Prevalence of intra-patient inter-metastatic heterogeneity in mCRPC patients based on triple-tracer PET imaging: The 3TMPO study.
Bibliographic record
Abstract
5033 Background: Intra-patient inter-metastatic heterogeneity (IIH) has been demonstrated in metastatic castration resistant prostate cancer (mCRPC) patients based on genomic and imaging studies, most often after several lines of therapies. IIH is of utmost importance for PSMA radioligand therapy (RLT) eligibility, biopsy-based precision medicine and/or treatment intensification decision-making. The Triple-Tracer strategy against Metastatic PrOstate cancer (3TMPO) study (NCT04000776) is a prospective multicenter PET imaging study that was designed to determine the prevalence of IIH in mCRPC patients and to determine candidacy for RLT. Methods: 3TMPO is a PET-imaging trial including mCRPC patients showing at least 3 metastases on conventional imaging with evidence of biochemical or radiographic progression, at least 3 months after initiation of the last systemic therapy. 68Ga-PSMA-617 and 18F-FDG PET/CT scans were performed within 10 days and analyzed quantitatively. A third scan with 68Ga-Octreotate was done when a PSMA-/FDG+ lesion was found. For all tracers, positivity of a lesion was defined as its SUVpeak being 1.5 times higher than the SUVmean of the liver. Lesions smaller than 1 cc and likely benign foci of uptake were excluded. IIH prevalence was the primary outcome, defined as the percentage of patients having at least two lesions with discordant features on PET imaging. Results: We included 98 patients in the final analysis. Patients had a mean age of 69 years and a median PSA of 51.1 ng/mL. Number of metastases were <5 in 46.9% and ≥10 in 33.7% of patients and 10.2, 20.4, 18.4 and 51.0% had received 0, 1, 2 or >2 lines of systemic therapies for mCRPC, respectively. Prevalence of IIH was 83.7% based on pre-specified PET criteria. Overall, seven different combinations of lesion phenotypes were found among patients based on FDG and PSMA PETs, and at least one PSMA-/FDG+ lesion was found in 46 patients (46.9%). Of the 44 patients who underwent Octreotate PET, six (13.6%) had at least one Octreotate-positive lesion. In this FDG/PSMA/Octreotate-imaged subgroup, 11 different combinations of phenotypes were observed between metastases of individual patients. Overall, 52.0% (IC95: 41.7-62.2) of patients were found to be candidate for PSMA RLT, but none for Octreotate RLT. Conclusions: The majority of mCRPC patients showed IIH. Based on a multi-tracer approach, up to 11 lesion phenotype combinations were found amongst patients. Correlation of these imaging phenotypes with genomics and treatment response will be highly relevant for optimized precision medicine, especially with respect to PSMA-RLT. Clinical trial information: NCT04000776 . [Table: see text]
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".