SU‐E‐T‐06: Investigating in Vitro Gamma‐H2AX Response and Chromosome Damage in Human Lymphocytes and Lymphocyte Subsets for Biomarkers of Radiation Sensitivity
Bibliographic record
Abstract
Purpose: To examine the in vitro gamma‐H2AX response in lymphocytes and lymphocyte subsets from patients who have shown severe radiosensitive response (severe late toxicity) in order to determine whether radiation responsive subsets would provide more specific markers for radiosensitivity. To concurrently examine cytogenetic endpoints as potential markers for radiosensitivity in addition to providing additional information about the mechanisms of radiosensitivity. Methods: Ten prostate cancer patients were identified with grade 3 Late Proctitis (RTOG/EORTC Late Radiation Morbidity Scoring Schema) along with twelve matched normal responding patients (Grade 0 Toxicity). These patients had been treated with dose escalated (76Gy) 3D Conformal Radiotherapy as part of an ongoing Phase III clinical trial. Peripheral blood samples were taken from each patient, irradiated with 250kV, 12.5mA x‐rays and examined for gamma‐H2AX response in lymphocytes, CD4+ and CD8+ T‐cells, and CD19+ B‐cells. A dose course experiment was conducted with 6 dose points ranging from 0 to 10 Gy, processed 1 hour after irradiation. The time response of gamma‐H2AX was also monitored, with 2 Gy irradiated samples being incubated for 7 time points ranging from 0 to 24 hours before processing. Samples were fixed stained with gamma‐HAX‐FITC, CD4‐PE, CD8‐APC and CD19‐PC7 before being analyzed by flow cytometry. Furthermore, 0 and 6 Gy irradiated blood samples were analyzed for chromosome aberrations and excess fragments per cell.Results: In a subset of the data for the radiosensitive population, the gamma‐H2AX response tended to be higher in the time course experiment. It was also found that, at 6 Gy, the number of excess fragments per cell in the radiosensitive population (1.65 +/− 0.29) was higher than in the normal population (2.20 +/− 0.27) (p‐value < 0.001) Conclusions: These preliminary results suggest the existence of potential for markers for predicting radiosensitivity which could be useful for tailoring radiotherapy treatments.
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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 | 0.000 |
| 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) | 0.003 | 0.001 |
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".