Integration of somatic molecular profiling for rare epithelial gynaecologic cancer patients.
Bibliographic record
Abstract
5509 Background: Rare gynaecologic cancers (R-GYN) represent over 50% of all gynaecologic malignancies. Conducting clinical trials in R-GYN is challenging due to the limited number of patients (pts) and differences in biologic behavior. Somatic molecular profiling (SMP) may increase biologic understanding of R-GYN and identify pts for target specific therapies. Methods: A cohort of epithelial R-GYN pts was analyzed for somatic variants (SV) through an institutional SMP screening (NCT01505400) using a customized Sequenom SNP genotyping panel or targeted sequencing (NGS) using the Illumina MiSeq TruSeq Amplicon Cancer Panel or the Ion Proton Ampliseq Cancer Hotspot Panel version 2, in a CLIA certified laboratory. Outcomes of genotype-matched (GM) versus genotype-unmatched (GUnM) trials were compared. Results: 721 GYN pts underwent SMP and 189 were classified as R-GYN (26%), with a median of 1.5 prior systemic treatments [0-4]. 52 low grade serous, 2 transitional and 1 squamous OC, 10 cervical adenosquamous/adenocarcinomas, 23 serous endometrial, 2 vaginal, 12 vulvar, 37 clear cell, 17 mucinous, 1 small cell and 32 carcinosarcomas. Pathology review confirmed diagnosis in 95%. A total of 134 pts (71%) had ≥ 1 SV (range 1-4), being the most common: 37% TP53; 39% KRAS; 37% PIK3CA. Upon SMP, 75 pts were not treated further, 64% due to progressive disease (PD). 91/189 pts were referred for clinical trials and 39/189 (21%) participated in 45 studies. 19/189 pts (10%), with a median of 0.5 prior systemic treatments [0-1], participated in GM trials (1 pt with vaginal cancer participated in two consecutive GM trials). Main reasons for non-enrollment were not fulfilling eligibility criteria (49%) and PD (29%). RECIST 1.1 response among evaluable pts showed: 3 PR (7%) (2 in GM trials) and 18 pts had SD ≥ 4 months(m) [9/18 pts (50%) in GM vs. 9/26 pts (35%) in GUnM]. Of 9/18 pts who had received prior systemic therapy for recurrent disease, the median time to progression of GM was 5.3 m (0.9-22) compared with 2.8 m (1.7-25.1) for the immediate prior line of therapy (p = 0.17). Conclusions: SMP screening of R-GYN identified actionable SV in 71% of pts, expanding the spectrum of therapeutic approaches in a population with limited standard options.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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".