Kosmas Daskalakis1,2, Marina Tsoli3, Raj Srirajaskanthan4, Eleftherios Chatzellis3, Krystallenia Alexandraki3, Anna Angelousi3, Michail Pizanias5, Harpal Randeva6,7, Gregory Kaltsas3,6,7, Martin O Weickert8,6,7. 1. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden, Kosmas.Daskalakis@surgsci.uu.se. 2. 1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece, Kosmas.Daskalakis@surgsci.uu.se. 3. 1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece. 4. Department of Gastroenterology, King's College Hospital, London, SE5 9RS, Neuroendocrine Tumour Unit, KHP ENETS Centre of Excellence, King's College Hospital, London, United Kingdom. 5. Department of Liver Transplantation, Hepatobiliary Pancreatic Surgery, King's Healthcare Partners, King's College Hospital, NHS FT, Institute of Liver Studies, Denmark Hill, London, United Kingdom. 6. Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry, United Kingdom. 7. Centre of Applied Biological & Exercise Sciences, Faculty of Health & Life Sciences, Coventry University, Coventry, United Kingdom. 8. The ARDEN NET Centre, European Neuroendocrine Tumour Society (ENETS) Centre of Excellence (CoE), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
Abstract
BACKGROUND/AIMS: To evaluate the impact of lung metastases (LM) on overall survival (OS) in well-differentiated (WD) stage IV gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) patients along with developing surveillance strategies for thoracic imaging. METHODS: Thirty-four patients with LM, from 3 centres, were identified (22 small intestine/12 pancreatic; 17 grade 1/15 grade 2/2 of unknown grade). For comparison, we used 106 stage IV WD, grade 1 and 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 months). 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 OS of WD GEP-NEN patients with LM was shorter than for 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 < 0.0001). CONCLUSION: LM, although 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.
BACKGROUND/AIMS: To evaluate the impact of lung metastases (LM) on overall survival (OS) in well-differentiated (WD) stage IV gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) patients along with developing surveillance strategies for thoracic imaging. METHODS: Thirty-four patients with LM, from 3 centres, were identified (22 small intestine/12 pancreatic; 17 grade 1/15 grade 2/2 of unknown grade). For comparison, we used 106 stage IV WD, grade 1 and 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 months). 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 OS of WDGEP-NEN patients with LM was shorter than for 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 < 0.0001). CONCLUSION: LM, although 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.
Authors: Ashley Kieran Clift; Mark Kidd; Lisa Bodei; Christos Toumpanakis; Richard P Baum; Kjell Oberg; Irvin M Modlin; Andrea Frilling Journal: Neuroendocrinology Date: 2019-09-27 Impact factor: 5.135