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

• 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
• Subjects: Small bowel mixed adeno-neuroendocrine carcinoma (MANEC); BRCA1 mutation; Germline-related; PARP-inhibition; Personalized treatment
• Online Access: http://link.springer.com/article/10.1186/s12876-018-0803-1

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.