Complete and Durable Response to Nivolumab in Recurrent Poorly Differentiated Pancreatic Neuroendocrine Carcinoma with High Tumor Mutational Burden

Poorly differentiated pancreatic neuroendocrine carcinomas (NECs) are rare and aggressive malignancies with rapid disease progression and early widespread metastasis. Given histology similarity, they are commonly treated with platinum-based chemotherapy as small cell lung cancer (SCLC). However, no standard treatment has been established for recurrent or progressive disease. We present an Asian patient with recurrent poorly differentiated pancreatic NEC after curative surgery and adjuvant chemotherapy with cisplatin and etoposide. The tumor mutational burden (TMB) was high. The patient received chemotherapy combined with maintenance immunotherapy with nivolumab and achieved promising and durable response, suggesting TMB could be a biomarker to identify NEC patients for immune checkpoint inhibitor (ICI) treatment.

Successful Neoadjuvant Chemotherapy for Small-Cell Neuroendocrine Carcinoma of the Pancreas: A Case Report

Neoadjuvant therapy for pancreatic neuroendocrine tumors may potentially aid downstaging, increase the possibility of radical surgery. We herein report a case of a 63-year-old man who had been diagnosed with locally advanced small-cell neuroendocrine carcinomas of the pancreas according to the diagnostic biopsy. The patient received 6 courses of etoposide and cisplatin as neoadjuvant therapy in an attempt to stop tumor progression, which promoted obvious tumor shrinkage without adverse effects and allowed subsequent Appleby procedure, the distal pancreatectomy with celiac artery resection. The patient showed no recurrence in the follow-up of a contrast-enhanced computed tomographic scan, which is 8 months after surgery. To the best of our knowledge, this is a rare case to report etoposide and cisplatin administration before surgery for unresectable pancreatic neuroendocrine carcinoma promoted a pathological partial response and finally achieved a radical surgery, providing a novel therapeutic option for patients with locally advanced pancreatic neuroendocrine carcinoma.

cfDNA in pancreatic neuroendocrine carcinoma management with Cushing’s syndrome

We report a case of metastatic pancreatic neuroendocrine carcinoma associated with paraneoplastic Cushing’s syndrome, successively treated with five lines of treatment (platin-etoposide, LV5FU2-dacarbazine, Folfirinox, pembrolizumab, and paclitaxel) and anti-secretory treatment. Circulating-free DNA (cfDNA) was analysed at each morphological evaluation starting from the second-line treatment. cfDNA changes were well-correlated with the disease course, and cfDNA may be used as a predictive marker and/or an early marker of response. In addition, absolute count of atypical cells was elevated upon disease progression.

PNI, As a Nutritional and Inflammatory Index, Was Able to Predict Prognosis of Patients With Pancreatic Neuroendocrine Carcinoma

Background: Recent studies have indicated that there is a strong link between the prognosis of cancer and the nutritional status. The purpose of this study is to investigate whether an indicator of nutritional status- the prognostic nutritional index (PNI), could affect overall survival in patients with pancreatic neuroendocrine carcinoma (p-NEC). Methods: A total of 147 patients with p-NEC, who had successfully undergone biopsy by surgical operation in Shandong Provincial Hospital Affiliated to Shandong University from October 2010 to February 2019, were investigated. The serum albumin concentration and absolute lymphocyte count were used to calculate the PNI: serum albumin concentration (g/L) +5×total lymphocyte count (×109/L).Results: Mean pretreatment PNI was 47.6. Weight loss (P = 0.003), lymphatic metastasis (P=0.006) and tumor ENETS (European Neuroendocrine Tumor Society) stage (P = 0.024), were significantly associated with PNI. Univariate analysis showed that the following factors caused decreased overall survival (OS): age (≧60years, p=0.006, vs. <60years), abdominal pain (p=0.038, vs absence of abdominal pain), weight loss (p=0.025, vs. absence of weight loss), lymphatic metastasis (p=0.0000 vs. absence of lymphatic metastasis) and tumor ENETS stage (I–II，p=0.0000, vs. III–IV). Following the multivariate analysis, PNI remained an independent prognostic factor in p-NEC. Patients with lower PNIs (PNI < 47.6) had higher risk of death than those with higher PNIs (PNI ≧ 47.6; hazard ratio: 4.508; 95 % confidence interval: 1.903–10.678; P = 0.001). Conclusions: Our present study indicated that pretreatment PNI may be a novel independent prognostic factor in patients with p-NEC.