TABLE 2.

Selection of de-escalation trials with reported outcomes: primary chemoradiation: de-escalation of chemoradiotherapy dose.

Study name, ID	AJCC, HPV, smoking	Design and primary endpoint	Adverse events	Survival data
NCT01530997 n = 43	7th AJCC T0T3-N0N2c 8th AJCC I, II, III HPV testing: p16 IHC or HPV ISH Smoking:<10py	Design: Stage I: RT 60 Gy. All others: 60 Gy RT + weekly cisplatin (30 mg/m2). Response monitoring: pathologic. Primary endpoint: pathologic complete response	Feeding tube: during treatment: 39%, 0% permanent; EORTC QLQ QLO–C30: pre and 2 years post global 80/82 (lower worse); CTCAE: 0% grade 3–4 adverse events at 36 months	pCR: 86% 2 years OS: 95% 2 yearS PFS: 100% 2 years: LC: 100% 2 years DM: 100%
NCT02281955 n = 114	7th AJCC: T0T3 N0N2c 8th AJCC I, II, III HPV testing: p16 IHC or HPV ISH Smoking: 80% with <10 py 20%with >10 py	Design: Stage I: RT 60 Gy. All others: 60 Gy RT + weekly cisplatin (30 mg/m2). Response monitoring: post-treatment PET and CT. Primary endpoint: 2-year PFS	Feeding tube during treatment: 34%, 0% permanent; EORTC QLQ QOL–C30: pre and 2 years post global 79/84 (lower worse); CTCAE: 0% grade 3–4 adverse events at 36 months	2 years PFS: 86% 2 years OS: 95% 2 years LR: 95% 2 years DM-free survival (DMFS): 91%
NRG HN002 NCT02254278 n = 316	7th AJCC: T1T2-N1N2b T3-N0N2b 8th AJCC I, II HPV testing: p16 IHC Smoking:<10py	Design: Arm 1: IMRT 60 Gy in 6 weeks + cisplatin (40 mg/m2). Arm B: IMRT alone 60 Gy in 5 weeks. Primary endpoint: 2-year PFS acceptability >85% with an MDADI threshold of >60% (α = 0.05)	IMRT + Cis vs. IMRT 1 year MDADI 85.3 vs. 81.76%; CTCAE: acute toxicity; Grade 4: 15.1 vs. 2.0%; Grade 3: 65.5 vs. 50.3%. Late toxicity: Grade 4: 1.3 vs. 1.4%; Grade 3: 20.0 vs. 16.7%	IMRT + Cis vs IMRT alone: 2 years PFS: 90.5 vs. 87.6% IMRT arm did not meet acceptability criterion (>85%, p = 0.228) 2 years OS: 96.7 vs. 97.3% 2 years LRF: 3.3 vs 9.5% (p = 0.02)