Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
BMA-TSC2_GERMLINE_TUBEROUS_SCLER · Algorithm: ALGO-RCC-METASTATIC-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-TSC2-GERMLINE | TSC2 germline pathogenic (tuberin loss-of-function) | IIA | Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap. | TSC2 germline pathogenic variants drive Tuberous Sclerosis Complex (TSC) — the more clinically severe of the two TSC genotypes (TSC2 carriers have earlier onset and broader phenotype than TSC1). Same multi-organ tumor spectrum as TSC1: SEGA, renal AML (typically more numerous and earlier in TSC2), LAM, cardiac rhabdomyoma, cortical tubers. Confirmed-carrier surveillance protocol identical to TSC1 (per TSC Consensus Conference 2012 + 2021 update / NCCN CNS): brain MRI q1-3y through age 25 for SEGA, renal MRI/US q1-3y lifelong, PFT + HRCT chest q5-10y in adult females, baseline echocardiogram, annual dermatology + ophthalmology exam. Contiguous-gene TSC2/PKD1 deletions present with severe polycystic kidney disease in addition to AML and require nephrology co-management. mTOR inhibitors (everolimus, sirolimus) active across SEGA, renal AML ≥3 cm, and LAM. ESCAT IIA. | everolimus 10 mg PO daily — TSC-associated SEGA or renal AML ≥3 cm
sirolimus — LAM with FEV1 decline (off-label)
multidisciplinary surveillance per TSC Consensus Conference
nephrology co-management for contiguous-gene TSC2/PKD1 deletion carriers | |
Primary current-line option
- Indication
- IND-RCC-METASTATIC-1L-PEMBRO-AXI
- Regimen
- Pembrolizumab + axitinib (RCC, 1L all-risk)
- Drugs + NSZU
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w · Up to 2 years · IV ⚠ NSZU — not for this indication
- Axitinib (DRUG-AXITINIB) 5 mg PO BID continuous · Continuous · PO ⚠ NSZU — not for this indication
- Reason
- Provisional current-line default from ALGO-RCC-METASTATIC-1L: step 1 did not select a treatment branch. Non-clear cell RCC: use cabozantinib 60mg monotherapy (REG-CABOZANTINIB-RCC) for papillary subtype (NCCN preferred, MET pathway rationale); clinical trial enrollment preferred for chromophobe, collecting duct, translocation RCC. Algorithm does not cover these subtypes.
Other current-line alternatives (3 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-RCC-METASTATIC-1L-NIVO-IPI
- Regimen
- Nivolumab + ipilimumab (RCC, 1L IMDC intermediate/poor)
- Drugs + NSZU
- Nivolumab (DRUG-NIVOLUMAB) 3 mg/kg IV induction → 480 mg flat IV q4w maintenance · Induction q3w x 4 + ipi · IV ✓ NSZU covered
- Ipilimumab (DRUG-IPILIMUMAB) 1 mg/kg IV · Days 1 of cycles 1-4 only · IV ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-RCC-METASTATIC-1L-LENV-PEMBRO
- Regimen
- Lenvatinib + pembrolizumab (RCC, 1L)
- Drugs + NSZU
- Lenvatinib (DRUG-LENVATINIB) 20 mg PO daily · Continuous daily dosing · PO ⚠ NSZU — not for this indication
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w (or 400 mg q6w) · Until progression or 2 years maximum · IV ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-RCC-METASTATIC-1L-NIVO-CABO
- Regimen
- Nivolumab + cabozantinib (RCC, 1L)
- Drugs + NSZU
- Nivolumab (DRUG-NIVOLUMAB) 240 mg IV q2w (or 480 mg IV q4w) · Until progression or max 2 years · IV ✓ NSZU covered
- Cabozantinib (DRUG-CABOZANTINIB) 40 mg PO daily · Continuous daily dosing (note: 40 mg in combination — lower than 60 mg monotherapy) · PO ✗ Not registered in UA
- 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-CECT-CAP | CECT chest/abdomen/pelvis | Critical | imaging | — | all tracks |
| TEST-BRAIN-MRI-CONTRAST | Brain MRI with contrast | Standard | — | — | aggressive |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- 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).
Pan-disease eligibility gate. ECOG 0-1 is the canonical entry criterion for intensified regimens across DLBCL (CHOEP-21 in age ≤60 with elevated LDH per German High-Grade NHL Study Group), Hodgkin (BEACOPP-escalated), Burkitt…
RF-FITNESS-ECOG-FITSRC-NCCN-BCELL-2025SRC-ESMO-DLBCL-2024 - Solitary kidney OR baseline CrCl <50 mL/min — limits cisplatin alternatives + impacts surveillance imaging.
Many RCC patients are post-nephrectomy by metastatic stage.
RF-RCC-ORGAN-DYSFUNCTIONSRC-NCCN-KIDNEY-2025SRC-ESMO-RCC-2024 - CNS metastases — ICI doublet retains intracranial activity; cabozantinib + nivolumab also CNS-active.
RCC brain-met rate ~10%.
RF-RCC-TRANSFORMATION-PROGRESSIONSRC-NCCN-KIDNEY-2025SRC-ESMO-RCC-2024
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-RCC-METASTATIC-1L-LENV-PEMBRO)
- Do NOT use in ECOG ≥ 2 — lenvatinib toxicity (hypertension, proteinuria, stomatitis) is poorly tolerated
- Do NOT use with uncontrolled hypertension — manage BP to <140/90 before starting
- Do NOT add sunitinib or other TKI — triplet not studied and expected additive toxicity
- Do NOT extend pembrolizumab beyond 2 years (35 cycles)
- Do NOT apply CLEAR dose (lenvatinib 20mg) without monitoring — dose reductions are common and expected
Standard plan (IND-RCC-METASTATIC-1L-NIVO-CABO)
- Do NOT use cabozantinib 60mg in combination — use 40mg per CheckMate-9ER protocol
- Do NOT use in active autoimmune disease
- Do NOT extend nivolumab beyond 2 years (NCCN guidance)
- Do NOT add anti-VEGF agents (bevacizumab/sunitinib) — triplet not studied
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Pembrolizumab + axitinib (RCC, 1L all-risk)
21-day cycles × Pembro up to 2 years; axitinib until progression
Aggressive plan
Induction · Nivolumab + ipilimumab (RCC, 1L IMDC intermediate/poor)
21-day cycles × 4 induction; nivo maintenance until progression
Aggressive plan
Induction · Lenvatinib + pembrolizumab (RCC, 1L)
21-day cycles × Until progression or max 35 cycles (~2 years) for pembrolizumab; lenvatinib continues until progression
Standard plan
Induction · Nivolumab + cabozantinib (RCC, 1L)
28-day cycles × Until progression or max ~24 cycles nivolumab; cabozantinib continues until progression
MDT brief
Discussion questions (1, 0 blocking)
MDT talk tree (2 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
Skills (recommended) — for consideration (1)
Data quality
Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.
- Biomarker coverage: 0/0 known (100%), 0 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-BAP1-CONFIRMED-CARRIER, RF-BAP1-FAMILY-HISTORY-SUSPICION, RF-BHD-FLCN-CONFIRMED-CARRIER, RF-CASCADE-VHL-FDR-POSITIVE, RF-COWDEN-CONFIRMED-CARRIER, RF-COWDEN-FAMILY-HISTORY-SUSPICION, RF-HLRCC-CONFIRMED-CARRIER, RF-HLRCC-FAMILY-HISTORY-SUSPICION, RF-HPRC-CONFIRMED-CARRIER, RF-HPRC-FAMILY-HISTORY-SUSPICION, RF-LIFESTYLE-OBESITY-CANCER-PREVENTION, RF-RCC-FRAILTY-AGE, RF-RCC-HIGH-RISK-BIOLOGY, RF-RCC-IMDC-INTERMEDIATE-POOR-RISK, RF-RCC-INFECTION-SCREENING, RF-RCC-ORGAN-DYSFUNCTION, RF-RCC-TRANSFORMATION-PROGRESSION, RF-SDH-CONFIRMED-CARRIER, RF-SDH-FAMILY-HISTORY-SUSPICION, RF-TSC-CONFIRMED-CARRIER, RF-VHL-FAMILY-HISTORY-SUSPICION
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-CHECKMATE-9ER-CHOUEIRI-2021: Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma (2021)
- SRC-CLEAR-MOTZER-2021: Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma (2021)
- SRC-ESMO-RCC-2024: ESMO Renal Cell Carcinoma (2024)
- SRC-NCCN-KIDNEY-2025: NCCN Kidney Cancer (2025.v3)
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 Pembrolizumab + axitinib (RCC, 1L all-risk) (REG-PEMBRO-AXI-RCC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Nivolumab + ipilimumab (RCC, 1L IMDC intermediate/poor) (REG-NIVO-IPI-RCC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Lenvatinib + pembrolizumab (RCC, 1L) (REG-LENV-PEMBRO-RCC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Nivolumab + cabozantinib (RCC, 1L) (REG-NIVO-CABO-RCC) 1/2 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-03.