Background
Cancer of unknown primary (CUP) represents a heterogeneous group of metastatic tumours for which standardised diagnostic work-up fails to identify the tissue of origin at diagnosis. Despite improvement in conventional diagnostic processes the primary site is only identified ante mortem in < 30% of CUP patients. 18F-FDG-PET/CT aids in CUP patient management and identification of putative primary site however has limited sensitivity for detecting cancers with high stromal content, as in CUP. Fibroblast activation protein (FAP) is a type II transmembrane serine protease and highly expressed by cancer-associated fibroblasts abundant in desmoplastic tumours, such as CUP. 68Ga-FAPI-46 is a promising FAP-targeting PET tracer in multiple solid cancers but has not been directly compared to FDG-PET in CUP.
Aims
We aim to determine if the novel PET tracer (68Ga-FAPI-46) detects more primary sites compared with 18F-FDG-PET/CT and CT scans in CUP patients and if there is an association with FAPI avidity and response to treatment.
Methods
The FAPI-CUP study is a prospective cohort study currently recruiting CUP patients across three sites in Victoria. Key inclusion criteria are 1) patients considered CUP after preliminary diagnostic work-up, pathological review and gender appropriate tests; 2) adequate haematologic and organ function to commence systemic treatment; 3) not commenced current line of systemic treatment (exception palliative radiotherapy for symptom control); 4) ECOG 0-2 and life expectancy > 3months. 5) up to 1 prior line of systemic treatment. Patients undergo imaging with CT chest/abdomen/pelvis, 18F-FDG-PET/CT and 68Ga-FAPI-PET/CT scan which are reviewed at a multidisciplinary meeting and results are relayed back to the treating clinician. Patients start systemic treatment and have follow-up as part of standard of care with information regarding survival outcome and further lines of treatment collected at 3 monthly intervals for a total of 12 months. Clinical trial information: NCT05263700.