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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Cite this

@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 -