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

BMC Gastroenterology

P. Kasper¹  T. Goeser¹  D. Waldschmidt¹  M. Daheim¹  M. Schmidt²  T. Zander³  A. Bunck⁴  H. Alakus⁵  P. Plum⁵  C. Bruns⁵  A. Brunn⁶  A. Quaas⁷  S. Merkelbach-Bruse⁷  R. Buettner⁷  H. Göbel⁷  L. Tharun⁷  C. Heydt⁷  N. Hartmann⁸  W. Roth⁸ 

[1] Department of Hepato- and Gastroenterology, University of Cologne;Department of Nuclear-Medicine, University of Cologne;Department of Oncology and Hematology, University of Cologne;Department of Radiology, University of Cologne;Department of Visceral Surgery, University of Cologne;Institute of Neuropathology, University of Cologne;Institute of Pathology, University of Cologne;Institute of Pathology, University of Mainz;

关键词: Small bowel mixed adeno-neuroendocrine carcinoma (MANEC);    BRCA1 mutation;    Germline-related;    PARP-inhibition;    Personalized treatment;   

DOI  :  10.1186/s12876-018-0803-1

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown