Examination of TIMP-1 Levels and Relapse-Free Survival for Patients in NCIC CTG MA.14 Who Received Adjuvant Tamoxifen +/- Octreotide LAR.
Bibliographic record
Abstract
Abstract Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been shown to have diverse multifunctional roles in tumorigenesis. AL/KL/SA postulated from first line metastatic endocrine therapy that elevated pre-treatment serum TIMP-1 required additional therapy. NCIC CTG MA.14 adjuvant endocrine trial permitted examination of whether TIMP-1 serum levels post-chemotherapy was associated with RFS. Methods: NCIC CTG MA.14 is a trial where 667 postmenopausal patients were randomized to receive adjuvant tamoxifen +/- octreotide LAR with a stratification factor of no, concurrent or sequential chemotherapy. For the purposes of this work, this was simplified to whether a patient had or had not received adjuvant chemotherapy prior to the serum draw. Serum TIMP-1 was assessed on >90% of the trial patients. We examined the effect of baseline TIMP-1 levels on relapse-free survival (RFS) of 1) all types, 2) bone only, 3) all types of bone, and 4) non-bone, by timing of chemotherapy before the serum draw utilizing continuous TIMP (ng/ml) and categorical TIMP (<454, >454 ng/ml, based on 95% non-parametric cut-point for healthy post-menopausal females). Data were available on patient and tumour characteristics of age (years), pathologic tumour size (cm), pathologic lymph node status (# nodes), IGF-1, C-peptide, IGFBP-3. Step-wise forward Cox multivariate models were used where a factor was added if p<=0.05, and interaction terms were added for TIMP-1 level and timing of chemotherapy. Results: High (categorical) TIMP-1 was significantly associated with longer RFS (p=0.04) in the non-bone RFS multivariate model in the subgroup of patients who had prior chemotherapy, but not in those who did not. The interaction between TIMP-1 and administration of chemotherapy before serum draw was significant (p=0.02). High (continuous) TIMP-1 was significantly associated with longer bone only RFS (p=0.04) in subgroup who had no chemotherapy before the serum draw, but not in those who may or may not have had it after. There was no significant interaction effect. Categorical and continuous TIMP-1 were not associated with any other type of RFS. Conclusions: We found a predictive benefit with the assessment of serum TIMP-1 in hormone receptor positive patients, that high TIMP-1 levels after adjuvant chemotherapy were predictive of a reduction in non-bone RFS. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3022.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".