Table 10.

Summary of Deintensification Trials

De-Escalation Strategy	Relevant Trials	Results
Definitive CRT (SOC=HD cisplatin)
Attenuation with cetuximab	RTOG 1016 15	Cetuximab is inferior to HD cisplatin
	De-ESCALaTE 16	Cetuximab is inferior to HD cisplatin
	TROG 12.01 29	Cetuximab is inferior to LD cisplatin
Omission of cisplatin	HN002 17	Cisplatin cannot be omitted from Definitive RT
Attenuation with LD cisplatin	HN009 (not exclusive to HPV+ OPC)	Trial ongoing
Surgery (SOC=Open/Transmandibular/Transcervical Resection + ND)
TORS + ND ± adj RT VS. Def RT ± chemo	ORATOR 54–56	TORS does not have less toxicity than def RT
	ORATOR2 57	TORS has inferior PFS and more grade 5 toxicity than def RT
Adjuvant Radiation Therapy (SOC= 60Gy PORT)
TORS + ND + De-escalated Adj Therapy	ECOG 3311 45	50Gy PORT appears feasible with postoperative IR factors
	MC1273 58–59 , MC1675 61–62	30Gy BID PORT + chemo is comparable to SOC with postoperative IR factors
	PATHOS	RCT ongoing (50Gy PORT vs. SOC for IR factors; SOC ± chemo for HR factors)
Definitive Radiation Therapy (SOC=70Gy)
De-escalate Def RT Dose	ECOG E1308 86 , OPTIMA 78–79 , Univ of CA 87 , Quarterback 88–89	NAC with deintensification to 45–60Gy in responders with bulky HPV+ OPC is feasible
	HN002 17 , UNC/UF 82–83	Upfront de-escalation to 60Gy CRT appears feasible in non-bulky HPV+ OPC
	30ROC 137	Selective de-escalation to 30Gy CRT appears feasible in hypoxia-negative patients
	HN005	RCT ongoing (SOC 70Gy CRT vs. upfront de-escalation to 60Gy CRT)

adj=adjuvant, chemo=chemotherapy, CRT=chemoradiation therapy, def=definitive, HD=high-dose, HPV=human papillomavirus, HR=high-risk, IR=intermediate-risk, LD=low-dose, NAC=neoadjuvant chemotherapy, ND=neck dissection, OBS=observation, OPC=oropharyngeal cancer, +=positive, PFS=progression-free survival, PORT=postoperative radiation therapy, RCT=randomized control trial, RT=radiation therapy, SOC=standard of care, TORS=transoral robotic surgery