validation_report.md

HC-ONC-009 — Melanoma

Validation Report

• 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+

Scorecard

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

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.