Abstract 3740: Circulating endothelial progenitor cells as a predictive biomarker of acute skin toxicity in early breast cancer patients undergoing radiation therapy
Bibliographic record
Abstract
Abstract Background/Purpose: Acute skin toxicity is a common side effect of radiation therapy (RT) in breast-cancer patients. We hypothesized that RT modulates the levels of circulating endothelial cells with a progenitor-like phenotype (EPCs) and/or circulating endothelial cells (CECs), which in turn may affect the repair of radiation injury. So far, the association between the mobilization of EPCs, the levels of CECs and RT-induced skin toxicity has not been investigated in breast cancer patients. We assessed whether RT increased the levels of EPCs and/or CECs and whether this increase may predict RT-induced skin toxicity in early breast cancer patients undergoing RT in a prospective clinical study. Patients/Methods: Sixty-five early breast cancer patients were treated with adjuvant RT after lumpectomy. The dose delivered to the entire breast was 50 Gy in 25 fractions over 5 weeks. Patients were evaluated weekly for acute skin toxicity using the National Cancer Institute's Common Toxicity Criteria, version 3.0. EPCs (CD45dim, CD31+ and CD133+), CECs (CD45-, CD31+ and CD146+), and vascular endothelial growth factor receptor 2 (VEGFR-2)-positive cells (CD45dim, CD31+ and VEGFR-2+) were enumerated from blood samples by multicolor flow cytometry before RT (T1) and 24h post-RT (T3). Total RNA was extracted from blood samples and the levels of CD133, CD146 and VEGFR-2 were determined using quantitative real-time reverse transcription polymerase chain reaction (Q-RT-PCR). Results: Flow cytometry analysis revealed that RT within 24h significantly increased EPCs (CD45dim, CD31+ and CD133+, p = 0.0027), (CD45dim, CD31+, VEGFR-2+, p = 0.0020)-positive cells, but not CECs (CD45-, CD31+ and CD146+, p = 0.8415) using Chi-square test. Increased EPCs was highly correlated to the increase of (CD45dim, CD31+, VEGFR-2+)-positive cells using Pearson correlation coefficient (p = 0.0118). Accordingly, as assessed by Q-RT-PCR, expression of CD133 and VEGFR-2, but not CD146 was significantly increased (p = 0.0027; p = 0.1615; p = 0.5485, using normalized gene expression values). Univariate analysis showed that increased CD133 or VEGFR-2 levels, 24h following RT was significantly correlated with acute toxicity (logrank p-value 0.0163; 0.0025, respectively). Conclusions: Our preliminary results suggest that focal RT is able to induce a systemic response, which promotes rapid mobilization of bone marrow-derived cells EPCs (within 24h), and does not significantly affect the levels of CECs. Furthermore, quantitative analysis of EPCs levels by flow cytometry or Q-RT-PCR correlates with increased acute skin toxicity. Our findings suggest for the first time that mobilization of EPCs following RT could be proposed as an early surrogate biomarker for acute skin toxicity in breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3740.
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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) | 0.002 | 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".