FULCRUM CDS
Pancreatic adenocarcinoma
DEMOJames MorrisonAisha PatelRobert ChenMaria Santos|Enter Real Patient
MS

Maria Santos

62 y/o FemaleMRN: 0518934Pancreatic adenocarcinomaMSS, BRCA wild-typePD-L1 %
Stage IVWindow constrained — structural barriers

Treatment Window

S4 Confusion
The immune system has lost orientation to the tumour. Standard single-agent checkpoint blockade is unlikely to be sufficient. Consider combinations that address multiple steps, or non-immune approaches.
Critical question: Is there anything left to rebuild from?
If renewal capacity exists, the immune system can potentially be restarted by addressing the earliest broken link. If no renewal, the immune path may be exhausted — consider non-immune approaches.
■ STRUCTURAL CONSTRAINT — standard ICI may be insufficient

Immune Advantagei

Likely Non-Responder
0.04×
Immune deficit (adjusted: 0.0×)
Immune system vastly outpaced by tumour. Checkpoint blockade alone is unlikely to work. Consider non-immune approaches or combinations addressing multiple steps.
Is there anything left to rebuild from?
If renewal capacity exists, the immune system can potentially be restarted by addressing the earliest broken link. If no renewal, the immune path may be exhausted — consider non-immune approaches.
Primary drain
Innate signal
Secondary drain

Step Coverage

1/4 Steps
⚠
Detection
Open
✓
Priming
Gemcitabine
⚠
Encounter
Open
⚠
Maintenance
Open
AgentStepMechanism
Gemcitabine—Antimetabolite — immunogenic cell death
Paclitaxel—Taxane — immunogenic cell death
Open Escape Routes
Detection, Encounter, Maintenance steps uncovered.

Structural Recommendations

✕

Do not add Paclitaxel

Paclitaxel covers the same step (Priming) as Gemcitabine. No additional escape route closed.

?

Consider LAG-3 inhibitor if available

LAG-3 addresses antigen presentation (Detection step) — genuinely different from PD-1.

FULCRUM CDS is a structural analysis tool. It does not replace clinical judgement. Not FDA approved.

Trial Evidence — Pancreatic adenocarcinoma

Observed ORR
RegimenTrialORRnYear
fu_p+iri_p+oxa_pPRODIGE 431.6%1712011
gem+nabpMPACT23.0%4312013
gemBurris 19975.4%631997
Source: published Phase II/III trial results. Observed outcomes, not model predictions.

Tumour Immune Profile

GZMB
2.1 log₂
PRF1
1.8 log₂
IFNG
1.2 log₂
GZMA
2.0 log₂
MKI67
8.4 log₂
Immune Adv.
0.04×
Host Drain
IL1B
5.6 log₂
CXCL8
5.2 log₂
SPP1
6.1 log₂
MARCO
4.8 log₂

Host Capacity

Albumin
3.1 g/dL
NLR
7.9
CA 19-9
842 U/mL

Timeline

Dec 2025
Diagnosis — Stage IV PDAC, liver metastases
Jan 2026
Molecular — MSS, BRCA WT, no actionable targets
Feb 2026
RNA-seq — immune cold tumour confirmed
Mar 2026
Treatment decision — FULCRUM CDS consulted
—
Gemcitabine + nab-paclitaxel (immune escape unlikely)
New Patient
SMART on FHIR · FULCRUM v0.2.0 · generativegeometry.science