OpenOnco · Treatment Plan

Treatment plan — Head and neck squamous cell carcinoma

PLAN-AUTO-HNSCC-001-V1 · v1 · 2026-06-11

Patient

AUTO-HNSCC-001 · Algorithm: ALGO-HNSCC-RM-1L

DiagnosisHead and neck squamous cell carcinoma

MOH / ICD-10C00-C14, C30-C32

ICD-O-38070/3; C00, C01, C02, C03, C04, C05, C06, C07, C08, C09, C10, C11, C12, C13, C14, C30, C31, C32

Etiological driver

Etiological driver · etiologically_driven archetype

Head and neck squamous cell carcinoma

Tobacco (smoked + smokeless) — dominant in HPV-negative disease
Alcohol (synergistic with tobacco)
HPV (high-risk, mostly type 16) — defines HPV+ oropharyngeal SCC, distinct biology and better prognosis
EBV — defines nasopharyngeal carcinoma (separate entity in many guidelines but tracked under HNSCC umbrella)
Betel nut chewing (South / Southeast Asia)
Fanconi anemia, dyskeratosis congenita (germline susceptibility)

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
BIO-PDL1-CPS	(gene-level)	IA	SRC-NCCN-HNSCC-2025 SRC-ESMO-HNSCC-2020 Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.	PD-L1 CPS is the primary predictive biomarker for pembrolizumab in recurrent/metastatic HNSCC (KEYNOTE-048). Two threshold-stratified eligibility bands: CPS ≥1 — pembrolizumab + platinum + 5-FU 1L (superior to EXTREME regimen in CPS≥1 population); CPS ≥20 — pembrolizumab monotherapy 1L (preferred over chemo in high-expressors; mOS 14.9 mo). Both are FDA-approved and NCCN/ESMO Category 1 recommendations. Testing by IHC 22C3. Threshold selection is performed by the algorithm layer (ALGO-HNSCC-RM-1L); this BMA entry surfaces ESCAT tier context for tumor-board discussion only.	pembrolizumab monotherapy (CPS≥20 1L per SRC-NCCN-HNSCC-2025, SRC-ESMO-HNSCC-2020) pembrolizumab + platinum + 5-FU (CPS≥1 1L per SRC-NCCN-HNSCC-2025)	SRC-NCCN-HNSCC-2025 SRC-ESMO-HNSCC-2020

Primary current-line option

Standard plan

★ DEFAULT

Indication

IND-HNSCC-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 covered
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 covered
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

Primary current-line option selected by ALGO-HNSCC-RM-1L at step 2.

Other current-line alternatives (2 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Aggressive plan

Indication

IND-HNSCC-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

Standard plan

Indication

IND-HNSCC-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 covered
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 covered
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 covered

Reason

Current-line alternative presented for HCP consideration

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. RF-HNSCC-INFECTION-SCREENING
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). RF-HNSCC-ORGAN-DYSFUNCTION

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-HNSCC-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-HNSCC-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-HNSCC-RM-1L-EXTREME)

Do not prescribe EXTREME without HPV testing — HPV+ status does not change EXTREME selection in the recurrent setting, but is important for prognosis + clinician feedback.
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 especially in SE US (alpha-gal IgE).
Do not skip prophylactic doxycycline + emollient + sunscreen for acneiform rash — substantially reduces severity + improves adherence.
Do not start 5-FU without discussion of DPD testing — DPD-deficient patients can have fatal toxicity.
Do not skip monitoring of magnesium / electrolytes — cetuximab + cisplatin substantially lower Mg; replacement is mandatory.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

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 (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

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)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

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: 1/1 known (100%), 0 missing, 0 default-track gaps
Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-HNSCC-FRAILTY-AGE, RF-HNSCC-HIGH-RISK-BIOLOGY, RF-HNSCC-INFECTION-SCREENING, RF-HNSCC-ORGAN-DYSFUNCTION, RF-HNSCC-TRANSFORMATION-PROGRESSION, RF-OCC-FORMALDEHYDE-PREVENTION, RF-OCC-WOOD-LEATHER-DUST-PREVENTION

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	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-ESMO-HNSCC-2020: Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2020)
SRC-EXTREME-VERMORKEN-2008: Platinum-based chemotherapy plus cetuximab in head and neck cancer (2008)
SRC-NCCN-HNSCC-2025: NCCN Clinical Practice Guidelines — Head and Neck Cancers (2025.v3)
SRC-ONCOKB: OncoKB — Precision Oncology Knowledge Base (continuous (last verified 2026-04-25))

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: 2026-06-11.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT07044635	Shortened Course of Radiation Therapy After Trans-oral Robotic Surgery in Patients With HPV-Mediated Oropharyngeal Squamous Cell Carcinoma.	PHASE2	RECRUITING	University of Utah	—	Small N (<50) Single country
NCT07359417	MR-Guided Radiotherapy Dose Escalation Trial for Esophageal Squamous Cell Carcinoma	PHASE1	RECRUITING	UMC Utrecht	—	Phase 1 only Small N (<50) Single country
NCT05799274	Safety of RAD301 in Healthy Human Volunteers and Patients With Pancreatic Cancer or Other Solid Tumors	PHASE1	RECRUITING	Radiopharm Theranostics, Ltd	—	Phase 1 only Small N (<50) Single country
NCT06975410	Clinical Trial of YH32364 in Patients With Locally Advanced or Metastatic EGFR Overexpressing Solid Tumors	PHASE1 / PHASE2	RECRUITING	Yuhan Corporation	—	Surrogate endpoint only Single country
NCT05267626	Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer	PHASE1 / PHASE2	RECRUITING	Aulos Bioscience, Inc.	—	—
NCT06272214	Adjuvant Radiotherapy for Esophageal Squamous Cell Carcinoma in the Era of Immunotherapy	PHASE2	RECRUITING	Zhejiang Cancer Hospital	—	Surrogate endpoint only Single country
NCT07290010	The Efficacy and Safety of Iparomlimab and Tuvonralimab Injection Combined With Chemotherapy as the First-line Treatment for Esophageal Squamous Cell Carcinoma	PHASE2	RECRUITING	Hebei Medical University Fourth Hospital	—	Small N (<50) Surrogate endpoint only Single country
NCT06657222	First in Human Study of TUB-030 in Patients With Advanced Solid Tumors	PHASE1 / PHASE2	RECRUITING	Tubulis GmbH	—	—
NCT06345287	Response Adaptive Radiotherapy Following Immunotherapy-based Induction for Non-HPV Related HNSCC	PHASE2	RECRUITING	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	—	Surrogate endpoint only Single country
NCT07546383	A Study Investigating the Efficacy and Safety of the Combination of Iparomlimab and Tuvonralimab With or Without Chemotherapy in Second-line and Subsequent Treatments for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma	NA	RECRUITING	The Second Affiliated Hospital of Hainan Medical University	—	Small N (<50) Surrogate endpoint only Single country

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).

Option	UA registration	NSZU	Cost orientation	Access pathway
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
Trial · NCT07044635 Shortened Course of Radiation Therapy After Trans-oral Robotic Surgery in Patients With HPV-Mediated Oropharyngeal Squamous Cell Carcinoma. No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07359417 MR-Guided Radiotherapy Dose Escalation Trial for Esophageal Squamous Cell Carcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05799274 Safety of RAD301 in Healthy Human Volunteers and Patients With Pancreatic Cancer or Other Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06975410 Clinical Trial of YH32364 in Patients With Locally Advanced or Metastatic EGFR Overexpressing Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05267626 Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06272214 Adjuvant Radiotherapy for Esophageal Squamous Cell Carcinoma in the Era of Immunotherapy No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07290010 The Efficacy and Safety of Iparomlimab and Tuvonralimab Injection Combined With Chemotherapy as the First-line Treatment for Esophageal Squamous Cell Carcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06657222 First in Human Study of TUB-030 in Patients With Advanced Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06345287 Response Adaptive Radiotherapy Following Immunotherapy-based Induction for Non-HPV Related HNSCC No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07546383 A Study Investigating the Efficacy and Safety of the Combination of Iparomlimab and Tuvonralimab With or Without Chemotherapy in Second-line and Subsequent Treatments for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma 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: 2026-06-11.

plan_id: PLAN-AUTO-HNSCC-001-V1 | version: 1 | generated: 2026-06-11T11:52:06.355503+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.