Therapy susceptible germline-related BRCA 1-mutation in a case of metastasized mixed adeno-neuroendocrine carcinoma (MANEC) of the small bowel

Abstract Background Adenocarcinomas or combined adeno-neuroendocrine carcinomas (MANEC) of small bowel usually have a dismal prognosis with limited systemic therapy options. This is the first description of a patient showing a germline-related BRCA1 mutated MANEC of his ileum. The tumor presented a...

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Main Authors: A. Quaas, D. Waldschmidt, H. Alakus, T. Zander, C. Heydt, T. Goeser, M. Daheim, P. Kasper, P. Plum, C. Bruns, A. Brunn, W. Roth, N. Hartmann, A. Bunck, M. Schmidt, H. Göbel, L. Tharun, R. Buettner, S. Merkelbach-Bruse
Format: Article
Language:English
Published: BMC 2018-05-01
Series:BMC Gastroenterology
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Online Access:http://link.springer.com/article/10.1186/s12876-018-0803-1
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spelling doaj-af89001d0e334ac2a100650cab5309fe2020-11-25T03:28:57ZengBMCBMC Gastroenterology1471-230X2018-05-011811710.1186/s12876-018-0803-1Therapy susceptible germline-related BRCA 1-mutation in a case of metastasized mixed adeno-neuroendocrine carcinoma (MANEC) of the small bowelA. Quaas0D. Waldschmidt1H. Alakus2T. Zander3C. Heydt4T. Goeser5M. Daheim6P. Kasper7P. Plum8C. Bruns9A. Brunn10W. Roth11N. Hartmann12A. Bunck13M. Schmidt14H. Göbel15L. Tharun16R. Buettner17S. Merkelbach-Bruse18Institute of Pathology, University of CologneDepartment of Hepato- and Gastroenterology, University of CologneDepartment of Visceral Surgery, University of CologneDepartment of Oncology and Hematology, University of CologneInstitute of Pathology, University of CologneDepartment of Hepato- and Gastroenterology, University of CologneDepartment of Hepato- and Gastroenterology, University of CologneDepartment of Hepato- and Gastroenterology, University of CologneDepartment of Visceral Surgery, University of CologneDepartment of Visceral Surgery, University of CologneInstitute of Neuropathology, University of CologneInstitute of Pathology, University of MainzInstitute of Pathology, University of MainzDepartment of Radiology, University of CologneDepartment of Nuclear-Medicine, University of CologneInstitute of Pathology, University of CologneInstitute of Pathology, University of CologneInstitute of Pathology, University of CologneInstitute of Pathology, University of CologneAbstract Background Adenocarcinomas or combined adeno-neuroendocrine carcinomas (MANEC) of small bowel usually have a dismal prognosis with limited systemic therapy options. This is the first description of a patient showing a germline-related BRCA1 mutated MANEC of his ileum. The tumor presented a susceptibility to a combined chemotherapy and the PARP1-inhibitor olaparib. Case presentation A 74-year old male patient presented with a metastasized MANEC of his ileum. Due to clinical symptoms his ileum-tumor and the single brain metastasis were removed. We verified the same pathogenic (class 5) BRCA1 mutation in different tumor locations. There was no known personal history of a previous malignant tumor. Nevertheless we identified his BRCA1 mutation as germline-related. A systemic treatment was started including Gemcitabine followed by selective internal radiotherapy (SIRT) to treat liver metastases and in the further course Capecitabine but this treatment finally failed after 9 months and all liver metastases showed progression. The treatment failure was the reason to induce an individualized therapeutic approach using combined chemotherapy of carboplatin, paclitaxel and the Poly (ADP-ribose) polymerase- (PARP)-inhibitor olaparib analogous to the treatment protocol of Oza et al. All liver metastases demonstrated with significant tumor regression after 3 months and could be removed. In his most current follow up from December 2017 (25 months after his primary diagnosis) the patient is in a very good general condition without evidence for further metastases. Conclusion We present first evidence of a therapy susceptible germline-related BRCA1 mutation in small bowel adeno-neuroendocrine carcinoma (MANEC). Our findings offer a personalized treatment option. The germline background was unexpected in a 74-year old man with no previously known tumor burden. We should be aware of the familiar background in tumors of older patients as well.http://link.springer.com/article/10.1186/s12876-018-0803-1Small bowel mixed adeno-neuroendocrine carcinoma (MANEC)BRCA1 mutationGermline-relatedPARP-inhibitionPersonalized treatment
collection DOAJ
language English
format Article
sources DOAJ
author A. Quaas
D. Waldschmidt
H. Alakus
T. Zander
C. Heydt
T. Goeser
M. Daheim
P. Kasper
P. Plum
C. Bruns
A. Brunn
W. Roth
N. Hartmann
A. Bunck
M. Schmidt
H. Göbel
L. Tharun
R. Buettner
S. Merkelbach-Bruse
spellingShingle A. Quaas
D. Waldschmidt
H. Alakus
T. Zander
C. Heydt
T. Goeser
M. Daheim
P. Kasper
P. Plum
C. Bruns
A. Brunn
W. Roth
N. Hartmann
A. Bunck
M. Schmidt
H. Göbel
L. Tharun
R. Buettner
S. Merkelbach-Bruse
Therapy susceptible germline-related BRCA 1-mutation in a case of metastasized mixed adeno-neuroendocrine carcinoma (MANEC) of the small bowel
BMC Gastroenterology
Small bowel mixed adeno-neuroendocrine carcinoma (MANEC)
BRCA1 mutation
Germline-related
PARP-inhibition
Personalized treatment
author_facet A. Quaas
D. Waldschmidt
H. Alakus
T. Zander
C. Heydt
T. Goeser
M. Daheim
P. Kasper
P. Plum
C. Bruns
A. Brunn
W. Roth
N. Hartmann
A. Bunck
M. Schmidt
H. Göbel
L. Tharun
R. Buettner
S. Merkelbach-Bruse
author_sort A. Quaas
title Therapy susceptible germline-related BRCA 1-mutation in a case of metastasized mixed adeno-neuroendocrine carcinoma (MANEC) of the small bowel
title_short Therapy susceptible germline-related BRCA 1-mutation in a case of metastasized mixed adeno-neuroendocrine carcinoma (MANEC) of the small bowel
title_full Therapy susceptible germline-related BRCA 1-mutation in a case of metastasized mixed adeno-neuroendocrine carcinoma (MANEC) of the small bowel
title_fullStr Therapy susceptible germline-related BRCA 1-mutation in a case of metastasized mixed adeno-neuroendocrine carcinoma (MANEC) of the small bowel
title_full_unstemmed Therapy susceptible germline-related BRCA 1-mutation in a case of metastasized mixed adeno-neuroendocrine carcinoma (MANEC) of the small bowel
title_sort therapy susceptible germline-related brca 1-mutation in a case of metastasized mixed adeno-neuroendocrine carcinoma (manec) of the small bowel
publisher BMC
series BMC Gastroenterology
issn 1471-230X
publishDate 2018-05-01
description Abstract Background Adenocarcinomas or combined adeno-neuroendocrine carcinomas (MANEC) of small bowel usually have a dismal prognosis with limited systemic therapy options. This is the first description of a patient showing a germline-related BRCA1 mutated MANEC of his ileum. The tumor presented a susceptibility to a combined chemotherapy and the PARP1-inhibitor olaparib. Case presentation A 74-year old male patient presented with a metastasized MANEC of his ileum. Due to clinical symptoms his ileum-tumor and the single brain metastasis were removed. We verified the same pathogenic (class 5) BRCA1 mutation in different tumor locations. There was no known personal history of a previous malignant tumor. Nevertheless we identified his BRCA1 mutation as germline-related. A systemic treatment was started including Gemcitabine followed by selective internal radiotherapy (SIRT) to treat liver metastases and in the further course Capecitabine but this treatment finally failed after 9 months and all liver metastases showed progression. The treatment failure was the reason to induce an individualized therapeutic approach using combined chemotherapy of carboplatin, paclitaxel and the Poly (ADP-ribose) polymerase- (PARP)-inhibitor olaparib analogous to the treatment protocol of Oza et al. All liver metastases demonstrated with significant tumor regression after 3 months and could be removed. In his most current follow up from December 2017 (25 months after his primary diagnosis) the patient is in a very good general condition without evidence for further metastases. Conclusion We present first evidence of a therapy susceptible germline-related BRCA1 mutation in small bowel adeno-neuroendocrine carcinoma (MANEC). Our findings offer a personalized treatment option. The germline background was unexpected in a 74-year old man with no previously known tumor burden. We should be aware of the familiar background in tumors of older patients as well.
topic Small bowel mixed adeno-neuroendocrine carcinoma (MANEC)
BRCA1 mutation
Germline-related
PARP-inhibition
Personalized treatment
url http://link.springer.com/article/10.1186/s12876-018-0803-1
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