Undersøgelse af [18F]FAPI-74 PET hos patienter med gastrointestinale kræft (18F-FAPI-74 GI)

Patients receive [18F]FAPI-74 intravenously followed by PET/CT 60 minutes (+/-10minutes) later

[18F]FAPI-74 is a radioactive diagnostic agent indicated for use with Positron Emission Tomography (PET) imaging for the detection of Fibroblast Activation Protein (FAP) positive cancer cells and cancer-associated fibroblasts (CAF) in patients with gastrointestinal cancers.

The positive or negative status according to [18F]FAPI-74 PET imaging was determined based on a prespecified cut-off value for each appropriate test as determined by the clinician. Positivity was evaluated using the following prespecified H-score thresholds: > 50: Overall positive versus negative expression; > 100: Moderate to high expression and > 200: High expression only. The primary efficacy endpoint was the positive predictive value of [18F]FAPI-74 PET imaging, defined as the proportion of PET-positive results that were confirmed positive by IHC. PPV was summarized using proportions along with two-sided 95% asymptotic normal confidence intervals.

Sensitivity was defined as the proportion of participants with IHC confirmed FAP-expressing cells who had a positive [18F]FAPI-74 PET result for the primary lesion. Sensitivity was calculated as A / (A + C), where A represents true positive findings and C represents false negative findings. Higher sensitivity indicates a greater ability of [18F]FAPI-74 PET to detect IHC confirmed FAP expression and a lower likelihood of false negative results, thereby reflecting the effectiveness of the imaging modality relative to the IHC reference standard. Sensitivity was presented overall for all IHC-positive results and separately using stricter IHC cut-off values categorized as: > 50: Overall positive versus negative expression; > 100: Moderate to high expression and > 200: High expression only.

Specificity was defined as the proportion of participants without IHC-confirmed FAP-expressing cells who had a negative [18F]FAPI-74 PET result for the primary lesion. Specificity was calculated by comparing positive and negative [18F]FAPI-74 PET findings with the corresponding IHC results, using a single readable PET image matched to its reference IHC assessment. Specificity was calculated as D / (B + D), where B represents false-positive findings and D represents true-negative findings. PET results were compared with the corresponding IHC reference assessment using a single readable PET image per participant. Specificity was evaluated overall using IHC negativity defined as > 50: Overall positive versus negative expression; > 100: Moderate to high expression and > 200: High expression only.

Positive Predictive Value (PPV) of [18F]FAPI-74 PET imaging in detecting presence of disease using histopathology as the truth standard. The PPV is defined as the probability that one is indeed positive for an outcome given that they test positive for the outcome and is calculated as: PPV = A/(A + B), where A represents true-positive findings and B represents false-positive findings (PET positive but histopathology negative). PPV was summarized using proportions along with two-sided 95% asymptotic normal confidence intervals.

Sensitivity was defined as the proportion of participants with histopathology-confirmed cancers cells who had a positive [18F]FAPI-74 PET result for the primary lesion. Sensitivity was calculated by comparing positive and negative [18F]FAPI-74 PET findings with the corresponding histopathology results, using a single readable PET image matched to its reference histopathology assessment. Sensitivity was calculated as A / (A + C), where A represents true-positive findings and C represents false-negative findings. Sensitivity was summarized using proportions along with two-sided 95% asymptotic normal confidence intervals.

An adverse event (AE) is any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the trial intervention.

A TEAE is defined as any untoward medical occurrence that begins or worsens in intensity or frequency after the initiation of a treatment (e.g., drug, device, or procedure) in a clinical study.

A serious TEAE is defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization.