Use of zoledronic acid therapy–associated severe hypophosphatemia to identify poor-prognosis patients with metastatic castration-resistant prostate cancer.
Bibliographic record
Abstract
58 Background: Zoledronic acid (ZOL) therapy is associated with severe (i.e., grade 3/4 according to CTCAEv4.0) hypocalcemia and hypophosphatemia in a subset of patients with metastatic castration-resistant prostate cancer (mCRPC) to bone. However, as opposed to the distinct clinical picture of hypocalcemia, the symptoms of hypophosphatemia are less pathognomonic. Furthermore, the rate of hypophosphatemia is not regularly reported. Methods: To characterize the rate and circumstances of severe hypophosphatemia in mCRPC patients undergoing ZOL therapy, we identified mCRPC patients receiving at least 3 doses of ZOL therapy at our Centre between 2004 and 03/2011. Patient demographics, disease and laboratory parameters were extracted by using the Oncology Symptom Control and Information Resource database, and by means of manual chart review. Results: 11 of 112 patients (10%) developed grade 3/4 hypophosphatemia (nadir) after 241±223 days (mean±SD) following the first dose of ZOL. Only one patient presented with concomitant severe hypocalcemia. Interestingly, the hypophosphatemia nadir coincided with rising PSA readings in 9 out of 10 informative patients. Furthermore, ZOL-associated severe hypophosphatemia identified mCRPC patients with worse outcome (time from CRPC diagnosis to death 628±317 days, versus 901±526 days in CRPC patients without severe ZOL-associated hypophosphatemia, p < 0.028). Conclusions: 10% of mCRPC patients undergoing ZOL therapy presented with grade 3/4 hypophosphatemia. While hypocalcemia usually occurs within the first 6 months of ZOL therapy, ZOL-associated severe hypophosphatemia is a relatively late event. It appears to occur at the time of disease progression and is associated with a poor outcome.
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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 | 0.001 | 0.001 |
| 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) | 0.001 | 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".