Abstract A17: Neutrophil-to-lymphocyte ratio predicts response to neoadjuvant presurgical PD-1 inhibition in oral cancer
Authors: Horton Joshua , Knochelmann Hannah , Armeson Kent , Bobian Michael , Paulos Chrystal , Kaczmar John , Neskey David 
Published: September 2020

Introduction: Oral cavity cancer affects 350,000 patients yearly with ~50% recurrence rates despite the standard-of-care primary surgical resection followed by adjuvant (chemo)radiation. Immunotherapy in the form of PD-1 blockade has demonstrated efficacy in recurrent/metastatic head and neck cancer, and elevated neutrophil-to-lymphocyte ratio (NLR) has been shown to correlate with poorer outcomes in this setting. We have an ongoing phase II clinical trial of neoadjuvant, presurgical nivolumab in treatment-naive oral cavity cancer and sought to evaluate the relationship between NLR and response to immunotherapy in this context.

Methods: Patients with surgically resectable stage II-IVA squamous cell carcinoma of the oral cavity underwent baseline radiographic evaluation before receiving three doses of biweekly 3mg/kg nivolumab. Following the third dose, repeat imaging was obtained and if disease progression was noted by RECIST 1.1 criteria, patients proceeded directly to surgical resection. Conversely, if there was response or stable disease on repeat imaging, patients received a fourth dose of nivolumab before proceeding to surgical resection. Final response was defined as % change in tumor size on final pathology compared to size on enrollment imaging. Complete blood counts (CBC) were abstracted from the medical record pretreatment, at the time of each nivolumab dose, and post-treatment (presurgery). NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count.

Results: Nine patients have completed the trial: 4 responders, 1 stable disease, and 4 nonresponders. Elevated NLR after the third dose of neoadjuvant nivolumab (prior to surgery) is predictive of pathologic disease progression after surgical resection (p=0.013). NLR &gt; 3 has a positive predictive value of 100% for ultimate nonresponse to this therapy. A significant positive linear correlation between NLR and % change in tumor size through treatment exists (r=0.717, p=0.037), which mirrored the predictive value of interval imaging. Individual CBC values, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and derived NLR do not predict response. There was no confounding association of NLR with any baseline patient characteristic or enrollment tumor size, stage, or nodal status.

Conclusion: In this small cohort, presurgical NLR following neoadjuvant nivolumab is predictive of pathologic response after surgery for oral cavity cancer. This novel finding represents an important prognostic and patient counseling tool. If validated, NLR could serve as an adjunct to imaging to stratify patients to receive neoadjuvant immunotherapy before surgery in future trials or clinical practice.

Citation Format: Joshua Horton, Hannah Knochelmann, Kent Armeson, Michael Bobian, Chrystal Paulos, John Kaczmar, David Neskey. Neutrophil-to-lymphocyte ratio predicts response to neoadjuvant presurgical PD-1 inhibition in oral cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A17.