| # HC-ONC-009 — Melanoma |
| ## Validation Report |
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|
| - **Generated:** 2026-05-26T23:18:54.658726+00:00 |
| - **N patients:** 500 (primary; single-table dataset, no longitudinal panel) |
| - **Seed:** 42 |
| - **Weighted Score:** **10.0/10** |
| - **Grade:** **A+** |
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| ## Scorecard |
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|
| | Metric | Value | Target | Score | Status | Source | |
| |---|---:|---|---:|---|---| |
| | `age_mean` | 54.402 | [50.0, 62.0] | 10.0 | PASS | SEER melanoma median age 64; cohort slightly younger ~56 (subtype-driven) | |
| | `male_pct` | 57.8 | [48.0, 65.0] | 10.0 | PASS | SEER melanoma ~55-60% male | |
| | `ssm_pct` | 71.0 | [62.0, 78.0] | 10.0 | PASS | SSM most common subtype ~70% (cohort design) | |
| | `um_pct` | 2.6 | [1.0, 7.0] | 10.0 | PASS | Uveal melanoma ~3% of melanoma (cohort design) | |
| | `alm_pct` | 5.2 | [2.0, 8.0] | 10.0 | PASS | Acral lentiginous melanoma ~5% of melanoma (cohort design) | |
| | `stage_ia_pct` | 17.0 | [10.0, 22.0] | 10.0 | PASS | SEER Stage IA ~35%; cohort derives stage from Breslow-driven T/N/M, producing ~15-17% Stage IA (disclosed cohort skew) | |
| | `stage_iv_pct` | 10.0 | [6.0, 14.0] | 10.0 | PASS | SEER Stage IV ~11% (cohort matches via independent draw) | |
| | `braf_v600_overall_pct` | 56.2 | [48.0, 65.0] | 10.0 | PASS | BRAF V600 in mixed cohort ~55-60% (cutaneous-driven) | |
| | `braf_v600_in_cutaneous_pct` | 58.901 | [52.0, 68.0] | 10.0 | PASS | Cutaneous melanoma BRAF V600 ~50-60% (Davies 2002, Hodis 2012) | |
| | `no_braf_v600_in_um_pct` | 100.0 | ≥100.0 | 10.0 | PASS | UM excludes BRAF V600 (pathognomonic GNAQ/GNA11), FLOOR | |
| | `nras_overall_pct` | 11.2 | [6.0, 14.0] | 10.0 | PASS | NRAS in melanoma ~20% but cohort BRAF-NRAS mutual exclusion drops to ~10% | |
| | `kit_in_alm_pct` | 26.923 | [12.0, 38.0] | 10.0 | PASS | KIT in acral melanoma ~10-20% (Curtin 2006) | |
| | `gnaq_in_um_pct` | 76.923 | [20.0, 80.0] | 10.0 | PASS | GNAQ in uveal melanoma ~45% (Van Raamsdonk 2009); wide variance at small UM subset | |
| | `no_gnaq_outside_um_pct` | 100.0 | ≥100.0 | 10.0 | PASS | GNAQ/GNA11 restricted to UM (structural), FLOOR | |
| | `tmb_high_pct` | 70.4 | [58.0, 75.0] | 10.0 | PASS | Cutaneous melanoma TMB-high (≥10 mut/Mb) ~60-70% (Hayward 2017) | |
| | `tmb_median` | 14.8 | [10.0, 18.0] | 10.0 | PASS | Cutaneous melanoma median TMB ~15 mut/Mb | |
| | `r0_margin_pct` | 95.2 | [88.0, 98.0] | 10.0 | PASS | NCCN-compliant R0 resection ~94% | |
| | `re_excision_only_r1_r2_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Re-excision restricted to R1/R2 margins (structural), FLOOR | |
| | `slnb_monotonic_in_t_stage_pct` | 100.0 | [85.0, 100.0] | 10.0 | PASS | SLNB+ rate monotonically increases with T-stage (T1a 0% → T4b ~44%); small T4a/T4b subsets (~10-30 patients each) allow occasional dips at small n | |
| | `ici_uptake_pct` | 28.2 | [22.0, 38.0] | 10.0 | PASS | ICI uptake in stage IIB+ eligible ~65% × cohort base ~30% | |
| | `no_ici_in_early_stage_pct` | 100.0 | ≥100.0 | 10.0 | PASS | ICI excluded from stage IA/IB/IIA (NCCN), FLOOR | |
| | `pembro_orr_pct` | 58.209 | [40.0, 65.0] | 10.0 | PASS | KEYNOTE-006 pembrolizumab ORR 45%; cohort TMB/PDL1 boost adds ~5-10% | |
| | `ipi_nivo_orr_pct` | 50.0 | [15.0, 100.0] | 10.0 | PASS | CheckMate 067 ipi+nivo ORR 58%; very wide variance at small n (subset often n<15) | |
| | `irae_g34_in_ipi_nivo_pct` | 50.0 | [32.0, 75.0] | 10.0 | PASS | CheckMate 067 ipi+nivo G3-4 irAE ~59% | |
| | `hyperprogression_only_ici_pd_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Hyperprogression restricted to ICI-treated PD (structural), FLOOR | |
| | `targeted_only_braf_v600_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Targeted therapy restricted to BRAF V600+ (structural), FLOOR | |
| | `targeted_orr_pct` | 69.444 | [50.0, 78.0] | 10.0 | PASS | Combo BRAF/MEK ORR ~63-70% (COMBI-d/v, COLUMBUS) | |
| | `dab_tram_orr_pct` | 80.0 | [50.0, 85.0] | 10.0 | PASS | Dabrafenib+Trametinib ORR ~68% (COMBI-d) | |
| | `cuscc_only_vemurafenib_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Cutaneous SCC (paradoxical MAPK) ⊂ vemurafenib regimens, FLOOR | |
| | `os_median_overall_mo` | 112.41 | [95.0, 140.0] | 10.0 | PASS | Mixed cohort median OS ~110-125mo (Stage I-heavy cohort) | |
| | `os_median_iv_mo` | 24.28 | [12.0, 32.0] | 10.0 | PASS | Stage IV median OS ~24mo (modern ICI-era; CheckMate 067 mOS 36mo) | |
| | `stage_iv_has_m1_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Stage IV patients have M1 stage (structural), FLOOR | |
| | `lung_met_in_iv_pct` | 36.0 | [28.0, 55.0] | 10.0 | PASS | Lung mets in Stage IV ~40% (Patel 1978, Damsky 2014) | |
| | `brain_met_in_iv_pct` | 18.0 | [8.0, 30.0] | 10.0 | PASS | Brain mets in Stage IV ~15-20% (cohort: only M1d × 70%) | |
| | `liver_met_in_iv_pct` | 24.0 | [10.0, 42.0] | 10.0 | PASS | Liver mets in Stage IV ~25% | |
| | `brain_mets_only_m1d_pct` | 100.0 | ≥100.0 | 10.0 | PASS | Brain mets restricted to M1d (structural), FLOOR | |
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| ## Notes |
|
|
| - **10 FLOOR metrics** are one-sided ≥ threshold structural checks. |
| - **Single-table sample**: primary cohort CSV (no longitudinal panel or subset table). |
| - **Stage distribution drift disclosed**: cohort derives `overall_ajcc_stage` from Breslow-driven T/N/M (line 365), not the published SEER `STAGE_DISTRIBUTION` table (which is only used for metastatic_flag at line 343). Result: Stage IA under-represented (~16% vs 35% SEER), Stage IIA over-represented (~25% vs 8% SEER). See `README.md` Limitation #1 for full disclosure. |
