[18F]F-FAPI PET-CT to Identify Carcinoma of Unknown Primary Origin

• Age ≥ 18 years old
• Histologically-confirmed metastatic disease without identification of a primary tumor after standard diagnostic work-up, according to the national care pathway for CUP (in Dutch: Regionaal Zorgpad Primaire Tumor Onbekend), which includes at least an [18F]FDG PET-CT.

Exclusion Criteria:

• Patients with metastasis from a known primary tumor.
• Sarcomas, melanomas, germ cell tumors, neuroendocrine tumors and haematological malignancies whose exact site of origin is not established.
• History of malignancy within 5 years prior to [18F]F-FAPI PET-CT scan, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in-situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in-situ, or Stage I uterine cancer.
• Prior systemic therapy for the treatment of CUP.
• Radiotherapy prior to [18F]F-FAPI PET-CT. Off note: radiotherapy with palliative intent for symptomatic skeleton lesions is allowed.
• Impaired renal function, defined as eGFR (MDRD) \<25 ml/min/1,73 m2. An exception can be made in consultation with the treating physician.
• WHO performance status >2 (Vademecum).
• Pregnancy/breastfeeding. For the latter, temporary discontinuation may be considered.
• Known allergic reaction to therapeutic radiopharmaceuticals
• Inability to lie still on the back for the duration of PET-CT
• Any (other) condition, disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that may affect the interpretation of the results, or which might contribute substantially to the patient's experience of study burden (such as non-suppressible claustrophobia)