Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
VERIFIED-LARYNGEAL-L1-LARYNGEAL_LA_1L_CRT · Algorithm: ALGO-LARYNGEAL-1L
Etiological driver
Etiological driver · etiologically_driven archetype
Laryngeal squamous cell carcinoma
- Tobacco smoking — dominant; >90% attributable in heavy smokers
- Alcohol consumption — synergistic with tobacco (multiplicative risk)
- Occupational asbestos / nickel / wood-dust exposure (smaller incremental risk)
- HPV — small subset of supraglottic SCC (clinically less relevant than HPV+OPSCC)
- Prior laryngeal radiation
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 |
|---|
| No clinically actionable variants matched in this profile. |
Primary current-line option
Local therapy plan
★ DEFAULT- Indication
- IND-LARYNGEAL-LA-1L-CRT
- Regimen
- Cisplatin concurrent with definitive RT (larynx-preservation CRT; RTOG 91-11)
- Drugs + NSZU
- Cisplatin (DRUG-CISPLATIN) 100 mg/m² IV day 1 (preferred when ECOG 0-1, GFR ≥60, no neuropathy / ototoxicity / heart failure) · Day 1 of each 21-day cycle x3 cycles (days 1, 22, 43), concurrent with a 7-week definitive RT course · IV ⚠ NSZU — not for this indication
- Reason
- Provisional current-line default from ALGO-LARYNGEAL-1L: step 1 did not select a treatment branch. Histologic confirmation and complete staging workup (direct laryngoscopy/panendoscopy under anesthesia, cross-sectional imaging) required before treatment-pathway selection.
Other current-line alternatives (6 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-LARYNGEAL-EARLY-GLOTTIC-1L-RT
- Regimen
- —
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-LARYNGEAL-EARLY-GLOTTIC-1L-TLM
- Regimen
- —
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-LARYNGEAL-LA-1L-TOTAL-LARYNGECTOMY
- Regimen
- —
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-LARYNGEAL-RM-1L-PEMBRO-CHEMO
- Regimen
- Pembrolizumab + 5-FU + platinum (HNSCC R/M, 1L; PD-L1 CPS ≥1)
- Drugs + NSZU
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV (or 400 mg IV q6w) · Day 1 every 3 weeks (or q6w schedule), for up to 35 cycles (~2 years) or until progression / unacceptable toxicity · IV ⚠ NSZU — not for this indication
- 5-Fluorouracil (DRUG-5-FLUOROURACIL) 1000 mg/m² IV continuous infusion days 1-4 (96-hour infusion) · Days 1-4 of 21-day cycle, for 6 cycles · IV ⚠ NSZU — not for this indication
- Cisplatin (DRUG-CISPLATIN) 100 mg/m² IV day 1 (preferred when ECOG 0-1, GFR ≥60, no neuropathy / ototoxicity / heart failure) · Day 1 of 21-day cycle, for 6 cycles · IV ⚠ NSZU — not for this indication
- Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV day 1 (substitute for cisplatin if contraindicated — GFR <60, neuropathy, hearing loss, congestive heart failure, or ECOG 2) · Day 1 of 21-day cycle, for 6 cycles (in lieu of cisplatin) · IV ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-LARYNGEAL-RM-1L-PEMBRO-MONO-CPS-HIGH
- Regimen
- Pembrolizumab monotherapy (HNSCC R/M, 1L; PD-L1 CPS ≥20)
- Drugs + NSZU
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w (or 400 mg IV q6w) · Day 1 every 3 weeks (or q6w), for up to 35 cycles (~2 years) or until progression / unacceptable toxicity · IV ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-LARYNGEAL-RM-1L-EXTREME
- Regimen
- EXTREME (cetuximab + cisplatin/carboplatin + 5-FU; HNSCC R/M, 1L)
- Drugs + NSZU
- Cetuximab (DRUG-CETUXIMAB) Loading 400 mg/m² IV day 1; then 250 mg/m² IV weekly · Loading dose week 1; weekly maintenance through chemotherapy and beyond as monotherapy until progression / toxicity · IV ⚠ NSZU — not for this indication
- Cisplatin (DRUG-CISPLATIN) 100 mg/m² IV day 1 (preferred when ECOG 0-1, GFR ≥60, no neuropathy / ototoxicity / heart failure) · Day 1 of 21-day cycle, for up to 6 cycles · IV ⚠ NSZU — not for this indication
- Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV day 1 (substitute for cisplatin if contraindicated — GFR <60, neuropathy, hearing loss, congestive heart failure, or ECOG 2) · Day 1 of 21-day cycle, for up to 6 cycles (in lieu of cisplatin) · IV ⚠ NSZU — not for this indication
- 5-Fluorouracil (DRUG-5-FLUOROURACIL) 1000 mg/m² IV continuous infusion days 1-4 (96-hour infusion) · Days 1-4 of 21-day cycle, for up to 6 cycles · IV ⚠ NSZU — not for this indication
- 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-CBC | Complete Blood Count with Differential | Critical | lab | — | local_therapy |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | local_therapy |
| TEST-PDL1-IHC | PD-L1 IHC (TPS for NSCLC) | Critical | — | CSD Lab ✓ (code TBC) | aggressive, standard |
| TEST-RENAL-FUNCTION-EGFR | Renal function with eGFR | Critical | lab | — | local_therapy |
| TEST-AUDIOMETRY | Audiometry | Standard | clinical_assessment | — | local_therapy |
| TEST-CT-NECK-THORAX-ABDOMEN-PELVIS | CT neck/thorax/abdomen/pelvis | Standard | imaging | — | local_therapy |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Active or latent infection requiring resolution / prophylaxis before initiating cisplatin-based chemoradiation, cetuximab + RT, or pembrolizumab in HNSCC: HBsAg-positive (HBV reactivation on cytotoxic chemotherapy + checkpoint inhibitors), anti-HBc-positive (occult HBV on cetuximab — anti-EGFR class), HIV-positive (ART coordination, often comorbid in HPV-related HNSCC), or active TB.
Cetuximab — anti-EGFR mAb — has documented HBV reactivation reports (less than rituximab but non-zero); FDA label notes warning. Standard HBsAg + anti-HBc + anti-HBs serology pre-treatment; entecavir / tenofovir for HBsAg+. HIV-related…
RF-HNSCC-INFECTION-SCREENINGSRC-NCCN-HNSCC-2025SRC-ESMO-HNSCC-2020 - Baseline organ dysfunction precluding standard cisplatin-based chemoradiation or pembrolizumab + 5-FU + cisplatin / cetuximab in head and neck squamous cell carcinoma: CrCl <60 mL/min (cisplatin contraindicated at full dose, switch to carboplatin or cetuximab), hearing loss / ototoxicity baseline (cisplatin contraindicated), LVEF <50% (5-FU cardiac risk), bilirubin >3× ULN (taxane / 5-FU metabolism), or severe peripheral neuropathy (cisplatin + taxane contraindicated).
Cisplatin-based CRT is the curative-intent standard (Intergroup 0099, TAX 324, EORTC 24891) but ~30% of HNSCC patients are cisplatin- ineligible at presentation due to age + organ dysfunction. CrCl <60: switch to carboplatin (RTOG 81-17…
RF-HNSCC-ORGAN-DYSFUNCTIONSRC-NCCN-HNSCC-2025SRC-ESMO-HNSCC-2020 - Feature precluding larynx-preservation chemoradiation (RTOG 91-11 concurrent cisplatin + RT) as the preferred locally advanced treatment pathway, favoring primary total laryngectomy instead: radiographic cartilage invasion / destruction, tumor extension through cartilage into extralaryngeal soft tissue, substantial (≥1 cm) invasion of the tongue base, or pretreatment laryngeal dysfunction (severe aspiration, or feeding-tube / tracheostomy dependence) indicating a non-functional larynx that organ- preservation therapy would not salvage.
STUB pending Clinical Co-Lead sign-off (CHARTER §6.1). Larynx- preservation-candidacy gate for locally advanced laryngeal SCC — routes ALGO-LARYNGEAL-1L step 5 to primary total laryngectomy instead of RTOG 91-11 concurrent chemoradiation…
RF-LARYNGEAL-POOR-PRESERVATION-CANDIDACYSRC-NCCN-HNSCC-2025SRC-RTOG-9111-FORASTIERE-2003
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Local therapy plan (IND-LARYNGEAL-LA-1L-CRT)
- Do not offer concurrent cisplatin CRT to patients with cartilage invasion, a non-functional larynx, or other RF-LARYNGEAL-POOR-PRESERVATION-CANDIDACY features — primary total laryngectomy is preferred.
- Do not initiate high-dose cisplatin without baseline audiometry and renal function assessment.
- Do not omit post-treatment surveillance laryngoscopy — salvage laryngectomy remains available for recurrence.
Local therapy plan (IND-LARYNGEAL-EARLY-GLOTTIC-1L-RT)
- Do not omit MDT discussion of the TLM alternative before defaulting to RT — the choice is preference/expertise-driven, not oncologically forced.
- Do not skip baseline voice/laryngeal function assessment before treatment.
Local therapy plan (IND-LARYNGEAL-EARLY-GLOTTIC-1L-TLM)
- Do not perform TLM without adequate transoral exposure and visualization of tumor margins — poor exposure increases positive-margin risk.
- Do not omit MDT discussion of definitive RT as an equally effective alternative.
Local therapy plan (IND-LARYNGEAL-LA-1L-TOTAL-LARYNGECTOMY)
- Do not proceed to total laryngectomy without MDT discussion of the larynx-preservation CRT alternative when the patient is a candidate.
- Do not omit voice-rehabilitation counseling and referral before surgery.
- Do not omit postoperative pathology review (margins, extranodal extension) when determining adjuvant RT dose / need for concurrent chemotherapy.
Standard plan (IND-LARYNGEAL-RM-1L-PEMBRO-CHEMO)
- Do NOT initiate immunotherapy without confirmed PD-L1 CPS testing on representative tumor tissue (biopsy preferred).
- Do NOT use cisplatin in patients with GFR <60, gr ≥2 hearing loss, gr ≥2 neuropathy, or significant CHF — switch to carboplatin AUC 5.
- Do NOT continue pembrolizumab through gr ≥3 immune-related AE without high-dose corticosteroid initiation + multidisciplinary irAE management.
Aggressive plan (IND-LARYNGEAL-RM-1L-PEMBRO-MONO-CPS-HIGH)
- Do NOT use pembrolizumab monotherapy in CPS <20 — chemo-IO or EXTREME is preferred.
- Do NOT use pembrolizumab monotherapy as 1L in rapidly progressive / visceral-crisis disease — early progression risk before IO kinetics establish.
- Do NOT continue pembrolizumab through gr ≥3 immune-related AE without high-dose corticosteroid initiation + multidisciplinary irAE management.
Standard plan (IND-LARYNGEAL-RM-1L-EXTREME)
- Do not prescribe EXTREME without HPV testing — HPV+ status does not change EXTREME selection in the recurrent setting, but is prognostically relevant.
- Do not skip baseline GFR / audiogram / neuropathy assessment before cisplatin — carboplatin is an acceptable substitute if there are any contraindications.
- Do not use cetuximab without premedication at the first infusion — anaphylaxis risk (alpha-gal IgE).
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Local therapy plan
Induction · Cisplatin concurrent with definitive RT (larynx-preservation CRT; RTOG 91-11)
21-day cycles × 3 cycles (days 1, 22, 43) concurrent with 70 Gy / 35 fx definitive RT
Standard plan
Induction · Pembrolizumab + 5-FU + platinum (HNSCC R/M, 1L; PD-L1 CPS ≥1)
21-day cycles × 6 cycles of chemotherapy backbone, then pembrolizumab maintenance up to 35 cycles total (~2 years)
Aggressive plan
Induction · Pembrolizumab monotherapy (HNSCC R/M, 1L; PD-L1 CPS ≥20)
21-day cycles × Up to 35 cycles (~2 years) or until progression
Standard plan
Induction · EXTREME (cetuximab + cisplatin/carboplatin + 5-FU; HNSCC R/M, 1L)
21-day cycles × Up to 6 cycles of chemotherapy backbone; cetuximab continued weekly as monotherapy until progression or unacceptable toxicity
MDT brief
Discussion questions (2, 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
OQ-BIOMARKER-PDL1-CPS
What is the status of PD-L1 Combined Positive Score (CPS) (BIO-PDL1-CPS)? It is required by track(s): IND-LARYNGEAL-RM-1L-PEMBRO-CHEMO, IND-LARYNGEAL-RM-1L-PEMBRO-MONO-CPS-HIGH, IND-LARYNGEAL-RM-1L-EXTREME. Expected value: CPS ≥1.
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.
→ pathologist
MDT talk tree (3 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | pathologist | Biomarker status | What is the status of PD-L1 Combined Positive Score (CPS) (BIO-PDL1-CPS)? It is required by track(s): IND-LARYNGEAL-RM-1L-PEMBRO-CHEMO, IND-LARYNGEAL-RM-1L-PEMBRO-MONO-CPS-HIGH, IND-LARYNGEAL-RM-1L-EXTREME. Expected value: CPS ≥1. |
| 3 | 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: 0/1 known (0%), 1 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-LARYNGEAL-POOR-PRESERVATION-CANDIDACY
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|
BIO-PDL1-CPS | PD-L1 Combined Positive Score (CPS) | pathologist | no | IND-LARYNGEAL-RM-1L-PEMBRO-CHEMO, IND-LARYNGEAL-RM-1L-PEMBRO-MONO-CPS-HIGH, IND-LARYNGEAL-RM-1L-EXTREME | Verify result, method, specimen, and report date before sign-off. Expected/constraint: CPS ≥1 |
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-EXTREME-VERMORKEN-2008: Platinum-based chemotherapy plus cetuximab in head and neck cancer (2008)
- SRC-KEYNOTE-048-BURTNESS-2019: Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048) (2019)
- SRC-NCCN-HNSCC-2025: NCCN Clinical Practice Guidelines — Head and Neck Cancers (2025.v3)
- SRC-RTOG-9111-FORASTIERE-2003: Concurrent Chemotherapy and Radiotherapy for Organ Preservation in Advanced Laryngeal Cancer (2003)
Experimental options (clinical trials)
Last synced: 2026-09-09 · 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 |
|---|
| Local therapy plan Cisplatin concurrent with definitive RT (larynx-preservation CRT; RTOG 91-11) (REG-CISPLATIN-CONCURRENT-RT-LARYNX) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Local therapy plan — No regimen components on this track — availability unknown | — unknown | — unknown | ₴-? — verify pathway | not recorded |
| Local therapy plan — No regimen components on this track — availability unknown | — unknown | — unknown | ₴-? — verify pathway | not recorded |
| Local therapy plan — No regimen components on this track — availability unknown | — unknown | — unknown | ₴-? — verify pathway | not recorded |
| Standard plan Pembrolizumab + 5-FU + platinum (HNSCC R/M, 1L; PD-L1 CPS ≥1) (REG-PEMBRO-CHEMO-HNSCC-1L) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Pembrolizumab monotherapy (HNSCC R/M, 1L; PD-L1 CPS ≥20) (REG-PEMBRO-MONO-HNSCC-1L) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan EXTREME (cetuximab + cisplatin/carboplatin + 5-FU; HNSCC R/M, 1L) (REG-EXTREME-HNSCC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-09-09.