| Setting | Treatment |
|---|---|
| EARLY, RESECTABLE T1–2 N0 | SINGLE MODALITY — surgery OR definitive RT
chosen by functional outcome, not efficacy · glottic T1 → RT or transoral laser surgery · oropharynx T1–2 → RT or transoral robotic surgery (TORS) ⚠ Avoid dual modality — doubles toxicity for no gain |
| LOCALLY ADVANCED, RESECTABLE T3–4a and/or N+ | Oral cavity → SURGERY + neck dissection first
adjuvant RT ± cisplatin by pathology · ⚠ oral cavity does poorly with primary chemoradiation — resect if possible Larynx / hypopharynx, organ preservation wanted → concurrent cisplatin-chemoRT (RTOG 91-11)
superior locoregional control + larynx preservation vs induction or RT alone ⚠ T4a with cartilage destruction → total laryngectomy, not preservation |
| LOCALLY ADVANCED, RESECTABLE — perioperative IO PD-L1 CPS ≥1 | Perioperative pembrolizumab — neoadjuvant → surgery → post-op RT ± cisplatin → adjuvant pembrolizumab (KEYNOTE-689)
median EFS 51.8 vs 30.4 mo, HR 0.73 · FDA-approved Jun 2025 — the first major advance in this setting in 20 years |
| LOCALLY ADVANCED, UNRESECTABLE T4b | Definitive concurrent cisplatin-chemoRT Cisplatin-ineligible → carboplatin/5-FU, weekly carboplatin-paclitaxel, or cetuximab-RT ⚠⚠ Cetuximab-RT is for the platinum-ineligible, p16-NEGATIVE patient ONLY
never substitute for cisplatin in a fit patient, and never as HPV de-escalation |
| 🔴 p16-POSITIVE OROPHARYNX de-escalation is NOT standard | Stage on the p16+ system Standard remains cisplatin-based chemoRT, or TORS + adjuvant ⚠⚠ Do NOT substitute cetuximab
(RTOG-1016) (5-yr OS 77.9% vs 84.6%) and (De-ESCALaTE) (2-yr OS 89.4% vs 97.5%) both showed cetuximab inferior, with no toxicity reduction · off-trial de-escalation is not standard |
| 🔴 POST-OP, HIGH RISK extranodal extension and/or positive margins | Post-op RT + concurrent cisplatin (EORTC 22931) (RTOG 9501)
extranodal extension and positive margins are THE trigger for adding chemo to post-op RT ⚠ Treat as indications, not a clean biological switch
updated pooled analysis: the OS benefit is confirmed, but ENE / margin status are NOT clean predictive biomarkers — patients without them may still benefit, and the cancer-specific mortality gain is partly offset by increased other-cause mortality |
| POST-OP, INTERMEDIATE RISK ≥2 nodes, pT3–4, close margins, PNI, LVI, level IV/V nodes | Post-op RT alone |
| 🔴 NASOPHARYNGEAL CARCINOMA a distinct, never-surgical entity | Early (T1N0) → RT alone II–IVA → concurrent cisplatin-chemoRT Locoregionally advanced III–IVA → induction gemcitabine + cisplatin ×3 → chemoRT
NCCN category 1 Adjuvant capecitabine ×1 yr in high-risk disease Recurrent / metastatic 1st line → PD-1 inhibitor + gem/cisplatin (JUPITER-02)
toripalimab — mOS 64.8 vs 33.7 mo · monitor plasma EBV DNA |
| SALIVARY / ADENOID CYSTIC CARCINOMA | Complete surgical resection is the backbone Post-op RT when margins can't be secured ⚠ Perineural invasion is ACC's signature — name the nerve, cover it to the skull base
a "clear margin" often isn't · metastasises late; 10-yr survival <50% across grades |
| RECURRENT / METASTATIC, 1st line PD-L1 CPS drives the choice — always state the number | CPS ≥1 → pembrolizumab monotherapy
CPS ≥20 gives the largest benefit — mOS 14.9 vs 10.7 mo CPS <1, or rapid response needed → pembrolizumab + platinum + 5-FU (KEYNOTE-048) EXTREME (platinum + 5-FU + cetuximab)
reserved for IO-ineligible patients |
| RADIOTHERAPY — dose & schedule modality detail — RT is primary curative therapy here, not an adjunct | Definitive → 70 Gy/35 fx + concurrent cisplatin
IMRT-SIB 66 Gy @ 2.2 Gy/fx boost · cisplatin 100 mg/m² q3wk ×3, or weekly 40 mg/m² ((ConCERT): weekly non-inferior for 2-yr locoregional control, better tolerated) Post-op → 44–54 Gy elective / 60–66 Gy high-risk bed ⚠ Total package time (surgery → RT completion) is prognostic
start promptly — don't let dental work delay it |