Increased Levels of Urinary N-Telopeptide of Type I Collagen Correlate with Reduced Survival in Patients with Advanced Multiple Myeloma.
Bibliographic record
Abstract
Abstract Staging systems such as those of Durie-Salmon and the International Staging System provide important prognostic insight for patients (pts) with multiple myeloma (MM) throughout the disease continuum. However, detailed evaluations of prognostic factors in pts with advanced MM and primary bone lesions have not been reported. Therefore, an exploratory analysis of data was conducted from a randomized trial in pts with bone disease from MM to assess prognostic factors for survival (n=282). Patients received standard antineoplastic therapy including a bisphosphonate (zoledronic acid 4 mg, n=184; pamidronate 90 mg, n=98) every 3 to 4 weeks for up to 24 months. Dichotomous variables included sex, race (white/other), narcotic analgesics (yes/no), Eastern Cooperative Oncology Group performance status (active/impaired), prior skeletal-related event (SRE; yes/no), and values with a defined upper limit of normal (creatinine, lymphocyte %, hemoglobin, serum glutamic-oxaloacetic transaminase, albumin, lactate dehydrogenase [LDH], and calcium). Continuous variables included age, weight, cancer duration, Functional Assessment of Cancer Therapy-General score, Brief Pain Inventory score, and bone markers (eg, urinary N-telopeptide of type I collagen [NTX], deoxypyridinoline). Paraprotein type was also included. Univariate and multivariate analyses were developed to determine relative risks (RR) for reduced survival associated with baseline variables using Cox regression models, and those that were not significant at the 5% level were removed by backward elimination to generate a reduced model. In the reduced multivariate model, advanced age (P=.001), non-immunoglobulin (Ig) G myeloma subtype (IgA [P=.001] or light chain/nonsecretory/IgM [P=.051]), history of SREs before study enrollment (P=.004), anemia (P=.022), high urinary levels of NTX (P=.017), high serum levels of LDH (P=.014), and low serum levels of albumin (P=.025) significantly correlated with reduced survival. Because NTX levels were a significant covariate, the correlation between baseline NTX and survival was assessed. Normal NTX (< 50 nmol/mmol creatinine) was associated with a significant 47% lower risk of death versus elevated NTX in pts who received zoledronic acid (n=210; RR=0.53; P=.026); it was associated with a 38% lower risk in the smaller population of pts who received pamidronate (n=108; RR=0.62; P=.135). After 3 months of bisphosphonate treatment, a 50% reduction in NTX was achieved in approximately 83% of patients with an elevated baseline NTX (median, 82.5 nmol/mmol creatinine) who were treated with zoledronic acid. However, the same NTX reduction at 3 months was achieved in only 67% of pts with an elevated baseline NTX (median, 80.0 nmol/mmol creatinine) who were treated with pamidronate. In these analyses, age, albumin, Igs, and anemia were identified as prognostic factors for reduced survival in pts with advanced MM. In addition, a history of SREs before study enrollment and elevated levels of bone metabolism markers—specifically NTX—were identified. Bisphosphonates can delay the onset of potentially life-limiting skeletal complications and reduce NTX levels. Therefore, studies are under way to investigate whether bisphosphonates can improve survival in this setting.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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 | 0.001 |
| 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".