# Patient Outcomes Reference

> **Canonical source.** This file is the single authoritative narrative for what the
> Precision Medicine MCP Platform found for each synthetic patient. All other docs must
> link to the relevant anchor rather than restating these findings.
>
> Source of truth for numeric values: `tests/fixtures/pat00X_canonical.py`
> Last updated: 2026-05-09 (v17 — PAT002 deep-stage hypotheses added)

---

## PAT001 — HGSOC Stage IV {#pat001}

**Profile:** 58-year-old female, Stage IV high-grade serous ovarian cancer (HGSOC),
BRCA1+, platinum-resistant. Standard workup found BRCA1 germline mutation and initiated
platinum-based chemotherapy. Standard liquid biopsy and genomic panels did not surface
additional therapeutic hypotheses.

**What standard workup missed:** Three independent, convergent investigational paths:

- **Personalized neoantigen vaccine** — TP53 R175H mutation produces the RMPEAAPPV
  peptide, which binds HLA-A*02:01 with IC50 7.8 nM (strong binder; < 50 nM threshold).
  The neoantigen burden (TMB POLE-corrected: 47.3 mut/Mb) supports vaccine candidacy.

- **NNMT/CAF inhibition** — Cancer-associated fibroblast (CAF) fraction: 18.2%.
  GEARS GNN perturbation modelling predicts that NNMT knockdown recovers immune
  infiltration markers, suggesting CAF remodelling as a combination strategy.

- **Convergent checkpoint blockade** — POLE-corrected TMB 47.3 mut/Mb (ultra-high)
  combined with spatial CD8+ T-cell exclusion pattern on Visium data supports
  dual anti-PD-1/CTLA-4 blockade.

**Canonical numeric outcomes** (source: `tests/fixtures/pat001_canonical.py`):

| Metric | Value | Unit |
|---|---|---|
| TMB (POLE-corrected) | 47.3 | mut/Mb |
| Top neoantigen IC50 | 7.8 | nM |
| HRD score | 54 | — |
| CAF fraction | 18.2 | % |

---

## PAT002 — ER+ Breast Cancer (Stage IIA) {#pat002}

**Profile:** Stage IIA invasive ductal carcinoma (IDC), ER+/PR+/HER2−, BRCA2+ germline,
PIK3CA H1047R somatic. Standard workup identified ER+ status and initiated endocrine
therapy (aromatase inhibitor). BRCA2 germline result was returned but HRD score of 35
fell below the myChoice CDx 42-point PARP-eligibility threshold, so olaparib was not
offered.

**What standard workup missed:** Three investigational hypotheses and PARP reclassification.

- **Inavolisib over alpelisib** — PIK3CA H1047R somatic mutation makes PAT002 eligible
  for PI3K inhibition. The platform ranked inavolisib over alpelisib based on the 2024
  FDA approval for PIK3CA-mutant ER+/HER2− breast cancer, a distinction not surfaced by
  standard genomic panel reporting.

- **MYC-driven triple therapy** — MYC amplification detected alongside PIK3CA and BRCA2
  suggests a CDK4/6 inhibitor + PI3K inhibitor + endocrine therapy combination. Standard
  workup initiated single-agent endocrine therapy only.

- **YSAPLSSSL neoepitope vaccine + CAF depletion + anti-PD-1** — The YSAPLSSSL peptide
  binds HLA-A\*02:01. Quantum immune evasion scoring (0.41) indicates partial immune
  engagement despite ER+ BC being conventionally classified as immunologically cold.
  Combined with CAF depletion, this suggests a vaccine + checkpoint strategy.

Additionally, the platform reclassified PARP eligibility: HRD 35 falls below the
myChoice CDx 42-point threshold, but current FDA labeling for olaparib (OlympiA trial)
supports germline BRCA2-positive status as an independent eligibility criterion
regardless of HRD score.

The same 19-server stack handled this second cancer type with zero disease-specific
code changes — validating architecture generalizability.

**Canonical numeric outcomes** (source: `tests/fixtures/pat002_canonical.py`):

| Metric | Value | Unit |
|---|---|---|
| HRD score | 35 | — |
| TMB | 2.8 | mut/Mb |
| Immune evasion score | 0.41 | — |
| Top neoantigen peptide | YSAPLSSSL | — |
| Luminal stability score | 0.78 | — |

---

## PAT003 — Preventive Cardiovascular Health {#pat003}

**Profile:** 67-year-old post-menopausal female. Standard annual physical + Helix Tier 1
population genetic screen — all results returned as "normal." Standard lipid panel
ordered to evaluate statin candidacy.

**What standard workup missed:** Three high-priority evidence gaps and intermediate
10-year CVD risk confirmed by three independent algorithms.

### Risk scores

| Algorithm | 10-yr Risk | Category | Notes |
|---|---|---|---|
| Reynolds Risk Score | 14.3% | Intermediate | Women-specific; incorporates hsCRP and family history |
| Framingham Risk Score | 12.0% | Intermediate | Standard community-based model |
| ACC/AHA Pooled Cohort Equation | 10.3% | Intermediate | Above 7.5% statin-consideration threshold |

All three algorithms converged on intermediate risk (7.5–20%). Convergence across
partially overlapping models strengthens the intermediate classification.

### Three high-priority gaps missed by standard workup

**Gap 1 — Serum Lp(a) not measured.**
Lp(a) is genetically determined, does not respond to standard LDL-lowering statins,
and is an independent cardiovascular risk factor. The 2023 ESC/EAS guidelines recommend
measuring Lp(a) once in every adult's lifetime. PAT003's standard lipid panel reported
LDL 118 mg/dL — Lp(a) was not included and not ordered.

**Gap 2 — APOE genotype unknown.**
APOE is the strongest common genetic determinant of both cardiovascular disease and
Alzheimer's risk. It is not included in the Helix Tier 1 panel or any current
population-level screening programme. The negative Tier 1 result ruled out monogenic
familial hypercholesterolaemia (FH) but did not address polygenic or APOE-mediated risk.

**Gap 3 — Coronary artery calcium (CAC) score not obtained.**
At intermediate CVD risk (7.5–20%), CAC is the best-validated reclassification tool
per the 2018 ACC/AHA cholesterol guidelines. A CAC of 0 would support deferring statins
("statin holiday"); a CAC > 100 or ≥ 75th percentile for age/sex would strengthen the
case for initiation. Not ordered; not mentioned in the standard workup.

### Clinical reframe: the negative genetic screen is not "nothing"

The Helix Tier 1 negative result ruled out monogenic FH — a high-penetrance, single-gene
cause of premature CVD. This shifts the clinical question: if monogenic risk is absent,
the primary remaining mechanisms are polygenic accumulation and modifiable risk factors.
That reframe makes Lp(a), APOE, and CAC the three tests most likely to change clinical
management — precisely the three the platform flagged.

### hsCRP and JUPITER trial context

hsCRP: 1.8 mg/L — just below the 2.0 mg/L threshold used in the JUPITER trial
(Ridker et al. NEJM 2008), at which rosuvastatin demonstrated significant cardiovascular
event reduction in patients with LDL < 130 mg/dL. This margin is clinically meaningful
to track: a repeat hsCRP measurement above 2.0 mg/L would bring PAT003 into JUPITER
criteria.

**Canonical numeric outcomes** (source: `tests/fixtures/pat003_canonical.py`):

| Metric | Value | Unit |
|---|---|---|
| Reynolds Risk Score | 14.3 | % (10-yr) |
| Framingham Risk Score | 12.0 | % (10-yr) |
| ACC/AHA ASCVD Risk | 10.3 | % (10-yr) |
| hsCRP | 1.8 | mg/L |
| LDL | 118 | mg/dL |
| HDL | 58 | mg/dL |
| Systolic BP | 138 | mmHg |

---

## Quick-reference table

| Patient | Use case | Key finding missed by standard workup | Anchor |
|---|---|---|---|
| PAT001 | HGSOC Stage IV | 3 investigational paths (neoantigen vaccine, NNMT/CAF, checkpoint) | [#pat001](#pat001) |
| PAT002 | ER+ breast cancer | 3 investigational hypotheses (inavolisib, MYC triple therapy, neoepitope vaccine) + PARP reclassification | [#pat002](#pat002) |
| PAT003 | Preventive CVD | 3 evidence gaps (Lp(a), APOE, CAC) missed by lipid panel + Helix Tier 1 | [#pat003](#pat003) |

---

*To update this file: first update the fixture at `tests/fixtures/pat00X_canonical.py`,
then update the table above. All other docs should link here — do not copy these values.*
