An Open Label, Single-Centre, Pilot Study of Everolimus With EBRT for the Treatment of mNET Liver Metastasis

Inclusion Criteria: 1. Histological and/or cytological diagnosis of unresectable neuroendocrine tumor with liver metastases confirmed on imaging scans 2. Ki-67\<55% 3. No prior Everolimus within 3 months prior to registration 4. No prior radiotherapy to the liver 5. 1-3 liver metastatic lesions confirmed on imaging scans 6. Size of target metastatic lesion is 6 cm or less 7. At least 700 cc of liver uninvolved by tumor 8. Previous liver resection, systemic therapy or local ablation therapy (radiofrequency ablation, transarterial chemoemolization, radioemolization) is allowed. 9. Extrahepatic disease is allowed if maximum involved organs (including the liver) is 3 or less (i.e. oligometastases). 10. Child-Pugh's A liver function 11. Male or female: Age ≥ 18 years 12. Life expectancy \> 6 months 13. ECOG PS ≤1 14. Laboratory Requirements - within 14 days prior to registration: Hematology Absolute Neutrophils Count ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 90 g/L Biochemistry Serum Bilirubin ≤ 1.5 x upper limit of normal Serum Creatinine ≤ 1.5 x upper limit of normal AST ≤ 3 x upper limit of normal ALT ≤ 3 x upper limit of normal INR ≤ 1.5 Fasting Serum Cholesterol ≤ 300 mg/dl or 7.75 mmol/L Fasting Triglycerides ≤ 2.5 x ULN Adequate Glucose Control Urinalysis Proteinuria ≤ grade 1 (by dipstick) 15. Before patient registration/randomization, written informed consent must be given according to local Institutional and/or University Human Experimentation Committee requirements. The patient must sign the consent form prior to randomization or registration. 16. Patients that have a positive HBV-DNA result at screening must agree to take prophylactic treatment for 1-2 weeks prior to beginning Everolimus treatment. See section 7.2 for further information on Viral Hepatitis management 17. Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events response assessment and follow-up. Exclusion Criteria: 1. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to registration (i.e. patients must have recovered to less than or equal to grade 1 from any major surgery), or anticipation of need for major surgical procedure during or within 7 weeks after chemo-radiotherapy 2. Known to have clinical or radiological evidence of CNS metastases 3. Patients with hepatitis 4. Patients with neuroendocrine tumor of a pancreatic origin 5. Patients with a past or current history (within last 2 years) of other malignancies, except for the indication under this study and curatively treated basal and squamous skin cancer or in-situ cancer of the cervix. Prior treatment of localized prostate cancer is permitted if treatment was greater than 5 years ago and the patient currently has no biochemical evidence of recurrence. 6. Uncontrolled diabetes mellitus 7. Active bleeding diathesis, or an oral anti-vitamin K medication (except low dose warfarin, LMWH, or acetylsalicylic acid or equivalent) as long as the INR is \<1.5. 8. Patients with known history or present encephalopathy 9. Gross clinically detectable ascites 10. Any comorbidity or concomitant medication that would contraindicate treatment with Everolimus 11. Women of childbearing potential with a positive pregnancy test at baseline or lactating. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Females patients must not be pregnant or become pregnant during this study and for 6 months after the last dose of Everolimus 12. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study. Patients of childbearing potential must be willing to use a reliable method of birth control. i.e.: double barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device or tubal ligation during the study. 13. Prior radiotherapy to the right upper quadrant of the liver 14. Contraindication to CT dye injection 15. Contraindication to MRI 16. Contraindication to CEUS dye injection 17. Body habitus and or tumor location not allowing for CEUS 18. Any other serious intercurrent illness such as cardiovascular disease, HIV or any neurological disease 19. Patients taking other approved or investigational drug/anticancer treatment (other than ongoing androgen ablation and oral prednisone which are permitted) during the study period, including chemotherapy, biological response modifiers, immunotherapy, surgery or radiotherapy. 20. Patients concurrently participating in another clinical trial 21. Patients unwilling to or unable to comply with the treatment plan 22. Patients who have metastatic liver lesions that are candidates for resection