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Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC): An Aggressive Disease Course and Limitations for
Celine Oanæs1,2,3, Herish Garresori4, Dordi Lea5
1Department of Gastrointestinal Surgery, HPB Unit, Stavanger University Hospital, Stavanger, Norway. celine.oanes@sus.no.
Abstract:
Neuroendocrine carcinoma (NEC) is a rare, aggressive malignancy with limited treatment options and poor prognosis. We report a male patient diagnosed with a gastroenteropancreatic (GEP)-NEC with synchronous liver metastasis at the time of surgery who underwent a radical resection attempt. Despite radical-intent surgery followed by adjuvant carboplatin/etoposide, early recurrence developed with progression through multiple subsequent chemotherapy lines. During the treatment process, genetic profiling was performed twice to identify actionable genomic targets, with inclusion in the national IMPRESS study as a last resort. Comprehensive genomic profiling revealed TP53 mutation and RB1 loss but no actionable alterations. A patient-derived organoid (PDO) was successfully established from resected tumor tissue and retained key neuroendocrine and proliferative features, with partial genomic concordance to the primary tumor. Differences between the primary and subsequent PDO in variant allele frequencies suggest clonal selection during culture. Exploratory metabolomic profiling of tryptophan pathway metabolites in patient serum and PDO-culture media indicated tumor-associated metabolic alterations. We present clinical and translational efforts in difficult-to-treat NEC, illustrating both the translational challenges and the potential role of PDOs in advancing personalized treatment strategies for a cancer with very limited treatment options.
Insights
This study highlights challenges in treating aggressive neuroendocrine carcinoma (NEC). Patient-derived organoids show potential for personalized medicine in difficult-to-treat NEC cases.
Area of Science:
- Oncology
- Genetics
- Translational Medicine
Background:
- Neuroendocrine carcinoma (NEC) is a rare, aggressive malignancy with limited therapeutic options and poor prognosis.
- Gastroenteropancreatic NEC (GEP-NEC) presents unique challenges, especially with metastasis.
- Standard treatments often fail, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate personalized treatment strategies for a patient with advanced GEP-NEC.
- To evaluate the utility of patient-derived organoids (PDOs) in understanding tumor biology and guiding treatment.
- To explore metabolic alterations in NEC.
Main Methods:
- Case report of a patient with GEP-NEC and liver metastasis undergoing radical resection.
- Adjuvant chemotherapy and subsequent treatment lines.
- Comprehensive genomic profiling and patient-derived organoid establishment.
- Metabolomic profiling of serum and PDO culture media.
Main Results:
- Despite aggressive treatment, the patient experienced early recurrence.
- Genomic profiling revealed TP53 mutation and RB1 loss but no actionable targets.
- A PDO was successfully established, retaining key tumor features and showing partial genomic concordance.
- Metabolic alterations in the tryptophan pathway were observed.
Conclusions:
- Difficult-to-treat NEC poses significant therapeutic challenges.
- Patient-derived organoids offer a promising platform for personalized medicine research in NEC.
- Further research into PDOs and metabolic profiling may advance NEC treatment strategies.
