Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
BMA-SUFU_GERMLINE_MEDULLOBLASTOM · Algorithm: ALGO-GBM-NEWLY-DIAGNOSED-1L
Clinical significance of mutations (ESCAT)
Tumor-board context — the engine does not use these tiers to rank tracks
| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|
| ESCAT: clinical review pendingBIO-SUFU-GERMLINE | SUFU germline pathogenic (NBCCS-like, medulloblastoma-predominant) | IIA | Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap. | SUFU germline pathogenic variants cause a Gorlin-syndrome–like predisposition with much higher medulloblastoma risk than PTCH1 (~30% lifetime vs ~5% in PTCH1), and lower BCC burden. SUFU-driven medulloblastomas cluster in the SHH-activated molecular subgroup (infant/young-child onset, desmoplastic / MBEN histology in many cases). Confirmed-carrier surveillance protocol (per Foulkes et al. 2017 / AACR Pediatric Predisposition Working Group): brain MRI q4mo from diagnosis through age 3, q6mo from age 3-5, annually to age 8 — denser-than-PTCH1 cadence reflects higher MB risk. Dermatology surveillance for BCC q6-12mo from puberty. Avoid craniospinal external-beam radiation when alternatives exist (second-malignancy risk in carriers). Hedgehog-pathway inhibitors (vismodegib, sonidegib) have limited activity in SUFU-mutant SHH-MB — downstream-of-SMO position renders SMO inhibitors ineffective; this is a critical distinction from PTCH1-driven disease. ESCAT IIA. | brain MRI q4mo to age 3, q6mo to age 5, annual to age 8 — earlier and denser than PTCH1 cadence
dermatology surveillance q6-12mo from puberty
neurosurgery + COG-based protocols for medulloblastoma (avoid EBRT where alternatives available)
do NOT default to vismodegib / sonidegib for SUFU-driven SHH-MB — downstream-of-SMO position renders SMO inhibition ineffective; consider GLI-pathway investigational agents in trial setting | |
Primary current-line option
- Indication
- IND-GBM-NEWLY-DIAGNOSED-STUPP
- Regimen
- Stupp protocol — Temozolomide concurrent + adjuvant
- Drugs + NSZU
- Temozolomide (DRUG-TEMOZOLOMIDE) Concurrent: 75 mg/m² PO daily during RT 6 weeks; Adjuvant: 150 mg/m² PO days 1-5 cycle 1 (escalate to 200 if tolerated) every 28 days × 6 cycles · Concurrent daily × 42 days then 4-week break then adjuvant cycles 1-6 · PO ✓ NSZU covered
- Reason
- Provisional current-line default from ALGO-GBM-NEWLY-DIAGNOSED-1L: step 1 did not select a treatment branch. IDH-mutant glioma grade 4: not GBM per WHO 2021. Manage as astrocytoma IDH-mutant (vorasidenib INDIGO). Separate disease pathway.
Other current-line alternatives (2 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-GBM-NEWLY-DIAGNOSED-ELDERLY-TMZ
- Regimen
- Temozolomide monotherapy
- Drugs + NSZU
- Temozolomide (DRUG-TEMOZOLOMIDE) ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-GBM-NEWLY-DIAGNOSED-ELDERLY-HYPORT
- Regimen
- Hypofractionated radiotherapy for GBM
- Reason
- Current-line alternative presented for HCP consideration
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-IDH-MUTATION | IDH1/IDH2 mutation | Critical | histology | CSD Lab ✓ (code TBC) | all tracks |
| TEST-MGMT-METHYLATION | MGMT methylation | Critical | histology | CSD Lab ✓ (code TBC) | all tracks |
| TEST-MRI-BRAIN-CONTRAST | MRI brain with contrast | Standard | imaging | — | all tracks |
| TEST-NGS-COMPREHENSIVE | Comprehensive NGS tumor panel (DNA + RNA, ≥300 genes) | Desired | histology | CSD Lab: M065 | desired (standard) |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Symptomatic raised intracranial pressure / mass effect in glioblastoma: declining GCS, new focal deficit, papilledema, midline shift on imaging, or seizure cluster. Mandates immediate neurosurgical / corticosteroid intervention BEFORE oncologic systemic therapy.
Mass effect emergency — dexamethasone 8-16 mg IV stat, neurosurgical consult for resection / debulking / VP shunt. Anti-epileptics for seizure cluster (levetiracetam preferred — no enzyme induction vs older AEDs that interfere with TMZ…
RF-GBM-INTRACRANIAL-PRESSURE-EMERGENCYSRC-NCCN-CNS-2025SRC-EANO-GBM-2024 - Glioblastoma progression on or after first-line Stupp regimen: MRI evidence of true progression (RANO criteria — distinguished from pseudoprogression by serial imaging / advanced techniques), early recurrence <6 months post-RT (often pseudoprogression — repeat MRI at 4-8 weeks before re-treatment decision), or distant new lesion. Routes from upfront Stupp to recurrent-GBM algorithm (re-resection + bevacizumab / TTF / regorafenib / lomustine / re-irradiation).
Pseudoprogression occurs in ~30% post-Stupp at 3 mo MRI — does not represent true tumor growth (treatment-related inflammation / radiation effect); RANO criteria require either second confirmatory MRI or outside-RT-field new disease…
RF-GBM-TRANSFORMATION-PROGRESSIONSRC-NCCN-CNS-2025SRC-EANO-GBM-2024
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-GBM-NEWLY-DIAGNOSED-STUPP)
- Do NOT delay starting RT beyond 6 weeks post-resection
- Do NOT skip MGMT testing — defines elderly (≥70) regimen choice
- Do NOT skip PJP prophylaxis (universal lymphopenia → opportunistic infection)
- Do NOT use enzyme-inducing AEDs (phenytoin, carbamazepine) — accelerate TMZ clearance; use levetiracetam
Standard plan (IND-GBM-NEWLY-DIAGNOSED-ELDERLY-TMZ)
- Do NOT use TMZ alone in MGMT-unmethylated GBM ≥70 — minimal benefit; prefer hypofractionated RT
- Do NOT use full Stupp (60 Gy/30 fx) in patients ≥70 or KPS <60 — excessive toxicity
- Do NOT skip MGMT testing before choosing TMZ vs RT — this is the key biomarker in elderly
- Do NOT skip PJP prophylaxis (co-trimoxazole) — lymphopenia risk applies to TMZ mono too
Standard plan (IND-GBM-NEWLY-DIAGNOSED-ELDERLY-HYPORT)
- Do NOT use full Stupp 60 Gy/30 fx in patients ≥70 or KPS <60 — unacceptable toxicity in elderly
- Do NOT omit TMZ without first checking MGMT status — methylated patients benefit significantly
- Do NOT skip MGMT testing — drives concurrent TMZ decision
- Do NOT start RT without post-resection MRI (within 48h of surgery)
- Do NOT delay RT beyond 6 weeks post-surgery
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Stupp protocol — Temozolomide concurrent + adjuvant
28-day cycles × Concurrent phase 6 weeks + adjuvant 6 cycles (~7 months total)
Standard plan
Induction · Temozolomide monotherapy
28-day cycles × Until progression or unacceptable toxicity; schedule per GBM protocol
MDT brief
Discussion questions (1, 1 blocking)
BLOCKING OQ-BIOMARKER-MGMT-METHYLATION
What is the status of MGMT promoter methylation status (BIO-MGMT-METHYLATION)? It is required by track(s): IND-GBM-NEWLY-DIAGNOSED-STUPP, IND-GBM-NEWLY-DIAGNOSED-ELDERLY-TMZ. Expected value: MGMT methylation status (methylated / unmethylated) — required input; methylated patients have substantially better TMZ response (~21.7 mo vs ~12.7 mo OS) but Stupp protocol applies regardless.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ molecular_geneticist
MDT talk tree (1 steps)
| # | Owner | Topic | Action |
|---|
| 1 | molecular_geneticist | Biomarker status BLOCKING | What is the status of MGMT promoter methylation status (BIO-MGMT-METHYLATION)? It is required by track(s): IND-GBM-NEWLY-DIAGNOSED-STUPP, IND-GBM-NEWLY-DIAGNOSED-ELDERLY-TMZ. Expected value: MGMT methylation status (methylated / unmethylated) — required input; methylated patients have substantially better TMZ response (~21.7 mo vs ~12.7 mo OS) but Stupp protocol applies regardless. |
Skills (recommended) — for consideration (1)
Data quality
Incomplete for default-track review. Default-track review is incomplete until required biomarker gaps are resolved.
- Biomarker coverage: 0/1 known (0%), 1 missing, 1 default-track gaps
- Unevaluated RedFlags: RF-CASCADE-LFS-FDR-POSITIVE, RF-GBM-FRAILTY-AGE, RF-GBM-HIGH-RISK-BIOLOGY, RF-GBM-INFECTION-SCREENING, RF-GBM-INTRACRANIAL-PRESSURE-EMERGENCY, RF-GBM-TRANSFORMATION-PROGRESSION, RF-IATROGENIC-CRANIAL-RT-LATE-PREVENTION, RF-LI-FRAUMENI-FAMILY-HISTORY-SUSPICION
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|
BIO-MGMT-METHYLATION | MGMT promoter methylation status | molecular_geneticist | yes | IND-GBM-NEWLY-DIAGNOSED-STUPP, IND-GBM-NEWLY-DIAGNOSED-ELDERLY-TMZ | Verify result, method, specimen, and report date before sign-off. Expected/constraint: MGMT methylation status (methylated / unmethylated) — required input; methylated patients have substantially better TMZ response (~21.7 mo vs ~12.7 mo OS) but Stupp protocol applies regardless |
Technical MDT skill metadata (1/16 activated in this plan)
All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
| Specialist | skill_id | Version | Last reviewed | Sign-offs | Domain |
|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
Sources cited
- SRC-CCTG-CE6-PERRY-2017: Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma (2017)
- SRC-EANO-GBM-2024: EANO Guidelines on Diagnosis and Treatment of Diffuse Gliomas of Adulthood (2024 update)
- SRC-NCCN-CNS-2025: NCCN Central Nervous System Cancers (v.3.2025)
- SRC-NORDIC-GBM-MALMSTROM-2012: Temozolomide versus Standard 6-Week Radiotherapy versus Hypofractionated Radiotherapy in Patients Older than 60 Years with Glioblastoma (2012)
Experimental options (clinical trials)
Last synced: 2026-08-03 · ctgov.
No active trials matched this scenario in ctgov.
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).
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|
| Standard plan Stupp protocol — Temozolomide concurrent + adjuvant (REG-STUPP-TMZ) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Temozolomide monotherapy (REG-TMZ-MONO) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Hypofractionated radiotherapy for GBM (REG-HYPOFRACTIONATED-RT-GBM) No regimen components on this track — availability unknown | — unknown | — unknown | ₴-? — verify pathway | not recorded |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-03.