Derks
, H. J. M. Groen
, J. A. Stigt
, R. J. van Suylen
, L. M. Hillen
, E. C. van den Broek
, E. J. M. Speel
, A-M C. Dingemans^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Introduction: Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung generally presents as disseminated and aggressive disease with a Ki-67 proliferation index (P1) 40-80%. LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small-cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small-cell lung carcinoma (NSCLC)-like). Here we evaluated 11 LCNEC patients with only a solitary brain metastasis and evaluate phenotype, genotype and follow-up.

Methods: Eleven LCNEC patients with solitary brain metastases were analyzed. Clinical characteristics and survival data were retrieved from medical records. Pathological analysis included histomorphological analysis, immunohistochemistry (pRB and Ki-67 PI) and next-generation sequencing (TP53, RB1, STK11, KEAP1 and MEN1).

Results: All patients had NO or N1 disease. Median overall survival (OS) was 12 months (95% confidence interval (CI) 5.5-18.5 months). Mean Ki-67 PI was 59% (range 15-100%). In 6/11 LCNEC Ki-67 PI was 40% (17 months (95% CI 11-23 months) vs 5 months (95% CI 0.7-9 months), P = 0.007). Two patients were still alive at follow-up after 86 and 103 months, both had Ki-67

Conclusion: Stage IV LCNEC with a solitary brain metastasis and NO/N1 disease show in the majority of cases Ki-67 PI

Original language	English
Pages (from-to)	1600-1606
Number of pages	7
Journal	Endocrine Connections
Volume	8
Issue number	12
DOIs	https://doi.org/10.1530/EC-19-0372
Publication status	Published - Dec 2019

Keywords

large cell neuroendocrine carcinoma
LCNEC
solitary brain metastasis
prognosis
Ki-67
LUNG
TUMORS
NETHERLANDS
FEATURES
CANCER

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@article{beb0f2899a7a4eb98ed6f6f608e49648,

title = "Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype",

abstract = "Introduction: Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung generally presents as disseminated and aggressive disease with a Ki-67 proliferation index (P1) 40-80\%. LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small-cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small-cell lung carcinoma (NSCLC)-like). Here we evaluated 11 LCNEC patients with only a solitary brain metastasis and evaluate phenotype, genotype and follow-up.Methods: Eleven LCNEC patients with solitary brain metastases were analyzed. Clinical characteristics and survival data were retrieved from medical records. Pathological analysis included histomorphological analysis, immunohistochemistry (pRB and Ki-67 PI) and next-generation sequencing (TP53, RB1, STK11, KEAP1 and MEN1).Results: All patients had NO or N1 disease. Median overall survival (OS) was 12 months (95\% confidence interval (CI) 5.5-18.5 months). Mean Ki-67 PI was 59\% (range 15-100\%). In 6/11 LCNEC Ki-67 PI was 40\% (17 months (95\% CI 11-23 months) vs 5 months (95\% CI 0.7-9 months), P = 0.007). Two patients were still alive at follow-up after 86 and 103 months, both had Ki-67Conclusion: Stage IV LCNEC with a solitary brain metastasis and NO/N1 disease show in the majority of cases Ki-67 PI",

keywords = "large cell neuroendocrine carcinoma, LCNEC, solitary brain metastasis, prognosis, Ki-67, LUNG, TUMORS, NETHERLANDS, FEATURES, CANCER",

author = "Hermans, \{B. C. M.\} and Derks, \{J. L.\} and Groen, \{H. J. M.\} and Stigt, \{J. A.\} and \{van Suylen\}, \{R. J.\} and Hillen, \{L. M.\} and \{van den Broek\}, \{E. C.\} and Speel, \{E. J. M.\} and Dingemans, \{A-M C.\}",

note = "Funding Information: B C M H reports grants from Bristol-Myers Squibb, non-financial support from Abbvie, outside the submitted work. J L D reports personal fees from BMS, personal fees from Pfizer, personal fees from Boehringer-阀ngelheim, personal fees from Novartis, personal fees from Ipsen, outside the submitted work. E J M S reports grants from Bristol-Myers Squibb, Astra Zeneca, Pfizer, Novartis and MSD, personal fees from AbbVie and Roche, non-financial support from Abbvie, outside the submitted work. A-M C D reports grants from Bristol-Myers Squibb, personal fees from Roche, BMS, Eli Lily, Takeda and Boehringer 阀ngelheim, non-financial support from Abbvie, outside the submitted work. The other authors have nothing to disclose. Publisher Copyright: {\textcopyright} 2019 The authors Published by Bioscientifica Ltd.",

year = "2019",

month = dec,

doi = "10.1530/EC-19-0372",

language = "English",

volume = "8",

pages = "1600--1606",

journal = "Endocrine Connections",

issn = "2049-3614",

publisher = "BioScientifica Ltd.",

number = "12",

}

TY - JOUR

T1 - Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67

T2 - a unique subtype

AU - Hermans, B. C. M.

AU - Derks, J. L.

AU - Groen, H. J. M.

AU - Stigt, J. A.

AU - van Suylen, R. J.

AU - Hillen, L. M.

AU - van den Broek, E. C.

AU - Speel, E. J. M.

AU - Dingemans, A-M C.

N1 - Funding Information: B C M H reports grants from Bristol-Myers Squibb, non-financial support from Abbvie, outside the submitted work. J L D reports personal fees from BMS, personal fees from Pfizer, personal fees from Boehringer-阀ngelheim, personal fees from Novartis, personal fees from Ipsen, outside the submitted work. E J M S reports grants from Bristol-Myers Squibb, Astra Zeneca, Pfizer, Novartis and MSD, personal fees from AbbVie and Roche, non-financial support from Abbvie, outside the submitted work. A-M C D reports grants from Bristol-Myers Squibb, personal fees from Roche, BMS, Eli Lily, Takeda and Boehringer 阀ngelheim, non-financial support from Abbvie, outside the submitted work. The other authors have nothing to disclose. Publisher Copyright: © 2019 The authors Published by Bioscientifica Ltd.

PY - 2019/12

Y1 - 2019/12

N2 - Introduction: Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung generally presents as disseminated and aggressive disease with a Ki-67 proliferation index (P1) 40-80%. LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small-cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small-cell lung carcinoma (NSCLC)-like). Here we evaluated 11 LCNEC patients with only a solitary brain metastasis and evaluate phenotype, genotype and follow-up.Methods: Eleven LCNEC patients with solitary brain metastases were analyzed. Clinical characteristics and survival data were retrieved from medical records. Pathological analysis included histomorphological analysis, immunohistochemistry (pRB and Ki-67 PI) and next-generation sequencing (TP53, RB1, STK11, KEAP1 and MEN1).Results: All patients had NO or N1 disease. Median overall survival (OS) was 12 months (95% confidence interval (CI) 5.5-18.5 months). Mean Ki-67 PI was 59% (range 15-100%). In 6/11 LCNEC Ki-67 PI was 40% (17 months (95% CI 11-23 months) vs 5 months (95% CI 0.7-9 months), P = 0.007). Two patients were still alive at follow-up after 86 and 103 months, both had Ki-67Conclusion: Stage IV LCNEC with a solitary brain metastasis and NO/N1 disease show in the majority of cases Ki-67 PI

AB - Introduction: Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung generally presents as disseminated and aggressive disease with a Ki-67 proliferation index (P1) 40-80%. LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small-cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small-cell lung carcinoma (NSCLC)-like). Here we evaluated 11 LCNEC patients with only a solitary brain metastasis and evaluate phenotype, genotype and follow-up.Methods: Eleven LCNEC patients with solitary brain metastases were analyzed. Clinical characteristics and survival data were retrieved from medical records. Pathological analysis included histomorphological analysis, immunohistochemistry (pRB and Ki-67 PI) and next-generation sequencing (TP53, RB1, STK11, KEAP1 and MEN1).Results: All patients had NO or N1 disease. Median overall survival (OS) was 12 months (95% confidence interval (CI) 5.5-18.5 months). Mean Ki-67 PI was 59% (range 15-100%). In 6/11 LCNEC Ki-67 PI was 40% (17 months (95% CI 11-23 months) vs 5 months (95% CI 0.7-9 months), P = 0.007). Two patients were still alive at follow-up after 86 and 103 months, both had Ki-67Conclusion: Stage IV LCNEC with a solitary brain metastasis and NO/N1 disease show in the majority of cases Ki-67 PI

KW - large cell neuroendocrine carcinoma

KW - LCNEC

KW - solitary brain metastasis

KW - prognosis

KW - Ki-67

KW - LUNG

KW - TUMORS

KW - NETHERLANDS

KW - FEATURES

KW - CANCER

U2 - 10.1530/EC-19-0372

DO - 10.1530/EC-19-0372

M3 - Article

C2 - 31751303

SN - 2049-3614

VL - 8

SP - 1600

EP - 1606

JO - Endocrine Connections

JF - Endocrine Connections

IS - 12

ER -

Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype

Abstract

Keywords

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