Correlation Of Toxicity And Response With Pd-L1 Expression In Oropharyngeal Cancers Receiving Definitive Chemo-Radiotherapy

The Programmed Death Receptor Ligand 1 (PD-L1), is a cell-surface glycoprotein expressed on cancer cells, macrophages, T cells and other tissues. The interaction of PD1 and PD-L1 can suppress the cytotoxic CD8 T-cell mediated immune response. Several studies have shown correlation of PD-L1 expression with tumor burden and survival in head and neck cancers. Thus we intend to evaluate the correlation of toxicity and response with PD-L1 expression in oropharyngeal cancer patients receiving definitive chemo-radiation. The study was a prospective observational study in histopathologically proven squamous cell carcinoma of oropharynx of stage II to IVA (AJCC 8th) and Karnofsky performance status 70 or above. PD-L1 expression was evaluated both in tumor cell and Tumor Infiltrating leucocytes (TILs) in the biopsy specimen. Definitive radiotherapy (RT) of 70 Gy in 35 fractions (#) at 2 Gray /#, 5 # a week in two phases was delivered by linear accelerator using 3 Dimensional Conformal radiotherapy techniques along with concurrent chemotherapy, Cisplatin 35 mg/m2 weekly. Patients were assessed once weekly during radiation. Toxicities were recorded according to Toxicity criteria of Radiation therapy oncology group (RTOG) acute toxicity criteria. Post treatment follow up was done monthly. Response assessment was done 3 months post RT according to World health organization (WHO) response assessment criteria. Grade ≤2 versus >2 toxicities and complete response vs partial or stable disease was correlated with PD-L1 expression using Chi square test. P value of < 0.05 was considered statistically significant. 40 patients were enrolled with a median age of 55.5 years (range 26-75). 90% patients had history of tobacco abuse & Base of tongue was most common subsite (58%).15/40 patients were positive for PD-L1 in tumor cells. Among these, 8 were also positive for PD-L1 in TILs (Tumor infiltrating lymphocytes) and 4 were co-positive for P16. 44% of low and intermediate grade tumor were PD-L1+ve and all the high grade tumors were PD-L1 +ve (p = .014). Median RT dose was 70 Gy and median RT duration was 49 days. None of the patients had grade IV or above toxicity. Overall grade >2 toxicity was 50% oral mucositis, 45% dysphagia & 28% laryngeal toxicity. Radiation toxicity in terms of oral mucositis, dysphagia was more in PD-L1 -ve patients in comparison to PD-L1 +ve patients (table 1). At a median follow up of 10 months (range 3-18) overall survival was 96% in the PD-L1 –ve arm and 80% in PD-L1 +ve arm (p=0.04). PD-L1+ve is strongly correlated with high tumor grade. Patients with PD-L1 positivity have lower radiation toxicity and may have poorer survival compared to PD-L1 –ve patients.Abstract 2978; Table 1Relation of toxicity and treatment response with PD-L1 +veAcute ToxicityGrade ≤2 (n)Grade >2 (n)P valueOral MucositisPD-L1+1140.048PD-L1 -916DysphagiaPD-L1+123.021PD-L1-1015Laryngeal ToxicityPD-L1 +1230.29PD-L1-1510ResponsePD-L1 +PD-L1 –CR (+)9170.4CR (-)38n - Number of patients Open table in a new tab