157 - A Multi-Site 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
Presenter(s)
J. K. Molitoris1, M. E. Witek1, M. J. Ferris1, K. Kitzmiller1, R. F. Krc2, J. Jatczak3, K. Schotz4, K. Weir4, K. Lehman2, T. N. Tyer2, K. Steacy2, J. Wolf5, K. Moyer5, K. J. Cullen6, R. Taylor5, S. M. Bentzen7, W. F. Regine Jr1, R. Mehra6, and K. Hatten5; 1Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 2Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, 3Maryland Proton Treatment Center, Baltimore, MD, 4University of Maryland Medical Center, Baltimore, MD, 5Department of Otorhinolaryngology – Head & Neck Surgery, University of Maryland School of Medicine, Baltimore, MD, 6Division of Hematology/Oncology, University of Maryland School of Medicine, Baltimore, MD, 7Department of Epidemiology and Public Health, Biostatistics and Bioinformatics Division, University of Maryland School of Medicine, Baltimore, MD
Purpose/Objective(s): Contralateral elective nodal radiation therapy (RT) improves regional control in p16+ oropharyngeal SCC (p16+OPC) but increases acute and long-term toxicity. In this single arm multi-site phase I/II study we hypothesize that an empirically designed volume reduction in the contralateral neck is effective in p16+OPC receiving definitive or adjuvant RT.
Materials/Methods: Patients with newly diagnosed p16+OPC without contralateral nodal involvement but with clinical or pathological features to recommend contralateral elective nodal treatment were eligible for enrollment. Treatment included primary proton or photon-based (chemo)radiation or adjuvant (chemo)radiation following Transoral Robotic Surgery (TORS) approaches. The reduced contralateral nodal volume included regions of level II and III based on previously defined high-risk locations for contralateral nodal disease. The primary endpoint was elective out-of-field contralateral nodal failure at two years with a 1-sided 95% confidence interval (CI) maximum of less than 10%. Dosimetric comparisons between standard versus reduced elective nodal volumes were analyzed. Acute toxicity was collected using CTCAE v4.0.
Results: Fifty-two patients were enrolled of which 36 (69.2%) received definitive (chemo)radiation. Sixteen (30.8%) patients underwent adjuvant radiation following TORS of which 5 (31.2%) received concurrent platinum-based chemotherapy for high-risk features. Proton therapy was used in 38 (73.1%) patients. With a median follow up of 24 months (range 1-25mths) there were no contralateral nodal failures with an upper limit 95% CI for contralateral nodal failure of 6.1%. There was one local failure in the 70Gy field, four distant failures, and 3/4 (75%) observed deaths were unattributed to diagnosis or treatment. Two-year OS and PFS were 89.6% (95% CI 85.2 - 94.0%) and 86.1% (95% CI 81.2 – 91.0%), respectively. For the first 20 patients enrolled, dosimetric comparison of the reduced contralateral elective nodal volumes to consensus elective nodal volumes demonstrated a decrease in the mean dose (18.5 Gy to 14.1 Gy [p<0.05]) and V30 Gy (21.3% to 11.6% [p<0.01]) 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 6 (11.5%) who received a PEG tube during treatment. There were no grade 4-5 acute toxicities, and at 6 months follow up no patients had retained a PEG tube.
Conclusion: Selective avoidance of nodal volumes at minimal risk in the N0 contralateral neck of patients with p16+OPC can be safely performed while maintaining excellent regional control in the definitive and adjuvant settings and meets the primary endpoint. Both dose to contralateral organs at risk and toxicities were favorable. This study validates a rationally developed volume reduction strategy and is now standard of care within our academic medical system.