Abstract 3545: ATM, TS and RRM1 protein expression in nasopharyngeal carcinomas (NPC) treated with curative intent.
Bibliographic record
Abstract
Abstract Background: Although NPC is a radiation and chemotherapy sensitive tumour, some patients still relapse with distant metastatic disease. Biomarkers are needed to help identify which patients are at higher risk of relapse and/or who will respond to therapy. Ataxia telangiectasia mutated (ATM) is a putative marker for radiation sensitivity while, thymidylate synthetase (TS), and ribonucleotide reductase subunit M1 (RRM1) levels have been associated with response to 5FU and gemcitabine, two chemotherapy agents often used in NPC. We characterized the protein expression of ATM, TS, and RRM1 in tumours from 146 patients with non-metastatic NPC treated at two Canadian institutions between Jan 2000-Dec 2007 and explored the relationship of each marker with clinical outcomes. Methods: Pre-treatment, formalin-fixed, paraffin-embedded NPC tumour specimens were assembled in a tissue microarray. ATM, TS and RRM1 protein expression were evaluated by quantitative fluorescence immunohistochemistry and with automated quantitative digital image analysis (AQUA) using the Y170, TS106 and 60073-2-Ig monoclonal antibodies respectively. Protein expression levels were assessed in tumour, tumour cytoplasm, tumour nuclear, and non-malignant tumour stroma compartments. The effect of protein expression levels on overall survival (OS) and disease-free survival (DFS) was examined using Cox regression. For all biomarkers, AQUA scores were analyzed in quartiles. Results: Patient characteristics were: mean age=52 years (SD=12.2; range 18 to 85), 67% male, 73% KPS ≥ 90%, WHO type 1/2/3=11%/28%/61%, stage III/IV=65%. Fifty-eight (40%) patients received platinum-based CRT; the remainder was treated with RT alone. With a median follow-up of 50 months (range 3 to 120), the 5 year survival rates were 71% (95% CI=62%-78%) for OS and 48% (95% CI=39%-57%) for DFS. After adjusting for KPS, stage, and WHO type, OS was worse for the group with tumour:stromal (T/S) ATM ratios in the top quartile versus those in the lowest quartile (p=0.049). OS was also worse for tumours with TS levels in the lowest quartile versus the top quartile (p=0.033). RRM1 was not associated with outcomes (p=0.748). There was no significant effect of any of the biomarkers on disease-free survival (ATM T/S p=0.708; TS p=0.978; RRM1 p=0.918). Conclusions: In our cohort of non-metastatic NPC patients, relative overexpression of ATM and low TS protein levels were associated with worse outcomes suggesting further investigation of these potential biomarkers is warranted. Citation Format: Alexander C. Klimowicz, Amanda Jagdis, Tien Phan, Janessa J. Laskin, Harold Y. Lau, Jodi E. Siever, Stephanie K. Petrillo, Thomas A. Thomson, M. Sarah Rose, Anthony M. Magliocco, Desirée Hao. ATM, TS and RRM1 protein expression in nasopharyngeal carcinomas (NPC) treated with curative intent. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3545. doi:10.1158/1538-7445.AM2013-3545
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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".