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

• Published in: BMC gastroenterology Vol. 18; no. 1; p. 75
• Main Authors: Quaas, A, Waldschmidt, D, Alakus, H, Zander, T, Heydt, C, Goeser, T, Daheim, M, Kasper, P, Plum, P, Bruns, C, Brunn, A, Roth, W, Hartmann, N, Bunck, A, Schmidt, M, Göbel, H, Tharun, L, Buettner, R, Merkelbach-Bruse, S
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31-05-2018; BioMed Central; BMC
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - secondary; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Brain Neoplasms - secondary; Brain tumors; BRCA mutations; BRCA1 mutation; BRCA1 protein; BRCA1 Protein - genetics; Cancer therapies; Carboplatin; Carboplatin - therapeutic use; Carcinoma; Carcinoma, Neuroendocrine - drug therapy; Carcinoma, Neuroendocrine - genetics; Carcinoma, Neuroendocrine - secondary; Case Report; Chemotherapy; Deoxyribonucleic acid; DNA; Dosage and administration; Drug therapy; Gastroenterology; Gemcitabine; Genetic aspects; Genomes; Germ-Line Mutation; Germline-related; Humans; Ileal Neoplasms - drug therapy; Ileal Neoplasms - genetics; Ileal Neoplasms - pathology; Ileum; Liver; Liver Neoplasms - secondary; Male; Metastases; Metastasis; Mutation; Neuroendocrine tumors; Olaparib; Ovarian cancer; Paclitaxel; Paclitaxel - therapeutic use; PARP-inhibition; Patients; Personalized treatment; Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use; Radiation therapy; Ribose; Small bowel mixed adeno-neuroendocrine carcinoma (MANEC); Small intestine; Small intestine cancer; Tumors; United States > US; BRCA1 mutation; PARP-inhibition; Small bowel mixed adeno-neuroendocrine carcinoma (MANEC); Personalized treatment; Germline-related
• ISSN: 1471-230X; 1471-230X
• DOI: 10.1186/s12876-018-0803-1

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.
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.
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.