OpenOnco v0.1.2 · 2026-04-30
OpenOnco · DIS-PDAC · BIO-HRR-PANEL (ESCAT IIA)
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OpenOnco · Treatment Plan
Treatment plan — DIS-PDAC
PLAN-BMA-ATM_GERMLINE_PDAC-V1 · v1 · 2026-05-04
Patient
BMA-ATM_GERMLINE_PDAC · Algorithm: ALGO-PDAC-METASTATIC-1L

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks
BiomarkerVariantESCATEvidenceClinical significanceDrugsSources
BIO-HRR-PANELATM germline pathogenicIIAATM germline pathogenic confers ~5-10× pancreatic-cancer risk; PARPi activity in ATM-mutated PDAC is modest (POLO germline-only, BRCA-restricted). NCCN recommends platinum-based chemo first; PARPi off-label or trial-only. ESCAT IIA / OncoKB Level 3A.FOLFIRINOX or gem-cis (platinum induction)
olaparib maintenance (off-label, NCCN-listed for HRR-mut)
  • SRC-NCCN-PANCREATIC-2025
  • SRC-ESMO-PANCREATIC-2024
BIO-HRR-PANELPALB2 germline pathogenicIIA
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
PALB2 germline pathogenic in metastatic PDAC: behaves BRCA-like; case series support platinum sensitivity and PARPi activity. POLO germline-only and BRCA- restricted; NCCN allows off-label olaparib for HRR-mutated. ESCAT IIA / OncoKB Level 3A.FOLFIRINOX (platinum induction)
olaparib maintenance (off-label per NCCN)
  • SRC-NCCN-PANCREATIC-2025
  • SRC-ESMO-PANCREATIC-2024

Treatment options (3 tracks)

Standard plan
★ DEFAULT
Indication
IND-PDAC-METASTATIC-1L-FOLFIRINOX
Regimen
FOLFIRINOX
Drugs + NSZU
  • Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² · IV day 1 every 14d · IV ✓ NSZU covered
  • Irinotecan (DRUG-IRINOTECAN) 180 mg/m² (full); 150 mg/m² in modified FOLFIRINOX (mFOLFIRINOX) · IV day 1 · IV ⚠ NSZU — not for this indication
  • Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV day 1 · IV ⚠ NSZU — not for this indication
  • 5-Fluorouracil (DRUG-5-FLUOROURACIL) 400 mg/m² IV bolus + 2400 mg/m² CIV over 46h (modified omits bolus to reduce mucositis) · Day 1 bolus, day 1-2 CIV · IV ✓ NSZU covered
Reason
Engine default per algorithm ALGO-PDAC-METASTATIC-1L: {'step': 3, 'outcome': True, 'branch': {'result': 'IND-PDAC-METASTATIC-1L-FOLFIRINOX'}, 'fired_red_flags': ['RF-FITNESS-ECOG-FIT', 'RF-PDAC-FIT-FOR-FOLFIRINOX'], 'winner_red_flag': 'RF-PDAC-FIT-FOR-FOLFIRINOX'}
Standard plan
Indication
IND-PDAC-METASTATIC-1L-GEM-NAB-PAC
Regimen
Gemcitabine + nab-paclitaxel (MPACT)
Drugs + NSZU
  • Gemcitabine (DRUG-GEMCITABINE) 1000 mg/m² · IV days 1, 8, 15 of 28-d cycle · IV ✓ NSZU covered
  • Nab-paclitaxel (albumin-bound paclitaxel) (DRUG-NAB-PACLITAXEL) 125 mg/m² · IV days 1, 8, 15 of 28-d cycle · IV ✓ NSZU covered
Reason
Alternative track presented for HCP consideration
Aggressive plan
Indication
IND-PDAC-MAINTENANCE-OLAPARIB-BRCA
Regimen
Olaparib maintenance (BRCA-mut PDAC post-platinum, POLO)
Drugs + NSZU
  • Olaparib (DRUG-OLAPARIB) 300 mg PO BID continuous · Continuous · PO ⚠ NSZU — not for this indication
Reason
Alternative track presented for HCP consideration

Why this branch was chosen

Triggers from the patient profile that fired and drove the chosen branch.
Step 3 → branch IND-PDAC-METASTATIC-1L-FOLFIRINOX
  • RF-FITNESS-ECOG-FIT: Fit performance status (ECOG 0-1): patient is fully active or restricted in physically strenuous activity but ambulatory and able to carry out light work. Eligible for full-dose chemotherapy and intensive regimens (CHOEP, BEACOPP-escalated, HD-MTX, ASCT consolidation, CAR-T). SRC-NCCN-BCELL-2025SRC-ESMO-DLBCL-2024
  • RF-PDAC-FIT-FOR-FOLFIRINOX ★ winner: Fitness for FOLFIRINOX in metastatic PDAC per PRODIGE-4 / ACCORD-11 inclusion criteria (Conroy NEJM 2011): ECOG 0-1, age ≤75 (≤76 by protocol; convention <=70-75 in real-world), bilirubin ≤1.5× ULN (resolved post-biliary stenting if needed), no significant cardiac comorbidity, adequate hepatic / renal / bone-marrow function. Selects IND-PDAC-METASTATIC-1L-FOLFIRINOX over IND-PDAC-METASTATIC-1L-GEM-NAB-PAC (mOS 11.1 vs 6.8 mo in PRODIGE-4; toxicity tradeoff acceptable in fit patients). Frail / ECOG ≥2 / bilirubin elevated → de-escalate to gem-nab-paclitaxel (MPACT, Von Hoff NEJM 2013). SRC-NCCN-PANCREATIC-2025SRC-ESMO-PANCREATIC-2024

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks
IDNamePriorityCategoryWhere to orderNeeded for
TEST-CBCComplete Blood Count with DifferentialCriticallaball tracks
TEST-CT-CHEST-ABDOMEN-PELVISCT chest + abdomen + pelvis with IV contrastCriticalimagingstandard
TEST-LFTLiver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)Criticallabstandard
TEST-CT-PETPET-CT with FDGDesiredimagingdesired (standard)
TEST-NGS-COMPREHENSIVEComprehensive NGS tumor panel (DNA + RNA, ≥300 genes)DesiredhistologyCSD Lab: M065desired (standard)

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track
  • Obstructive jaundice / cholangitis in PDAC: total bilirubin ≥3 mg/dL with pancreatic-head mass causing biliary tree dilation, OR active cholangitis (fever + RUQ pain + jaundice). Mandates biliary drainage (ERCP-stent or PTC) BEFORE chemo, which is hepatotoxic and reduces clearance of cytotoxics. RF-PDAC-BILIARY-OBSTRUCTION-CHOLANGITIS

CONTRA-AGGRESSIVE

Hard contraindications to escalation

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-PDAC-METASTATIC-1L-FOLFIRINOX)
  • Do NOT initiate without resolved jaundice (bilirubin <1.5-2 ULN) — irinotecan hepatotoxic
  • Do NOT use in PS ≥2 — substantial Grade 3-4 toxicity
  • Do NOT skip UGT1A1 testing for high-risk populations (preventable severe diarrhea + neutropenia)
Standard plan (IND-PDAC-METASTATIC-1L-GEM-NAB-PAC)
  • Do NOT use without addressing biliary obstruction first
  • Do NOT continue past Grade 2 functional neuropathy without dose reduction
Aggressive plan (IND-PDAC-MAINTENANCE-OLAPARIB-BRCA)
  • Do NOT start without confirmed CR/PR/SD to platinum-induction
  • Do NOT skip pre-treatment counseling on long-term MDS/AML risk
  • Do NOT use in tumor-only-BRCA without germline confirmation (POLO inclusion was germline)

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · FOLFIRINOX
14-day cycles × 12 cycles (PRODIGE-24 adjuvant); until progression / toxicity (metastatic)

Standard plan

Induction · Gemcitabine + nab-paclitaxel (
28-day cycles × Until progression / unacceptable toxicity

MDT brief

Skills (recommended) — for consideration (2)

  • Clinical pharmacist recommended
    Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
    skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
  • Molecular geneticist / molecular oncologist recommended
    Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
    skill: molecular_geneticistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open questions (1, 0 blocking)

  • OQ-LDH-CURRENT
    What is the current LDH? Marker of tumor burden and transformation.
    LDH is part of the prognostic indices of indolent lymphomas.
    → hematologist

Data quality

  • Unevaluated RedFlags: RF-PAN-ATM-CHEK2-CDK12-PARPI-CANDIDATE, RF-PAN-BRCA-SOMATIC-PARPI-CANDIDATE, RF-PAN-PALB2-PARPI-CANDIDATE, RF-PDAC-BILIARY-OBSTRUCTION-CHOLANGITIS, RF-PDAC-FRAILTY-AGE, RF-PDAC-HIGH-RISK-BIOLOGY, RF-PDAC-INFECTION-SCREENING, RF-PDAC-TRANSFORMATION-PROGRESSION

Skill catalog (2/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
Specialistskill_idVersionLast reviewedSign-offsDomain
Cellular therapy specialist (CAR-T)cellular_therapy_specialistv0.1.02026-04-250cellular_therapy
Clinical pharmacistclinical_pharmacistv0.1.02026-04-250clinical_pharmacy
Hematologist / oncohematologisthematologistv0.1.02026-04-250hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)hematopathologistv0.1.02026-04-250hematopathology
Infectious disease / hepatologyinfectious_disease_hepatologyv0.1.02026-04-250infectious_diseases
Medical oncologist (solid-tumor chemotherapist)medical_oncologistv0.1.02026-04-250solid_oncology
Molecular geneticist / molecular oncologistmolecular_geneticistv0.1.02026-04-250molecular_oncology
Palliative carepalliative_carev0.1.02026-04-250palliative_care
Pathologist (general)pathologistv0.1.02026-04-250pathology
Primary care / family physicianprimary_carev0.1.02026-04-250primary_care
Psycho-oncologistpsychologistv0.1.02026-04-250psychosocial
Radiation oncologistradiation_oncologistv0.1.02026-04-250radiation_oncology
Radiologistradiologistv0.1.02026-04-250diagnostic_imaging
Social worker / case managersocial_worker_case_managerv0.1.02026-04-250psychosocial
Surgical oncologistsurgical_oncologistv0.1.02026-04-250surgical_oncology
Transplant specialist (BMT)transplant_specialistv0.1.02026-04-250cellular_therapy

Sources cited

Experimental options (clinical trials)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-05-04.
NCTTitlePhaseStatusSponsorUAEligibility (excerpt)
NCT07094113AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid TumorsPHASE1RECRUITINGAmgen
NCT07186842A Clinical Trial to Test if the Investigational Drug BNT329 is Safe and Potentially Beneficial for People With Advanced Solid Tumors Known to Express the Tumor Marker CA19-9PHASE1 / PHASE2RECRUITINGBioNTech SE
NCT06835569A Study to Learn About Study Medicine ALTA3263 in Adults With Advanced Solid Tumors With KRAS MutationsPHASE1RECRUITINGAlterome Therapeutics, Inc.
NCT06060405Durvalumab and Oleclumab in Resectable PDACPHASE2RECRUITINGUniversity Health Network, Toronto
NCT06158139Autologous CAR-T Cells Targeting B7-H3 in PDACPHASE1RECRUITINGUNC Lineberger Comprehensive Cancer Center
NCT06921928Study for AZD4360 in Participants With Advanced Solid TumoursPHASE1 / PHASE2RECRUITINGAstraZeneca
NCT07261631Phase I Study of [177Lu]Lu-DFC413 in Patients With Solid TumorsPHASE1RECRUITINGNovartis Pharmaceuticals
NCT05518903Investigational Scan (68Ga-FAPI-46 PET/CT) for Imaging of Cancer-Associated Fibroblasts for Localized Pancreatic Ductal AdenocarcinomaPHASE2RECRUITINGMayo Clinic
NCT07144917Immunoparalysis After PancreaticoduodenectomyN/ARECRUITINGHospices Civils de Lyon
NCT04900818Study of TJ033721 (Givastomig) in Subjects With Advanced or Metastatic Solid TumorsPHASE1RECRUITINGI-Mab Biopharma US Limited

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

Option availability in Ukraine

Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).
OptionUA registrationNSZUCost orientationAccess pathway
Standard plan
FOLFIRINOX (REG-FOLFIRINOX)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Standard plan
Gemcitabine + nab-paclitaxel (MPACT) (REG-GEM-NAB-PAC)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Aggressive plan
Olaparib maintenance (BRCA-mut PDAC post-platinum, POLO) (REG-OLAPARIB-MAINT-PDAC)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Trial · NCT07094113
AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT07186842
A Clinical Trial to Test if the Investigational Drug BNT329 is Safe and Potentially Beneficial for People With Advanced Solid Tumors Known to Express the Tumor Marker CA19-9
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT06835569
A Study to Learn About Study Medicine ALTA3263 in Adults With Advanced Solid Tumors With KRAS Mutations
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT06060405
Durvalumab and Oleclumab in Resectable PDAC
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT06158139
Autologous CAR-T Cells Targeting B7-H3 in PDAC
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT06921928
Study for AZD4360 in Participants With Advanced Solid Tumours
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT07261631
Phase I Study of [177Lu]Lu-DFC413 in Patients With Solid Tumors
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05518903
Investigational Scan (68Ga-FAPI-46 PET/CT) for Imaging of Cancer-Associated Fibroblasts for Localized Pancreatic Ductal Adenocarcinoma
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT07144917
Immunoparalysis After Pancreaticoduodenectomy
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT04900818
Study of TJ033721 (Givastomig) in Subjects With Advanced or Metastatic Solid Tumors
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.