Purpose:
As noninvasive biomarkers are an important unmet need for neuroendocrine neoplasms (NEN), biomarker potential of genome-wide molecular profiling of plasma cell-free DNA (cfDNA) was prospectively studied in patients with NEN.
Experimental Design:
Longitudinal plasma samples were collected from patients with well-differentiated, metastatic gastroenteropancreatic and lung NEN. cfDNA was subjected to shallow whole-genome sequencing to detect genome-wide copy-number alterations (CNA) and estimate circulating tumor DNA (ctDNA) fraction, and correlated to clinicopathologic and survival data. To differentiate pancreatic NENs (PNEN) from pancreatic adenocarcinomas (PAAD) using liquid biopsies, a classification model was trained using tissue-based CNAs and validated in cfDNA.
Results:
One hundred and ninety-five cfDNA samples from 43 patients with NEN were compared with healthy control cfDNA (N = 100). Plasma samples from patients with PNEN (N = 21) were used for comparison with publicly available PNEN tissue (N = 98), PAAD tissue (N = 109), and PAAD cfDNA (N = 96). Thirty percent of the NEN cfDNA samples contained ctDNA and 44% of the patients had at least one ctDNA-positive (ctDNA+) sample. CNAs detected in cfDNA were highly specific for NENs and the classification model could distinguish PAAD and PNEN cfDNA samples with a sensitivity, specificity, and AUC of 62%, 86%, and 79%, respectively. ctDNA-positivity was associated with higher World Health Organization (WHO) grade, primary tumor location, and higher chromogranin A and neuron-specific enolase values. Overall survival was significantly worse for ctDNA+ patients and increased ctDNA fractions were associated with poorer progression-free survival.
Conclusions:
Sequential genome-wide profiling of plasma cfDNA is a novel, noninvasive biomarker with high specificity for diagnosis, prognosis, and follow-up in metastatic NENs.
2 (1,8%) patients. There were 4 (3,6%) abscesses and 2 (1,8%) fistulas post PC. Drain dislodgment was found without sequelae in 8 (7,2%) patients. Elective cholecystectomy was performed in 35/111 (31,5%). Fifty-one of 87 (58,6%) patients with gallstones underwent cholecystectomy; 36/87 (41,3%) did not undergo surgery due to a too short follow-up or death of nonbiliary disease. In the AAC group, there was no recurrent cholecystitis in 17/24 (70,8%) patients; 3/24 (12,5%) underwent surgery and 4/24 (16,6%) patients died in the ICU. Conclusion: PC is a minimally invasive treatment with low complication rate for patients with acute cholecystitis whom considered being at high-risk for urgent cholecystectomy. Good selection (ASA III and IV) and indication is needed in patients with ACC before PC because the majority will be operated later on. AAC can be managed nonoperatively and further treatment might not be needed.
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