Hepatic metastases of neuroendocrine tumors: treatment options and outcomes of local patients treated with radioembolization

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1 Hepatic metastases of neuroendocrine tumors: treatment options and outcomes of local patients treated with radioembolization JP King PGY2 May 22, 2015

2 Neuroendocrine Tumor (NET) WHO Classification Location based Pancreatic, Foregut, Midgut, Hindgut, Other Differentiation Well (Low Grade), Good Prognosis, Low Mitoses, low KI- 67, No necrosis Moderate (Intermediate Grade), Moderate Prognosis, Intermediate Mitoses, Moderate KI-67, Necrosis not well characterized Poor (High Grade), Poor Prognosis, High Mitoses, High KI-67, Necrosis

3 Neuroendocrine Tumor (NET) TMN Staging Separate Classification for Pancreatic lesions vs GI Lesions Clinical Symptoms Functional vs Nonfunctional Carcinoid Syndrome PNET > Insulinoma > Gastrinoma > VIPoma > Somatostatinoma

4 Presentation Liver metastases Bone, Lung Hypersecretion Zollinger-Ellison Syndrome Carcinoid syndrome Secretion of serotonin and activation of bradykinin Highly correlated with liver disease

5 Prognosis 40% of NET s will develop liver metastases Variable (10% insulinomas, 70% VIPoma) 5 year Survival for liver metastases: 46-80% Slow and indolent Median survival months Surgical Therapy Can be curative in nonmetastatic Somatostatin Inhibitors Mainstay of treatment for symptom control

6 Intra-Arterial Therapy Trans-Arterial Embolization (TAE) Trans-Arterial Chemoembolization (TACE) High Dose Targeted Chemotherapy Drug Eluting Beads (DEB-TACE) Radioembolization (TARE) Ytrium-90 Conjugated Glass beads (Therasphere)

7 Treatment Surgery versus Intra-Arterial therapy 123 months versus 34 months 74% versus 30% Asymptomatic disease correlated with worse outcome No difference between 2 groups in asymptomatic disease Volume of disease dictates management High recurrence rates 5 years post-op

8 Intra-Arterial Y90

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10 Ytrium KeV, % Beta Decay Decays to zirconium-90 Maximum penetration 8-10 mm Average penetration 2.5mm Half-life 61 hours Dose Calculation Approximately 100 Gy delivery

11 Tissue Tolerance Doses Emami et al, 1991, International Journal of Radiation Oncology Biology Physics TD 5/5 whole organ Liver: 28 Gy Lung: 5 Gy Kidney: 17 Gy GI Tract: Gy

12 Delivery System SIR-Sphere Sirtex Resin micrometers 50 Bq/particle million per dose Therasphere Nordion (BTG) glass micrometers 2500 Bq/particle 1.2 million per dose

13 Preparation Angiography Planning approach Plan for Embolization of branches Aorta, SMA, Celiac, Right Hepatic, Left Hepatic Tc-99m MAA Micro aggregated albumin

14 Access

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18 Liver Volume

19 Treatment Multidisciplinary Interventional Radiology, Nuclear Medicine, Physicists, Radiation Technologists, Interventional Technologists Radiation Precautions

20 Post Therapy PET Not a PET-FDG scan Not a measure of metabolic activity Bremsstrahlung scan Y90 99% Beta minus (electron + antineutrino) Beta plus decay (positron + neutrino) Y90 decay has a minor percentage of decay that via internal pair production (beta + and beta-) Transient but allows detection of the positron Localization of Y90 therapy

21 Post Therapy PET

22 Assess Response? M.S.

23 Our Patients Type of malignancy Primary HCC: 11 Metastases Neuroendocrine: 8 GI Adenocarcinoma: 10 GB Adenocarcinoma: 1 First treatment September 2013

24 NET Patients Age Demographics 62 Years Toxicities Sex Ratio 7M : 1F ECOG 0 7 Functional Tumor 5 Nonfunctional Tumor 3 Abdominal Pain 6 Fatigue 4 Diarrhea 1 Weight loss 1 Flushing 2 GI Primary 3 Unknown Primary 1 Pancreatic Primary 4 Hyperbilirubinemia 2 AST 1 ALP 2 Prior TAE 4 Prior TACE 1 Tumor greater than 10 cm 5

25 G.U.

26 G.U.

27 D.S.

28 P.Y.

29 P.Y.

30 D.D.

31 D.D.

32 Treatment Response All patients have showed stable disease by WHO and RECIST criteria First patient shows Partial response in the treated lobe by RECIST criteria One patient died from complications of severe tricuspid regurgitation One patient died in hospital (cause not yet known) ECOG 2 At least 2 patients have reduced somatostatin therapy (1 discontinued breakthrough)

33 Future Analysis mrecist, EASL Doses to individual lesions Long term outcomes: Need for somatostatin therapy Histologic classification Impact of prior therapy Time between diagnosis to treatment Other Tumors

34 Survival Benefit? Need RCT of best medical vs best medical + Y90

35 Acknowledgements Dr. Rob Berry Dr. Bob Abraham

36 Questions?