Abstract P1-14-13: Increased Pathologic Complete Response Rate and Reduced Tumour RNA Levels Upon Treatment of Locally Advanced Breast Cancer with Neoadjuvant Concurrent Chemotherapy and Radiation
Bibliographic record
Abstract
Abstract Introduction: Patients with locally advanced breast cancer (LABC) have a 5-year survival rate of 50% using standard treatment that includes neo-adjuvant chemotherapy, surgery and adjuvant radiation. Given this poor prognosis, we proposed use of an adjuvant regimen in the neoadjuvant setting, involving radiation with docetaxel for radiosensitization. Pathological complete response (pCR) at surgery (the best surrogate for overall survival) was the primary end-point of this single-arm prospective Phase II trial. Given that dose-dependent reductions in tumour RNA integrity mid-treatment were correlated with post-treatment pCRs in similar patients in the NCIC-CTG-MA.22 clinical trial (Breast Cancer Research and Treatment 119:347–56), we also assessed whether changes in tumour RNA integrity and concentration could be observed following this regimen. Methodology: Thirty-two patients with stage III non-metastatic LABC were enrolled at a single institution from 2009–2011. They were treated with neoadjuvant 5-Fluoro-uracil, Epirubicin, and Cyclophosphamide (FEC) q3 weekly for 4 cycles followed by weekly Docetaxel (35 mg/m2) concurrently with regional radiation (45 Gy with 16 Gy boost in 25 & 5 fractions) for the first 6 of 9 weeks (D/R). Serial 14 gauge tumour core biopsies were taken from the patients pre-, mid- and post-treatment and 1 mm3 samples used to assess RNA quantity and quality using an Agilent 2100 Bioanalyzer. This was followed by a modified radical mastectomy. Results: Treatment-related toxicities included grade 3 resolving pneumonitis (6 patients), grade 3 dermatitis (6 patients) and one treatment-related death. The pCR rate was 23%–about twice the provincial rate for LABC. At a mean 21 months follow-up, the relapse-free survival was 100% in the pCR cohort and 65% among partial responders (PRs). While biopsies were not normalized for mass, little difference in RNA concentration was observed between pre-treatment and post-FEC tumour biopsies (means of 50 ± 15 nanograms/microliter and 50 ± 12 nanograms/microliter, respectively). In contrast, the mean tumour RNA concentration was reduced to 10 ± 2.1 nanograms/microliter post-D/R. While the post-treatment biopsies often yielded insufficient RNA for assignment of tumour RNA integrity (RIN) values, treatment response appeared to be associated with low tumour RNA integrity, since patients with disease progression or stable disease had higher RIN values than patients exhibiting PRs or pCRs. Conclusions: This is the first study to use a full chemotherapy regimen with radiation in the neo-adjuvant setting for LABC. Although not without toxicity, the regimen appeared to significantly improve the pCR rate for this high-risk group, resulting in a much-improved outcome even at short-term follow-up. In addition, the FEC→D/R regimen produced reductions in tumour RNA concentration, and treatment response appeared to be associated with reduced RNA integrity. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-13.
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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) | 0.002 | 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".