Serial FDG-PET imaging of metastatic prostate cancers reveals intrapatient intermetastases polyclonality through same patient heterogeneous responses to systemic therapy.
Bibliographic record
Abstract
e590 Background: Although intrapatient prostate cancer (PCa) metastasis polyclonality has been recently characterized by genomic and transcriptomic studies, systemic treatment response heterogeneity has yet to be reported or imaged. It remains unknown if polyclonal differentiation leads to heterogeneous treatment responses between metastases in a single patient undergoing therapy. Methods: Between 2010 and 2015, fifteen patients with metastatic PCa were imaged by FDG-PET/CT before and during systemic therapy, and metabolic response was recorded for individual metastatic lesions. Intermetastasis heterogeneity was defined by opposite metabolic responses of at least two metastases from the same compartment (bone or soft tissue) between the two scans. We examined intrapatient intermetastasis heterogeneity of response to systemic therapy based on the assessment of metabolic response in a total of 165 individual lesions (change in SUVmax, complete response, or new lesion). Change in total lesion glycolysis (TLG) was assessed for each patient. Biochemical response and progression-free survival (PFS) were also recorded. Results: Intrapatient intermetastasis response heterogeneity was found in 40% of cases. In univariate statistical analysis, response heterogeneity was associated with a decrease in PFS (p-value= 0.001), but not with age, CRPC status, Gleason score, PSA-DT, TLG, maximum SUVmax, or sum of SUVmax. In two cases, new metastasis and complete metastasis responses were observed in the same patients. Conclusions: Our results suggest that systemic therapies can induce heterogeneous responses among individual metastases in patients with PCa, supporting the polyclonal evolution of PCa in advanced disease. Molecular imaging may thus be useful to identify clinical resistance earlier after therapy initiation and could also enable targeted biopsy of resistant clones for molecular analysis.
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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".