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Understanding the treatment algorithm of patients with advanced G2 gastroenteropancreatic neuroendocrine neoplasms: A single-institution retrospective analysis
Background
Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are rare and heterogeneous malignancies and there is no consensus on treatment sequences, especially for intermediate grade subgroup (G2). The aim of our study is to provide additional information on response to subsequent oncological treatments.
Methods
Clinical records of patients (pts) with a histological diagnosis of G2 well differentiated GEP NENs and distant metastases, evaluated at the University of Palermo – Regional Reference Center for Rare Tumors- between 2006 and 2021 were retrospectively analyzed. Data on patient demographics, pathology, imaging exams, oncological treatments and clinical outcomes were collected. The analysis was focused on patients who had received at least two lines of systemic therapy. Kaplan-Meier analysis was used for overall survival (OS).
Results
A total of 32 pts with G2 metastatic GEP NEN were included in the study. Median age was 55 years (range 30-72), with a slight prevalence of male pts (59%). The high number of small-bowel as primary tumor (61%) and the presence of liver metastases in the majority of cases (90%), might justify the relatively high percentage of functional clinical presentation (33%). Median Ki67 level was 8,5% (range 3-20), and synchronous metastatic disease was reported in 68%. The median mOS of overall population was 48 months (range 6-177). Considering that most pts showed high level of somatostatin receptor (SSTR) expression on functional imaging (92%), the 18F-fluorodeoxyglucose (FDG) PET/TC confirmed its prognostic role, with significant worse survival outcomes in high FDG uptake tumors (HR 0.12; 95% CI 0.008-0.77, p=0.003). Somatostatin analogue (SSA) was the most common first-line treatment (68%), with stable disease as best response (BR) in 74% of cases, followed by peptide receptor radionuclide therapy (PRRT) (13%) and temozolomide or oxaliplatin-based chemotherapies (CT) (13%). Patients treated with CT upfront were characterized by higher Ki67 level (>7%) and showed partial response as BR in 50% of cases. PRRT as first-line treatment showed more durable response, expressed by PFS (26 months), compared with SSA and CT (15,5 and 16 months respectively). Second-line treatment was mainly performed with PRRT (48%) and targeted therapies (TT) (36%), including everolimus and sunitinib. Patients who performed PRRT as second line showed an advantage in OS compared to the ones who received TT (HR 0.22; 95% CI 0.01-1.01, p=0.05) and higher mPFS (13,5 vs 8 months).
Conclusions
Decision making in advanced G2 GEP NENs is an interesting research field, because the rarity of this condition and the recent increase of the therapeutic armamentarium. A multidisciplinary discussion within a dedicated team remains critical. We need considering several factors, such as primary tumor, Ki67 level, tumor burden, functional disease, combined functional imaging and goals of treatment. Our study confirmed the prognostic role of FDG PET/TC in G2 GEP NENs. Independently from ki67 level, SSA represents the backbone of the first-line treatment. As Second-line treatment, PRRT showed a survival advantage and a more durable response than TT. Temozolomide or oxaliplatin-based chemotherapies might be a choice in Ki67>10% tumors and when cytoreduction is the aim.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
