Lung Metastases in Patients with Well-Differentiated Gastroenteropancreatic Neuroendocrine Neoplasms: An Appraisal of the Validity of Thoracic Imaging Surveillance.

<br>Background/Aims: To evaluate the impact of Lung Metastases (LM) on overall survival (OS) in WD Stage IV GEP-NEN patients along with developing surveillance strategies for thoracic imaging.

METHODS: Thirty-four patients with LM, from three Centres, were identified (22 small intestinal/12 pancreatic; 17 Grade1/15 Grade2/2 unknown). For comparison, we used 106 Stage IV WD, Grade 1 and 2(G1-2) GEP-NEN patients with metastatic disease confined in the abdomen.

RESULTS: LM prevalence was 4.9% (34/692). Eleven patients (32%) presented with synchronous LM whereas 23 (68%) developed metachronous LM at a median of 25 months (range 1-150). Patients with metachronous LM had already established liver and/or para-aortic lymph node metastases. Eighteen of 23 patients (78%) with metachronous LM exhibited concomitant progression in the abdomen. Median overall survival (OS) of WD GEP-NEN patients with LM, was shorter than those with Stage IV disease without extra-abdominal metastases (56 [95%CI: 40.6-71.6] vs. 122.7 [95%CI: 70.7-174.8] months; log-rank p=0.001). Among patients with progressive stage IV disease, the subset of patients with LM exhibited shorter OS (log-rank p =0.005). LM were also confirmed as an independent prognostic factor for survival in multivariable analysis (HR: 0.18, 95%CI: 0.07-0.45; p-value <0.0001).

CONCLUSION: LM although are relatively rare in patients with WD Stage IV GEP-NENs may impact patients' outcome. The development of metachronous LM is associated with concomitant disease progression in established abdominal metastases in most patients. These patient-related parameters could be utilized for a stratified surveillance approach, mainly reserving thoracic imaging for GEP-NEN patients with progressive disease in the abdomen. <br>.