Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors.

Inclusion Criteria:

• Age ≥18 years

• Written informed consent

• Eastern Cooperative Oncology Group (ECOG) 0-1

• Presence of histologically confirmed, advanced, well-differentiated, inoperableneuroendocrine tumors (NET) of any primary tumor origin and any grade, except forpheochromocytoma and paraganglioma.

• Somatostatine receptor (SSTR)-expression in tumor lesions > basal liver uptake on 68Ga-DOTA-PET

• Radiologically progressive disease within the last 1-24 months according to commonclinical criteria and confirmed by the institutional multidisciplinary conferencefor the treatment of NETs. The CT/MRI that shows tumor progression compared toscreening/baseline must have been performed 1-24 months earlier.

• All previous anti-tumor treatment except SSA must be terminated at least 4 weeksbefore start of treatment within the trial.

• Measurable disease according to RECIST v 1.1

• Given the available, approved anti-tumor treatments and the specific characteristicsof the patient and the tumor, the investigator judges peptide receptor radionuclidetherapy (PRRT) to be the treatment of choice

• GFR > 50 ml/min/1.73 m2 as determined by iohexol- or 51Cr-EDTA clearance, calculatedaccording to a combination of LMR18 and CAPA formulas, or equally accurate method

• Hemoglobin > 90 g/L, platelets >100 x109/L, leukocytes > 3.0x109/L, neutrophils > 1.5 x109/L, aspartate transaminase (ASAT)/alanine aminotransferase (ALAT) < 3 x ULN,bilirubin < 2 x upper limit of normal (ULN), albumin > 25 g/L

• For women of child-bearing potential, highly effective contraception should be usedfrom the time of inclusion up to at least six months after the end of treatment (EOT) visit.

Exclusion Criteria:

• Pregnancy or lactation

• Previous treatment with PRRT

• Concomitant systemic anti-tumor therapy other than somatostatin analogue (SSA)

• Contraindications for treatment with capecitabine according to the approved label.

• Discordance between CT/MRI/18F-FDG-PET and 68Ga-DOTA-PET, with evidence of tumorlesions without uptake on 68Ga-DOTATOC.

• Any other serious, uncontrolled medical or psychiatric condition that, in theopinion of the investigator, precludes the patient from participation in the trial

• Unwillingness, or inability, to participate in any part of the trial procedures ortreatments.