. 2022 Feb 1;19(5):306–327. doi: 10.1038/s41571-022-00603-7

Table 6.

Trials investigating de-escalation of adjuvant therapy in HPV⁺ OPSCC

Study	Cohort	Treatment	Outcomes	Toxicity profile	Ref.
SIRS (2021)	54 patients with stage I, II, III and intermediate stage IVa (T1 N0–2b, T2 N0–2b, AJCC 8th edn) disease, with stratification based on pathological prognosis (based on ECS, LVI, PNI)	TORS with follow-up monitoring for patients with a good prognosis (group 1); reduced-dose adjuvant RT or CRT based on risk status for patients with a poor prognosis (group 2 or 3)	mPFS 91.3%, 86.7% and 93.3% for groups 1–3, respectively, at a median follow-up duration of 43.9 months	Group 1: dysphagia in 37%, severe pain in 29.6%, anxiety in 11.1%; group 2: altered taste/dysgeusia in 100%, xerostomia in 66.6% and severe pain in 66.6%; group 3: dysphagia in 100%; pain in 100%; dysarthria in 50.0%	²⁴⁸
E3311 (2021)	495 patients with cT1–2 stage III/IV disease (AJCC 7th edn)	TORS only (group A); TORS with low-dose IMRT (group B) or TORS with standard-dose IMRT (group C) or TORS with standard-dose IMRT with concurrent cisplatin or carboplatin (group D)	2-year PFS 96.6%, 94.9%, 96.0% and 90.7% in arms A–D, respectively	17% of patients had grade 3–4 AEs following TORS; grade 3–4 AEs observed in 0%, 15%, 24% and 60% in groups A–D, respectively, common AEs included oral mucositis and dysphagia	²⁰⁰
AVOID (2020)	60 patients with pT1–pT2 N1–3 disease with favourable prognostic features underwent TORS at the primary site	Adjuvant RT omitting the tumour bed	2-year local control 98.3%; 2-year OS 100%	AEs in 30%: including radiation dermatitis (13.33%), oral mucositis (5.00%) and dysphagia (3.33%)	²⁴⁹

An overview of ongoing trials is provided in Supplementary Information. AEs, adverse events; AJCC, American Joint Committee on Cancer; CRT, chemoradiotherapy; ECS, extracapsular spread; HPV, human papillomavirus; IMRT, intensity-modulated radiotherapy; LVI, lymphovascular invasion; mPFS, median progression-free survival; OPSCC, oropharyngeal squamous cell carcinoma; OS, overall survival; PNI, perineural invasion; PFS, progression-free survival; RT, radiotherapy; TORS, transoral robotic surgery.