UKINETs 2010 Platform Abstracts

OC01The role of liver transplantation in treatment of neuroendocrineliver metastasesA. FrillingDepartment of Surgery and Cancer, Imperial College London, UK

Introduction: In contrast to other secondary liver malignancy, livertransplantation (LT) is considered as a treatment modality for non-resectable neuroendocrine (NE) liver metastases (LM). Strict selec-tion of the candidates for LT is the key issue of the approach.

Aims: Selection criteria for LT in NE LM will be highlighted and asingle-centre experience presented.

Methods: Between 1992 and 2007, 38 patients with NE LMunderwent evaluation for LT according to the institutional protocol.The pre-transplant work-up included octreotide scintigraphy or 68-Ga PET/CT and tumour grading (Ki-67 and mitotic index).

Results: Somatostatin receptor imaging detected extra-hepaticmetastases not diagnosed in standard imaging in 45% of patients.Thus far, 16 patients, 10 men and 6 women, aged 37 to 67 years, weresubjected to the transplant procedure (12 deceased donor LT, 3 livingdonor liver transplantations, and 1 cluster transplantation). Fourpatients died during the hospital treatment. The median follow-up ofthe discharged patients was 60.8 months. The actuarial patientsurvival was 78.3% at 1 year and 67.2% at 5 years. The actuarial 1-,2-, and 5-year tumour-free survival amounted to 69.4%, 48.3%, and48.3%, respectively. Two patients underwent surgery for isolatedtumour recurrence. In 2 patients, peptide receptor radiotherapy wascarried out because of multilocular recurrent disease.

Discussion: Liver transplantation is a realistic therapeutic optionfor highly selected patients with NE LM. Our strategy, whichimplements strict pre-transplant selection and aggressive approach,in case of disease recurrence led to an excellent long-term survival,cure however, is unlikely to be achieved.

doi:10.1016/j.regpep.2010.07.016

OC02Transarterial embolization/chemoebolization for hepatic NETmetastases: recent efficacy and toxicity dataR.J.E. Walker, C. Toumpanakis, L. Marelli, D. Yu, N. Davies, N.Woodward, A. Goode, D. Chilkunda, J. Buscombe, T. Meyer, M.E. CaplinNeuroendocrine Tumour Unit, Royal Free Hospital, Pond Street, London,NW3 2QG, UK

Introduction: Transarterial embolization (TAE) and transarterialchemo embolization (TACE) are established therapies for treatmentof hepatic metastases from neuroendocrine tumours (NETs). There is

a paucity of outcome data for these procedures in the recent pub-lished literature.

Aims: To evaluate the last five years experience of TAE/TACE aspart of a treatment algorithm for hepatic NETs’ metastases.

Methods: Early radiological response was assessed with CT/MRI in4-6 weeks after treatment, using RECIST criteria. Symptomaticresponse was assessed with a symptom score within 6-8 weeks aftertreatment.

Subjects: Thirty seven patients in whom liver surgery was notfeasible were included in this retrospective study. All had sympto-matic and/or radiological progression despite previous treatments.

Results: Overall 46 embolizations were performed. TACE withdoxorubicin was performed in 13 patients (pancreatic and or/highgrade NETs), whilst 24 patients (metastatic midgut and low-gradeNETs of unknown primary) had TAE with particles only. In 7 of thelatter patients TAE was combined with Y-90 octreotate infusion. 29/37(78%) had symptomatic response. 32/37 (86.5%) had radiologicalresponse (10/37,27% partial response and 22/37,59.5% diseasestabilization). 24 (75%) of these responders had sustained responsefor over 1 year. One patient died (2.7%) 24 h post-treatment and onepatient experienced a ruptured gall bladder at the time of procedure.Other adverse effects included mild/moderate post embolizationsyndrome, sepsis and transient renal failure in 21, 3 and 2 patientsrespectively.

Discussion: In the era of new treatment options for NETs, TAE/TACE are effective interventional treatment options for symptomaticand radiological control of the disease with no significant toxicity.

doi:10.1016/j.regpep.2010.07.017

OC03Phase-3 randomized trial of everolimus (RAD001) vs. placebo inadvanced pancreatic NET (RADIANT-3)Jonathan Chambersa, Nick Reedb, Was Mansoorc,Paul Rossd, Ashley Grossmane

aNovartis, UKbBeatson, Glasgow, UKcChristie, Manchester, UKdKings, London, UKeBarts, London, UK

Introduction: RADIANT-3 is a phase 3 prospective, double-blind,randomized, parallel group, placebo controlled, multi-centre study.The trial examined efficacy/safety of Everolimus + Best SupportiveCare (BSC) vs placebo/BSC to assess improvements in ProgressionFree Survival (PFS) in patients with progression of their advancedpancreatic neuroendocrine tumour (PNET).

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Regulatory Peptides 164 (2010) 6–7

Aims: RADIANT-3 provides clinical support for combining Ever-olimus and Octreotide LAR.

Methods: 410 patients were randomized (1:1) between August2007 and May 2009 to receive Everolimus + BSC (n=207) orPlacebo+BSC (n=203). Patients on placebo could be switched toactive treatment upon disease progression.

Subjects: Baseline characteristics: Everolimus arm (n=207) andPlacebo arm (n=203); Median age (years; range): Everolimusarm=58 [23-87] and Placebo arm = 57 [20-82]; WHO PS 0:Everolimus (67%) and Placebo (66%); PS 1: Everolimus (30%) andPlacebo (31%); PS 2: Everolimus (3%) and Placebo (3%).

Prior therapies: Antineoplastic medication: Everolimus (58%) andPlacebo (58%); Chemotherapy: Everolimus (50%) and Placebo (50%);Targeted therapy: Everolimus (5%) and Placebo (7%); Immunother-apy: Everolimus (3%) and Placebo (4%); Other therapies: Everolimus(11%) and Placebo (14%); History of Somatostatin analog: Everolimus(49%) and Placebo (50%).

Results: For PNET patients there is a 65% risk reduction ofprogression for the combination Everolimus+BSC. Median PFS forEverolimus + BSC=11.0 months vs 4.6 months for Placebo+BSC(p<0.001). Most common adverse reactions include stomatitis, rash,fatigue, and diarrhoea.

Discussion: The RADIANT-3 trial of Everolimus+BSC met theprimary endpoint. Everolimus is a new treatment for patients withPNETs.

doi:10.1016/j.regpep.2010.07.018

OC04Neurokinin A is a sensitive marker and excellent prognosticindicator for serotonin secreting tumours of the ileum and colonJoy E.S. Ardill, Lee Armstrong, David R. McCance, Brian T. JohnstonNET Tumour Group, Queens University Belfast and The Royal VictoriaHospital Belfast, Northern Ireland, UK

Chromogranin A (CgA) and urinary 5 hydroxy indole acetic acid(5HIAA) have been traditionally used in the diagnosis and monitoringof patients with serotonin producing tumours of the ileum and colon(MGC). In a retrospective study we have shown Neurokinin A (NKA)to be a more sensitive marker for MGC and an independent prog-nostic indicator, the most recent NKA concentration giving the mostaccurate prognosis.

In an ongoing prospective study we aim to validate the previouswork.

All newly diagnosed patients with MGC receive standard work upwhich includes measurement of circulating CgA, NKA and 24hoururinary 5HIAA. Treatment addresses disease, tumour bulk, symptomsand aims to maintain NKA<50 ng/l. Standard treatment is somatos-tatin analogues, with addition of interferon alpha in some patients.Interventional procedures include surgical excision of the primaryand resection of liver metastases where possible. Further treatment ofhepatic metastases includes microwave technique, hepatic emboliza-tion, RFA and radionucleotide therapy.

In the retrospective study median three year survival was 53%.When this group was divided into tertiles according to NKA concen-tration at presentation, three year survival was 88% (NKA<20 ng/L),66% (NKA20-63 ng/L) and 12% (NKA >63 ng/L). Five year survivalwas, 88%, 58% and 0% respectively.

In the ongoing prospective study median three year survival is70% and when this group is divided as above, three year survivalsare 98%, 67% and 47% and five year survivals 93%, 70% and 49%respectively.

We conclude that circulating NKA is a sensitive prognosticindicator for MGC and is helpful for the clinician.

doi:10.1016/j.regpep.2010.07.019

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