TABLE 4.
Surgical approaches: de-escalation of adjuvant radiotherapy or chemoradiotherapy.
| Study name, ID | AJCC, HPV, smoking | Design and primary endpoint | Adverse events | Survival data |
|---|---|---|---|---|
| MC1273 Ma et al. (2019) NCT01932697 N = 80 | 7th AJCC: III-IV with high risk features: ECE or LVI, PNI ≥2 LN, any LN > 3 cm or ≥ T3) 8th AJCC: I-II-III HPV testing: p16-IHC Smoking: <10 py | Design: surgery (R0) + neck dissection. Cohort A: ECE-: 30 Gy/1.5 Gy twice daily + 15 mg/m2 docetaxel. Cohort B: ECE+: 36 Gy/1.8 Gy twice daily + docetaxel. Primary endpoint: 2-year LRC rate of 20% or less (with 2-sided 85% CI) and <20% rate of acute grade 3 or worse toxicity, α = 0.06 | 2-year grade III toxicity (CTCAE): 0% | 2 years LC: cohort A; 100%, cohort B: 93% 2 years DM: cohort A: 97.2%, cohort B 79% 2 years PFS: 91.1% 2 years OS: 98.7% |
| NCT02760667 Sadeghi et al. (2019) n = 54 | 7th AJCC: T1T2-N1N2cT3-N0N2c T4-N0N2c 8th AJCC: I-II-III HPV testing: p16-IHC Smoking: Unknown | Design: 3 cycles of ICT (cisplatin + docetaxel) and then TORS + ND. Primary endpoint: pathologic response | — | Complete pathologic response: primary tumor: 72%; nodal site: 57%; both: 44% |
| ECOG3311 NCT01898494 N = 511 Ferris et al. (2020) | 7th AJCC: T1T2-N1N2b 8th AJCC: I-II HPV testing: p16-IHC Smoking: Unknown | Design: low risk: Arm A: TORS only; intermediate risk (R0, N2, ECE<1 mm): Arm B: TORS +50 Gy IMRT Arm C: TORS + 60 Gy IMRT; high risk (R1, ECE+) into Arm D: TORS + 66 Gy IMRT + cisplatin (40 mg/m2). Primary endpoint: 2-year PFS, grade 3–4 bleeding events during surgery, and positive margins | — | 2-year PFS: Arm A: 96.9%; Arm B: 94.9%; Arm C: 96.0%; Arm D: 90.7% |
| DART-HPV NCT02908477 N = 194 | 7th AJCC: ≥T3, ≥N2, LVI, PNI and R0 HPV testing: p16-IHC 8th AJCC: II-III Smoking: <10py | Design: TORS and then intermediate risk: ECE-Twice daily RT30 Gy/1.5 Gy + Docetaxel; high risk: ECE + Twice daily RT36 Gy/1.8 Gy + Docetaxel. Standard arm: RT 60 + cisplatin weekly (40 mg/m2) | 2-year grade III AES (CTCAE): 1.6% for the experimental arm and 7.1% for the standard p = 0.058 | 2 years PFS 86.9 vs. 95.8% for experimental vs. standard pN2 and ECE: 2 years PFS 42.9% for experimental arm vs. standard |