Platinum deposition in skin as a possible mechanism for peripheral sensory neuropathy (PSN) in patients (pts) with colorectal cancer (CRC) following oxaliplatin-based therapy.
Bibliographic record
Abstract
685 Background: Oxaliplatin plus fluorouracil (FOLFOX) is a standard treatment for CRC pts. One of the most common and dose-limiting side effects of oxaliplatin is PSN. The mechanism of this phenomenon is poorly understood. Previous studies suggested that higher serum platinum levels were related to more severe neuropathy in testicular cancer pts. Methods: CRC pts who completed adjuvant FOLFOX at least 6 months prior to enrollment are eligible. Baseline demographic and treatment information were collected. EORTC CIPN20 (with EORTC QLQ-C30) questionnaire was used for self-reported PSN symptom assessment. Peripheral blood samples were collected for total/free platinum concentrations using high-performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS). Skin biopsies were obtained from the lower leg of consented pts. Imaging mass cytometry (IMC) was used to visualize platinum deposition (195Pt) and intra-epidermal nerve fiber (IENF) (PGP9.5-154Sm) in formalin-fixed paraffin embedded (FFPE) skin biopsy samples stained with a metal-conjugated antibody cocktail. Results: Nine patients were enrolled. Median age was 51.8 yr (range: 34.5-69.4 yr); male/ female: 5/4; mean cumulative dose of oxaliplatin was 800.7 ± 188.2 mg/m2; median time from last dose of oxaliplatin to enrollment was 48 months (range: 7.2-65.6 months). The mean sensory score from CIPN20 was 15.4 ± 4.3 (range: 10-25). Platinum was undetectable in plasma samples collected from all 9 patients. In skin samples, IMC showed significant platinum depositions and IENF. Conclusions: Severity of PSN was not related to cumulative dose of oxaliplatin or interval from last dose of oxaliplatin. Although platinum was undetectable in plasma in these patients, platinum was readily detectable in skin biopsies up to 65.6 months post completion of FOLFOX. This is the first demonstration of platinum deposition in skin post oxaliplatin treatment and it provides a possible mechanism for oxaliplatin-induced PSN.
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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 | 0.000 | 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) | 0.001 | 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".