Clinical and molecular profiling of locally advanced compared with metastatic pancreatic adenocarcinoma.
Bibliographic record
Abstract
747 Background: It is unclear whether locally advanced pancreatic cancer (LAPC) should be treated similarly to metastatic pancreatic cancer (MPC). Clinical trials often exclude LAPC. We compare clinical and genomic characteristics of LAPC and MPC. Methods: Patients with LAPC and MPC were enrolled in the COMPASS trial (NCT02750657). Clinical, demographic and survival data was collected (cut off 8/31/19). WGS, RNAseq and modified Moffitt classification was performed. Results: Patients with LAPC (n = 28) and MPC (n = 180) did not differ in terms of age, gender, smoking or diabetes history. Patients with LAPC had lower BMI (p = 0.005) and lower baseline Ca19-9 (p = 0.02) than those with MPC. LAPC/MPC tumors had similar rates of KRAS, p53, CDKN2A and SMAD4 mutations and similar levels of ploidy, indels and neoantigens. There were increases in single nucleotide variants (p = 0.026) and structural variants (p = 0.04) in MPC compared with LAPC. No LAPC tumors were homologous recombination deficient (HRD) or KRAS wild type (WT), compared with 14 (8%) HRD and 16 (9%) KRAS-WT MPC. All LAPC were classical subtype compared with 77% MPC (p = 0.0052). OS data is shown in the table. MPC classical subtype tumors had improved OS compared with basal-like tumors (p = 0.008). Patients with MPC and p53 mutation trended towards worse OS compared with those without p53 mutation (p = 0.07); this was not seen in LAPC. There was a significant correlation between time on chemotherapy and OS in LAPC (p = 0.002) and MPC (p < 0.0001). Conclusions: Patients with LAPC have similar molecular profiles to those with MPC with similar rates of altered drivers. LAPC tumors are more likely to be Moffitt classical subtype and have similar OS to classical subtype MPC. LAPC patients benefit from local therapy; all patients benefit from increased time on chemotherapy. These data suggest that patients with LAPC should be treated similarly to those with classical subtype MPC but should be offered local therapy when possible. Clinical trial information: NCT02750657 . [Table: see text]
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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 | 0.001 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".