Platinum-based chemotherapy (Pt-chemo) in pancreatic adenocarcinoma (PC) associated with BRCA mutations: A translational case series.
Bibliographic record
Abstract
217 Background: Prognosis of PC is poor and responses to chemotherapy are minimal and short lived. In prior randomized studies, cisplatin and gemcitabine provided no additional benefits over gemcitabine alone. Preclinical data and case reports suggest BRCA cancers have increased sensitivity to Pt-chemo. Our case series characterizes the benefits of Pt-chemo in germline BRCA mutated PC. Methods: Patients with PC and deleterious germline BRCA mutations treated with Pt-chemo were identified using the Ontario Pancreatic Cancer Study and pharmacy databases. Review of clinical records provided demographic, treatment and survival data. Radiology review assessed responses to Pt-chemo. RNA was extracted from tumor samples for gene expression studies using a panel of DNA repair genes and Nanostring technology. BRCA loss of heterozygosity (LOH) was also investigated. Results: We identified 5 PC patients with BRCA mutations (4 BRCA2, 1 BRCA1) who were treated with Pt-chemo: 1 had resectable disease, 1 locally advanced (LA) and 3 metastatic. The resectable patient (T1N0) had 3 cycles of neoadjuvant Pt-chemo, achieving a partial response (PR) and normalization of CA19-9; curative resection and adjuvant Pt-chemo (3 cycles) followed and the patient remains disease free after almost 3 years. The LA patient (T4N0) had 2 cycles of Pt-chemo, achieving a PR and becoming resectable; curative resection and adjuvant Pt-chemo (4 cycles) followed and the patient remains disease free for over 3 years. One metastatic patient remains on Pt-chemo (5 cycles) having achieved a PR and normalization of CA19-9. The other 2 metastatic patients completed 6 and 22 cycles of Pt-chemo, achieving best response of PR and complete response respectively, with progression free survival of 12 and 45 months. Gene expression and LOH results will be presented. Conclusions: Survival and responses to Pt-chemo observed in our case series of BRCA mutant PC adds to existing data supporting the use of Pt-chemo in this subgroup. Although the incidence of BRCA mutations in PC is small, potential survival benefits gained from personalizing treatment using Pt-chemo supports BRCA testing in selected patients.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".