OpenOnco · Treatment Plan

Treatment plan — Head and neck squamous cell carcinoma

PLAN-VAR-HNSCC-HIGHRISK-V1 · v1 · 2026-05-12

Patient

VAR-HNSCC-HIGHRISK · 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

MDT talk tree (2 steps)

#	Owner	Topic	Action
1	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
2	radiologist	Specialist review	Imaging findings present — radiologist needed for staging/restaging.

Skills (recommended) — for consideration (2)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
Radiologist recommended
Imaging findings present — radiologist needed for staging/restaging.

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

Technical MDT skill metadata (2/16 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: 2026-05-12.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT05544136	A Study of Decreasing Radiation Therapy and Chemotherapy in People With Head and Neck Cancer	PHASE2	RECRUITING	Memorial Sloan Kettering Cancer Center	—	Small N (<50) Single country
NCT05286619	A Study of Pembrolizumab (MK-3475) Plus Platinum and Gemcitabine as First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (PIPER)	PHASE2	RECRUITING	University of Malaya	—	Surrogate endpoint only Single country
NCT07554521	A Study to Evaluate Efficacy and Safety of Tislelizumab Plus Chemotherapy for Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma in Racial and Ethnic Minority Patients in the United States	PHASE2	RECRUITING	BeOne Medicines	—	Small N (<50) Single country
NCT07524452	Becotatug Vedotin (MRG003) in Combination With PD-1 Inhibitor Versus PD-1 Inhibitor for the Treatment of EGFR-positive, CPS≥1 Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma	PHASE3	RECRUITING	Ming-Yuan Chen	—	Single country
NCT04068155	Alpha Radiation Emitters Device for the Treatment of of Malignant Cutaneous Tumors	NA	RECRUITING	Alpha Tau Medical LTD.	—	Surrogate endpoint only Single country
NCT05872880	TPExtreme Induced Chemotherapy Followed by Surgery and Radiotherapy in the Oral Carcinoma.	N/A	RECRUITING	Xiangya Hospital of Central South University	—	Surrogate endpoint only Single country
NCT06747585	A Study to Investigate ALE.P02 as Monotherapy in Adult Patients With Selected CLDN1+ Solid Tumors	PHASE1 / PHASE2	RECRUITING	Alentis Therapeutics AG	—	Surrogate endpoint only
NCT05343325	The Efficacy and Safety of Neoadjuvant Low-dose Radiotherapy Combined With Chemoimmunotherapy in Locally Advanced HNSCC	PHASE2	RECRUITING	Fifth Affiliated Hospital, Sun Yat-Sen University	—	Small N (<50) Single country
NCT06725368	Carboplatin + Paclitaxel + Cetuximab (PCC) After Failure of Pembrolizumab +/- First-line Chemotherapy in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck	PHASE2	RECRUITING	Centre Paul Strauss	—	Small N (<50) Surrogate endpoint only Single country
NCT07224750	A Noninvasive and Screening miRNA Signature for Gastrointestinal Cancer	N/A	RECRUITING	City of Hope Medical Center	—	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 · NCT05544136 A Study of Decreasing Radiation Therapy and Chemotherapy in People With Head and Neck Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05286619 A Study of Pembrolizumab (MK-3475) Plus Platinum and Gemcitabine as First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (PIPER) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07554521 A Study to Evaluate Efficacy and Safety of Tislelizumab Plus Chemotherapy for Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma in Racial and Ethnic Minority Patients in the United States No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07524452 Becotatug Vedotin (MRG003) in Combination With PD-1 Inhibitor Versus PD-1 Inhibitor for the Treatment of EGFR-positive, CPS≥1 Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04068155 Alpha Radiation Emitters Device for the Treatment of of Malignant Cutaneous Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05872880 TPExtreme Induced Chemotherapy Followed by Surgery and Radiotherapy in the Oral Carcinoma. No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06747585 A Study to Investigate ALE.P02 as Monotherapy in Adult Patients With Selected CLDN1+ Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05343325 The Efficacy and Safety of Neoadjuvant Low-dose Radiotherapy Combined With Chemoimmunotherapy in Locally Advanced HNSCC No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06725368 Carboplatin + Paclitaxel + Cetuximab (PCC) After Failure of Pembrolizumab +/- First-line Chemotherapy in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07224750 A Noninvasive and Screening miRNA Signature for Gastrointestinal Cancer 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: 2026-05-12.

plan_id: PLAN-VAR-HNSCC-HIGHRISK-V1 | version: 1 | generated: 2026-05-12T18:41:26.468734+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.