Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Program Number: AHNS11
Session Name: Scientific Session 3 - Immunotherapy
Session Date: Wednesday, May 14, 2025
Session Time: 3:15 PM - 4:00 PM
Five-year OS and DFS in HPV-associated HNSCC following neoadjuvant immunotherapy + GTV-only SBRT from the Providence NIRT-1 study
Robert H Hermann1; Rom Leidner1; Marka Crittendon1; Kristina Young1; Ashish A Patel2; Allen C Cheng2; George Morris3; Lessli Rushforth3; Hong Xiao3; Carlo Bifulco1; Walter J Urba1; Michael Gough1; Alexa K Dowdell1; Ryan Meng1; Brian D Piening1; R. Bryan Bell1; 1Earle A. Chiles Research Institute, Portland, OR; 2Head and Neck Surgical Associates; 3Providence Cancer InstituteBackground: Initial results of the Neoadjuvant ImmunoRadiotherapy Trial (Providence NIRT-1) of gross tumor volume only (GTV-only) SBRT+immunotherapy in locally advanced HPV+ HNSCC, were first presented in 2019.1,2 Subsequently, two independent groups convincingly demonstrated the rationale for the GTV-only+immunotherapy approach in pre-clinical models.3,4 We now report 5 year clinical outcomes from the NIRT-1 study (NCT03247712).
Methods: 16 patients with HPV+ HNSCC were treated under an IRB approved, single-institution, neoadjuvant clinical trial, the full details of which have been previously published.2 As pre-specified per trial protocol, surgery was performed at 6 weeks post-SBRT, as scheduled, in all cases, followed by tumor board final pathology review to assess indications for standard risk-adapted adjuvant radiation+/-chemotherapy.
Results: At surgical resection, we observed a major pathologic response rate of 94%, defined as less than 10% viable tumor cells remaining in the resection specimen, (mPR-90; 15/16), and a pathologic complete response rate of 75% (pCR; 12/16). One patient did not qualify as mPR-90 (1/16), with pCR at the primary, but only 10% treatment effect in a non-irradiated ipsilateral cervical node (non-avid on staging PET/CT, therefore not included in GTV-only SBRT plan), found to be involved on neck dissection final pathology; this patient remains free of recurrence at greater than 5 years. No patient met indications for risk-adapted adjuvant therapy by standard criteria. In subsequent follow-up, we observed overall 5-year overall survival (OS) of 100% and disease-free survival (DFS) of 88% (14/16). Two recurrences were observed, both locoregional and out-of-field. The first patient, a 62-year-old male with cT2N1M0 left tonsil SCC with pCR at surgery, recurred in a contralateral right level IIa node after 1 year, requiring contralateral salvage neck dissection. The second patient, a 67-year-old male with cT2N1M0 left tonsil SCC with pCR at surgery, recurred in an ipsilateral left level IV node after 5 months requiring salvage neck dissection, then recurred 9 months later at the same site. He was treated on a phase I trial, followed by re-SBRT 8Gyx3 and nivolumab for 2 years. Both patients remain free of disease beyond 5 years.
Conclusions: We observed 94% mPR-90 / 75% pCR at surgery, with subsequent 5-year OS 100% / DFS 88% in a group of 16 locally advanced HPV+ HNSCC patients treated with neoadjuvant GTV-only SBRT+immunotherapy. Limited recurrences at 5 years (2/16) were both locoregional and out-of-field, rather than distant M1, involving non-avid cervical lymph nodes by baseline PET/CT used for GTV planning; and both cases were readily salvaged. Although an exploratory approach, it is promising that 5-year OS/DFS were achieved, whilst: reducing duration of radiation from 6.5 weeks to 5 days (8Gy x3; M-W-F); eliminating elective nodal irradiation with attendant long-term sequelae; eliminating chemotherapy, and offering a potential framework for risk-adaptive surgery. A companion phase II study of neoadjuvant GTV-only SBRT+immunotherapy, in HPV-negative HNSCC, will assess risk-adapted surgical approaches and has nearly completed accrual (NCT04938609). Consensus around the 8Gy x3 schedule for neoadjuvant GTV-only SBRT+immunotherapy appears to be emerging in multiple cancer types since our initial 2019 report (see table).
