Where Should I Draw the Line: PET-Driven, Data-Driven, or Manufacturer Cut-Off?

Background: The optimal cut-off for Alzheimer's disease (AD) CSF biomarkers remains controversial. Objective: To analyze the performance of cut-off points standardized by three methods: one that optimized the agreement between 11C-Pittsburgh compound B PET (a-PET) and CSF biomarkers (Aß1-42, pTau, tTau, and Aß1-42/Aß1-40 ratio) in our population, called PET-driven; an unbiased cut-off using data from a healthy research cohort, called data-driven, and that provided by the manufacturer. We also compare changes in ATN classification. Methods: CSF biomarkers measured by the LUMIPULSE G600II platform and qualitative visualization of amyloid positron emission tomography (a-PET) were performed in all the patients. We established a cut-off for each single biomarker and Aß1-42/Aß1-40 ratio that optimized their agreement with a-PET using ROC curves. Sensitivity, Specificity, and Overall Percent of Agreement are assessed using a-PET or clinical diagnosis as gold standard for every cut-off. Also, we established a data-driven cut-off from our cognitively unimpaired cohort. We then analyzed changes in ATN classification. Results: One hundred and ten patients were recruited. Sixty-six (60%) were a-PET positive. PET-driven cut-offs were: pTau > 57, tTau > 362.62, Aß1-42/Aß1-40 < 0.069. For a single biomarker, pTau showed the highest accuracy (AUC 0.926). New PET-driven cut-offs classified patients similarly to manufacturer cut-offs (only two patients changed). However, 20 patients (18%) changed when data-driven cut-offs were used. Conclusions: We established our sample's best CSF biomarkers cut-offs using a-PET as the gold standard. These cut-offs categorize better symptomatic subjects than data-driven in ATN classification, but they are very similar to the manufacturer's.

Effect of positive carbon-11-choline PET/CT results in the therapeutic management of prostate cancer biochemical relapse.

OBJECTIVE: Carbon-11-(C)-choline PET/computed tomography (CT) has shown good results in re-staging of prostate cancer (PCa) with raised serum levels of prostate-specific antigen. Our aim was to evaluate the effect of positive C-choline PET/CT results in the therapeutic management of patients with PCa with biochemical relapse (BR) after curative intention treatment. PATIENTS AND METHODS: A total of 112 patients with PCa BR and positive C-choline PET/CT were retrospectively evaluated. PET/CT was acquired 20 min after intravenous administration of 555-740 MBq of C-choline. The therapeutic management after C-choline PET/CT was obtained from the clinical records. The minimum follow-up time was 18 months. RESULTS: In 80 (71.4%) of 112 patients, C-choline PET/CT showed local recurrence of PCa; in 17 (15.2%) patients, distant recurrence; and in 15 (13.4%) patients, local plus distant recurrence. A second malignancy was detected in five (4.5%) patients. The planned therapeutic management was changed as per positive C-choline PET/CT result in 74 (66.1%) patients and were treated as follows: 31 (27.7%) patients with HT, combined with other treatments in eight (7.1%), 17 (15.2%) with BT, 13 (11.6%) with external beam radiotherapy, one (0.9%) with RP, and four (3.6%) with chemotherapy. Treatment approach was not modified in 37 (33%) patients. No data was available from one (0.9%) patient. CONCLUSION: Positive C-choline PET/CT result had an important effect in the therapeutic management of patients with PCa and BR, leading to a change in the planned approach in two (66.1%) out of three patients. In addition, in 4.5% of the patients, the C-choline PET/CT allowed the detection of a second malignancy.