Early outcomes for a single-arm, single-stage phase I/II trial of Selective Avoidance of nodal VolumEs at minimal Risk (SAVER) in the contralateral neck of patients with p16-positive oropharynx cancer

Most patients with p16-positive oropharynx cancer (p16+OPC) receive elective nodal radiation therapy 

that improves regional control but increases acute and long-term toxicity. We evaluated the efficacy and 

toxicity profile of a reduced contralateral elective nodal volume in patients with p16+OPC receiving 

definitive or adjuvant radiation therapy.

Patients with newly diagnosed p16+OPC without contralateral nodal involvement treated with primary 

proton or photon-based (chemo)radiation therapy or adjuvant (chemo)radiation therapy following transoral 

robotic surgery (TORS) were eligible for enrollment. The reduced contralateral nodal volume included high-

risk regions of  levels II and III¹. The primary endpoint was elective out-of-field contralateral nodal failure. 

Dosimetric studies comparing standard versus reduced elective nodal volumes were analyzed with the t-

test. Acute toxicity was collected using CTCAE v4.0.

Fifty-two patients were enrolled of which 36 (69.2%) received definitive (chemo)radiation therapy. Sixteen 

(30.8%) patients underwent adjuvant radiation therapy following TORS of which 5 (31.2%) received 

concurrent chemotherapy. Proton therapy was used in 38 (73.1%) of patients. There were no elective 

nodal failures at a median follow up of 15 months (range 1-24 months). For the first 20 patients enrolled, 

dosimetric comparison of the reduced contralateral elective nodal volume to a consensus elective nodal 

volume demonstrated a decrease in mean dose (14.1 Gy to 18.5 Gy [p<0.05]) and V30 Gy (11.6% to 

21.3% [p<0.01]) of the contralateral parotid gland. Significant differences were independent of radiation 

modality or technology. Acute grade 3 toxicity was observed in 13 (25%) patients including 6 (11.5%) who 

received a gastrostomy tube during treatment. There were no grade 4-5 acute toxicities, and no patients 

with 6 months of follow up retained gastrostomy tube.

Precise delivery of radiation therapy to high-risk areas for contralateral nodal disease results

in excellent regional control regardless of treatment approach. Dose to contralateral organs at risk and 

toxicity profile were favorable. Longer follow-up is needed to further support this de-intensification strategy.