Dramatic, durable response to therapy in gBRCA2-mutated pancreas neuroendocrine carcinoma: Opportunity and challenge Journal Article
| Authors: | Keane, F.; Bajwa, R.; Selenica, P.; Park, W.; Roehrl, M. H.; Reis-Filho, J. S.; Mandelker, D.; O’Reilly, E. M. |
| Article Title: | Dramatic, durable response to therapy in gBRCA2-mutated pancreas neuroendocrine carcinoma: Opportunity and challenge |
| Abstract: | Poorly differentiated pancreatic neuroendocrine tumors (PDNEC), are a subtype of pancreatic cancer encompassing both small cell and large cell neuroendocrine carcinoma subtypes, and are characterized as distinct in terms of biology and prognosis compared to the more common pancreatic adenocarcinoma. Until recently, there has been a paucity of data on the genomic features of this cancer type. We describe a male patient diagnosed with PDNEC and extensive metastatic disease in the liver at diagnosis. Genomic analysis demonstrated a germline pathogenic variant in BRCA2 with somatic loss-of-heterozygosity of the BRCA2 wild-type allele. Following a favorable response to platinum-based chemotherapy (and the addition of immunotherapy), the patient received maintenance therapy with olaparib, which resulted in a further reduction on follow-up imaging (Fig. 1). After seventeen months of systemic control with olaparib, the patient developed symptomatic central nervous system metastases, which harboured a BRCA2 reversion mutation. No other sites of disease progression were observed. Herein, we report an exceptional outcome through the incorporation of a personalized management approach for a patient with a pancreatic PDNEC, guided by comprehensive genomic sequencing. © 2023, The Author(s). |
| Keywords: | cancer chemotherapy; clinical article; human tissue; treatment response; aged; human cell; sequence analysis; somatic mutation; fatigue; histopathology; pathogenesis; case report; postoperative period; cisplatin; drug withdrawal; systemic therapy; liver dysfunction; cancer radiotherapy; nuclear magnetic resonance imaging; follow up; ki 67 antigen; allele; cancer immunotherapy; quality of life; computer assisted tomography; multiple cycle treatment; etoposide; peripheral neuropathy; tumor differentiation; maintenance therapy; genetic variability; brca2 protein; wild type; protein p53; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; liver metastasis; hospitalization; death; laboratory test; family history; hepatomegaly; clinical evaluation; tumor cell; brain metastasis; gene loss; craniotomy; lactate dehydrogenase; heterozygosity loss; physical examination; stereotactic treatment; liver function test; cytokeratin 7; general condition improvement; cancer control; retinoblastoma protein; genetic screening; chromogranin; liver biopsy; disease exacerbation; lymphadenopathy; treatment withdrawal; dura mater; brain edema; endoscopic retrograde cholangiopancreatography; olaparib; sample; arm weakness; parietal lobe; pancreas islet cell carcinoma; synaptophysin; medical history; coordination disorder; falling; vein embolism; clinical outcome; brain damage; intrahepatic bile duct; germline mutation; tumor invasion; common bile duct; superior mesenteric vein; interdisciplinary research; genomic mutation; proliferation index; human; male; article; revertant; atezolizumab; liver lobe; hepatic portal vein; bile duct dilatation; eye jaundice |
| Journal Title: | npj Precision Oncology |
| Volume: | 7 |
| ISSN: | 2397-768X |
| Publisher: | Springer Nature |
| Date Published: | 2023-04-22 |
| Start Page: | 40 |
| Language: | English |
| DOI: | 10.1038/s41698-023-00376-x |
| PROVIDER: | scopus |
| PMCID: | PMC10122663 |
| PUBMED: | 37087482 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged via PDF -- MSK corresponding author is Eileen O'Reilly -- Export Date: 1 June 2023 -- Source: Scopus |
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