By Ali Hosni, MBBCh, MSc, PhD, Princess Margaret Cancer Centre
Jason Molitoris, MD, PhD, and team from University of Maryland, reported early outcomes of a single-arm phase I/II trial of Selective Avoidance of nodal VolumEs at minimal Risk (SAVER) in the contralateral N0 neck of patients with p16-positive oropharynx cancer. Oropharyngeal carcinoma (OPC) is rapidly increasing in incidence, due to an association with the human papillomavirus (HPV) infection. The standard of care for the majority of OPC is radiation therapy (RT) to the primary tumor and neck lymph nodes with or without concurrent chemotherapy. Due to concern of microscopic contralateral neck nodal involvement, most OPC patients are treated with bilateral neck RT, while unilateral neck RT is only offered to highly selected OPC patients with low risk of contralateral neck failure. However, bilateral neck RT results in higher rates of severe RT-associated acute and late toxicities.
In this trial, p16+ve OPC patients without contralateral nodal involvement were treated with primary proton or photon-based (chemo)radiation or adjuvant (chemo)radiation following Transoral Robotic Surgery (TORS). The reduced contralateral nodal volume included regions of level II and III based on high- risk locations for contralateral nodal disease. The primary endpoint was elective out-of-treated volume contralateral nodal failure. Dosimetric comparisons between standard versus reduced elective nodal volumes were analyzed. Acute toxicity was collected using CTCAE v4.0.
A total of 52 patients were enrolled to the trial, of which 46% had primary tonsil cancer, 80.8% had T1-2-category, 13.5% N0, 80.8% N1, 5.8%N3; 69.2% received definitive (chemo) radiation and 30.8% underwent adjuvant (chemo) radiation following TORS. Proton therapy was used in 73.1% of enrolled patients.
The study showed there were no contralateral nodal failures at a median follow up of 19 months (range 6-33 months). For the first 20 patients enrolled, dosimetric comparison of the reduced contralateral elective nodal volumes to standard elective nodal volumes demonstrated a decrease in the mean dose (18.5 Gy to 14.1Gy [p<0.001]) and V30Gy (21.3% to 11.6% [p<0.001]) of the contralateral parotid dose. Significant differences were independent of radiation modality or technology. Acute grade 3 toxicity was observed in 13 (25%) patients including six (13.5%) who received a PEG tube during treatment. There were no grade 4-5 acute toxicities, and at six months follow up no patients had retained a PEG tube.
Overall, this phase I/II trial shows that selective avoidance of nodal volumes at minimal risk in the N0 contralateral neck of patients with p16-positive OPC can be safely performed while maintaining excellent regional control. Dose to contralateral parotid and toxicities was favorable. Maturation of follow-up is required to further support this de-intensification strategy.
Identifying OPC patients who might be at low risk of contralateral neck failure remains an active research area. Phase I/II trials evaluated the feasibility and clinical benefit of several strategies of RT volume de-escalation based on:
An ongoing CCTG-led phase III randomized controlled trial (HN.11, SELECT: NCT05451004) is also evaluating omitting elective nodal irradiation of the uninvolved contralateral neck based on lymphatic drainage after SPECT-CT.
Abstract 17 - Early outcomes for a single-arm phase I/II trial of Selective Avoidance of nodal VolumEs at minimal Risk (SAVER) in the contralateral N0 neck of patients with p16-positive oropharynx cancer was presented during the Plenary II session at the 2024 Multidisciplinary Head and Neck Cancers Symposium on March 1, 2024.
