# HC-ONC-005 — Pancreatic Cancer (PDAC)
## Validation Report

- **Generated:** 2026-05-26T21:18:53.369921+00:00
- **N patients:** 500 (primary) + ~4,400 CA 19-9 panel rows + ~100 surgical rows + 500 molecular rows + ~860 treatment-history rows
- **Seed:** 42
- **Weighted Score:** **10.0/10**
- **Grade:** **A+**

## Scorecard

| Metric | Value | Target | Score | Status | Source |
|---|---:|---|---:|---|---|
| `age_mean` | 70.704 | [66.0, 75.0] | 10.0 | PASS | SEER PDAC median age 70-71 |
| `female_pct` | 45.8 | [38.0, 52.0] | 10.0 | PASS | SEER PDAC female ~45-48% |
| `diabetes_pct` | 41.2 | [28.0, 48.0] | 10.0 | PASS | PDAC enriched in diabetes ~30-40% (Aggarwal 2013, Mizrahi 2020) |
| `stage_iv_pct` | 47.0 | [38.0, 58.0] | 10.0 | PASS | SEER PDAC Stage IV at-dx ~50-55% |
| `stage_i_pct` | 5.2 | [2.0, 9.0] | 10.0 | PASS | SEER PDAC Stage I at-dx ~5% (most present advanced) |
| `head_tumor_pct` | 71.4 | [60.0, 80.0] | 10.0 | PASS | PDAC: pancreatic head ~65-75% (Hidalgo 2010) |
| `jaundice_in_head_pct` | 64.986 | [60.0, 80.0] | 10.0 | PASS | Head PDAC presents with obstructive jaundice ~70-80% |
| `kras_mutation_pct` | 93.6 | ≥90.0 | 10.0 | PASS | TCGA PAAD KRAS mutation ~93%, FLOOR (PDAC hallmark) |
| `kras_g12d_pct` | 30.4 | [28.0, 42.0] | 10.0 | PASS | TCGA PAAD KRAS G12D ~36% (most common variant) |
| `kras_g12v_pct` | 24.6 | [15.0, 28.0] | 10.0 | PASS | TCGA PAAD KRAS G12V ~22% |
| `kras_variants_exclusive_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Structural: KRAS variants categorical (exactly one per patient), FLOOR |
| `tp53_mutation_pct` | 73.2 | [65.0, 82.0] | 10.0 | PASS | TCGA PAAD TP53 mutation ~70-75% |
| `smad4_lost_pct` | 48.2 | [38.0, 55.0] | 10.0 | PASS | TCGA PAAD SMAD4 loss ~50% (Iacobuzio-Donahue 2009) |
| `cdkn2a_lost_pct` | 63.2 | [52.0, 68.0] | 10.0 | PASS | TCGA PAAD CDKN2A loss ~60% |
| `brca2_germline_pct` | 2.8 | [1.5, 8.0] | 10.0 | PASS | POLO PDAC trial: BRCA2 germline ~5% (~3-7% real-world) |
| `brca1_germline_pct` | 2.2 | [0.5, 4.0] | 10.0 | PASS | PDAC BRCA1 germline ~1-2% |
| `parp_eligible_pct` | 9.2 | [6.0, 18.0] | 10.0 | PASS | PDAC HRR/DDR composite (BRCA1/2, PALB2, ATM) ~10-15% |
| `msi_h_pct` | 0.8 | [0.1, 4.0] | 10.0 | PASS | PDAC MSI-H rare ~1% (Hu 2018; KEYNOTE-158 enrolled <1%) |
| `surgery_rate_pct` | 20.6 | [12.0, 30.0] | 10.0 | PASS | PDAC overall surgical resection rate ~15-20% (cohort-driven by Stage IV) |
| `whipple_in_head_surgical_pct` | 88.571 | ≥80.0 | 10.0 | PASS | Head PDAC undergoing surgery → Whipple/PPPD ~85-95%, FLOOR |
| `r0_resection_pct` | 72.816 | [60.0, 85.0] | 10.0 | PASS | Modern PDAC R0 ~65-75% (Strobel 2017) |
| `fistula_bc_pct` | 25.243 | [15.0, 32.0] | 10.0 | PASS | ISGPF Grade B/C fistula ~20-25% |
| `dge_bc_pct` | 20.388 | [12.0, 32.0] | 10.0 | PASS | ISGPS DGE Grade B/C ~15-25% |
| `folfirinox_in_palliative_pct` | 38.631 | [25.0, 50.0] | 10.0 | PASS | PRODIGE-4 era FOLFIRINOX uptake in fit patients ~30-40% |
| `gem_nabp_in_palliative_pct` | 43.046 | [35.0, 55.0] | 10.0 | PASS | MPACT era Gem+NabP uptake ~40-50% |
| `pembrolizumab_in_msi_h_pct` | 75.0 | ≥40.0 | 10.0 | PASS | KEYNOTE-158: Pembro for MSI-H PDAC, FLOOR (high variance at small n) |
| `olaparib_in_parp_eligible_pct` | 28.261 | [15.0, 50.0] | 10.0 | PASS | POLO era olaparib maintenance in HRR+ PDAC ~25-40% real-world |
| `os_median_overall_mo` | 5.75 | [4.5, 9.0] | 10.0 | PASS | PDAC overall median OS ~6-11mo; cohort heavily Stage IV-enriched |
| `os_median_stage4_mo` | 5.25 | [3.5, 8.0] | 10.0 | PASS | PDAC Stage IV median OS ~6-8mo (PRODIGE-4, MPACT) |
| `pfs_median_mo` | 2.385 | [1.5, 4.0] | 10.0 | PASS | PDAC mPDAC PFS ~3-6mo (regimen-dependent) |
| `orr_pct` | 22.6 | [15.0, 35.0] | 10.0 | PASS | PDAC palliative ORR ~20-30% (NAPOLI-3 ~42%, MPACT ~23%) |
| `ctdna_in_stage4_pct` | 89.362 | [70.0, 95.0] | 10.0 | PASS | PDAC ctDNA detection in advanced ~80-90% (Cohen 2018, Bachet 2020) |
| `liver_mets_in_stage4_pct` | 48.936 | [40.0, 65.0] | 10.0 | PASS | PDAC Stage IV liver mets ~50% (Yachida 2010) |
| `stage_resectability_monotonic_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Structural: Stage I→Resectable, Stage IV→Metastatic ordering preserved, FLOOR |
| `ca19_9_panel_median_visits_per_pt` | 6.0 | [4.0, 12.0] | 10.0 | PASS | CA 19-9 longitudinal: variable visits per patient (depends on OS); median 6-7 |

## Notes

- Floor metrics (`kras_mutation_pct`, `whipple_in_head_surgical_pct`, `kras_variants_exclusive_pct`, `pembrolizumab_in_msi_h_pct`, `stage_resectability_monotonic_pct`) are one-sided ≥ threshold checks.
- **Five-table output**: primary cohort + CA 19-9 longitudinal panel + surgical-cohort subset + molecular panel + treatment history. All tables join on `patient_id`.
- **Patched generator**: the original generator had a fatal `rng.integers(0, 2**128)` overflow at line 60 (numpy max int64). The wrapper applies a minimal in-place patch composing a 128-bit UUID from four 32-bit draws. See `README.md` for full disclosure.