Dramatic, durable response to therapy in gBRCA2-mutated pancreas neuroendocrine carcinoma: opportunity and challenge.
Fergus KeaneRaazi BajwaPier SelenicaWungki ParkMichael H RoehrlJorge Sergio Reis-FilhoDiana L MandelkerEileen M O'ReillyPublished in: NPJ precision oncology (2023)
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.
Keyphrases
- case report
- wild type
- single cell
- small cell lung cancer
- neuroendocrine tumors
- stem cells
- cell therapy
- squamous cell carcinoma
- oxidative stress
- machine learning
- papillary thyroid
- radiation therapy
- locally advanced
- mass spectrometry
- mesenchymal stem cells
- smoking cessation
- fluorescence imaging
- dna repair
- rectal cancer
- bone marrow
- replacement therapy
- drug induced