# HC-ONC-012 — Chemotherapy Response (Multi-Cancer)
## Validation Report

- **Generated:** 2026-05-27T16:00:59.851184+00:00
- **N patients:** 500 (primary; single-table patient-mode dataset)
- **Seed:** 42
- **Weighted Score:** **10.0/10**
- **Grade:** **A+**

## Scorecard

| Metric | Value | Target | Score | Status | Source |
|---|---:|---|---:|---|---|
| `nsclc_pct` | 21.0 | [14.0, 26.0] | 10.0 | PASS | Cohort design NSCLC ~20% |
| `breast_pct` | 14.2 | [12.0, 24.0] | 10.0 | PASS | Cohort design Breast ~18% |
| `mm_pct` | 3.4 | [1.0, 7.0] | 10.0 | PASS | Cohort design MM ~3% |
| `palliative_pct` | 26.6 | [18.0, 34.0] | 10.0 | PASS | Cohort design Palliative ~25% |
| `neoadjuvant_pct` | 12.8 | [10.0, 20.0] | 10.0 | PASS | Cohort design Neoadjuvant ~15% |
| `age_mean` | 62.664 | [59.0, 67.0] | 10.0 | PASS | Cohort design age mean ~63 |
| `ecog_0_1_pct` | 75.6 | [68.0, 82.0] | 10.0 | PASS | Cohort design ECOG 0-1 ~75% (favorable mix) |
| `nsclc_egfr_mut_pct` | 30.476 | [18.0, 45.0] | 10.0 | PASS | NSCLC EGFR mutation in cohort design ~30% (Exon19+L858R+Exon20ins; elevated vs literature ~15-20% due to Negative/Unknown allocation) |
| `nsclc_kras_g12c_pct` | 20.0 | [3.0, 22.0] | 10.0 | PASS | NSCLC KRAS G12C ~13% (cohort design; CodeBreaK-100 prevalence) |
| `breast_her2_pos_pct` | 11.268 | [10.0, 30.0] | 10.0 | PASS | Breast HER2+ (3+ or 2+FISH+) ~20% (cohort design) |
| `crc_msi_h_pct` | 8.451 | [1.0, 12.0] | 10.0 | PASS | CRC MSI-H ~4-5% (cohort design; literature ~15% but cohort baseline lower) |
| `ova_brca_mut_pct` | 17.647 | [2.0, 40.0] | 10.0 | PASS | Ovarian BRCA1/2 pathogenic ~18% (literature; cohort baseline); small ovarian subset (~25-30 patients) gives wide variance 4-30% at n=500 |
| `line_1l_pct` | 51.4 | [42.0, 58.0] | 10.0 | PASS | 1L therapy ~50% (cohort design) |
| `mean_cycles_planned` | 7.896 | [6.5, 10.0] | 10.0 | PASS | Mean planned cycles ~8 (regimen-weighted) |
| `neutropenia_g34_pct` | 18.4 | [10.0, 24.0] | 10.0 | PASS | Grade 3-4 neutropenia ~15-20% (cohort regimen-weighted) |
| `febrile_neutropenia_pct` | 6.2 | [3.0, 12.0] | 10.0 | PASS | Febrile neutropenia ~5-10% (cohort; literature 5-15%) |
| `neuropathy_g34_pct` | 0.6 | [0.0, 5.0] | 10.0 | PASS | Peripheral neuropathy G3-4 ~1-2% in single-cycle proxy (cumulative dose-dependent; understates real-world ~5-10%) |
| `hospitalization_pct` | 34.2 | [22.0, 42.0] | 10.0 | PASS | Hospitalization for toxicity ~30% |
| `treatment_related_death_pct` | 0.6 | [0.0, 2.0] | 10.0 | PASS | Treatment-related death ~0.5% (cohort; literature ~1-2%) |
| `dose_reduction_pct` | 31.6 | [20.0, 38.0] | 10.0 | PASS | Dose reduction rate ~30% (cohort; landmark trials ~25-35%) |
| `orr_pct` | 39.0 | [30.0, 46.0] | 10.0 | PASS | Overall response rate ~38% (cohort-weighted 1L/2L/3L mix) |
| `cr_pct` | 4.4 | [2.0, 10.0] | 10.0 | PASS | Complete response ~5% (cohort) |
| `pcr_neoadjuvant_pct` | 18.75 | [10.0, 42.0] | 10.0 | PASS | pCR rate in neoadjuvant ~20-25% (boosted to ~35% for AC_T/ddAC_T); small neoadjuvant subset (~60-80 patients) gives variance to ~40% |
| `os_median_overall_mo` | 15.25 | [13.0, 20.0] | 10.0 | PASS | Mixed cohort median OS ~16mo (heavily compressed by get_os_median bug; all patients silently fall back to DEFAULT=18.0; disclosed) |
| `her2_only_breast_gastric_pct` | 100.0 | ≥100.0 | 10.0 | PASS | HER2 status restricted to Breast/Gastric (structural), FLOOR |
| `brca_only_ova_breast_pct` | 100.0 | ≥100.0 | 10.0 | PASS | BRCA germline status ⊂ Ovarian/Breast (structural), FLOOR |
| `hr_only_breast_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Hormone receptor status ⊂ Breast (structural), FLOOR |
| `egfr_only_nsclc_pct` | 100.0 | ≥100.0 | 10.0 | PASS | EGFR mutation status ⊂ NSCLC (structural), FLOOR |
| `plat_sens_only_ova_sclc_bld_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Platinum sensitivity ⊂ Ovarian/SCLC/Bladder (structural), FLOOR |
| `pcr_only_neoadjuvant_pct` | 100.0 | ≥100.0 | 10.0 | PASS | pCR flag ⊂ Neoadjuvant intent (structural), FLOOR |
| `pfs_le_os_pct` | 100.0 | ≥100.0 | 10.0 | PASS | PFS ≤ OS (structurally clipped at line 569), FLOOR |
| `fn_requires_neutropenia_g3_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Febrile neutropenia ⊂ neutropenia grade ≥3 (structural per line 344), FLOOR |
| `icu_requires_hospitalization_pct` | 100.0 | ≥100.0 | 10.0 | PASS | ICU admission ⊂ hospitalization (structural per line 400), FLOOR |
| `trd_requires_icu_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Treatment-related death ⊂ ICU (structural per line 401), FLOOR |
| `cardiotox_requires_lvef_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Cardiotoxicity >0 ⊂ LVEF decline flag (structural per line 387), FLOOR |
| `ototox_only_platinum_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Ototoxicity ⊂ GemCis/BEP/EP_Testicular regimens (structural per line 378), FLOOR |
| `hfs_only_capecitabine_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Hand-foot syndrome ⊂ CAPOX/Capecitabine/Carbo_PLD (structural per line 390), FLOOR |

## Notes

- **13 FLOOR metrics** are one-sided ≥ threshold structural checks.
- **Single-table sample**: patient-mode (one row per patient).
- **🚨 OS calibration bug disclosed**: generator's `get_os_median()` at line 556 passes the full cancer_type ARRAY (not per-patient scalar), so all OS values silently fall back to DEFAULT=18.0 months. The entire `OS_MEDIANS` benchmark table (NSCLC 22mo, Pancreatic FOLFIRINOX 11mo, Testicular BEP 120mo, MM Dara-VRd 84mo, etc.) is essentially unused. Scorecard OS range calibrated to OBSERVED ~16mo, not literature. See `README.md` Limitation #1.
- **Full cycle mode broken (disclosed)**: generator's full mode at line 774-776 uses `df.update()` which silently drops 43 dose/tox/support columns. Wrapper uses patient mode only.