NET MASTERCLASS 5-7-2014 GI-NEUROENDOCRINE TUMORS: THERAPEUTIC APPROACHES: SYMPTOMATIC MANAGEMENT IOANNIS PILPILIDIS, MD, FEBGH GASTROENTEROLOGY – ONCOLOGY DEPT “THEAGENEIO” CANCER HOSPITAL OF THESSALONIKI

Long – term survival: A chronic disease Yao, JCO 2008; 26: 3063-3072

< 10 ή > 10

Common symptoms are not typical

Typical symptoms are not common

Diagnosis according to the primary Appediceal (8) 100% surgery Upper GI track (duodenal) (31) 100% endoscopy (anemia, dyspepsia) SI (18) 10% incidentaloma 15% liver biopsy 60% obstructive symptoms 15% diarrhea – flushing P-NET (9) 20% hypoglycemia (2) 10% jaundice (1) 40% pain (4) 10% rash (1) 10% weight loss (1) Colon – rectal (4) 25% colon – abdominal pain 75% rectal - incidentaloma

3.000 years of misdiagnosis ΜΕΝ I Pituitary tumor Hyperparathyroidism God’s help!!! ΜΕΝ I Pituitary tumor Hyperparathyroidism Insulnoma Gene’s help!!! MENIN GENE: 11q13

Liver mets Peritoneal disease/ retroperitoneal involvement ovary/testicular

TREATMENT DOES NOT NEED A DIAGNOSIS

Symptoms presentation - Functionality/hormone activity carcinoid syndrome gastrin, insulin, etc paraneoplastic syndromes Location of primary SI (peritoneal fibrosis, heart disease, etc) p-NET Tumor stage (tumor load, liver mets etc)

Symptoms presentation Functionality/hormone activity deal with symptoms even if no effective tumor treatment Location of primary Tumor stage (tumor load, liver mets etc)

Differential diagnosis: Diarrhea: hormone secretion bile acids bacterial overgrowth short bowel syndrome intestinal bypass pancreatic insufficiency (SSAs treatment) Hypoglycemia: insulinoma ? IGF-1, pro-IGF2 Hypergastrinemia: PTH ? (secondary hyperPTH) HyperPTH: Gastrinoma ? (gastrin secretion)

Carcinoid syndrome: response to somatostatin analogues Clinical response 70-90% Biological response 35-75% Objective response 0-5%

Symptoms presentation Functionality/hormone activity Location of primary deal with complications Tumor stage (tumor load, liver mets etc)

Patient selection bias?

Median Survival: 8.5y Median Survival (non cytoreduction): 7.9y vs 11.5y 5-y Survival 75%

In the absence of other data, the resection of the primary tumour only for patients with PNETs and unresectable metastatic liver disease should only be considered in high-volume referral centres, with strict selection criteria and in a multidisciplinary setting of patients’ care

Symptoms presentation Functionality/hormone activity Location of primary Tumor stage (tumor load, liver mets etc) cytoreduction

TACE/TAE: Symptom Control Clinical response: 67% - 100% Biological response: 46% - 91% Ruszniewski Cancer 1993, Therasse Radiol 1993, Tomassetti 1994, Diaco Am J Surg 1995, Ruszniewski Eur J Gastroenterol Hepatol 2000, Roche Hepatogastroenterol 2004, Ruszniewski 2007 PRRT: Symptom Control Global Health QoL = 36% Fatigue = 49% Nause – Vomiting = 70% Pain = 53% Dyspnoea = 44% Insomnia = 59% Appetite loss = 63% Constipation = 60% Diarrhoea = 67%

CLARINET PROMID

MULTIDISCIPLINARY APPROACH Diarrhea: (serotonin secretion, bacterial overgrowth - bypasses): medical treatment Pain: (tumor load)liver directed therapies (TAE/PRRT) Weight loss: (cachexia) tumor control (TAE/PRRT) Pain: (mesenterial/ retroperitoneal fibrosis – ischemia): surgical intervention Weight loss: (undernutrition) surgical intervention MULTIDISCIPLINARY APPROACH