The Time Series Behavior of Neutrophil-to-Lymphocyte Ratio in Thyroid Cancer Patients on Tyrosine Kinase Inhibitor Therapy

Abstract

Introduction: The neutrophil-to-lymphocyte ratio (NLR) reveals the balance of immune system is and associated with survival in various type of cancers. Tyrosine kinase inhibitors (TKI) improve patient survival with progressing thyroid cancer and are said to have less side effects, and are considered good palliation. Objective: This study evaluated the time series behavior of NLR in advanced thyroid carcinoma patients on TKI therapy and examined what percentage of patients received TKIs in the last month of life. Methods: We retrospectively reviewed medical records on 72 patients with advanced thyroid carcinoma treated with TKIs between May 2015 and October 2018. All patients had progressive disease and/or uncontrolled distant metastasis. Fifty-two patients had differentiated thyroid carcinoma (DTC), 19 patients had anaplastic carcinoma (ATC), and 1 had squamous cell carcinoma. NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. Median follow-up time in DTC and ATC patients was 12.3 months (range 0.9–40.4) and 2.7 months (range 0.6–14.3), respectively. Results: In DTC patients, median NLR at initial treatment, at initiation of TKI, and for 20 patients who died at the time of death was 2.25 (range, 0.89–9.78), 3.55 (range, 0.86–28.3), and 11.78 (range, 0.98–98.0), respectively. In ATC patients, median NLR at initial treatment, at initiation of TKI, and for 16 patients who died at the time of death was 2.96 (range, 1.12–9.0), 11.43 (range, 2.32–95.0), and 16.9 (range, 3.45–95.0), respectively. NLR >10 at TKI initiation was significantly associated with shorter overall survival compared with NLR <4 and NLR 4–10 (p < 0.0001) in DTC patients. Among 46 dead patients, 32 patients (68.1%) received TKIs treatment in the last month of life (85% DTC patients and 61.5% ATC patients). In receiver operating characteristic curve analysis, cutoffs for DTC and ATC were 11.43 (p = 0.0488, area under the ROC curve 0.941) and 31.67 (p = 0.0034, area under the ROC curve 0.831) in patients who survived ≤6 weeks and >6 weeks, respectively. Conclusion: A substantial percentage of patients received TKIs in the last month of life. The NLR increased according to tumor progression and predicted survival after TKI initiation. We might refer the patients with NLR >11.43 in DTC and those with NLR >31.67 in ATC to a hospice/palliative care program.